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Acute oral toxicity of cottonseed oil

EFSA OK’s Glyphosates Irregardless of Cancer Effect

Garlic and Its Effects on Health with Special Reference to the Reproductive System

Sugar Detox- There's an enzyme for that

Persistent infections persist- Blame bacterial socialism

Liquid salts deliver drugs through the skin with enhanced efficacy, reduced toxicity

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Acute oral toxicity of cottonseed oil

Cottonseed oil given intragastrically to young, male albino rats in amounts over 70–80 ml/kg in one dose was immediately evacuated through the anus. When the total dose was divided into 4 equal parts, each part given daily for 4 days to segregated animals, deaths occurred on days 3 and 4. The LD50 (4 doses) ± SE of cottonseed oil so given was found to be 275 ± 22 ml/kg, the maximal LD0 was estimated at 203 and the minimal LD100 at 347 ml/kg. The clinical signs of intoxication were pallor, listlessness, diarrhea, cyanosis, epistaxis, ataxia, dyspnea, anorexia, loss of body weight, hypothermia, oligodypsia, oliguria and aciduria. At autopsy there was found a fulminating congestion of the brain associated with generalized capillary-venous congestion, lysis of the red blood cells, capillary hemorrhage, dehydration, loss of organ dry weight, and widespread deposits of oil droplets in tissues. The syndrome was accompanied by a stress reaction, large cell-infiltrated ulcers in the cardiac stomach, and degenerative changes in the renal tubules, skeletal muscle, and salivary glands.

 

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EFSA OK’s Glyphosates Irregardless of Cancer Effect

 

The spat started in November when EFSA concluded that “it is unlikely that this substance is carcinogenic”. This was contrary to an IARC analysis in July that glyphosate is “probably carcinogenic to humans”.Until now, the food safety authority has been reluctant to engage in what its executive director has referred to as “the Facebook age of science” . But this week Dr Bernard Uhl published an 18-page response to criticism of his team’s risk assessment of the world’s most popular weed-killer.“I agree that IARC carries out an important role in the screening assessment of the carcinogenic potential of agents,” he wrote.“However, we should not compare this first screening assessment with the more comprehensive hazard assessment done by authorities such as EFSA[F1] , which are designed to support the regulatory process for pesticides in close cooperation with the member states in the EU.”“Open and transparent”Last year 96 scientists – including a number from the IARC team – had hinted that EFSA’s process was also too cosy with industry in a letter, dated 27 November 2015 and addressed to EU health commissioner Vytenis Andriukaitis.Uhl hasn’t held his tongue on the issue by any means, but with a meeting slated with IARC in mid February as it is currently understood- he has been forced to defend the decision publicly. He wrote: “EFSA considers that the arguments brought forward in the open letter do not have an impact on the EFSA conclusion on glyphosate. The arguments expressed in the open letter reflect a misunderstanding of the evidence used for the EFSA evaluation.”Uhl detailed how transparent the EU system is and noted how EFSA isn’t afraid to blacklist a chemical when necessary. The assessments of hundreds of active substances in the past 12 years has led to the removal of more than 40 of them from the EU market, he explained.Contrary conclusions The bulk of the letter is used to address specific criticisms levied at the authority’s analysis. He detailed why, in particular, EFSA and IARC have come to different conclusions – and not for the first time either.“The screening aim of the IARC classification scheme explains why chemicals in pesticides such as glyphosate, or red meat, or frying food at high temperatures, can be included in the same IARC category as being probably carcinogenic. But it is important to remember that these classifications are only one part of the body of information in a risk assessment and on which public health decisions may be based.”Uhl’s response is certainly focused on the factual rather than “the Facebook of science”. However, he couldn’t resist a dig at the approach taken by those criticising the EU’s risk assessment system .“Glyphosate is currently a keenly debated issue, which makes it especially incumbent on those of us involved in its evaluation to describe clearly the legal frameworks in which we work. In that way, we avoid confusing the policy makers who rely on our advice and the general public who depend on us to maintain the highest standards in protecting public health.”Losing trust [F2] It isn’t clear whether Uhl’s letter will have appeased the commissioner. In a letter to the scientists seen by the UK’s Guardian newspaper, Andriukaitis reportedly referred to the diverging opinions on glyphosate as “disconcerting”.Pan Europe environmental toxicologist Angeliki Lysimachou said the “letters telling the other off is not getting [us] anywhere”.“I see people loosing their trust on the scientific coherence of EFSA since it insists to dismiss data on effects of glyphosate products from epidemiology and genotoxicity studies because they are done on the product rather than the active ingredient. After all we are all exposed to the whole product and Europeans trust the authorities that they will be protected from harmful pesticides,” she added.Last year bread companies were urged to drop glyphosate given that a third of UK samples contained traces of it. The levels were within safe limits, however, the industry said

 

 

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Garlic and Its Effects on Health with Special Reference to the Reproductive System

Carlo Valente, Guillaume Aboua and Stefan S. Du Plessis

Additional information is available at the end of the chapter http://dx.doi.org/10.5772/57191

 

1. Introduction

Garlic[F3]  is widely used around the world for its pungent flavour as a seasoning or condiment. From the history, it is known that garlic has been used for more than 7,000 years by humans[F4] . Originally the plant was native to central Asia [1], but it has long been used for consumption (raw or cooked) as seasoning in many other parts of the world such as the Mediterranean region, Africa, and Europe. It has specifically been used for its medicinal purposes in ancient Egypt. [2]. The garlic plant's bulb is the most commonly used part of the plant. As mentioned, garlic or more specifically the cloves is believed to have many medicinal properties ranging from positively affecting anything such as high blood pressure (BP) and lowering cholesterol to using it as a treatment for the common cold [3]. Even Hippocrates, Galen, and Dioscorides all mention the use of garlic for many conditions, including parasites, respiratory problems, poor digestion, and low energy [4]. Plants have always been the sources of important medicines since time immemorial. Currently there is a huge movement and emphasis towards scientifically and clinically unlocking the value of traditional phytomedicines in the service of humanity. With this in mind the scope of this chapter is to investigate garlic's effects on human health with special reference to the effect on the reproductive system. The chapter will furthermore aim to explain the mechanisms via which garlic can exert its effect.

 

© 2014 Valente et al.; licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.260

 

Antioxidant-Antidiabetic Agents and Human Health

 

2. Garlic: Overview and properties

Allium sativum, or commonly known as garlic, is a vegetable species that can be classified as either a food or a medicinal herb. It is a widely used plant product that is cultivated all over the world. Garlic falls into a family of Amaryllidaceae or the genus Allium. Its closest relatives in the onion genus include the onion, shallot, leek, rakkyo and chive [4]. The bulbs are mainly composed of water (approximately 84.09%), organic matter (13.38%) and inorganic matter (1.53%). The leaves consist of more or less the same components with slightly different ratios (water 87.14%, organic matter 11.27% and inorganic matter 1.59%) [5, 6]. The organic matter is mostly carbohydrates while the inorganic matter is compounds such as sulphur and iron. The large number of sulfur compounds contributes to the smell and taste of garlic. Allicin has been found to be the compound most responsible for the "hot" sensation of raw garlic (RG) [7]. Allicin, along with its decomposition products diallyl disulphide and diallyl trisulphide, are major contributors to the characteristic odour of garlic, while other allicin-derived compounds, such as vinyldithiins and ajoene show beneficial in vitro biological activity [4]. Despite having a minimal amount of ions and other compounds, those that are present play a very important role in the composition and overall beneficial effects that garlic potentially possesses [8]. When crushed, Allium sativum yields allicin, an antibiotic [9] and antifungal compound (phytoncide) discovered by Cavallito and colleagues in 1944. Fresh or crushed garlic also has enzymes, B vitamins, proteins, minerals, saponins[F5] , flavonoids, and Maillard reaction products. Furthermore, a phytoalexin (allixin) was found, a nonsulfur compound with a -pyrone skeleton structure with antioxidant effects, antimicrobial effect [10]antitumor promoting effects [11], inhibition of aflatoxin B2 DNA binding and neurotrophic effects [11]. There are different variants of the garlic root and each has its own properties that aid with good health. The white (natural) and black (fermented) garlic are just derivatives of how it is prepared, although each has its own unique effects. The white garlic is said to have medicinal properties while the black fermented garlic is more commonly used for cooking. Garlic can further be divided into two main subspecies being Ophioscorodon or hard necked garlic and Sativum or soft necked garlic [12]. Garlic can often be found in 4 forms namely; RG homogenate, garlic powder, aged garlic extract (AGE) and garlic oil. · The RG homogenate is prepared by collecting garlic cloves and removing several outer layers. The cloves are then blended with distilled water and left for half an hour at 25ºC. The solution is then filtered and a homogenate sample is obtained [13]. · Garlic powder is prepared by pulverising crushed and dehydrated garlic cloves. This is mainly used for cooking purposes.· AGE is obtained by placing garlic cloves in ethanol for a minimum of 20 months at room temperature. This reduces the concentration of allicin [13]. Which could reduce the medicinal properties of garlic as allicin is said to play a significant role. · Garlic oil is obtained through a complex steaming and distillation process and is used in cooking or as medicinal oil. The preparation of the garlic bulb is probably the most important factor in its effectiveness. Fresh garlic is often described as the best preparation to use to get superlative medicinal value out of the herb. Dried or cooked garlic often loses its potency because the amount of allicin present is significantly decreased in the cooking process [3]. Although the active ingredient in garlic is said to be unknown there is a lot of speculation around allicin as being the main constitutive/candidate [3]. More studies on sulphur are currently being done as this could also play a significant role, especially in organically grown garlic. Other studies state that the active ingredients are more directly associated with sulphur-containing amino acids, such as allicin, S-allylcysteine (SAC), S-allylmercaptocysteine (SAMC) S-methylcysteine, diallyl disulphide and sulfoxides [14]. Allicin is a very unstable molecule and breaks down very easily. This is why it is recommended to eat fresh garlic as it contains the highest amount of allicin. It is also the reason for the strong odour that garlic possesses. The more prominent this odour is the higher levels of allicin and beneficial values the bulb is said to have [15]. Due to this instability medical companies have now started to develop garlic supplements that contain Alliin - a stable precursor to allicin. It is only released upon digestion meaning the body will have the added benefit of having a sufficient amount of the favourable metabolite along with the safer more stable option [15]. The preparation of the garlic is of vital importance and studies have shown that each preparation has its own beneficial effects and more importantly its own threshold to when it starts becoming detrimental to the body. 2-5g of RG and 10-15g of boiled garlic provide beneficial effects with regard to prevent cancer development [F6] [16]. Likewise a certain amount of garlic supplementation would be beneficial in the male reproductive system. Unfortunately this amount is still unknown.

 

3. Garlic and human health

Garlic has been considered as a disease preventative food and its effects on the human health have been studied. Garlic infused medicine is on the increase due to the proposed beneficial effects on human health. The effects of garlic on both plant and animal models is best known for its ability to decrease the amount of lipids or free fatty acids, as well as its anti-atherogenic effects in both models [8]. Garlic supplements are now also being widely developed and recent studies have shown just that by mimicking the effect garlic has on the body. Allium products have the potential to reduce the risk of developing cancer or the potential to decrease the risk factors associated with cancers [17]. Research has been done on this and some evidence has been found that it has beneficial effects but there are also studies that show no effect at all [18]. Garlic has shown to have therapeutic effects, but the side effects are poorly investigated. The medicinal effects of garlic on certain diseases and specific systems will subsequently be discussed. 3.1. Effects on cardiovascular system Cardiovascular disease (CVD) also known as heart disease is becoming an increasingly alarming problem in developing countries as it is the most common form of mortality [14]. Countries such as Spain and the USA have always been associated with heart disease, but developing countries are now showing an increasing trend in developing heart conditions [19]. With risk factors such as hypertension and hypercholesterolemia present, the onset of heart disease becomes more likely [20]. The effects of garlic on the cardiovascular system have been attracting a lot of interest in recent times with the development of modern medicine in particular [3]. An increase in the amount of cholesterol in the body can lead to the formation of atherosclerotic plaques and this is a risk factor for both heart attacks and strokes. Low-density lipoprotein (LDL) cholesterol levels can greatly be reduced without affecting the good High-density lipoprotein (HDL) cholesterol levels. The mode of action is said to be that garlic blocks the liver from making too much LDL because of its bio-active ingredients [15]. The high levels of cholesterol result in an increase in free-radical producing peptides. Reactive oxygen species (ROS) and oxidative stress (OS) levels are also key markers in CVD and by decreasing these levels the onset of heart disease can be delayed. Unfortunately the likeliness of developing heart disease increases with age and decreasing the amount of harmful oxidation in the body would be beneficial. Garlic can delay the onset of heart disease due to its antioxidant properties. The type of extract used is of vital importance as it will influence the beneficial effects. Garlic reduces the amount of cholesterol in the body and by doing this the heart becomes more protected. Garlic also plays an important role in maintaining the structure and efficacy of endothelial cells [F7] and endothelial function [21]. The administration of AGE inhibits the progression of coronary artery calcification and reduces the risk of a myocardial infarction or a heart attack [20]. Similarly, Allicor (a garlic powder tablet) was given to people suffering from coronary heart disease (CHD). This resulted in decreasing the risk of myocardial infarction, more significantly noted in males as opposed to females [14]. Studies have shown that the most effective way to reduce CVD is to try and reduce all the risk factors. Garlic-based preparations is thought to be promising agents for multifunctional risk reduction, but the mode of action remains slightly obscure [14]. With an increase in age the metabolic parameters of an individual is likely to change and this is evident in the onset of menopause in females. The end of the fertile phase in a woman's life is known as menopause and generally occurs during midlife or typically between the ages of 40 and 50. Together with diabetes, excessive weight, hypertension and endothelial dysfunc tion, menopause is a well-known risk factor for CVD which could lead to an increase in metabolic parameters. Evidence shows that the vascular function in postmenopausal women could be affected by the changes in the reproductive hormones. One of the main precautionary measures for postmenopausal women with an increased CVD risk is exercise, however since ancient times garlic has been used as a treatment for CVD. It is said that AGE combined with exercise resulted in greater body weight loss than either AGE or exercise on its own. With the onset of menopause, fat and cholesterol levels are increased as well as the degree of oxidative stress. AGE has shown to reduce all these factors and is more easily absorbed in the body than other garlic preparations [21]. 3.2. Effects on blood pressure Blood pressure or arterial BP is the pressure exerted by circulating blood upon the walls of blood vessels [22]. BP can fluctuate from person to person depending on the individual and their health. A healthy patient should have an ideal BP of 120/80. If the BP exceeds 140/100 the patient is said to be hypertensive and if it is below 90/60 the person is hypotensive [F8] [23]. Hypertension and diabetes is said to be lifestyle-related diseases that has become a serious issue for countries previously not associated with it. Asian countries have now started to show a large increase in the amount of people suffering from high BP, with Japan having an estimated total of seven million people living with the disease [24]. Moreover one billion adults worldwide are affected by hypertension with about sixty-five million of them residing in the USA. This has led to approximately 40% of cardiovascular related deaths [25]. Hypertension has been considered to be the most important bio-marker in the onset of CVD. Anti-hypertensive treatment has not always resulted in the desired effect of reducing the BP and alternative means of medication have now been developed. Garlic supplements and garlic derived products are becoming more and more popular in western medicine. AGE and RG showed to have the highest effect on lowering BP [24]. Interestingly, it is well known that AGE contains less allicin than RG. This has led to more studies being performed in order to establish the compound specifically responsible for lowering of the BP and reducing hypertension. The lowering effect that garlic has on BP is said to be due to the fact that the nitric oxide (NO) system is more active than the renin-angiotensin system. NO and Hydrogen sulphide (H2S) play major roles in the progression of diseases, both NO and H2S are considered to be important vasodilators. In a recent study both serum NO and H2S were measured in diabetic rats and it was shown that chronic administration of garlic normalised both gaseous molecules and reduce BP [26]. It was found that both aged garlic and raw RG produce the same amount of NO implying that nitric oxide synthase (NOS) is the key to lowering BP. Both forms of garlic resulted in an increase in the activation of NOS. An increase in NO will lead to an increase in the relaxation of the blood vessels, and will therefor lead to a decrease in the BP. However, studies have shown that both AGE and RG require at least 3-4 weeks of daily administration before their action is expressed and this suggests that there could be a different mechanism for the lowering of BP

The administration of AGE improved the condition of arteries as well as prevented the stiffening of the blood vessels which is a key marker in aging. By doing this it also improves erythrocytes which are the main component of blood. And there for improves peripheral circulation and leads to a decrease in erythrocyte deformation. The improvement of blood circulation caused by AGE could be one of the causes of lowering BP, but RG showed to cause an increase in erythrocyte deformation and could lead to anaemia [25]. Garlic's medicinal properties in relation to its ability to lower BP have been studied extensively. It has been shown to significantly reduce BP in hypertensive patients when compared to those receiving a placebo [28]. Chronic feeding of AGE and RG decreased BP. Unfortunately the exact mechanism is not entirely elucidated as of yet. However, RG showed more harmful than beneficial effects. These results suggest that with regard to decrease in hypertension aged garlic would be the better and safer option [24]. It is also a safer treatment to use in conjunction with conventional antihypertensive therapy [25]. 3.3.

 Effects on diabetes Diabetes mellitus, or simply diabetes, is an endocrine disorder that forms part of a group of metabolic diseases characterised by elevated blood sugar levels or an insulin deficiency. Between one and two percent of the global population is affected by diabetes and there are roughly 100 million patients worldwide [29]. The most common form of diabetes is type two diabetes mellitus and comprises 80 percent of all diabetic populations [30]. A predicted increase from 51 to 72 million individuals affected by diabetes is expected in developed countries in the next decade; this translates to an increase of more than 42 percent. Developing countries will however face the brunt of the pandemic as it is expected to show an increase of 170 percent [31]. Diabetes is divided into two categories based on its mechanisms. Type 1 diabetes results from an individual's body failing to produce insulin, and currently requires the person to inject insulin or wear an insulin pump. It is also referred to as insulin-dependent diabetes mellitus (IDDM) or juvenile onset diabetes due to the fact that it is prominent in children [32]. This is a rare case of diabetes in comparison to its counterpart. Type 2 diabetes results from insulin resistance, a condition in which cells fail to use insulin properly, in some cases it is combined with an absolute insulin deficiency. It is also referred to as non-insulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes [32]. An individual's dietary factors play a key role in both the onset as well as the prevention of diabetes and other metabolic disorders [33]. Garlic is recognised for its therapeutic potential for controlling diabetes and its subsequent metabolic complications. The hypoglycaemic effect that garlic is said to have is attributed to the presence of allicin and sulphur compounds. Studies have shown that the oral administration of RG significantly reduced blood glucose levels and improved insulin sensitivity in garlic treated rats. Administration of aqueous garlic in patients with Type 1 diabetes has been reported to increase insulin sensitivity[F9] . Furthermore, metabolic complications such as increased serum-triglyceride, insulin and uric acid levels usually observed in diabetic rats were normalised after garlic administration [30]. Interestingly it has been observed that chronic administration of RG significantly reduced body weight[F10] , however the mechanism as to how garlic contributes to a reduction in body wait is still unclear. A study by Elkayam [26] has shown that allicin administered for 2-3 weeks reduced weight gain in fructose fed rats. Together with reducing glucose levels allicin also has the added advantage of decreased weight gain. Glycation is the spontaneous phenomenon that occurs whenever proteins are exposed to reducing sugars and is depended on the degree and duration of hyperglycaemia in the body. It has been suggested that a direct reaction referred to as the Maillard reaction takes place during hyperglycaemia. This is a reaction that occurs between the sugars and proteins in the body. Advanced glycation end products (AGEPs) are formed when glycated proteins react with dicarbonyl intermediates to form complex heterogeneous, cross-linked and fluorescent molecules. Little is known about the chemistry of AGEPs but AGEPs are said to generate free radicals and lead to oxidative damage and this inevitably leads to diabetic complications [29]. The exact mechanism as to how garlic decreases glycation is uncertain but it is said to be due to decreasing the free radicals in the body, and it also increases anti-oxidant enzymes. Garlic also plays a role in the regulation of the Maillard reaction by inhibiting AGEP production/ formation, but more research is required on the exact mechanism [29]. 3.4. Effects on dementia and the brain Increased homocysteine levels damages the endothelial cells that line blood vessels and prompts apoptosis by producing strand breaks in the DNA. This causes thrombotic activity that could result in heart attacks and strokes. Individuals living with dementia have a much higher level of homocysteine than healthy people and there is a significant link between high levels of homocysteine and loss of cognition. It has also been indicated that the intake of AGE decreases homocysteine levels [20, 34]. Studies have also shown that there could be a link between heart diseases and dementia risks [34]. Risk factors such as hypertension, high cholesterol, increasing levels of homocysteine, inflammation and oxidative stress are all related to both heart disease and dementia. These risks factors occur in the brain due to an increase in - peptide levels or a restriction in the blood supply to tissues. This could then result in cardiovascular or cerebrovascular diseases of which dementia and Alzheimer's disease (AD) is included [20, 34]. In addition to oxidative stress, free radicals such as ROS are closely associated with CVDs, cerebrovascular diseases such as dementia and cancer. It is believed that the damage done to DNA, proteins and lipids are considered of the foremost causes in the commencement and development of the diseases. Free radicals increase in number when there is an infection, inflammation, hyperhomocysteinemia or exposure to smoking, drugs and radiation [35]. When the LDL cholesterol levels are changed due to oxidative stress and free radicals, the risk of atherosclerosis, cardio and cerebrovascular diseases increase. In addition neuronal apoptosis is triggered which leads to an increase in the risk of brain atrophy and dementia. AGE is known to lower homocystein levels, increase microcirculation and provide protection for endothelial cells from the effects of oxidation. Following a stroke the risk factors of neurodegenerative conditions and CVD include myocardial ischemic or reperfusion injury, AGE can protect the body against this by increasing the production of constitutive NO [20, 34]. AGE has also been shown to possess anti-aging properties, in studies AGE prevented the deterioration of the brain's frontal lobe, and enhanced learning and memory retention. 3.5. Effects on cancer Cancer or malignant neoplasm is a broad group of diseases involving unregulated cell growth. Cell division and uncontrollable growth of these cells form malignant tumours in individuals living with cancer. These tumours are very likely to invade nearby parts of the body. The lymphatic system or bloodstream may also spread the cancer to more distant parts of the body. However, not all tumours are cancerous. Benign tumours do not invade neighbouring tissues and do not spread throughout the body [36]. There are over 200 different known cancers that affect humans ranging from breast and prostate cancer to colorectal and lung cancer. In the year 2008 approximately 12 million people worldwide were said to be living with cancer and this figure is expected to rise to about 21 million by the year 2030. Lung cancer is responsible for the most deaths closely followed by breast and colorectal cancer [37]. Garlic is said to have chemo-preventive properties and its effects have been closely studied on various cancers. The antitumor effects that garlic potentially possesses are directly attributed to its anti-mutagenic properties [38]. The formations of tumours in vitro and in vivo were shown to be greatly decreased after the administration of fresh garlic, al though the mechanism of action is still unknown. The timing and dose of the garlic could be the main factor in inhibition of the pro-carcinogens [38]. A possible mode of action as to how garlic can prevent cancer is by the effects of Diallyl trisulphide (DATS). DATS is a by-product of garlic that exhibits several pharmacological effects (e.g. anti-microbial and CVD), making this compound a promiscuous agent with possible beneficial chemoprevention properties due to the complex pathways in cancers [39]. Oral ingestion of aged garlic (that is lacking enzymatically produced allicin due to the fact that it was not chopped) reduced 1, 2-dimethylhydrazine induced colon tumours significantly [40]. With specific reference to skin cancer, the treatment results are inconclusive and more research will have to be conducted [41]. Stomach tumours were greatly decreased by administration of AGE. The toxicity of garlic was not directly responsible for the death of cancer cells alone although it does play an important role. Another key role in the prevention of cancers is garlics effect on the immune system. Macrophage activity, NK and killer cells as well as the cytokine TNF were all shown to have increased activity after administration of garlic and this resulted in an increase in antitumor response [42]. Colorectal cancer is the third leading cause of cancer death in the world. In this respect normal garlic cannot be administrated and would need to be introduced as part of a strict diet. The Garlic and low meat diet did however show a decrease in colorectal tumour growth [43].

3.6. Effects on reproductive system Infertility and especially idiopathic infertility has been on the increase during the last century. Infertility is the inability to conceive after having sexual intercourse for more than a year of trying [44]. In 19-57% of cases the male is at fault when a couple have infertility concerns [45]. This has led to a lot of research on male fertility and the male reproductive system. Garlic and its effects on the male reproductive system has caused a tremendous amount of interest in the Andrology[F11]  and reproductive field as some researchers believe it to have a beneficial influence and others believe it to have a detrimental effect on the male reproductive system. The possible reason as to why these discrepancies exist could be due to the preparation and the dosage. 3.6.1. Spermatogenesis and sperm function In a study performed by Qian and co-workers it was shown that the administration of garlic to rats showed a decrease in sperm quality and functionality. The amount and preparation of garlic will result in a decrease in specific seminal parameters. The crude extract of garlic results in an increase in the percentage of empty seminiferous tubules. It has been reported to reduce membrane disintegration and irreversible immobilization of sperm [46] while at the same time reducing sperm viability [47]. This is the reason as to why some researcher's believe that garlic acts as a natural contraceptive although more research would have to be performed [47]. The majority of data report garlic to have deleterious effects on specifically the male reproductive system. In another study testicular morphological alterations were noted after male adult rats were given 50 mg kg -1 of garlic powder for 45-75 days [48]. Hammami and El May (2009) found that garlic improved male sexual dysfunction in direct contrast to the studies previously mentioned which claimed garlic to have a negative impact on male reproductive function.[F12]  The main difference and possibly the reason between different results could be the lack of standardization between research models and the different amounts of garlic given to test subjects [3]. Spermatogenesis is the process whereby spermatozoa are produced. Needless to say it is a very important process in the male reproductive organs. The production of spermatozoa can be effected by various stimuli. ROS and heat are important in the formation of mature sperm but a large amount of ROS and higher than normal physiological temperatures levels may become hazardous to the spermatozoa. The daily administration of garlic powder and aqueous garlic to adult rats caused spermicidal effects and spermatogenetic arrest. However, feeding a higher garlic supplementation over a longer period of time to the adult rats caused an increase in Epididymal spermatozoa [3]. Although an animal model was used, comparisons can be linked to a human model to the similarities in the reproductive systems of the respective models. The effect of garlic on spermatogenesis and on testis also yielded contrasting findings. Administration of garlic over a period of time showed to have histological alterations on the cells within the testes. Both the Leydig and Sertoli cells showed lipid droplets along with a decrease in volume. Spermatocytes showed interrupted nuclear development and an increase in apoptosis was also evident [49].-268-Apoptosis is a physiological term used to explain programmed cell death [50]. Caspase 3 formation is a vital step in the activation of the apoptotic pathway and an increase in crude garlic intake leads to an increase in caspase 3 formation. Apoptosis effects the formation of spermatocytes and spermatids and the testes have shown an increase in apoptotic germ calls after the rat is exposed to crude garlic feeding [51].It was shown that supplementing the diet with crude garlic induced apoptosis in both spermatocytes and spermatids [51]. Dixit & Joshi [48] again noted that treating rats with garlic powder impaired spermatogenesis and led to an early arrest in the development of spermatozoa. This in turn reduced the amount of round spermatids converted into elongated spermatids furthermore impairing spermatogenesis. With regards to the testicular function, garlic and its metabolites have a protective function[F13] . The effects of garlic on the testes include prevention of hypogonadism caused by heat and protection against cadmium-induced testicular damage by reversing the alterations in the biochemical parameters [52]. Other beneficial properties are its ability to restore testicular histology[F14]  and decrease free radicals in the testes which are detrimental when in large amounts. 3.6.2. Hormonal levels and libido Garlic feeding has both positive and negative effects on testosterone production. It is important to note that between the different studies that were performed, different preparations, amounts and concentrations of garlic were administered. The preparation of the garlic could possibly be the key factor involved in the impact it will have. By administering crude garlic to Rat models it was recorded that there was a decrease in testosterone formation due to the decrease in responsiveness of the leydig cells to the luteinizing hormone. This decrease in responsiveness is due to the histological alteration in the testes (Figure 1). In contrast Oi et al. [53] showed an increase in testosterone levels due to the increase in the luteinizing hormones after administration of 8g of garlic powder[F15] . Again, the different preparations of the garlic plant are vital. Garlic's effects on the reproductive system have led to contradictory results. According to Hammami et al. [51] garlic has been used to improve male sexual dysfunction and this includes impotence. Heated garlic juice is effective in recovering testicular function after experimental hypogonadism[F16] , but powder or crude garlic (in large amounts) impairs male reproductive tract functions [51]. Benign prostatic hyperplasia (BHP) is an extremely common condition in older men and can affect the male reproductive system. Milk and other dairy products have been related to an increase in BHP but the results found are very inconsistent. The same trend applies for garlic as studies have shown that cooked garlic can decrease the onset of BPH but RG can increase the onset [54]. Aqueous garlic extract has however shown to improve disease parameters in patients with BPH [55]. Garlic extract also decreases the onset of prostatic cancers and other malignancies [56]. The results are however inconclusive and very contrasting amongst published articles and no real conclusion can be drawn until more research is done on the effects of vegetable- more specific garlic ­ has on the male reproductive system.

4. Mechanisms

The scientific and pharmacologic explanations for most of the medicinal effects attributed to garlic treatment are still eluding researchers. There is however a few mechanisms via which garlic more than likely exert its effects which are worth mentioning and highly plausible. 4.1. Antioxidant properties An antioxidant is a molecule that inhibits the oxidation of other molecules in the human body [57]. A chemical reaction known as oxidation occurs when electrons or hydrogen atoms are transferred from a substance to an oxidizing agent. Once this oxidation reaction occurs, free radicals are produced and realised into the body. In turn, these radicals can start chain reactions. Antioxidants terminate these chain reactions by removing free radical intermediates, and inhibit other oxidation reactions [58]. Antioxidants are present in most of the foods we eat and drink like spinach, oranges, whole wheat bread and tea. Garlic is also very rich in antioxidants [59] (Table 1). The powerful odour that fresh garlic possesses is due to the amount of allicin that is present. This odour as well as the unique acquired flavour of garlic has resulted that not every one favours it [20]. This led to the emergence of the AGE. As mentioned previously AGE is obtained via a long and tedious process. The extract obtained through this process does not have the pungent flavour of garlic and is also odourless [60]. This is due to the fact that a large amount of allicin is lost and therefore it loses a lot of its beneficial properties. However, due to the amount of allicin lost, this means that the most prominent component in AGE is the organosulfurs like SAC and SAMC. These compounds are said to have potent antioxidant effects in the body. S-allylcysteine and S-allylmercaptocysteine increase with aging of the garlic. Therefore, the longer the garlic is aged the less allicin it will contain, but the more antioxidant effect it will have. This makes AGE the most potent form of garlic with regards to antioxidant ability. Oxidative stress is the term used to describe the process that transpires when there are too many free radicals or not enough antioxidant agents in the body [20]. This oxidative damage is often associated with aging and age-degenerative conditions such as dementia and AD. AGE has shown to inhibit this oxidative damaged caused and helps with reducing the risk factor or onset of neurodegenerative disease as well as slowing down the aging process or to be more specific the onset of deteriorating skin. However, the administration of garlic did not decrease the levels of iron mediated oxidative stress [61]. The antioxidant actions of AGE are based on decreasing the amounts of ROS and reactive nitrogen species (RNS) as well as inhibiting LDL oxidation and lipid peroxide formation. An increase in ROS in the body can lead to a host of issues including endothelial dysfunction which is a key marker in the development of cardiac injury. Likewise LDL oxidation could lead to vascular dysfunction and promotes the onset of atherosclerosis and possibly myocardial infarction [20]. A study was done to compare the antioxidant potential of the different garlic preparations. AGE which is predominantly SAC and SAMC was compared to a water extract of fresh garlic containing mostly alliin and RG that contains allicin [62]. AGE had the highest antioxidant effect and surprisingly the other two preparations served more as an oxidant [62]. the majority of the antioxidant affects are from the AGE there are incidents where other preparations were used as an antibiotic/antioxidant. A lot of the mechanisms by which garlic acquired its medicinal properties have been specifically ascribed to this potent antioxidant action. It has the ability to stimulate immunological responsiveness and its modulation of prostanoids synthesis[F17] . The antioxidant properties of garlic have been studied extensively and it does have a beneficial role in the body. AGE is however more effective in removing free radicals and LDL cholesterol than other preparations of the garlic root, but that does not mean the other preparations aren't important as well. 4.2. Antibiotic properties Allicin, found in the garlic bulb, serves as a powerful antibiotic which aids the body in inhibiting the growth and reproduction of bacteria [63]. One milligram of allicin is equal to 15 standard units of penicillin [63]. Allicin attacks over 23 types of bacteria, such as staph and salmonella, 60 types of fungi and yeast and is also effective against 17 of the most dangerous fungi [64]. Another example of where allicin serves as a potent antibiotic is in the treatment of Streptolysin O (SLO). SLO is a powerful cytolytic toxin found in almost all group A streptococci. Treatment of SLO with Allicin completely neutralized the haemolytic activity of the bacteria[F18] , while the aqueous garlic extract inhibited it altogether [F19] [65]. From these results it can be deducted that garlic and its metabolites have antibiotic properties. Extracts of fresh garlic contain antioxidant phytochemicals that prevent oxidative damage. 4.3. NO and H2S NO and H2S play major roles in the progression of diseases, both NO and H2S are considered to be important vasodilators. In a recent study both serum NO and H2S were measured in diabetic rats and it was shown that chronic administration of garlic normalised both gaseous molecules [26] and this decreased hypertension by inhibiting certain enzymes such as N omega-nitro-L-arginine-methyl-ester (L-NAME) [66].

 

5. Conclusion and recommendations

From this review it is evident that garlic certainly has some medicinal properties. Various studies highlighted its cardio protective, antibiotic, anti-hypertensive and cholesterol lowering effects. Some evidence also points to its ability to lower the risk of developing cancer. Not all the research data are as clear and conclusive and certain remain ambiguous. Garlic appears to exert both positive and negative effects on the male reproductive system. Interestingly enough crude garlic (if taken in large amounts) shows the most detrimental and AGE garlic the most beneficial results[F20] . The most crucial factor in determining the effects observed is possibly the manner in which the garlic was prepared as well as the amount that is being administered.[F21]  Interestingly, large amounts are deemed to be more detrimental. Some of the results found showed that the administration of garlic affected testicular function, histological properties and sperm quality [46, 48 & 51]. Hormone levels were subsequently also altered and an increase in testicular tissue apoptosis was recorded [51]. Furthermore crude garlic extracts and garlic juice showed to cause sperm immobilization (administered as 15g/100g and 30g/100g respectively)[F22]  [51, 67, 68]. More research definitely needs to be performed on the effect of garlic on acrosome and DNA integrity of spermatozoa. In general it can be said that garlic's therapeutic properties warrants further investigation in order to develop its full treatment potential as a phytotherapeutical agent impacting on human health and used for the treatment of various disease conditions. The specific mechanism of action also need to be identified as it can possible shed more light on and help with the development of more effective pharmacological agents. Additional human studies on AGE and its constituents are needed to elucidate their role in protecting human health, and molecular studies should be intensified to reveal the underlying mechanisms.

 

Product AGE A B C D E F G H

 

Source of commercial sample Kyolic liquid (Mission Viejo) Garlinase 4000 (Enzymatic Therapy, Green Bay, WI) Garlic powder (McCormick, Baltimore, MD) Quintessence caplet (Pur- Gar, Takoma, WA) Quintessence capsule (Pur- Gar, Takoma, WA) Garlicin (Nature's Way Product, Springville, UT) Kwai (Lichtwerpharma, Berlin, Germany) Garlique (Sunsource HealthProducts, Kihei, HI) Garlic Time (ArizonaNatural Products,Scottsdale, AZ)

 

Lot# 5LO1 213Y46QD 0208A 36698 63121 503369 94080700 5J0010 896210

 

% Inhibition2 (SD) +121.8 (2.73) -213.0 (4.67) -217.2 (5.20) -239.5 (4.85) -242.1 (5.15) -246.8 (9.24) -250.7 (3.01) -251.0 (10.6) -254.4 (7.14)

 

1 Laboratory Report, Wakunaga Pharmaceutical, Hiroshima, Japan, October 1995. Courtesy of Wakunaga of America Company. Garlic products were purchased from stores, as in Freeman and Kodera 1995. Each analysis was performed three times.

 

2 Antioxidant properties were measured by the ability of the various products to inhibit the emission of low level chem iluminescence, in a liver microsomal fraction, initiated by t-butyl hydroperoxide (Imai et al. 1994). Inhibition (+) de notes antioxidant activity, resulting from scavenging of reactive oxygen species (ROS) and reflected in the inhibition of light emission. Inhibition (-) denotes prooxidant activity of a product as reflected in an increased light emission, in duced by increased ROS activity.

 

*Table reproduced from `'Recent Advances on the Nutritional Benefits Accompanying the Use of Garlic as a Supple ment" held November 15­17, 1998 in Newport Beach, CA. The conference was supported by educational grants from Pennsylvania State University, Wakunaga of America, Ltd. and the National Cancer Institute. The proceedings of this conference are published as a supplement to The Journal of Nutrition 131:1010S­1015S, 2001.

 

Table 1. Antioxidant effects of aged garlic extract (AGE) compared with other garlic supplements1* -Figure 1. Photomicrographs of sections of testes of albino rats having received 20% of their daily food as crude garlic for two months (subgroup B1) showing: (A) intraepithelial vacuoles of variable sizes (V). Sertoli cell nuclei () on the basal portion of the tubules. Primary spermatocyte nuclei either dividing normally () or with condensed chromatin (). Some seminiferous tubules possess irregular basal lamina and are separated from each other. Interstitial tissue with Leydig cells (L), plasma cells (c) and lymphocytes (Y) (×200). (B) Giant cell () formation and exfoliation in the lumen of the seminiferous tubules (×200). (Reproduced from Abdelmalik, 2011)

 

Author details

Carlo Valente1, Guillaume Aboua2* and Stefan S. Du Plessis1 *Address all correspondence to: abouay@cput.ac.za 1 Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa 2 Department of Biomedical Sciences, Faculty of Health and Wellness, Cape Peninsula Uni versity of Technology, Bellville, South Africa

 

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Chronic crude garlic-feeding modified adult male rat testicular markers: mechanisms of ac tion. Reproductive Biology and Endocrinology 2009, 7:65 [52] Eteng MU, Onwuka FC, Akpanyung EO, Osuchukwu NC, Bassey SC, Nwankpa P.Reversal of cadmium induced toxicity following dietary supplementation with gar lic, ginger and cabbage in male Wistar rats. Journal of Natural Products and Plant Resources 2012; 2 (1):169-174 [53] Oi Y, Imafuku M, Shishido C, Kominato Y, Nishimura S, Iwai Garlic supplementation increases testicular testosterone and decreases plasma corticosterone in rats fed a high protein diet. Journal of Nutrition 2001; 131:2150­2156 [54] Bravi F, Bosetti C, Dal Maso L, Talamini R, Montella M, Negri E, et al. Food groups and risk of benign prostatic hyperplasia urology 67: 73­79, 2006 [55] Galeone C, Pelucchi C, Talamini R, Negri E, Dal Maso L, Montella M, et al.Onion and garlic intake and the odds of benign prostatic hyperplasia. 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[59] Rao A, Balachandran B. Role of oxidative stress and antioxidants in neurodegenera tive diseases. Nutrition and Neuroscience 2002; 5 (5): 291­309 [60] Moriguchi, T., Saito, H. & Nishiyama, N. Anti-aging effect of aged garlic in inbred brain atrophy model mouse. Clinical Experimental Pharmacology and Physiology 1997; 24: 235­242 [61] Nahdia A,B, Hammamia I, Brasse-Lagnelb C, Pilardb N, Hamdaouic MH, Beau montb C, El May M, Influence of garlic or its main active component diallyl disulfide on iron bioavailability and toxicity, Nutrition Research 2010; 30 85­95 [62] Imai, J, Ide, N., Nagae, S., Moriguchi, T., Matsuura, H. & Itakura, Y. Antioxidants and free radical scavenging effects of aged garlic extract and its constituents. Planta Medica 1994; 60: 417­420 [63] Pandya K, Solanki B, Maniar K, Gurav N, Bhatt S. Natural herbal supplements- A study on their nutritional value and their phytochemical constituents. International Journal of Pharmaceutical Sciences and Research 2011; 2:1480­94 [64] Ankri S, Mirelman D. Antimicrobial properties of allicin from garlic, Microbes and Infection, 2, 1999, 125-129 [65] Arzanlou M and Bohlooli S. Inhibition of streptolysin O by allicin ­ an active compo nent of garlic. Journal of Medical Microbiology (2010), 59, 1044­1049 [66] Pedraza-Chaverrí J, Tapia E, Medina-Campos ON, de los Angeles Granados M, Fran co M, Garlic prevents hypertension induced by chronic inhibition of nitric oxide syn thesis. Life Sciences; 1998; 62 71-77 [67] Chakrabarti K, Pal S, Bhattacharyya AK. Sperm immobilization activity of Allium sativum L. and other plant extracts. Asian Journal of Andrology 2003;5(2):131-5 [68] Abdelmalik SW. Histological and ultrastructural changes in the adult male albino rat testes following chronic crude garlic consumption. Annals of Anatomy 2011; 193: 134­141

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Sugar Detox- There's an enzyme for that

The recent discovery of a glucose detoxification enzyme provides novel therapeutics for obesity and diabetes, say scientists. This enzyme, named glycerol 3-phosphate phosphatase [F23] (G3PP), plays a central role in controlling glucose and fat utilization. The research team has demonstrated that G3PP is able to detoxify excess sugar from the cells, and their discovery should lead to the development of new therapeutics for illnesses associated with sugar intake. -- Scientists at the University of Montreal Hospital Research Centre (CRCHUM) have discovered an enzyme that can stop the toxic effects of sugar in various organs of the body. This enzyme, named glycerol 3-phosphate phosphatase (G3PP), plays a central role in controlling glucose and fat utilization. Led by Drs Marc Prentki and Murthy Madiraju, the research team has demonstrated that G3PP is able to detoxify excess sugar from the cells, and their discovery should lead to the development of therapeutics for obesity and type 2 diabetes. The findings were published in the journal Proceedings of the National Academy of Sciences.

"When glucose is abnormally elevated in the body, glucose-derived glycerol-3 phosphate reaches excessive levels in cells, and exaggerated glycerol 3 phosphate metabolism can damage various tissues. We found that G3PP is able to breakdown a great proportion of this excess glycerol phosphate to glycerol and divert it outside the cell, thus protecting the insulin producing beta cells of pancreas and various organs from toxic effects of high glucose levels," says Marc Prentki, a principal investigator at the CRCHUM and a professor at the University of Montreal.---Mammalian cells use glucose and fatty acids as the main nutrients. Their utilization inside cells governs many physiological processes such as insulin secretion by beta cells, production of glucose in liver, storage of fat in adipose tissue and breakdown of nutrients for energy production ( ATP). Derangement of these processes leads to obesity, type 2 diabetes and cardiovascular diseases. The beta cells sense changes in blood glucose levels and produce insulin according to body demand. Insulin is an important hormone for controlling glucose and fat utilization. However, when beta cells are presented with excess glucose and fatty acids, the same nutrients become toxic and damage them, leading to their dysfunction and diabetes. When glucose is being used in cells, glycerol-3-phosphate is formed, and this molecule is central to metabolism, since it is needed for both energy production and fat formation.--"By diverting glucose as glycerol, G3PP prevents excessive formation and storage of fat and it also lowers excessive production of glucose in liver, a major problem in diabetes," says Murthy Madiraju, a scientist at CRCHUM. How significant are the findings?"It is extremely rare since the 1960s that a novel enzyme is discovered at the heart of metabolism of nutrients in all mammalian tissues, and likely this enzyme will be incorporated in biochemistry textbooks," Professor Prentki said. "We identified the enzyme while looking for mechanisms enabling beta cells to get rid of excess glucose as glycerol, adds Murthy Madiraju. This mechanism has also been found to be operating in liver cells, and this enzyme is present in all body tissues."--The work offers a new therapeutic target for obesity, type 2 diabetes and metabolic syndrome. The research team is currently in the process of discovering "small molecule activators of G3PP" to treat cardiometabolic disorders. These drugs will be unique in their mode of action and first of their kind in this class of drugs. The treatment will first have to be confirmed in several animal models before drugs for human use can be developed.-Story Source-The above post is reprinted from materials provided by Universite de Montreal.-Journal Reference-Yves Mugabo, Shangang Zhao, Annegrit Seifried, Sari Gezzar, Anfal Al-Mass, Dongwei Zhang, Julien Lamontagne, Camille Attane, Pegah Poursharifi, José Iglesias, Erik Joly, Marie-Line Peyot, Antje Gohla, S. R. Murthy Madiraju, Marc Prentki. Identification of a mammalian glycerol-3-phosphate phosphatase: Role in metabolism and signaling in pancreatic β-cells and hepatocytes. Proceedings of the National Academy of Sciences, 2016; 201514375 DOI: 10.1073/pnas.1514375113 -Universite de Montreal. "Too much sugar? There's an enzyme for that." ScienceDaily. ScienceDaily, 11 January 2016. <www.sciencedaily.com/releases/2016/01/160111122701.htm>.

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Persistent infections persist- Blame bacterial socialism

New research to be published January 13 in the journal Scientific Reports shows that some bacterial cultures adopt an all-for-one/one-for-all strategy that would make a socialist proud in preparing for the possibility of an antibiotic onslaught.

The findings could have application for how persistent infections like those associated with cystic fibrosis are treated.

The paper, by three researchers at the University of Vermont, uses a series of time-lapse videos to show that single cells within a community of bacteria randomly use a cascade of proteins to become more or less antibiotic resistant, even when the community is not threatened by an antibiotic. A bacterial colony can regenerate if only a few cells survive antibiotic treatment.-----"It's costly from a metabolic standpoint for a cell to express the proteins that enable it to be resistant," said Mary Dunlop, assistant professor in the university's College of Engineering and Mathematics Sciences, and the paper's corresponding author. "This strategy allows a colony to hedge its bets by enabling individual cells within a population to assume high levels of resistance while others avoid this extra work."---Previous research has demonstrated that, when exposed to some antibiotics, all the cells within a bacterial population will use the protein cascade strategy, activated by a mechanism called MarA, to become resistant. ---But the new study is among the first to show that colonies use the protein cascade strategy even when they are not under threat.--"This transient resistance, distributed in varying degrees among individual cells in a population, may be the norm for many bacterial populations," Dunlop said.--That may explain why infection persists in diseases like cystic fibrosis, she said. For these diseases, clinicians know not to use antibiotics that will stimulate population-level MarA resistance.--But the persistence of a few straggler antibiotic-resistant cells after treatment with the appropriate antibiotic could be enough to keep the infection alive.--The study suggests that altering the frequency and timing of antibiotic treatment could be a way of waiting out an infection as bacteria trade off antibiotic resistance among its members, enabling the drug to kill the entire culture.-Some antibiotic-resistant bacteria, such as MRSA, are resistant due to genetic changes such as mutations. Those studied by Dunlop are her colleagues alter their traits -- protein expression, for instance -- but not their genomes, making them significantly more difficult to identify since the resistance level of each bacterium changes over time.--Story Source-The above post is reprinted from materials provided by University of Vermont. Journal Reference-Imane El Meouche, Yik Siu, Mary J. Dunlop. Stochastic expression of a multiple antibiotic resistance activator confers transient resistance in single cells. Scientific Reports, 2016; 6: 19538 DOI: 10.1038/srep19538 -University of Vermont. "Why do some infections persist? Blame bacterial socialism." ScienceDaily. ScienceDaily, 13 January 20

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Liquid salts deliver drugs through the skin with enhanced efficacy, reduced toxicity

Formulating drugs as liquid salts[F24]  may provide a safe and efficient strategy for topical delivery of drugs that cause skin toxicity. A team of researchers from the University of California, Santa Barbara (UCSB) in Santa Barbara, CA has demonstrated a novel formulation of propranolol as a liquid salt which enables delivery through skin with reduced toxicity. The report appears in the December 2015 issue of the journal TECHNOLOGY.--Skin toxicity remains a major challenge in the design and use of new topical drug formulations. Many drugs must be dissolved in organic solvents which are typically toxic to the skin. In addition, many drugs such as propranolol itself show dose-dependent skin toxicity. Formulating drugs as liquid salt mitigates both sources of toxicity. Given their fluid nature, liquid salts eliminate the necessity of organic solvents. In addition, counter ions used to form the liquid salts shield the drug charge, which further reduces drug-induced toxicity.--"Propranolol is positively charged which is a likely source of its toxicity. Shielding of this charge by association with a counter species in the liquid salt reduces its toxicity. These findings are broadly applicable to many charged drugs" says Professor Samir Mitragotri, Ph.D., of the University of California, Santa Barbara and senior author of the paper.--Previous studies have shown how liquid salts may enhance drug transport through the skin; however, this is the first study that reports the design of liquid salts to minimize skin toxicity. Such formulations can increase the spectrum of drugs that can be safely delivered via a transdermal patch.--"An ideal drug liquid salt would need to permeate through the skin as an associated ion pair. Eventually, however, the drug and the counter ion must dissociate in blood to preserve drug's therapeutic efficacy. We show that these attributes can be balanced through careful selection of counter ions" says Michael Zakrewsky, the co-first author on this paper. "This technology presents an exciting new, patient compliant solution for treating diseases," he added. Story Source-The above post is reprinted from materials provided by World Scientific. Journal Reference-Kazuhiro Aoyagi, Michael Zakrewsky, Samir Mitragotri. Formulating propranolol as an amorphous melt affords reduced skin irritation potential for transdermal drug delivery. TECHNOLOGY, 2015; 03 (04): 214 DOI: 10.1142/S2339547815500107 --World Scientific. "Liquid salts deliver drugs through the skin with enhanced efficacy, reduced toxicity." ScienceDaily. ScienceDaily, 29 December 2015. <www.sciencedaily.com/releases/2015/12/151229204650.htm>.

Suggestion –you could dissolve salt and add it to either a glycerol and a alcohol and possibly pectin ( stabilizer) and add to it  immune supporting minerals or even antioxidants to further increase the uptake

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Show Of the Month February  13 2016

Protocols for Reducing and Regenerating Colon health—Rebuilding Compromised Body with as well Listing of Foods -Alkaline and Acid Foods and Updates and Modifications and warnings of either mycotoxicity or nanotoxicity or genetic toxicity or processed through toxic means

 

Naturally Occurring Organic Sulfur Compounds- An Example of a Multitasking Class of Phytochemicals in Anti-Cancer Research

Role of D-Limonene[ in autophagy

Nisin

E-cigarette vapor boosts superbugs and dampens immune system

Rising carbon dioxide emissions pose 'intoxication' threat to world's ocean fish

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Role of D-Limonene in autophagy induced by bergamot essential oil in SH-SY5Y neuroblastoma cells.

PLoS One. 2014;9(11):e113682

Authors: Russo R, Cassiano MG, Ciociaro A, Adornetto A, Varano GP, Chiappini C, Berliocchi L, Tassorelli C, Bagetta G, Corasaniti MT

Abstract
Bergamot (Citrus bergamia, Risso et Poiteau) essential oil (BEO) is a well characterized, widely used plant extract. BEO exerts anxiolytic, analgesic and neuroprotective activities in rodents through mechanisms that are only partly known and need to be further investigated. To gain more insight into the biological effects of this essential oil, we tested the ability of BEO (0.005-0.03%) to modulate autophagic pathways in human SH-SY5Y neuroblastoma cells. BEO-treated cells show increased LC3II levels and appearance of dot-like formations of endogenous LC3 protein that colocalize with the lysosome marker LAMP-1. Autophagic [F2] flux assay using bafilomycin A1 and degradation of the specific autophagy substrate p62 confirmed that the observed increase of LC3II levels in BEO-exposed cells is due to autophagy induction rather than to a decreased autophagosomal turnover. Induction of autophagy is an early and not cell-line specific response to BEO. Beside basal autophagy, BEO also enhanced autophagy triggered by serum starvation and rapamycin indicating that the underlying mechanism is mTOR independent. Accordingly, BEO did not affect the phosphorylation of ULK1 (Ser757) and p70(S6K) (Thr389), two downstream targets of mTOR. Furthermore, induction of autophagy by BEO is beclin-1 independent, occurs in a concentration-dependent manner and is unrelated to the ability of BEO to induce cell death. In order to identify the active constituents responsible for these effects, the two most abundant monoterpenes found in the essential oil, d-limonene[F3]  (125-750 µM) and linalyl acetate (62.5-375 µM), were individually tested at concentrations comparable to those found in 0.005-0.03% BEO. The same features of stimulated autophagy elicited by BEO were reproduced by D-limonene, which rapidly increases LC3II and reduces p62 levels in a concentration-dependent manner. Linalyl acetate was ineffective in replicating BEO effects; however, it greatly enhanced LC3 lipidation triggered by D-limonene[F4] .PMID: 25419658 [PubMed - indexed for MEDLINE]

 

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 [F1]D-limonene is derived from the peels of citrus fruits. It showed anti-inflammatory, wound healing and anticancer effects in laboratory studies. D-limonene was shown to alter the signaling pathways within cancer cells in a way that stops cancer cells from multiplying and causes their death (this is called “apoptosis”). In animal models, D-limonene slowed the growth of pancreatic, stomach, colon, skin, and liver cancers. It also slowed formation of tumors and their progression in animals exposed to cancer-causing substances.

 [F2]Autophagia definition, controlled digestion of damaged organelles within a cell

 [F3]D-Limonene and its metabolites, perillic acid, dihydroperillic acid, uroterpenol, and limonene1,2-diol, may inhibit tumor growth via inhibition of p21-dependent signaling and apoptosis resulting from induction of the transforming growth factor beta-signaling pathway ^(9) (10). D-Limonene metabolites also cause G1 cell cycle arrest, inhibit post-translational modification of signal transduction proteins, and cause differential expression of cell cycle- and apoptosis-related genes ⁽⁶⁾.

D-limonene induces apoptosis via the mitochondrial death pathway and suppression of the PI3K/Akt pathway in human colon cancer cells ⁽¹⁶⁾. Animal studies show activity of D-limonene against pancreatic, stomach, colon, skin, and liver cancers ^(5) (17). Data also indicate that D-limonene slows the promotion/progression stage of carcinogen-induced tumors in rats ^(11) (12). The chemopreventive activity of D-limonene may be via inhibition of inflammation, oxidative stress and Ras-signaling as well as the induction of pro-apoptotic state in a mouse model of skin tumorigenesis ⁽¹⁸⁾.

D-limonene and its metabolite perillyl alcohol were shown to affect wound healing by decreasing systemic cytokine production, and by inhibiting endothelial P-selectin expression and neo-vascularization ⁽

 

 [F4]Limonene, (+/-)- is a racemic mixture of limonene, a natural cyclic monoterpene and major component of the oil extracted from citrus rind with chemo-preventive and antitumor activities. The metabolites of DL-limonene, perillic acid, dihydroperillic acid, uroterpenol and limonene 1,2-diol are suggested to inhibit tumor growth through inhibition of p21-dependent signaling, induce apoptosis via the induction of the transforming growth factor beta-signaling pathway, inhibit post-translational modification of signal transduction proteins, result in G1 cell cycle arrest as well as cause differential expression of cell cycle- and apoptosis-related genes.

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Nisin

'Magic MOLD' could wipe out two lethal conditions- Natural preservative that grows on dairy products 'kills cancer cells and antibiotic-resistant bacteria'

• Nisin is a naturally-occurring food preservative found on dairy products
• And, a study revealed it can wipe out cancer cells and bacteria
• Scientists tested nisin on tumors and as an antimicrobial in rats
• After nine weeks of treatment, 70-80% of cancer cells were killed off
• And, no bacteria has been found to be resistant to the effects of nisin 

By Lisa Ryan For Dailymail.com

Scientists have long searched for new, more effective treatments to tackle cancer. But, a new study suggests, the answer may have been lurking in dairy products the whole time.  Nisin – a naturally occurring food preservative that grows on daily products – can wipe out cancer cells and it can also combat antibiotic-resistant bacteria, scientists said. University of Michigan researchers studied the effect of nisin on cancerous tumors and as an antimicrobial to fight diseases in the mouth. After nine weeks of treatment, they found that the tumors had shrunk significantly and were comparable to tumors at three weeks. Dr Yvonna Kapila, a professor at the University of Michigan School of Dentistry, said: ‘To date, nobody had found bacteria from humans or living animals that is resistant to nisin.’Nisin is a naturally occurring food preservative that grows on dairy products. A new study revealed this 'magic mold' can wipe out cancer cells and antibiotic-resistant bacteria-The scientists found feeding rats a ‘nisin milkshake’ killed 70 to 80 per cent of head and neck tumor cells after nine weeks – and extended survival rates.-The team previously published positive results with less potent nisin. However, the highly purified nisin ZP used in the current study nearly doubled its effectiveness, they found. They gave a dosage of 800 mg/kg to mice – which would translate to a pill larger than a third of an Advil per kilogram of body weight for humans. --Nisin is a colorless, tasteless powder that is typically added to food at a rate of .25 to 37.5 mg/kg. While many foods contain nisin, none contain anywhere near the 800 mg/kg needed to kill cancer cells. Additionally, there are several consumer products that contain nisin – such as creams and pharmaceuticals to combat infection and mastitis, as well as a sanitizer in lactating cows[F1] . The results are promising, but scientists stress that that it’s too early to say if nisin will act the same way in humans. In addition to their findings regarding cancer, the scientists found nisin fights deadly bacteria, including antibiotic-resistant MRSA.

In a recent paper, they looked at experimental uses of nisin to treat 30 different types of cancer; infections of the skin, respiratory system and abdomen; and oral health. Nisin is lethal to bacteria for two reasons. First, it binds to a static area of bacteria. That gives nisin the chance to work before bacteria changes into an antibiotic-resistant superbug.  Scientists found feeding rats a ‘nisin milkshake’ killed 70-80 per cent of head and neck tumor cells after nine weeks. Also, nisin has been shown to fight deadly bacteria, including antibiotic-resistant MRSA Secondly, it kills biofilms, which are colonies of bacteria that group together in a fortress that blocks antibiotics. The scientists noted that nisin has ‘withstood the test of time'. Dr Kapila said: ‘Mother Nature has done a lot of the research for us, it’s been tested for thousands of years.’ Next, the team hopes to test nisin in a clinical setting. Dr Kapila said: ‘The application of nisin has advanced beyond its role as a food biopreservative. ‘Current findings and other published data support nisin’s potential use to treat antibiotic resistant infections, periodontal disease and cancer.’ The study was published in Journal of Applied Microbiology.

Read more: http://www.dailymail.co.uk/health/article-3395898/Magic-MOLD-wipe-two-lethal-conditions-Natural-preservative-grows-dairy-products-kills-cancer-cells-antibiotic-resistant-bacteria.html#ixzz3xNpyF1Xq
 

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E-cigarette vapor boosts superbugs and dampens immune system

Researchers at the University of California, San Diego School of Medicine and Veterans Affairs San Diego Healthcare System report data suggesting that e-cigarettes are toxic to human airway cells, suppress immune defenses and alter inflammation, while at the same time boosting bacterial virulence. The mouse study is published January 25 by the Journal of Molecular Medicine.--"This study shows that e-cigarette vapor is not benign -- at high doses it can directly kill lung cells, which is frightening," said senior author Laura E. Crotty Alexander, MD, staff physician at the Veterans Affairs San Diego Healthcare System and assistant clinical professor at UC San Diego School of Medicine. "We already knew that inhaling heated chemicals, including the e-liquid ingredients nicotine and propylene glycol, couldn't possibly be good for you. This work confirms that inhalation of e-cigarette vapor daily leads to changes in the inflammatory milieu inside the airways."--Crotty Alexander reported the preliminary results of this work at the American Thoracic Society annual meetings in 2014 and 2015. But now her team has also seen their findings hold up in mice. Inflammatory markers -- signs of full-body inflammation -- in the airways and blood of mice that inhaled e-cigarette vapors for one hour a day, five days a week, for four weeks were elevated by 10 percent compared to unexposed mice.--"We don't know specifically which lung and systemic diseases will be caused by the inflammatory changes induced by e-cigarette vapor inhalation, but based on clinical reports of acute toxicities and what we have found in the lab, we believe that they will cause disease in the end," Crotty Alexander said. "Some of the changes we have found in mice are also found in the airways and blood of conventional cigarette smokers, while others are found in humans with cancer or inflammatory lung diseases." --Conversely, bacterial pathogens exposed to e-cigarette vapor benefited. Specifically, Staphylococcus aureus bacteria were better able to form biofilms, adhere to and invade airway cells and resist human antimicrobial peptides after exposure to e-cigarette vapor. E-cigarette vapor extract-exposed bacteria were also more virulent in a mouse model of pneumonia. All mice infected with normal methicillin-resistant S. aureus (MRSA), an antibiotic-resistant "superbug," survived. Meanwhile, 25 percent of mice infected with MRSA pre-exposed to e-cigarette vapor died. The results were consistent with e-liquids from seven different manufacturers, demonstrating that the findings are not limited to one formula or brand. -Crotty Alexander and team also recently reported that MRSA bacteria exposed to conventional cigarette smoke are more resistant to killing by the immune system than unexposed bacteria.-Story Source-The above post is reprinted from materials provided by University of California, San Diego Health Sciences. The original item was written by Heather Buschman-Journal Reference-John H. Hwang, Matthew Lyes, Katherine Sladewski, Shymaa Enany, Elisa McEachern, Denzil P. Mathew, Soumita Das, Alexander Moshensky, Sagar Bapat, David T. Pride, Weg M. Ongkeko, Laura E. Crotty Alexander. Electronic cigarette inhalation alters innate immunity and airway cytokines while increasing the virulence of colonizing bacteria. Journal of Molecular Medicine, 2016; DOI: 10.1007/s00109-016-1378-3 --University of California, San Diego Health Sciences. "E-cigarette vapor boosts superbugs and dampens immune system." ScienceDaily. ScienceDaily, 26 January 2016. <www.sciencedaily.com/releases/2016/01/160126143759.htm>.

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Rising carbon dioxide emissions pose 'intoxication' threat to world's ocean fish

UNSW Australia researchers have found that carbon dioxide concentrations in seawater could reach levels high enough to make fish "intoxicated" and disoriented many decades earlier than previously thought, with serious implications for the world's fisheries. The UNSW study, published in the journal Nature, is the first global analysis of the impact of rising carbon dioxide emissions from fossil fuels on natural variations in carbon dioxide concentrations in the world's oceans. "Our results were staggering and have massive implications for global fisheries and marine ecosystems across the planet," says lead author, Dr Ben McNeil, of the UNSW Climate Change Research Centre.--"High concentrations of carbon dioxide cause fish to become intoxicated -- a phenomenon known as hypercapnia. Essentially, the fish become lost at sea. The carbon dioxide affects their brains and they lose their sense of direction and ability to find their way home. They don't even know where their predators are. -"We've shown that if atmospheric carbon dioxide pollution continues to rise, fish and other marine creatures in CO₂ hotpots in the Southern, Pacific and North Atlantic oceans will experience episodes of hypercapnia by the middle of this century -- much sooner than had been predicted, and with more damaging effects than thought.-"By 2100, creatures in up to half the world's surface oceans are expected to be affected by hypercapnia."-The study is by Dr McNeil and Dr Tristan Sasse of the UNSW School of Mathematics and Statistics. Ocean hypercapnia is predicted to occur when atmospheric carbon dioxide concentrations exceed 650 parts per million.-The UNSW scientists utilised a global database of seawater carbon dioxide concentrations collected during the past 30 years as part of a variety of oceanographic programs.-"We then devised a numerical method to work out the natural monthly peaks and troughs in carbon dioxide concentrations during the year across the surface of the world's oceans, based on these observations," says Dr Sasse.--"This allowed us to predict for the first time that these natural oscillations will be amplified by up to tenfold in some regions of the ocean by the end of the century, if atmospheric carbon dioxide concentrations continue to rise."-To help accelerate this important area of research, the UNSW scientists have also offered prizes to other researchers who can improve on their results. "Predicting the onset of hypercapnia is difficult, due to a lack of global ocean measurements of carbon dioxide concentrations," says Dr McNeil.-"We are challenging other scientists with innovative predictive approaches to download the dataset we used, employ their own numerical methods and share their final predictions, to see if they can beat our approach."-Story Source-The above post is reprinted from materials provided by University of New South Wales. Journal Reference-Ben I. McNeil, Tristan P. Sasse. Future ocean hypercapnia driven by anthropogenic amplification of the natural CO2 cycle. Nature, 2016; 529 (7586): 383 DOI: 10.1038/nature16156 --University of New South Wales. "Rising carbon dioxide emissions pose 'intoxication' threat to world's ocean fish." ScienceDaily. ScienceDaily, 20 January 2016. <www.sciencedaily.com/releases/2016/01/160120141525.htm>.

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 [F1]Salt (chemistry)

From Wikipedia, the free encyclopedia

This article is about the term as used in chemistry. For the chemistry of table salt, see Sodium chloride. For more information about table salt, see Salt.

 

The salt copper(II) sulfate as the mineral chalcanthite.

In chemistry, a salt is an ionic compound that results from the neutralization reaction of an acid and a base. Salts are composed of related numbers of cations (positively charged ions) and anions (negative ions) so that the product is electrically neutral (without a net charge). These component ions can be inorganic, such as chloride (Cl⁻), or organic, such as acetate (CH₃CO₂^-); and can be monatomic, such as fluoride (F⁻), or polyatomic, such as sulfate (SO₄²⁻).

There are several varieties of salts. Salts that hydrolyze to produce hydroxide ions when dissolved in water are basic salts, whilst those that hydrolyze to produce hydronium ions in water are acidic salts. Neutral salts are those that are neither acid nor basic salts. Zwitterions contain an anionic centre and a cationic centre in the same molecule, but are not considered to be salts. Examples of zwitterions include amino acids, many metabolites, peptides, and proteins.

Usually, non-dissolved salts at standard temperature and pressure are solid, but there are exceptions (see Molten salts and ionic liquids).

Molten salts and solutions containing dissolved salts (e.g., sodium chloride in water) are called electrolytes, as they are able to conduct electricity. As observed in the cytoplasm of cells, in blood, urine, plant saps and mineral waters, mixtures of many different ions in solution usually do not form defined salts after evaporation of the water. Therefore, their salt content is given for the respective ions.

Contents

• 1 Properties
  • 1.1 Color
  • 1.2 Taste
  • 1.3 Odor
  • 1.4 Solubility
  • 1.5 Conductivity
• 2 Chemical Compound
• 3 Formation
• 4 See also
• 5 References

Properties

Color

 

Potassium dichromate, a bright orange salt used as a pigment.

Salts can appear to be clear and transparent (sodium chloride), opaque, and even metallic and lustrous (iron disulfide). In many cases, the apparent opacity or transparency are only related to the difference in size of the individual monocrystals. Since light reflects from the grain boundaries (boundaries between crystallites), larger crystals tend to be transparent, while the polycrystalline aggregates look like white powders.

Salts exist in many different colors, for example:

• yellow (sodium chromate)
• orange (potassium dichromate)
• red (cobalt nitrate)
• mauve (cobalt chloride hexahydrate)
• blue (copper sulfate pentahydrate, ferric hexacyanoferrate)
• purple (potassium permanganate)
• green (nickel chloride hexahydrate)
• colorless (sodium chloride, magnesium sulfate heptahydrate)—may appear white when powdered or in small pieces

Most minerals and inorganic pigments, as well as many synthetic organic dyes, are salts. The color of the specific salt is due to the electronic structure in the d-orbitals of transition elements or in the conjugated organic dye framework.

Taste

Different salts can elicit all five basic tastes, e.g., salty (sodium chloride), sweet (lead diacetate, which will cause lead poisoning if ingested), sour (potassium bitartrate), bitter (magnesium sulfate), and umami or savory (monosodium glutamate).

Odor

Salts of strong acids and strong bases ("strong salts") are non-volatile and odorless, whereas salts of either weak acids or weak bases ("weak salts") may smell after the conjugate acid (e.g., acetates like acetic acid (vinegar) and cyanides like hydrogen cyanide (almonds)) or the conjugate base (e.g., ammonium salts like ammonia) of the component ions. That slow, partial decomposition is usually accelerated by the presence of water, since hydrolysis is the other half of the reversible reaction equation of formation of weak salts.

Solubility

See also: Solubility § Solubility of ionic compounds in water

Many ionic compounds can be dissolved in water or other similar solvents. The exact combination of ions involved makes each compound have a unique solubility in any solvent. The solubility is dependent on how well each ion interacts with the solvent, so there are certain patterns. For example, all salts of sodium, potassium and ammonium are soluble in water, as are all nitrates and many sulfates - barium sulfate, calcium sulfate (sparingly soluble) and lead(II) sulfate are examples of exceptions. However, ions that bind tightly to each other and form highly stable lattices are less soluble, because it is harder for these structures to break apart for the compounds to dissolve. For example, most carbonate salts are not soluble in water, such as lead carbonate and barium carbonate. Some soluble carbonate salts are: sodium carbonate, potassium carbonate and ammonium carbonate.

Conductivity

Solid salts do not conduct electricity. However, liquid salts do. Moreover, solutions of salts also conduct electricity.

Chemical Compound

The name of a salt starts with the name of the cation (e.g., sodium or ammonium) followed by the name of the anion (e.g., chloride or acetate). Salts are often referred to only by the name of the cation (e.g., sodium salt or ammonium salt) or by the name of the anion (e.g., chloride salt or acetate salt).

Common salt-forming cations include:

• Ammonium NH₄⁺
• Calcium Ca²⁺
• Iron Fe²⁺ and Fe³⁺
• Magnesium Mg²⁺
• Potassium K⁺
• Pyridinium C₅H₅NH⁺
• Quaternary ammonium NR₄⁺
• Sodium Na⁺

Common salt-forming anions (parent acids in parentheses where available) include:

• Acetate CH₃COO⁻ (acetic acid)
• Carbonate CO₃²⁻ (carbonic acid)
• Chloride Cl⁻ (hydrochloric acid)
• Citrate HOC(COO⁻)(CH₂COO⁻)₂ (citric acid)
• Cyanide C≡N⁻ (hydrocyanic acid)
• Fluoride F⁻ (hydrofluoric acid)
• Nitrate NO₃⁻ (nitric acid)
• Nitrite NO₂⁻ (nitrous acid)
• Phosphate PO₄³⁻ (phosphoric acid)
• Sulfate SO₄²⁻ (sulfuric acid)

Formation

 

Solid lead(II) sulfate (PbSO₄)

Salts are formed by a chemical reaction between:

• A base and an acid, e.g., NH₃ + HCl → NH₄Cl
• A metal and an acid, e.g., Mg + H₂SO₄ → MgSO₄ + H₂
• A metal and a non-metal, e.g., Ca + Cl₂ → CaCl₂
• A base and an acid anhydride, e.g., 2 NaOH + Cl₂O → 2 NaClO + H₂O
• An acid and a basic anhydride, e.g., 2 HNO₃ + Na₂O → 2 NaNO₃ + H₂O
• Salts can also form if solutions of different salts are mixed, their ions recombine, and the new salt is insoluble and precipitates (see: solubility equilibrium), for example:

Pb(NO₃)₂(aq) + Na₂SO₄(aq) → PbSO₄(s) + 2 NaNO₃(aq)

 

 [U2]These will be added to your regimen up the way in about 6 months---you may still consume these intermittently but as a baby food ---you can see my pate video to show how to make it

 [F3]If the colon is severely compromised then for a short time avoid---if uncertain about the seeds and nuts you are about to consume then make a nut  butter with added vitamin C and rosemary essential oil and salt to reduce any afllatoxin issue

 [U4]Best not to use at all---with the MYCOTOXINS and ESTROGENS  in these grains today it will be to your advantage not to consume and use alternatives

 [F5]organosulfur compounds (OSCs)

 [F6]glutamylcysteine and S-alk(en)ylcysteinesulfoxides (S-allylcysteinesulfoxide (alliin; 85%), S-methylcysteinesulfoxides (methiin; 10%) and Strans-1-propenylcysteinesulfoxides (isoalliin; 5%) (Verma S.K., 2008) that serve as precursors of volatile thiosulfinates

 [F7]Reason Why you plant this is the winter to achieve this effect in the garlic

 [F8]Diallyl disulfide (DADS or 4,5-dithia-1,7-octadiene) is an organosulfur compound derived from garlic and a few other genus Allium plants.^[3] Along with diallyl trisulfide and diallyl tetrasulfide, it is one of the principal components of the distilled oil of garlic

 [F9]Diallyl disulfide (DADS or 4,5-dithia-1,7-octadiene) is an organosulfur compound derived from garlic and a few other genus Allium plants.^[3] Along with diallyl trisulfide and diallyl tetrasulfide, it is one of the principal components of the distilled oil of garlic

 [F10]This is how to make an aged garlic soak in alcohol for almost 2 years then  strain and add water to it

 [F11]Diallyl trisulfide (DATS), also known as Allitridin, is an organosulfur compound. Derived from the hydrolysis of allicin, it is one of the main components in garlic oil. Although garlic contains many polysulfides, including diallyl disulfide and diallyl tetrasulfide, DATS is one of the most potent.

 [F12]Global Study Validating the effect of Garlics therapeutic effects and protective effects as well and with a multicultural group globally

 [F13]Garlic is Anti H pylori

 [F14]Garlic protects against Colorectal Cancer

 [F15]Ajoene is the blue antioxidant of garlic when you extract

 [F16]We are talking here Garlic Tea

 [F17]Protects against Copper free radicals

 [F18]Metalloprotein is a generic term for a protein that contains a metal ion cofactor.^[1][2] A large number of all proteins are part of this category.

 [F19]Chromatin is a complex of macromolecules found in cells, consisting of DNA, protein, and RNA. The primary functions of chromatin are 1) to package DNA into a smaller volume to fit in the cell, 2) to reinforce the DNA macromolecule to allow mitosis, 3) to prevent DNA damage, and 4) to control gene expression and DNA replication

 [F20]Diallyl disulfide (DADS or 4,5-dithia-1,7-octadiene) is an organosulfur compound derived from garlic and a few other genus Allium plants.^[3] Along with diallyl trisulfide and diallyl tetrasulfide, it is one of the principal components of the distilled oil of garlic

 

 [F21]DNA repair andd Cellular Adhesion

 [F22]two pro-apoptotic family members, Bax and Bak, which orchestrate the formation of specific channels

 [F23]this almost sounds like self assembling or a induced mutation  with a program to create this anomaly~ as if something was installed to create this effect

 [F24]Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels.^[---

Stimulator	Mechanism
FGF	Promotes proliferation & differentiation of endothelial cells, smooth muscle cells, and fibroblasts
VEGF	Affects permeability
VEGFR and NRP-1	Integrate survival signals
Ang1 and Ang2	Stabilize vessels
PDGF (BB-homodimer) and PDGFR	recruit smooth muscle cells
TGF-β, endoglin and TGF-β receptors	↑extracellular matrix production
MCP-1
Histamine
Integrins αVβ3, αVβ5 (?[8]) and α5β1	Bind matrix macromolecules and proteinases
VE-cadherin and CD31	endothelial junctional molecules
ephrin	Determine formation of arteries or veins
plasminogen activators	remodels extracellular matrix, releases and activates growth factors
plasminogen activator inhibitor-1	stabilizes nearby vessels
eNOS and COX-2
AC133	regulates angioblast differentiation
ID1/ID3	Regulates endothelial transdifferentiation

FGF

 

 [F25]Sounds more and more like a program

 [F26]Garlic oil for Stomach and intestinal cancers and leukemia ~ fused garlic oil or extracted garlic and simmered to an oil

 [F27]It would appear that for the reproductive organs for both men and women in thre respective parts would appear to have cancer negating effects or itwould appear that garlic seems to shut off the programming with the differing biochemistry

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HOME

Show Of the Month February 20 2016

Biological Weapons-agents for Life and Environmental Destruction

Chemical Warfare of WWII

Using Insects to Advance Cybernetics

Nuclear-Powered Transponder for Cyborg Insect 

Self-healing hybrid gel system

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Nuclear-Powered Transponder for Cyborg Insect

Engineers develop radioisotope MEMS power source for insect spy program

By Sally Adee

Posted 10 Dec 2009 | 5:00 GMT

10 December 2009—This week at the International Electron Devices Meeting (IEDM), in Baltimore, Md., Cornell University engineers presented research that shows progress in powering cybernetic organisms with a radioactive fuel source.

Electrical engineering associate professor Amit Lal and graduate student Steven Tin presented a prototype microelectromechanical systems (MEMS) transmitter—an RF-emitting device powered by a radioactive source with a half-life of 12 years, meaning that it could operate autonomously for decades. The researchers think the new RFID transmitter, which produces a 5-milliwatt, 10-microsecond-long, 100-megahertz radio-frequency pulse, could lead to the widespread use of radioisotope power sources.[F45] 

The work is funded by the Defense Advanced Research Projects Agency (DARPA), which also funds Lal and Tin’s work on another project, called Hybrid Insect Micro-Electro-Mechanical Systems (HI-MEMS), whose aim is the creation of hybrid cybernetic organisms. In his presentation, Tin said that part of the goal of the radioisotope transmitter work is to power the insects that the group is developing for DARPA. The HI-MEMS program, which is approaching its fourth year, has already grown several kinds of insects—moths and beetles—with implanted control electronics. With such controls, they can be driven by a remote operator for ”stealth applications” and disaster response.

The insects themselves are powered by their own living tissue, but the onboard electronics (sensors and transmitters) require a separate power source. But the insects are too light to carry batteries, and logistical problems would prevent regular battery changes regardless. Therefore, Lal and his group at Cornell turned to radioactive isotopes to generate the necessary power.

To retain memory state in a typical low-power wireless sensor node, you need between 1 and 10 nanowatts. For periodic sensing and processing, the requirement jumps to between 0.1 and 1 mW. If you want to imbue your sensor with the ability to carry on periodic communications, you’re looking at a power requirement of between 1 and 100 mW. By using just a small amount of radioactive material, the Cornell team’s MEMS-based piezoelectric generator was able to create enough output energy to enable a high-power RF pulse every three minutes. The material in question is nickel-63 (Ni-63), a mildly radioactive isotope having a few extra neutrons in its nucleus. When it decays, Ni-63 emits beta particles—high-energy electrons that are relatively innocuous.

The RFID transmitter converts the energy of radioactive decay into mechanical movement in a MEMS device. A tiny silicon and piezoelectric cantilever—40 micrometers thick and 4 to 8 millimeters long—is suspended on a chip over the radioactive thin film like a diving board over a pool. It is similar to the nuclear microbatteries Lal and University of Wisconsin nuclear engineer James Blanchard described in IEEE Spectrum in 2004.

Here’s how it works: Electrons ejected from the radioisotope accumulate on the cantilever, giving it a negative charge. Now the cantilever is attracted to the (relatively) positive Ni-63 thin film and begins to bend toward it. As soon as it bends enough to touch the Ni-63, the charges jump back onto the thin film, and the cantilever, freed of the accreted electrons, springs back to its starting position. The power is generated when the cantilever snaps back to its original position. It continues this way until the isotope’s radioactivity is depleted, which the authors estimate could take up to 100 years.

Each seesaw motion takes three minutes to complete. Tin explained to IEDM attendees that some trade-offs could be exploited between the amount of output power and the length of electron accumulation. To achieve a burst every 30 seconds, for example, the power of each burst would have to be reduced.

Because of the way the transmitter is engineered, only a small amount of Ni-63 is needed to generate high-power pulses. However, Tin said that because the device is still a prototype, no optimizing had been done, and its efficiency in converting the energy of the radioisotope was just 0.06 percent. The entire device is 1 square centimeter.

The work drew a mixed reaction. NEC Electronics research fellow Yoshihiro Hayashi wondered whether the device would be a stable source of power because of the stochastic nature of radioactivity.

Another engineer questioned the transmitter’s reliability. Would the beta particles emitted by the Ni-63 source degrade the insect’s onboard electronics—or possibly the insect itself? How much would the package need to be radiation hardened? Tin was sanguine on this point, pointing out that Ni-63 beta particles penetrate only about 21 µm into a surface, requiring minimal packaging.

Cyborg insects aren’t the only devices that stand to benefit from the new research. Lal and Tin claim that using radioisotopes as they suggest could revolutionize long-term reliable sensing and monitoring. HP Labs reported in October that it was making progress on such long-term sensors in its Central Nervous System for the Earth (CeNSE) project, whose goal is blanketing Earth with tiny sensors. But at that time, Peter Hartwell, a senior researcher at HP Labs, in Palo Alto, Calif., admitted that power was one of the last remaining fundamental challenges they had yet to work out. HP’s new sensor requires a little under 50 mW, an improvement over the high-performance sensors, which now require about 1 watt.

According to Lal and Tin, radioisotope-powered devices could be built directly into concrete infrastructures, such as bridges and highways, and could remain operational for ”hundreds of years,” they say.

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 [F1](Phys.org)—Scientists have fabricated a flexible electrical circuit that, when cut into two pieces, can repair itself and fully restore its original conductivity. The circuit is made of a new gel that possesses a combination of properties that are not typically seen together: high conductivity, flexibility, and room-temperature self-healing. The gel could potentially offer self-healing for a variety of applications, including flexible electronics, soft robotics, artificial skins, biomimetic prostheses, and energy storage devices.

The researchers, led by Guihua Yu, an assistant professor at the University of Texas at Austin, have published a paper on the new self-healing gel in a recent issue of Nano Letters.

The new gel's properties arise from its hybrid composition of two gels: a supramolecular gel, or 'supergel', is injected into a conductive polymer hydrogel matrix. As the researchers explain, this "guest-to-host" strategy allows the chemical and physical features of each component to be combined.

The supergel, or the "guest," provides the self-healing ability due to its supramolecular chemistry. As a supramolecular assembly, it consists of large molecular subunits rather than individual molecules. Due to its large size and structure, the assembly is held together by much weaker interactions than normal molecules, and these interactions can also be reversible. This reversibility is what gives the supergel its ability to act like a "dynamic glue" and reassemble itself.

Meanwhile, the conductive polymer hydrogel, or the "host," contributes to the conductivity due to its nanostructured 3D network that promotes electron transport. As the backbone of the hybrid gel, the hydrogel component also reinforces its strength and elasticity. When the supergel is injected into the hydrogel matrix, it wraps around the hydrogel in such a way as to form a second network, further strengthening the hybrid gel as a whole.

In their experiments, the researchers fabricated thin films of the hybrid gel on flexible plastic substrates to test their electrical properties. The tests showed that the conductivity is among the highest values of conductive hybrid gels, and is maintained due to the self-healing property even after repeated bending and stretching. The researchers also demonstrated that, when an electrical circuit made of the hybrid gel is cut, it takes about one minute for the circuit to self-heal and recover its original conductivity. The gel self-heals even after being cut multiple times in the same location.

The researchers explained that the conductive self-healing material has a variety of potential applications.

"The conductive self-healing gel we developed can be applied in many technologic areas, from flexible/stretchable electronics, artificial skins, energy storage and conversion devices, to biomedical devices," Yu told Phys.org. "For example, the gel can be potentially used in implantable biosensors as flexible yet self-healable electrodes, ensuring the durability of these devices. And in energy devices, for example, the gel can function as binder materials for advanced battery electrodes in high-density Li-ion batteries where high-capacity electrodes may experience substantial volume changes."

The researchers also hope that, by combining supramolecular chemistry and polymer nanoscience, the resulting hybrid gels may provide a useful strategy for designing new self-healing materials.

"We are planning to investigate the fundamental mechanisms of the self-healing properties of supramolecular gels and to better understand how different key factors, such as different metal ions, the molecules' geometries, and the interactions between the supramolecule and different solvents, affect the self-healing characteristics," Yu said. "A deeper fundamental understanding will allow better materials to be developed. Meanwhile, from a more 'practical applications' standpoint, some research efforts (together with our collaborators) will be devoted to developing scalable synthetic strategies of supramolecules and self-healing hybrid gels with even better mechanical strength and elasticity, for potential applications of these self-healing gels in different technology areas."

Read more at: http://phys.org/news/2015-08-electrical-circuit-gel.html#jCp

 

 [F2]This could also be done with other biological life the assembling of a conducting circuits

 [F3]Would explain why so many are having issues with son either not enough or havin developed squamous skin  cancers

 

 

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