Alzheimer’s disease (AD), the most common cause of dementia, is a neuro-degenerative disease that causes cognitive decline affecting memory and executive function. While rarely due to genetic mutation, the cause of most cases of Alzheimer’s disease is not known. However, new research indicates that the virus that causes cold-sores (fever-blisters) may also cause or contribute to the development of Alzheimer’s disease. Continue reading
Lead (Pb) is a persistent environmental contaminant that is toxic to humans, primarily in the developmental stages of life. It is believed that environment and nutrition play a role in determining health. Most recently, it has been recognized by the National Institute of Environmental Health Sciences that the interaction between pathogens and toxic agents may contribute to disease development in humans. In fact, epidemiological studies suggest that there may be a correlation between lead exposure and obesity in children and that this effect may be long-lasting, resulting in adulthood obesity.
Perinatal lead exposure in mice
The microbiome has recently been recognized as contributing to health and disruptions in gut microbiota constitution as been associated with chronic illnesses. To investigate the phenomena of Pb-induced obesity, mice were exposed to lead during the perinatal period. Researchers studied how lead exposure around the time of birth impacted gut microbiota, and then watched to observe whether changes to the microbiome influenced bodyweight.
They found that exposure to lead early in development did alter the bacterial composition of the digestive tract. Pb affected the resilience and diversity of bacteria normally present in the gut; disrupting the balance between aerobic and anaerobic bacterium. Continue reading
Seedless grapes are in fact as natural and as healthy as grapes with seeds, and unlike popular conjecture, they are not genetically modified organisms. Seedless grapes are used in the production of raisins, jelly, jam, juice, and wine, and are preferred over seeded grapes for reason of edibility.
Grapes have been cultivated for thousands of years. Vitis Vinifera was domesticated from the wild grape, V. Vinifera Sylvestris, but still bears close morphological and genealogical characteristics. In fact wild grapes can interbreed with domesticated grapes when they encounter each other, however they flower at different times which reduces the likelihood of gene transfer through pollination. Wild grapes are sometimes reintroduced into commercial grape breeding programs, but mutations occur frequently in grape cultivars leading to a diverse genetic pool Seedlessness is the result of a natural mutation that occurred in some cultivated grapes. This natural phenomenon was exploited by vineyards to improve the desirability of grapes by making them easier to grow and consume. Most seedless grapes are bred from the Sultania (Thompson seedless) landrace (traditional isolated cultivars), but also the Black Monukka, Malta, Beauty Seedless, and others. Continue reading
Fat Is Alive
Most people think of fat as being inert, having no real purpose in the body than to keep you warm, and to prevent you from ever having the perfect summer body. The role of fat in the body is so under-appreciated, that when the doctor says, “you need to lose weight”, people often see it as an issue of “body shaming” rather than one of health. This is because fat is not seen as being alive, but as a by-product of too much sugar and starch. While the reality is that fat IS alive, in fact the fat in our bodies is made up of cells called adipocytes, and these cells comprise the functional unit of adipose tissue. Adipocytes and adipose tissue are a part of the endocrine and central nervous system.
Adiocytes – Living Fat
Adipocyte are specialized cells within adipose tissue that contain lipids in the form of multiple round droplets of triglycerides. Triglycerides are the building blocks of fats, as amino acids are the foundation of proteins. Adipocytes simply put are fat cells that transport and produce fat.
There are three types of fat cells: Continue reading
Influenza, colloquially known as “flu” is an infectious disease and public health issue. On a global level, the flu infects millions of people worldwide and circulates yearly. In the United States, “flu season” occurs predominantly in the winter, but can begin as early as October and extend through May. Many people confuse the flu with a common cold, and though both are caused by viruses, unlike a cold, the flu can kill! The 2017-2018 flu season has seen increased hospitalizations and deaths due to Influenza across the country. This year’s flu has been quite severe, particularly in children.
According to the CDC (Centers for Disease Control and Prevention), 22 pediatric deaths from Influenza have been reported nationally, since the start of 2018 (it is now mid-February), bringing the current total of Influenza associated deaths in children to 84 for the 2017-2018 flu season. That number is likely to increase before the end of it all.
Influenza affects everyone, but the elderly and children, primarily infants under 6 months of age, are most susceptible and at risk for suffering severe illness or death. Children are also primarily responsible for the spread of Influenza throughout a community, since they shed the virus for a longer time period after infection, than adults. Continue reading
The banana’s we eat don’t have seeds, they are a result of a naturally occurring mutation that was subsequently exploited by human selection for breeding. Banana’s are a cultivar; they are a domesticated crop, reproduced in manner that selects for and maintains certain desired characteristic, such as, being seedless. Banana’s reproduce vegetatively through an asexually process known as parthenocarpy, in which no fertilization is required for their propagation. Parthenocarpy is a genetic trait or characteristic imparted by a gene, but this process has nothing to do with genetic modification, and banana’s are not genetically modified organisms (GMO) — at least not yet. Continue reading
A consequence of the obesity epidemic, which began in the United States during the 1980s, is the targeting of milk as a possible contributing factor for weight gain, metabolic syndrome, and cardiovascular disease, due to its high fat content. As a result, in the mid 1990’s, the U.S. Department of Agriculture recommended switching to reduced-fat milk, and the consumption of whole milk fell drastically. As this was happening, the growth of soy and soy “milk” paved the way for other milk-alternative beverages, such as, almond, coconut, and cashew “milk”, and consumers began to question whether it was healthy or natural for human to consume animal milk at all. In addition to fears that milk contributed to obesity, and the metabolic disorders that go along with excessive weight gain, milk allergy, and anecdotal reports of milk worsening rhinitis, and triggering asthma began to surface.
However, in the past decade, several studies have reported beneficial health effects of cow’s milk in the prevention of the development of asthma and allergy in children, as well as, protection against cancer, obesity, diabetes, and cardiovascular disease in adults.
Further investigation into the composition of milk, and its components haves revealed that it may be time to reconsider the health benefits of milk again. In addition to its nutritional value, the ingredients in milk possess bioactive functionality. The protein, lipid, and saccharide components of milk contain molecules that are anti-inflammatory, anti-microbial, and immunogenic (capable of modulating the immune system), in addition to improving the body’s response to insulin and regulation of fat. Continue reading
Americans are increasingly concerned with eating healthy. Over the past two decades, there has been a myriad of changes in the public’s perception of what is and isn’t healthy. Initially, it was generally agreed upon and understood that a diet consisting mainly of greasy food and too much sweets was unhealthy. However, the consensus on what foods are to be considered healthy versus harmful has become complex and the subject of much debate. For instance, it was once considered unhealthy to eat eggs, though the medical consensus has changed— it turns out that eggs are not as high in cholesterol as once thought—many people still maintain that the yolks should be removed, and that egg whites are healthier.
Much of the focus on health has revolved around a single nutrient, food, or food group. For example, whole wheat became preferred over bleached flour, then eventually, eating any wheat at all became controversial and wheat-free diets were promoted. The same happened with rice: white rice gave way to brown rice, which then gave way to quinoa. Super foods like soy, kale, and chia seeds became popular, along with fad diets, like the Atkins diet which emphasized low carbohydrate intake, and the Southbeach diet. Most recently, health gurus promoted health concepts which lead to the alkaline diet, out of which came alkaline water. Now, sensationalized documentaries are leading people to abandon meat and dairy all together.
As a result, many are unfortunately left confounded when it comes to what they should or should not eat. There is much fear surrounding food safety and health, due impart to a lack of understanding of nutritional requirements and technological advancements in food production, leaving many weary that meat and dairy, in particular, can lead to the development of Cardiovascular disease and Type 2 Diabetes. However, focusing on the beneficial effects of a single nutrient, food, or food group does not comprise a healthy diet. What is more important is dietary pattern; the amounts, frequency, and variety of nutrients and foods that are consumed habitually, coupled with other lifestyle factors, are the greatest determinants in the association of diet and health, as Cardiovascular Disease and Diabetes are consequences of leading a sedentary lifestyle while being overweight or obese. Continue reading
Aflatoxins are potential health hazard for human and animals, as it is a common natural contaminant of food and feed. Its prevalence is greatest in parts of the world where the climate is hot and humid. The Aspergillus fungi which produce the mycotoxins survive best in heat and humidity. As a result, although the prevalence of Aflatoxin is greatest in the developing world, climate change and global warming may lead to an increase in the occurrence of both the fungi and its toxic metabolites in parts of the world with temperate climates, like Europe and the United States.
There are thousands of metabolites produced by filamentous fungi within the Aspergillus family, some of which are beneficial. However, approximately 400 of these metabolites have been deemed mycotoxins and are hazardous. There are four major types of Aflatoxin: B1, B2, G1, and G2; according to their fluorescent color under ultraviolet light (blue or green). Aspergillus parasiticus produces all four, while Asperigillus Flavus produces strains B1 and B2. They are mutagenic, carcinogenic, and teratogenic; causing cancer and reproductive and development toxicity.
Commonly Contaminated Crops
Major sources of Aflatoxin in the food supply are peanuts, pistachios, Brazil nuts, cottonseed and maize. Aflatoxin is also a common contaminant of cereals (oats, rice, wheat, corn, and rye), dried fruit, coffee and cocoa beans, and cassava. Spices and herbs are often contaminated but to a lesser extent, and the toxin can be found in fermented beverages such as beer, wine, and fruit juices. Aflatoxin can enter the meat and dairy food supply through contaminated animal feed.
Of the major four, Aflatoxin B1 is of principal concern to human health. It is classified as a Group 1 carcinogen, meaning it definitely causes cancer in humans.
Specifically, Aflatoxin B1 causes Hepatic (liver) cancer. When ingested by ruminant animals like cows, Aflatoxin B1 is metabolized in the liver to Aflatoxin M1, which may be excreted into the milk. Aflatoxin M1, is a Group 2B carcinogen, in that it is possibly carcinogenic to humans. There are set limits on the amount of Aflatoxin B1 that is allowed in the foods to which they normally contaminate, since it is not possible to completely remove them. In the case of milk and other dairy products no amount of Aflatoxin B1 should be present, trace amounts of its metabolite Aflatoxin M1 however are permissible.
Aflatoxin Mechanism of Action
The toxic mechanism of action for all aflatoxin involve oxidative stress, lipid peroxidation, mitochondrial damage, and cell death as a result of apoptosis (versus necrosis).
Toxic exposure may be an acute single exposure at high levels, or a chronic with low but persistent levels—chronic exposure is most common. In addition to causing liver cancer, Aflatoxin may also have adverse affects on the immune system. It is also known that when Aflatoxin and infection with Hepatitis B are present at the same time, they cooperate to induce Hepatocellular carcinoma. Hepatitis B is the leading cause of Hepatocellular carcinoma, which is the fifth greatest malignancy worldwide, and is most prevalent in developing countries. As such the presence of Aflatoxin in the food supply, primarily in developing regions of the world, make it a significant pubic health concern.
Various treatment methods have been devised for the removal of Aflatoxin from contaminated food and feed. The amount of aflatoxin can be greatly reduced, but it does not appear that it can be completed removed. Physical methods of reduction include milling, microwave heating, and irradiation (ultra-violet or gamma). Chemical treatments involve using binders and sequestering agents or ozonation. However, ozonation is a rather expensive chemical process. Lastly, biodegradation can be used to decontaminate crops. Biodegradation is a biological method involving the use bacteria to detoxify aflatoxins. Flavobacterium aurentiacum as well as Mycobacterium are capable of this. However, lactobacillus does not metabolize aflatoxins, it only binds the toxin.
Aflatoxin are a family of toxic metabolites which contaminate crops used for food and feed, in humans and animals respectively. Aflatoxin contamination and the fungi that produce the toxin are most common in developing nations and regions of the world where the climate is hot and humid. However, food supplies are regularly and increasing imported due to globalization. Likewise, global warming and climate change, may make it so that the environment here in the United States or parts of Europe favor the growth of aspergillus fungi, increasing the burden of their toxic metabolites in the environment, and food supply. Therefore, the public should have an awareness and an understanding of the presence of this natural toxin in the foods supply chain, especially with the increase in organic, vegetarian, and vegan dietary patterns.
To date the only options men have for contraception are condoms or vasectomy. Studies have shown that many men would theoretically take a birth control pill if it were available to them. However, research into male reproduction has traditionally been geared towards treatment to reverse infertility not to induce it. Comparatively little effort has been spent on developing a male contraceptive analogous to the female birth control pill. Of the work that has been done, most of it has been on researching and developing hormonal methods of male contraception. Similar to the “pill”, which uses hormones to block ovulation in women, hormonal male contraceptives block the development of spermatozoa by inhibiting spermatogenesis; inducing a state of azoospermia.
Azoopermia is the absence of spermatozoa in the semen of adult males. Hormonal male contraception focuses mainly around modulating testosterone levels to produce the desired effect of diminished fertility in men. However, like their female counterpart, the use of hormonal methods have undesirable side effects that can negatively impact ones health. As a result, non-hormonal methods have been investigated, to develop safer and more practical contraceptives for men. Non-hormonal contraceptives are designed to directly impact either the development, motility, or capacity of spermatozoa.
One promising non-hormonal strategy that has been investigated is, immunocontraception, which is the use of immunization to temporarily and reversibly inhibit male fertility. Early studies into male fertility found that infertile men often had anti-sperm antibodies. Antibodies are proteins produces by immune cells in the body against pathogens like bacteria and viruses. This lead researches to postulate that sperm specific proteins found in the testis could be used for the development of a contraceptive for men. One protein, in particular, known as Eppin, has be shown to be a promising target for the development of a non-hormonal male contraceptive.
Eppin or Epididymal Protease Inhibitor, is a protein specific to the male reproductive system. Expressed in the testis and epididymis, it is found on the surface of sperm and is essential for male fertility. It forms a complex with another protein, known as Semenogelin, which is secreted by the seminal vesicles as the major component of seminal plasma coagulum.. Together they are essential for the proper function of ejaculated spermatozoa.
Eppin Targeted for the Development of Male Contraceptive
To study whether Eppin could successfully be used as an immunocontraceptive, scientist at the Indian Institute of Science conducted research to determine the effect of the immune response elicited by immunization with Eppin on spermatozoa. They tested whether antibodies to Eppin would cause infertility.
Adult male M. Radiate monkeys were immunized with human recombinant Eppin. Then their ability to impregnate several female monkeys was tested. Monkeys with a high antibody tither were unable to impregnate any females, and were therefore deemed infertile. Monkey’s that were not able to obtain a high antibody tither were excluded from the study. Over a year after immunization, 71% of the monkeys regained fertility. This showed that Eppin is essential to male fertility in humans and primates. In addition, immunization did not interfere with spermatogenesis (as is the case with hormonal methods). Neither testosterone levels nor sperm count were altered. Although safe and efficacious, anti-Eppin immunization was problematic mainly because infertility was not reversible in all subjects. In addition to irreversible infertility in some subjects receiving anti-Eppin, the antibody may elicit an adverse autoimmune responses, causing inflammation and infection, culminating in permanent infertility`. Antibodies are also degraded in the stomach, which would require that the method be delivered via injection.
At the time, the mechanism of action of many spermatozoa surface proteins like Eppin were just being studied, and the interplay of Eppin with Semenogelin and their role in sperm motility was not yet fully understood. It was determined that Eppins association with Semenogelin inhibited sperm motility. However, researchers observed that the infertile immunized monkeys lacked semen coagulum. The antibodies against Eppin, blocked Semenogelin from binding to Eppin on the surface of spermatozoa. Instead the anti-Eppin antibodies would bind Eppin in place of Semenogelin, thereby also retarding sperm motility. This showed that Semenogelin was also essential to male fertility.
The inhibition of sperm motility by the Eppin-Semenogelin complex differ from that of an Anti-Eppin-Eppin complex. One being necessary for fertility and the other inducing infertility. Figuring out the role that the Eppin-Semenogelin complex played in male fertility would be key to figuring out how induce infertility for the purpose of contraception.
Eppin Physiological Function
It was later understood that Eppin functions as a protective shield, guarding spermatozoa against bacterial and proteolytic attack while in the female reproductive tract. Prior to ejaculation spermatozoa travel through the ducts of the male reproductive system where they are mixed with secretions from the seminal vesicles and prostate gland. During this process Eppin binds other proteins at the surface of sperm, such as Semenogelin. Semenogelin stops sperm from swimming, and is responsible for the gelatinous nature of the initial ejaculate. By the binding of Eppin and Semenogelen. sperm are kept in an immotile state which prevents their hyperactivation (before reaching their target).
In order for sperm to be capacitated, the seminal coagulum needs to undergo liquefaction. This process takes from five to 30 minutes, and involves the cleavage of Semenogelin by a protease called, Prostate Specific Antigen (PSA), from the Eppin-Semenogelin complex. Eppin inhibits the displacement of Semenogelin by PSA, and since Eppin itself is not hydrolyzed by PSA, it modulates the gradual removal of Senemogelin from the surface of spermatozoa, enabling the progressive release of motile sperm. The removal of the Eppin-Semenogelin complex is necessary for fertility, failure to remove this complex results in impaired spermatozoa. Essentially the complex incapacitates spermatozoa, and its removal allows for gradual hyperactivation of the cell, allowing it to migrate up through the female reproductive tract. Without its formation sperm expend their energy immaturely.
Eppin: Immunocontraceptive to Small Molecule Drugs
In 2016, researchers at the University of North Carolina at Chapel Hill (UNC) submitted a patent application for a non-hormonal male contraceptive. The premise for their application, that small molecules that mimic Eppin can be used to inhibit male fertility, is based on the previous immunocontraceptive study in monkeys from 2004.
To overcome the shortcomings of immunocontraception, UNC researchers developed a series of small organic molecules that act like anti-Eppin antibodies, and prevent sperm motility. Because these compounds occupy the same sites, they block Anti-Eppin antibodies and Semenegelin from binding to Eppin. Binding to Eppin by either of these substances triggers a drop in pH level within spermatozoa, which subsequently decreases intracellular calcium levels, through the prevention of extracellular calcium uptake. This prevents the formation of contractile force energy needed for motion. For normal physiological function the pH level within sperm needs to increase in order to facilitate hyperactivation, which takes place after ejaculation with the gradual enzymatic removal of Semenogelin by PSA from the Semenogelin-Eppin complex. Unlike with semenogelin and PSA, there is no gradual enzymatic removal of Anti-Eppin Antibodies or these small molecules from Eppin binding sites after ejaculation.
Since there is no semenogelin binding, there is no seminal coagulum formed. Therefore, sperm motility is inhibited not by the physical encapsulation of sperm within coagulum, but by the reaction that takes place when Eppin binding sites are occupied.
Using small molecule drugs to impair male fertility is advantageous to current male contraceptive options, as their action is safe, efficacious, and reversible. Condoms may fail due to user error, hormonal contraceptives and immunocontraceptives vary in efficacy by the individual and may produce unwanted side effects, and like vasectomies, they are not readily reversible.
Small molecule targeting Eppin represent a new class of therapeutic agents that specifically target spermatozoa without disrupting spermatogenesis or altering hormone levels. They can be used administered orally to inhibit sperm motility prior to ejaculation, or applied topically after ejaculation, to directly inhibit motility on contact with spermatozoa. Therefore, these compounds can be used as a sole means of contraception or when applied topically, in conjunction with condoms, diaphragms, and spermicidal jellies.
- The University of North Carolina at Chapel Hill Applies for Patent on Small Molecules for Inhibiting Male Fertility. (2017, Mar 04). Global IP News.Pharmaceutical .
- John K Amory, 2016. Male Contraception. Fertility and Sterility Vol 106:6 p 1303-1309.
O’Rand Michael G., Silva Erick J.R., Hamil G. Katherine, 2016. Non-hormonal male contraception: A review and development of an Eppin based contraceptive. Pharmacology & Therapeutics Vol 157 p105-111.
Silva, Erick J.R., Hamil Katherine G., O’Rand Michael G., 2013. Interacting Proteins on Human Spermatozoa: Adaptive Evolution of the Binding of Semenogelin I to EPPIN. PLoS One 8:12 e82014.
O’Rand, ,M.G., Widgren, E. E., Sivashanmugam, P., Richardson, R. T., & al, e. (2004). Reversible immunocontraception in male monkeys immunized with eppin. Science, 306(5699), 1189-90.