Zinc and treating the common cold

 

Source

Since 1974, when a study titled “Zinc ions inhibit replication of rhinoviruses” by Korant, Kauer, and Butterworth was published in the journal Nature, the idea that zinc can prevent or cure the common cold has circulated. Many studies have looked at different zinc ionophores and lozenge formulas and their effect on the course of cold symptoms, as well as the potential biochemical mechanism at work. Though the exact mechanism of action is still unknown, there is some consensus that ionized zinc affects picornaviruses.

 

Zinc Against Cold Viruses

 

Rhinoviruses, of the family Picornaviridae, are only one type of almost 200 viruses that cause the acute respiratory infection symptoms known as the common cold. However, rhinoviruses are estimated to cause one-third to half of all colds, and preventing rhinovirus infections would severely limit the most common human infection.

Since the 1970s, studies have found that zinc ions may inhibit rhinovirus replication. Viral replication plays an important role in infection; inhibiting replication would prevent progression of the disease and ease symptoms. In addition, zinc ions have an affinity for the ICAM-1 receptor, which is bound by rhinovirus when infecting cells in the respiratory tract. Zinc binding the ICAM-1, or the rhinovirus-ICAM complex, would prevent infection of the nasal epithelium, preventing the duration of the common cold.

What Type of Zinc Reduces Cold Symptoms?

In the 1980s and 1990s, zinc gluconate lozenges were shown in some studies to decrease the duration of cold symptoms if taken within 24 hours of symptom onset, whereas other studies had no success. Zinc acetate lozenges appeared to have a better success rate, likely because of their formulation. The problem seems to lie in the concentration of ionic zinc in commercially available lozenges. The ionic zinc concentration is not measurable by the label on a package, it is dependent on what is released as the lozenge dissolves in the mouth over a period of time.

Zinc gluconate gels and nasal sprays have had experimental success in alleviating rhinovirus infection. Some formulations were even marketed, such as Zicam. However, these products were recently warned against due to users losing their sense of smell.

Potential Problems with Zinc Products

Though zinc lozenges have repeatedly been found to exert no side effects or create any problems, beyond the chalky taste, zinc nasal sprays have been shown to irreversibly damage the nasal lining. In particular, Zicam (zinc gluconate nasal spray from Matrixx Initiatives) was shown in an October 2009 study to have cytotoxic effects on both mouse and human olfactory sensory neurons, as well as a near complete loss of the nasal epithelium and submucosa. Sprays not containing zinc did not have this significant effect, indicating that the zinc was cytotoxic to the nasal mucosa.

Using Zinc to Stop a Cold

Though it is far from being a cure, there is evidence to suggest that zinc lozenges may help reduce cold symptoms, cutting the duration of the illness in half and alleviating symptoms more fully after the duration of the illness. A 2011 Cochrane Review concluded that zinc supplementation can reduce the duration and severity of a cold, though the change in duration is mostly by just 1 day. However, the exact mechanism of action is not known, and the exact dosage will differ by product. The guidance is to start with lozenges or tablets within 24 hours of the onset of a cold. In a 2017 meta-analysis, zinc acetate and zinc gluconate were shown to have similar effectiveness.

More studies are needed to better quantify zinc’s effect on rhinovirus and other cold viruses in order to reap the full benefit of this element.

Additional References:

Eby. Zinc lozenges as cure for the common cold: A review and hypothesis. Medical Hypotheses. 2009; doi 10.1016/j.mehy.2009.10.017

Hulisz. Efficacy of zinc against common cold viruses: An overview. Journal of the American Pharmacists Association. 2004; 44(5). Available on the Medscape website.

Lim et al. Zicam-induced damage to mouse and human nasal tissue. Public Library of Science (PLoS) One. 2009; 4(10), e7647.

 

The unrealized potential of treating disease at a personal level - the mythos of personalized medicine

Photo by National Cancer Institute on Unsplash

 

Originally published at Medium in August 2020.

By Alicia M Prater, PhD (Aliconia Publishing) 

When I was a graduate student, my advisor would light up when explaining how our work was going to lead to personalized medicine. We were working on understanding the genetics underlying hypertension. The idea was that by knowing which gene polymorphism a person has, the doctor would know which class of drugs would have an effect on their blood pressure and correct the derangement.

Symptoms and treatment of lithium overdose

 

Lithium capsules. James Heilman, MD, CC4.0 license

Lithium, the third element of the period table of chemical elements, is a soft metal pharmaceutically altered for use to treat bipolar disorder since the 1800s. 

OTC painkillers - are we taking too many?

Ibuprofen tablets. Ragesoss, CC3.0 license

A study published in the journal Pharmacoepidemiology & Drug Safety in January 2018 found that people are taking too much ibuprofen.

Ibuprofen is part of a group of drugs known as NSAIDs (non-steroidal anti-inflammatory drugs). Another popular over-the-counter NSAID is naproxen. They are generally used to treat pain, often chronically. Another well known pain killer that is not an NSAID is acetaminophen, more popularly known by its brand name Tylenol (which is manufactured by the company that sponsored this study).

NSAIDs do have side effects, especially if the daily dose limit is exceeded. The drugs act to reduce inflammation, which has effects on blood pressure, the heart, liver, and kidneys. And it's important to follow dosing guidelines, as they've been established based on toxicity studies.

However, the study authors were quoted in the New York Post as recommending NSAIDs become prescription only, pushing acetaminophen as a safer option (though that drug has liver toxicity and a known history of being pulled from shelves). It's a bit of an extreme conclusion based on a single week of self-reporting and limited findings. For example, less than 10% of subjects recorded exceeding the dose with NSAIDs, and they also exceeded the dosing on other drugs they took in that same time period at near the same levels.

So maybe the conclusion should be that we need to communicate dosing better, or find better pain killers in general, rather than limit the availability of what currently works for people. And because of the conflicts of interest regarding the sponsorship of the work, this study just comes across as industry shill.

Zithromax warning

The FDA has issued a warning for the use of azithromycin, an antibiotic sold under the brand name Zithromax. The agency warns that the drug may cause an irregular heart rhythm, potentially fatal in nature, in people with pre-existing risk factors, including QT prolongation, low blood potassium or magnesium, a slow heart rate, and arrythmia treated with medication.

Statins get FDA warning label

Statins, popular drugs used to lower cholesterol, will be sporting a new FDA warning label. The drugs have been associated with increased blood sugar levels, which could lead to or exacerbate type 2 diabetes. They are also associated with confusion and memory loss in some patients.These drugs include Crestor, Lipitor and Zocor.

Statins have had some controversy since their approval due to questionable use in women and men with no history of heart disease. Though studies have shown repeatedly that the drugs lower cholesterol in men with previous heart disease and reduce the chance of a second heart attack, they have not been definitively linked to the same success in women or men with no established heart disease, despite news reports to the contrary. One meta-analysis in January 2012 combined women's data from various studies (they generally don't enroll enough women to test for an effect in a single study) found a benefit, but this still isn't proof, as pointed out by the authors of that study!

Antibiotics and asthma in children

Asthma is a chronic respiratory condition that compromises a person’s ability to breathe due to inflammation of the airways. Children are particularly susceptible to the complications of restricted and inflamed airways, experiencing wheezing, coughing and chest tightness, as well as difficulty breathing. A number of triggers have been associated with the disorder, including allergens, stress and infections, but research over the last decade has found that antibiotic use in young children may also be a risk factor for early development of the disorder.

The studies

The earliest studies showing an association between antibiotic use and asthma in children were uncertain if the asthma occurred because of the respiratory infection being treated with the antibiotics or because of the antibiotics. So a large Canadian study in 2007 separated out children who did not have respiratory infections and found that they also had antibiotic-associated asthma. Two courses of antibiotics before the age of 1 year resulted in a 20 percent greater risk of asthma by the age of 7. Risk increased with more antibiotic use, topping out at a 50 percent increase with more than four courses by the age of 1 year.

The following year, another study published in Pediatrics and using an even larger group of children from industrialized countries found the same results. More than a quarter million children born between 1997 and 2003 had an increased risk of asthma if treated with antibiotics before the age of 1 year, and this risk increased with greater use. A Yale study published in December 2010 also found similar, but more extreme, results. In a group of approximately 1400 children, those who were treated with antibiotics in the first 6 months of life were 52 percent more likely to develop asthma and allergies by their sixth birthday.

The mechanism

The 2007 study also had some indication that children living in a more sterile environment (i.e. without allergens) made them more susceptible to antibiotic-associated asthma. The thinking was that the immune system did not develop properly. The lead author of the Yale study told Yale Daily News in January 2011 that antibiotics change the balance of bacteria in the gut. This can compromise stimulation of the immune system. The work aimed to address the hygiene hypothesis – that the developing immune system needs to be exposed to a variety of pathogens to develop properly, and subsequently react normally later in life.

Though the tissues of the immune system develop during fetal life, the function of the system matures during the first year of life. The various aspects of the system develop at different rates. Babies cannot produce their own antibodies until almost 9 months to 1 year of age. This makes them particularly susceptible to infection. It also means that environmental factors can affect the development of the immune system responsible for protecting them throughout life as the lessons the immune cells learn during early childhood shape how it responds as a mature, adult system. Some studies have even shown potential genetic mechanisms underlying environmental influence on the immune system.

Striking a balance

Researchers and doctors recommend that infants should not be treated with antibiotics unless the bacterial infection is severe. Preventing overuse and potential long-term effects on the developing immune system is going to require changing habits among many groups, including doctors and parents. Something as simple as putting Neosporin on an infant’s cut will have to be avoided to prevent increasing the risk of asthma developing later in childhood.

Why does cortisone work?

Cortisone is an anti-inflammatory hormone. It's injected into areas that are inflamed - swollen joints, painful plantar fasciitis - or used systemically (e.g., allergy). It may also be used cutaneously as a cream (hydrocortisone) in the case of rashes. Sometimes it's a broader name given to corticosteroid injections, which are various types of steroid hormones.

Essentially, the drug utilizes the natural system of the body to alleviate pain caused by inflammation by getting rid of the inflammation.

Natural cortisone production

The adrenal gland naturally produces cortisone, which is then metabolized to cortisol, the major stress hormone in humans. A synthetic version of cortisone was developed after researchers noticed that women experienced alleviation of their rheumatoid arthritis during pregnancy (a state in which cortisol is not cleared as quickly). The cortisone injections, which are sometimes combined with local anesthetics to reduce pain, are used to treat adrenal insufficiency and inflammatory disorders, but hydrocortisone also plays a role in chemotherapy for cancer.

How cortisone exerts actions

Steroids like cortisone treat inflammation by decreasing the production of pro-inflammatory mediators in the body. The actions are carried out by its metabolite, cortisol. Briefly, this molecule binds to receptors in the cytoplasm of cells and then travels to the nucleus of the cell to affect DNA transcription. More specifically, cortisol is a glucocorticoid and binds the glucocorticoid receptor. The glucocorticoid complex translocates to the nucleus and binds the glucocorticoid response element to affect the expression of pro-inflammatory genes. Cortisol also has effects on metabolism and the immune response. 

 

We take advantage of their properties and inject them locally to increase their effects in that area (and some injections contain pain relievers that help) and systemically to give the system a boost. The hormone is metabolized to cortisol once it is in the body - the infamous stress hormone.

How cortisol affects inflammation

Specific actions of glucocorticoids such as cortisone in inflammation include blockade of the secretion of certain interleukins by macrophages, which reduces the number of circulating T cells and prevents B-cell proliferation. The production of lipocortin is stimulated, which prevents phosphatidyl choline from being converted to arachidonic acid. This blocks the synthesis and release of the pro-inflammatory mediators known as prostaglandins and thromboxanes by the enzyme cyclooxygenase (COX), which prevents vasodilation. The lack of arachidonic acid also blocks the actions of leukotrienes in the immune response.

Cortisone injections in local inflammation

Under normal conditions, the body regulates inflammatory responses via endogenous (i.e. produced by the body) hormones like cortisol. The endocrine system is stimulated by the stressors (there are many theories about inflammation and stress), which results in the secretion of hormones to counteract it. The actions of cortisol affect nearly every tissue and cell in the body. This is a systemic response. When the inflammation is localized, such as in plantar fasciitis, cortisone injections can help the body alleviate the inflammation at a more local level. Injection of the hormone into, for example, a swollen and inflamed joint can act on the cells in that area, reducing the inflammatory mediators and local inflammation. However, there are side effects due to the myriad actions of the molecule, which requires a limit on how often a person can be treated with the injections.

 

 

New Antibiotics

Today ScienceDaily reported on a study published in Bioorganic and Medicinal Chemistry by researchers at Brown University that identifies the potential for a new compound in treating bacterial infections, specifically those that are drug-resistant.

Antibiotic resistance is becoming increasingly worrisome as strains like MRSA become household words and bacteria evolve new genetic mechanisms against treatment.

One antibiotic, which means a compound that acts against bacteria (and only bacteria - antibiotics cannot fight viral infections like a cold or the flu), is chloramphenicol. The new compound, BU-005, prevents bacteria from pumping this antibiotic out of their cellular structure, leaving the bacterial cell susceptible to the agent.

The research team used the same synthesis method for other types of compounds that may make headlines in the near future.

Bacteria can be used to fight dengue fever-causing viruses

Wolbachia infected insect cell, by Scott O'Neill

 

Dengue fever is caused by four viruses that are spread by mosquitoes. Some infections are severe, leading to a hemorrhagic fever. The common fever is generally not fatal, but infection causes uncomfortable and unpleasant symptoms for a week or longer without any available treatment. Dengue hemorrhagic fever, on the other hand, has a higher mortality rate due to blood loss and shock. Dengue fever affects 100 million people each year and kills more than 12,000. Because the mosquitoes that transmit the virus are active during the day, the preventative measures used to curb other mosquito-borne diseases, like bed nets for malaria, are not helpful in preventing its spread. Infective agents and the introduction of anti-dengue genetic strains into the mosquito populations have been pursued as alternatives.

Aedes aegypti mosquitoes are the primary vector of dengue virus. Wolbachia is an intracellular bacterium that tends to be endosymbiotic with the host mosquito and passed to its offspring. This bacterium has been found to inhibit viral replication within the mosquitoes that harbor it and prevent its transmission without the need for genetic engineering. In the journal PLoS Pathogens in 2010, researchers at Michigan State University showed that Wolbachia bacteria completely block the transmission of dengue from more than one-third of the infected Aedes aegypti mosquitoes they evaluated.

As noted in the journal Nature in August 2011 by Walker et al., several Wolbachia strains have been identified, each with their own effects on the mosquitoes. The strain wMelPop-CLA was shown to reduce the lifespan of the Aedes aegypti mosquitoes, which in turn reduces the transmission of dengue. Another strain causes cytoplasmic incompatibility, which reduces the reproductive activity of the mosquitoes. Female mosquitoes infected with Wolbachia pipentis had half the reproductive lifespan as female mosquitoes that were not infected. Reducing the number of mosquitoes that a mosquito can have aids in controlling the dengue-spreading populations. This feature of Wolbachia infection has been known since at least the 1990s (as noted in PNAS in 2004).

This strategy against dengue transmission has been shown to be possible based on the natural infection of two mosquito populations in Australia, as described by Hoffmann et al. in Nature in August 2011. Though the exact mechanism underlying the bacterium’s effect on the virus is not certain, researchers find the current results promising as the bacteria are naturally occurring endosymbiotes, spread quickly in the mosquito population, and appear effective at controlling both the mosquito populations and viral transmission.

Treatment can improve vision in macular degeneration

Source: Erin Silversmith, Wikimedia

 

Macular degeneration is a form of age-related blindness that develops over time. The "wet" form is caused by the growth of new blood vessels in the back of the eye, called neovascularization. The new vessels swell and leak, leading to loss of central vision. VEGF-A (vascular endothelial growth factor-A) has been found to be a key player in the process of angiogenesis, which is necessary for the new vessel growth. Treatments for macular degeneration aim at inhibiting this molecule.

Menopause

Another uniquely female health concern is menopause. Women are capable of conceiving children because of both the reproductive organs in their lower abdomen and the hormones the ovaries and adrenals produce. Estrogen and progesterone cycle, causing the release of an egg, its maturation, and if sperm is present and infiltrates the egg - implantation of the zygote to mature as an embryo, fetus, and child. When the egg is not fertilized, the hormones cause the uterine lining to be refreshed in case there is a zygote to nourish during the next cycle. This menstrual cycle repeats itself monthly (approximately 28 days, but this varies by woman and her natural hormonal rhythm, which changes with age as well) from puberty to middle age.

Like the rest of the body, the ovaries age and the decreased estrogen in the body results in a cessation of the menstrual cycle around the age of 50 (earlier or later, varies by woman), known as menopause. This hormonal change also causes symptoms - hot flashes being the most stereotypical, though many women don't have symptoms. Hormonal replacement therapy (estrogen pills) were used as a way to treat these symptoms, but it was found to have unplanned cardiovascular risks. Similar to hormonal birth control, synthetic and combination therapies were tested to reduce the side effects while keeping options open for women. Prempro is one such treatment. However, anyone opting to take Prempro should discuss the potential adverse effects with their doctor

Prempro is a combination hormonal therapy used to treat symptoms of menopause, such as hot flashes. The pill contains conjugate estrogens and medroxyprogesterone acetate. Estrogen used alone was found to increase the risks of uterine cancer, dementia, strokes, and blood clots. Progestins (like progesterone) were added to reduce these risks, but the combination treatment has its own adverse effects, such as an increased risk of breast cancer.

The Women's Health Initiative was a 15-year program that investigated the most common causes of death and disease in postmenopausal women. The study included an evaluation of hormone therapy in 60,000 women. The estrogen plus progestin substudy was halted early, after a little more than 5 years, due to the risks outweighing the benefits. Women treated with the combination therapy in the study had increased risk of heart attack, stroke, venous thrombosis, and blood clots.

Breast and lung cancer risks are also increased by Prempro use. As reported in USA Today in October 2010, a study comparing Prempro use to placebo found an increased risk of breast cancer, and an increased risk of that cancer’s spread to the lymph nodes (metastasis). Women taking the drug were also more likely to die from breast cancer. A previous study that year had found an increased risk of death from lung cancer, though it did not increase the risk of lung cancer per se.

A positive side effect though is a decreased colorectal cancer risk in those who are treated. In addition, stopping treatment results in normal breast cancer risk within 2 years of stopping.

The FDA also warns of potential increased risk of dementia with Prempro use in women aged 65 years and older. The exact combination in the Prempro pill was not studied in the Women’s Health Initiative substudies (cardiovascular and dementia risks), but the FDA assumes, in the absence of that specific data, that the estrogen plus progestin study findings are applicable to estrogen plus medroxyprogesterone.

In addition, Pfizer's label includes the following side effects: high blood pressure, liver problems, depression, increased benign fibroid size in the uterus, high blood sugar, benign breast lumps and breast discomfort, unusual vaginal bleeding and spotting, fatigue and dizziness, severe headaches, chest pain, changes in vision and speech, leg pain, shortness of breath, fluid retention and bloating, vaginal dryness and yeast infection, hair loss, stomach pain, and headaches, sometimes severe.

The discomfort of menopause will subside on its own once the hormones become regulated, usually over the course of a year or two, though the symptoms may recur for up to 5 years. Women with severe symptoms may find relief in treatment, though they may have their own side effects to consider.

Woman's choice - Hormonal contraception

Source: Ceridwen, Wikimedia Commons

Women have the unique characteristic among the two sexes of the human species as the one capable of giving birth. Pregnancy has many emotional topics that surround it, including that of prevention. Contraception has been a topic of study for thousands of years, with spermicidal plants being a focal point of ancient Egyptian medicine. This same culture is credited as using the first condoms roughly 3000 years ago.

In the 20th century, contraception reached the woman's control again with the advent of hormonal contraception - the birth control pill. Rather than relying on the spermicidal effects of chemicals, the pill alters the levels of hormones in a woman's body, redirecting, or sometimes altogether preventing, ovulation. Basically restricting the body's ability to conceive.

In the last half century, synthetic hormones and combinations have been tested and marketed in order to fine tune the process, achieving as high as 99% reliability when used properly, as well as eliminate side effects, which can include cardiovascular problems and female cancers.

Each woman can decide just how she wants to control her ability to conceive - see WebMD for a list of available types, along with their pros and cons.

Genetic engineering may cure leukemia

Taking a patient's T cells and engineering them to destroy leukemia cells has had success in three leukemia patients. The very small clinical trial was carried out by researchers at the University of Pennsylvania. Using a virus to alter the cells and then inoculating the patients with the result allowed two of the three patients to live cancer-free for a year (and still counting).

The results are an important step forward in treating advanced cancers. Much larger studies are needed, but the proof of concept and how dramatic the results could be will help groups working on the cures receive funding.

More about the study can be read at the LATimes and MSNBC.

Red blood cell dysfunction - Anemia

From Wikimedia

Anemia is the name for the condition when the body doesn't have enough red blood cells, which means there isn't enough oxygen getting out to the tissues. There are many causes of anemia, as PubMed Health indicates by its very long list. Red blood cells have a normal life span of 3 to 4 months, and then they are broken down by the spleen and removed from the body to make way for the newer ones. Sometimes, though, the body just isn't producing them as fast as they're being broken down, or they're being broken down too soon.

Iron is an important mineral for the blood, and it is often cited as a treatment of anemia. Iron is a part of hemoglobin, the protein that binds oxygen in red blood cells. So a lack of iron means a lack of hemoglobin, and a lack of hemoglobin means a lack of red blood cells.

But also, there are proteins produced by the body that stimulate red blood cell creation in the bone marrow (that's where red blood cells are made!). Some treatments for anemia, like the brand Procrit, but there are side effects to treatment - as the number of cells in the blood is increased, the blood volume increases, which could increase blood pressure. Clotting is also an issue.

Procrit is the brand name for epoetin alfa, an injectable solution that mimics erythropoietin and stimulates the bone marrow to produce red blood cells, a process called erythropoiesis. Patients who undergo chemotherapy or use certain antiretroviral drugs to treat HIV infection may require such treatment, as well as some who may be treated prophylactically in preparation for blood loss during surgery. However, triggering blood cell development can cause increases in hemoglobin, which should be monitored by the prescribing doctor.

Use of the drug to treat anemia may correct menstruation issues brought about by the condition and increase the odds of becoming pregnant. Procrit may result in increased blood pressure, as well as the following common side effects: headache, muscle or joint aches and soreness, sleeping problems, burning or itching of the extremities, pain or inflammation at the injection site, and gastrointestinal issues. Gastrointestinal symptoms include constipation, stomach pain, diarrhea, indigestion, nausea, and vomiting. A doctor should be notified if the symptoms worsen or do not go away.

The use of epoetin alfa has been associated with an increased risk of blood clots, particularly in the legs, lungs, and brain. Pain, tenderness, swelling, redness, and/or warmth in the legs or a cool feeling and numbness in the arm or leg should be seen immediately by a doctor. Chest pain, coughing up blood, or sudden shifts in the senses (sudden vision issues) or cognition (sudden confusion, slurred speech, seizures, trouble understanding language, lack of coordination) are also signs of a medical emergency.

A doctor should be notified if any severe adverse effects are experienced. A spreading rash, hives, or swelling may indicate an allergic reaction. Some other reported adverse effects include signs of infection, such as fever, chills, sore throat, or cough, as well as hoarseness, wheezing and trouble breathing, lack of energy, and feeling cold all the time.

Doctors may avoid use of the drug in individuals with high blood pressure, and individuals with bleeding or clotting disorders should be wary of use as well. The effects of increasing blood volume by triggering erythropoiesis may adversely affect individuals who already have these issues. Patients on hemodialysis may experience blood clots in the vascular access. The FDA has also issued a warning that some patients with certain cancers have experienced increased tumor growth and an increased risk of death.

The reason for the anemia would determine what treatment - whether it be with iron supplementation or synthetic erythropoietin, or any other stimulant of red blood cell creation or prevented destruction - will depend on its cause.

What about white blood cells? Read about that tomorrow.

Oral rehydration solution: Bangladesh solution to dehydration

Dehydrated children cared for by the US Navy

The human body is made up of 50-70 percent water, and human blood plasma is 91 percent water, making up more than half the blood volume. Water plays a role in human cell structure and nutrient transport, as well as maintaining blood pressure, blood pH, and ion balances within the tissues. Dehydration is the result of water loss - the body simply cannot maintain its functions and causes illness. Similar to summer dehydration by sweating, a person who suffers from a diarrheal disease also loses water, but through the intestines and bowel. Worldwide, up to 4 million children die each year from diarrhea.

Oral rehydration salt-sugar solution (ORS) is a simple at-home concoction containing “a pinch of salt, a fistful of sugar, a half liter of water”. The solution was first taught in Bangladesh households 26 years ago, after being tested in a cholera outbreak in 1971.

The oral rehydration solution replaces the lost water, but it also provides ions and minerals that help the absorption process and the maintenance of homeostasis within the body, minimizing the severity of the diarrhea’s effects on the sufferer. Bangladesh has been a beneficiary of the efforts of aid organizations that have been teaching households how to mix the solution, which is sometimes referred to as "Poor man's Gatorade". It has integrated into the regular treatment of diarrheal disease, as well as hydration after exertion in the hot sun, preventing dehydration from other factors. However, the International Center for Diarrheal Disease Research still treats 100,000 patients a year, because the ORS is not a cure for what causes diarrhea, only a treatment for dehydration.

Water is an important treatment of dehydration in developed countries, but when electrolytes require replenishment or fresh water is not available, enriched drinks are an option. Avoid alcohol, caffeine, and sugary drinks to avoid further dehydration. See the CDC for more information about the importance of water to the human body.

Genetics of Plavix responsiveness

 

Source: Trounce, CC2.5SA license

Responsiveness to clopidogrel, sold under the brand name Plavix, is an issue for some patients who undergo anti-platelet treatment to prevent heart attack and stroke. Particularly susceptible are patients who receive the drug to prevent clotting and embolism after coronary stenting. Approximately 30 to 40 percent of people have a genetic mutation that makes them unresponsive to clopidogrel treatment. In 2009, Scripps Health began offering, for the first time in the US healthcare arena, a genetic test for patients undergoing coronary stenting to determine upfront whether they will be nonresponsive to anti-platelet treatment with clopidogrel.

Clopidogrel is metabolized by the cytochrome P450 (CYP) enzyme family. This metabolism is necessary for activation of the molecule and its anti-platelet effects. Patients with genetic variants of CYP2C19 (known as CYP2C19*2, CYP2C19*3, and so forth) have reduced enzyme activity and, accordingly, reduced activation of the drug. Scripps patients undergoing coronary stenting are tested by Quest Diagnostics for CYP2C19 variants that may affect clopidogrel responsiveness, allowing physicians to choose other anti-platelet drugs (such as prasugrel or ticagrelor) or to adjust dosage to the best benefit of the patient.

Some feel that this testing was debuted too soon. Research is still indicating other potential genes involved in treatment response, including controversial findings regarding PON-1, which encodes the paraoxonase-1 enzyme. The December 2010 findings that PON-1 is the enzyme responsible for bioactivation of clopidogrel have been refuted by more than one study, and CYP2C19 involvement supported. Experts consulted by Heartwire in October 2009 upon Scripps’ announcement felt that platelet function tests were necessary companions to genetic testing at this stage of the research on clopidogrel responsiveness. A number of companies now offer tests similar to Quest's.

In March 2010, the U.S. Food and Drug Administration (FDA) required a warning on Plavix to warn patients that a portion of them may be poor metabolizers of the drug. The warning also reminds health care provides that CYP2C19 genetic tests are available to aid in treatment planning. 25 million prescriptions were written for the drug in 2008 according to MedPage Today, leading to a great number of genetic tests. Some experts feel that, at best, the testing will aid in researching more appropriate dosing of the drug among those with genetic variants.

According to Heartwire in June 2010, the American Heart Association and American College of Cardiology do not recommend genetic testing as a determinant of therapy. They issued statements that urged care givers to follow current prescribing guidelines. The chair of the joint committee that issued the statement reiterated that the alternative drugs lack the track record of clopidogrel, and others urge platelet function tests in conjunction with genetic testing to ensure successful treatment planning that benefits the patient.

Contradictory findings on PON-1 and clopidogrel responsiveness

An example of how knowledge progresses in fits and starts:

Clopidogrel is an anti-platelet drug used to prevent clotting, which can cause heart attack or stroke. Some people are not responsive to the drug - so researchers have explored genetic mutations that may alter the enzymes involved in its activation. The cytochrome P450 enzymes have been of particular interest because of their role in drug metbolism.

However, other research surprisingly identified PON-1 (paraoxanase-1) as being involved in clopidogrel's metabolism. Then research found that the mutation of interest wasn't actually associated with responsiveness. They did, however, confirm the CYP (cytochrome P450) enzyme mutations.

Provenge

Provenge is a first in the medical field – a therapeutic vaccine for cancer. Its maker, Dendreon, sought Food and Drug Administration (FDA) approval of Provenge from 2005 to 2010, conducting clinical trials since at least 2002. In 2007, the company was told that they still lacked data, and the FDA wanted survival statistics. They found that use of the vaccine added 4 months to the lifespan of men with advanced prostate cancer. On April 29, 2010, the FDA finally approved Provenge for the treatment of metastatic castration-resistant (hormone refractory) prostate cancer, an advanced form of the disease.

 The drug increases the body’s immune response against the cancer, leading many to call it a vaccine. However, vaccines are usually preventative therapies, and this is a treatment for advanced stage disease.

Provenge is made by Dendreon Corporation, which was founded in 1992 and is based in Seattle with production facilities in New Jersey. The drug is meant to treat metastatic castration-resistant prostate cancer, meaning that the cancer does not respond to hormone therapies. The drug was rejected by the FDA in 2007 because the company had not shown that it increases survival. Clinical studies on 512 men since that time have shown that Provenge increases a patient’s life span by 4 months compared to placebo (no drug). Men who receive the drug can still only be expected to live about 2 years, though roughly a third survive to 3 years.

The drug is tailored to the individual patient, and this is due to the technique used to administer the therapy. First, a sample of the patient’s white blood cells are isolated and sent to a lab facility where the drug is “made”. The cells are exposed to a prostate cancer-specific protein, much as they would be if mounting an immune response in the body. About 3 days later, the patient receives their blood cells back in a transfusion. Two weeks later, they carry this out again, a total of three times. The white blood cells are primed to fight the cancer when they’re back in the patient’s bloodstream. Because of this intensive production method, Dendreon expects it can only treat 2000 men in the next year, but they expect to expand beyond the 50 centers that participated in the study in the future.

The treatment is expected to cost $93,000 a person. This price is similar per month of survival as the only other option for men in the treatment group – chemotherapy with Taxotere (docetaxel) – which only extends life by two or three months. Clinical trials have shown that Provenge produces few side effects, but men receiving the therapy may experience chills, fever, headache, fatigue, nausea, joint aches, and back pain, which usually pass in a few days. This places the drug as a potential first choice before chemotherapy, which has severe and often debilitating side effects.

Provenge is a first in the medical field – a therapeutic vaccine for cancer. It is also Dendreon’s first FDA approval. Some in the field feel that this step will also open up the way some researchers approach treating other diseases, such as HIV. Dendreon is currently planning production facilities in Los Angeles and Atlanta. However, the concern among researchers and clinicians still is that the drug does not slow the progression of the disease. So there is still much work to be done on treating advanced prostate cancer.

Fibrates

Fibric acid derivatives, or fibrates, are drugs prescribed to prevent heart disease by lowering triglyceride levels, though they are known as "cholesterol-lowering drugs", they are antilipemic agents. The drugs lower triglyceride levels as much as 25 to 50 percent according to WebMD, mainly by inhibiting the production of very low density lipoprotein (VLDL) in the liver and speeding up the removal of triglycerides from the blood. Lipoproteins transport insoluble fatty substances in the blood, including cholesterol and triglycerides; VLDL is the triglyceride-rich fraction. Triglycerides are fatty substances made up of three fatty acids and found in vegetable oil and animal fats. They play an important role in metabolism as they provide twice as much energy as carbohydrates and protein.

High circulating levels of triglycerides (hypertriglyceridemia) have been linked to atherosclerosis and heart disease, specifically the risk for coronary artery disease, and very high levels (>1000 mg/dl) can cause painful inflammation of the pancreas called pancreatitis. Fibrates are used to prevent pancreatitis and in conjunction with lifestyle changes (a low cholesterol and low-fat diet, exercise, smoking cessation) and statins to lower cholesterol. Fibric acid derivatives can not lower low density lipoprotein (LDL, also known as "bad" cholesterol) levels on their own, though they can increase high density lipoprotein (HDL, so-called "good" cholesterol) levels as much as 10 to 35 percent according to WebMD.

Fibrates activate peroxisome proliferator-activated receptors, known by their acronym PPAR, a group of intracellular receptors that activate the transcription of proteins used in lipid metabolism. Fibric acid derivatives mainly affect PPAR alpha, which is present in the liver and other tissues that metabolize fatty acids and is also involved in the inflammatory response in the blood vessel wall, an event associated with atherosclerosis. Fibrates are pharmacologically related to anti-diabetic drugs that also act on certain subtypes of PPAR. Fibrates in the United States include Lopid (gemfibrozil) and Tricor (fenofibrate). Gemfibrozil has been shown to decrease the risk of heart attack in individuals with coronary artery disease and low HDL levels.

Most patients tolerate fibric acid derivatives well, but like any other pharmaceutical treatment they can have side effects. Gastrointestinal pain and discomfort, headache, and gas or heartburn are common, but a doctor should be contacted if muscle pain, nausea or vomiting, fever, weakness, severe abdominal pain, or signs of allergy (hives, trouble breathing, swelling) occur. Patients on fibrates also have an increased risk of gallstones, which are small, hard accumulations of cholesterol in the gall bladder. Fibrates may alter the function of other medications, so your doctor should be aware of all other prescriptions and over the counter drugs you take.