Friday, 21 July 2017

The Potential Role of Cows in Preventing HIV Infections

The HIV virus is a nasty entity that attacks the immune system and stops it from doing its job. The infection can be deadly. Fortunately, the disease can be controlled, provided patients have access to antiretroviral therapy and follow its protocol correctly. The therapy inhibits or slows the replication of the virus. The therapy isn’t available everywhere in the world, however. People are still dying from AIDS, the end stage of the infection. It would be wonderful to stop the disease before it starts. The impressive immune system of cows may enable us to create a vaccine and/or new treatments for the disorder.


The green particles are HIV virions, or individual virus particles.
The blue object is a white blood cell.
Public domain photo from the CDC

Effects of HIV


The HIV or Human Immunodeficiency Virus destroys cells called helper T cells or CD4 cells. The latter name arises from the fact that the cells have a protein called CD4 on their membrane. Helper T cells are essential for activating other cells that either directly or indirectly destroy invading viruses, bacteria, and fungi.

As the viral disease progresses, so many CD4 cells are destroyed in the patient that their body can no longer fight infections or the types of cancer that are caused by an infection. Eventually the immune system is in such a weakened condition that is person is said to have AIDS, or Acquired Immunodeficiency Syndrome.

The HIV virus is transmitted by the transfer of specific body fluids from an infected person to an uninfected one. The CDC article in the “References” section below has more information about transmission.

The Controlled and the Uncontrolled Virus


For people who have access to proper therapy, an HIV infection is no longer an automatic death sentence. The therapy must be followed carefully and consistently, however.
"Today, someone diagnosed with HIV and treated before the disease is far advanced can live nearly as long as someone who does not have HIV." Quote from the CDC, or the Centers for Disease Control and Prevention

HIV is a horrible virus if it's not controlled, not only because of its dangerous effects but also because the active virus is so hard for the body to fight. The virus often mutates (changes genetically), even while it’s inside a patient's body. The mutation gives the virus new characteristics. This makes it difficult for the patient to create effective antibodies. Antibodies are proteins that attack harmful viruses and bacteria.

A very small number of patients manage to create antibodies that attack parts of the virus that are unaffected by mutations. This is the case even if the patients don’t receive antiviral therapy. The antibodies that they create are said to be “broadly neutralizing” because they attack many different versions, or strains, of HIV.

Cow Antibodies


Researchers have discovered that cows—or at least four of them—also make broadly neutralizing antibodies to the HIV virus. In addition, some of these antibodies appear and work in weeks instead of the years required in the human body. Specifically, the researchers found that after the cows were exposed to proteins from the HIV virus, the antibodies that they made were able to neutralize 26% of HIV strains within 42 days and 96% of them within 381 days.

"From the early days of the epidemic, we have recognized that HIV is very good at evading immunity, so exceptional immune systems that naturally produce broadly neutralizing antibodies to HIV are of great interest - whether they belong to humans or cattle." Quote from Dr. Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases

Cows don't experience HIV infections in their normal lives. The researchers suspect that because the digestive tract of cows is exposed to so many bacteria in their diet, the animals have developed the ability to produce a wide variety of antibodies relatively rapidly. Their ability may help us to obtain new chemicals to fight the HIV virus in humans and perhaps to create a vaccine to prevent the infection.

References


HIV information from the CDC

HIV antibody production in cows

Tuesday, 11 July 2017

Human Herpesvirus 6 and Multiple Sclerosis: A Possible Link

Human herpesvirus 6 (HHV-6) is a very common virus. Researchers estimate that more than 80% of us were exposed to the virus in childhood, usually without realizing it. The immune system can generally fight the active form of HHV-6, but the virus has a technique to avoid complete destruction. It has the ability to become latent. This means that it’s present in our cells but is hiding from the immune system and is apparently inactive. Researchers think that the latent virus isn’t completely inactive, however, and that it may be involved in some cases of multiple sclerosis.
Illustration by LadyofHats, public domain license

Multiple sclerosis or MS is a demyelinating disorder. Myelin is a fatty material that covers and insulates the nerves. For an unknown reason, in MS patients the immune system destroys myelin surrounding the nerve cells in the brain and spinal cord. This disrupts the flow of nerve impulses through the body and can cause a wide variety of debilitating symptoms, including muscle weakness, coordination problems when moving, and problems with sensation.

As long ago as 2003, researchers found latent HHV-6 in the brain cells of people with severe multiple sclerosis. HHV-6 may not be a direct cause of MS, but it’s thought that the virus prevents the body from repairing loss of myelin. When myelin is damaged in our body, oligodendrocyte progenitor cells normally migrate to the injured area and produce oligodendrocytes. These cells then make myelin to repair the injury. This process may not happen in someone with MS.

HHV-6 becomes latent by incorporating its own DNA into the DNA of its host. The virus then produces a protein called U94. This protein helps the virus to remain in the DNA and prevents it from being detected by the immune system. Researchers from the University of Rochester in the United States have discovered that when the HHV-6 virus is present in the DNA of human oligodendrocyte progenitor cells placed in lab animals, the U94 protein that’s made prevents the cells from migrating to nerves with injured myelin. As a result, the myelin of the animals disappears and the nerves are damaged.

                                           Possible symptoms of multiple sclerosis 
                               Illustration by Mikael Haggstrom, public domain license

The discovery about the possible relationship between the virus and MS is interesting, but there are some questions that need to be answered. 
  • One question is whether the inability of oligodendrocyte progenitor cells to migrate when they are infected by the virus is true in human cells as well as in the cells of lab animals. 
  • Another is whether the latent virus is harmful in people with MS or whether it needs to become active in order to be harmful. 
  • Yet another topic to investigate is the location of the virus in the bodies of healthy people and in the bodies of those with MS. 
  • We also need to know how the body of people with MS responds to the latent and active virus compared to the body of someone without MS. 
It certainly seems that the potential link between human herpesvirus 6 and multiple sclerosis should be investigated further. It’s sad that we still don’t know the cause or causes of the disorder. Understanding how the disease arises could enable us to treat it better and perhaps prevent it. 

References

The possible role of HHV-6 in multiple sclerosis
Facts about multiple sclerosis

Tuesday, 6 June 2017

Modified Vancomycin: Preventing Antibiotic Resistance in Bacteria

Vancomycin is an antibiotic that is prescribed to treat some potentially serious bacterial infections. For many years, it's been a powerful ally in our fight against disease. In recent times, however, it's lost some of its effectiveness. Bacteria are developing resistance to many of our current antibiotics, including vancomycin. In what could be a very significant discovery, scientists have found a way to modify the vancomycin molecule so that it becomes effective again.


Methicillin-resistant Staphylococcus aureus or MRSA is 
   being absorbed by a white blood cell in this colorized photo.
Vancomycin is used to treat MRSA. (Public domain photo)


The Importance of Antibiotics


Antibiotics are chemicals made by bacteria or fungi in order to attack other organisms. Their discovery was a wonderful time in history. Some very serious and previously fatal diseases were able to be cured by the chemicals. We are currently experiencing the reverse situation, however. As antibiotics stop working due to bacterial resistance, the spectre of untreatable diseases is reappearing.



How Do Bacteria Become Resistant to Antibiotics?


Antibiotic resistance in bacteria develops because of the genetic variability of the individuals in a species. Some individuals in a species of bacteria may contain a gene (or genes) that prevents them from being harmed by a particular antibiotic. When other members of the population are killed by the medication, the resistant ones survive. When they reproduce, they pass on the gene for resistance to some of their offspring. Over time, the population as a whole may become resistant to the antibiotic.



Vancomycin and Its Action


Vancomycin has been prescribed for over sixty years. It was discovered in 1953 in a soil sample from Borneo and is made by a bacterium named Amycolatopsis orientalis. It's prescribed as a treatment for some serious conditions that other antibiotics can no longer cure. Vancomycin may have some major side effects, however. These effects don't always occur, but if they do, they may include hearing and kidney problems.


All forms of vancomycin—natural and modified—work by interfering with the process in which bacteria produce their cell wall. The wall surrounds the cell membrane and has protective functions. Vancomycin does its job by binding to protein fragments (peptides) in the cell wall. Peptides and proteins consist of a chain of amino acids.


Unmodified vancomycin binds to two copies of an amino acid called D-alanine that end some of the peptides in bacterial cell walls. This stops the wall from being assembled and kills the bacteria. Many of the once-susceptible bacteria have now evolved to have a D-alanine paired with a D-lactic acid combination at the end of their peptides instead of a double D-alanine combination, however. Natural vancomycin can't bind with this combination and is therefore rendered ineffective.



Modified Vancomycin


A group of scientists at The Scripps Research Institute in the United States has made modifications to the vancomycin molecule to restore its effectiveness. The first modification was the creation of a form that can bind with with a D-alanine—D-lactic acid pair in a bacterium's cell wall. Other scientists created two additional modifications to the structure of the antibiotic. One prevents the cell wall from being made while the other causes the wall to burst. The Scripps team has now created vancomycin with all three modifications. This means that the altered antibiotic prevents bacteria from making their cell wall in a total of three different ways.


Resistance should be much less likely to develop when the new version of vancomycin is used. If any bacteria become resistant to one of the antibiotic's new abilities, they should be unable to resist the other two, perhaps for a long time into the future.


Animal and human trials are needed before the modified vancomycin can be prescribed by doctors. The information announced so far is both hopeful and exciting, however. We badly need either new antibiotics or old ones that work successfully again. 



References


A modified antibiotic in the fight against drug resistance from The Guardian newspaper


The creation of a more effective antibiotic from sciencemag.org

Friday, 26 May 2017

Lack of High-Quality Sleep May Contribute to Weight Gain

Getting a good night's sleep (or day's sleep for those with a night job) is important for many reasons. Research suggests that one of these reasons is to prevent or reduce weight gain. Over the last few years, researchers in different institutions have found a link between poor quality sleep and an increase in body weight. Though the exact reason for the link is unknown, several proposals have been made based on the evidence obtained so far. One of the leading theories is that the balance between chemicals that influence appetite and satiety is altered.


Adequate sleep is important.
Public domain photo by claudioscott


Some Possible Reasons for Weight Gain After Sleep Loss


Weight gain after inadequate sleep may be due to one or more factors, including changes in appetite, metabolism, motivation, or the desire for exercise. Researchers at Uppsala University in Sweden recently presented some interesting discoveries at the European Congress of Endocrinology in Lisbon. Some of their discoveries are described in the quote below.


Following sleep loss, normal-weight men prefer larger food portions, seek more calories, exhibit signs of increased food-related impulsivity, experience more pleasure from food, and expend less energy. Christian Benedict, Uppsala University
The researchers made some other interesting discoveries. They found that after sleep loss the level of hormones that promote appetite (such as ghrelin) increased and the level of those that promote satiety (such as glucagon-like peptide 1) decreased. Ghrelin is made by the stomach and glucagon-like peptide 1 is made by the intestine.


The Endocannabinoid System


Like some other scientists who have investigated the effects of sleep loss, the Swedish researchers also found that the level of endocannabinoids that increase appetite rose after lack of sleep. The endocannabinoid system was discovered relatively recently. It seems to be involved in the regulation of a variety of processes, including motivation, reward, and appetite control. It's composed of chemicals that act as signaling molecules and activate the same receptors as delta-9-tetrahydrocannabinol, or THC. THC is also found in marijuana (scientific name Cannabis sativa), which is known to increase appetite.


The Role of Gut Bacteria 


The researchers also claim that sleep loss alters the composition of the bacterial community in our gut. Scientists are discovering that this community seems to have important effects on our lives. Many of these effects are helpful. Some bacteria are harmful, but they are normally kept in check by the good bacteria. If the balance between "good" and "bad" bacteria is altered, we may develop a health problem.


Peer Review


Uppsala University is a respected institution, but at the time of this post their research hadn't yet been peer reviewed. A peer review is performed by researchers who work in the same area as the scientists whose work is being published. The review looks for obvious flaws in the research that make the report unsuitable for publication. Nevertheless, the results of the Swedish research are interesting. Since other scientists have had similar results to some of those made by the Uppsala team, the team's claims may well be accurate.



 A healthy diet as well as adequate sleep is needed to prevent weight gain.
                                               Photo by Linda Crampton


Tips for Getting a Good Night's Sleep 


Sleep experts have some suggestions for helping us rest properly during the night. They say that eating a heavy meal shortly before bed is not a good idea. Neither is drinking caffeine. Some people may need to avoid caffeine in the afternoon as well. Exercise close to bedtime may not be a good idea, either, but this varies in different individuals. Using electronic devices in bed—even small ones like a cell phone—is a bad idea. The light from the device can trick the brain into thinking that it's day time and stop a person from relaxing and falling asleep.

Researchers have pointed out that getting enough high-quality sleep probably won't be very helpful for weight loss if we make lots of poor diet choices or never exercise during the day. Combined with a healthy diet and adequate exercise, it could be very beneficial, however.



References


Sleep loss and weight gain: Uppsala University research


Lack of sleep and endocannabinoid level: University of Chicago research


Weight gain after insufficient sleep from the Mayo Clinic

Saturday, 20 May 2017

Chili Peppers, the Scoville Heat Scale, and a World Record

Chili peppers or chilis are known for the hot sensation that they produce in the mouth and digestive tract when they're eaten. The heat is produced by a chemical called capsaicin, which has health benefits when used appropriately. The hotness of the pepper is indicated by a number on the Scoville heat scale. Plant breeders have recently created a chili that is said to be so hot and have such a high Scoville number that it may be dangerous, depending on the amount that's eaten. The pepper may have medicinal uses, however.

Paprika
Photo by Pixel2013, public domain license


Chili Peppers or Chilis


Chili peppers belong to the genus Capsicum, which in turn belongs to the nightshade family, or the Solanaceae. Bell peppers also belong to the genus Capsicum, but unlike their relatives they don't contain capsaicin and aren't hot. Chili and bell peppers contains seeds and are therefore fruits.

Eating chili peppers can irritate the digestive tract, causing a burning sensation—which can sometimes be severe—as well as a flushed face, tears, and sweating. Interestingly, though, researchers have found that although the lining of the digestive tract is temporarily irritated by hot pepper and may feel as though it's on fire, it's not being burned. Nevertheless, the abdominal pain created by the irritation and the nausea and vomiting that may accompany the pain may need medical treatment.

According to the American Chemical Society article referenced below, as someone becomes used to eating hot peppers, they become more tolerant of their effects. A person who is new to eating peppers may experience the most severe effects. It therefore seems like a good idea to start by eating a very small quantity of pepper. It might also be a good idea to have a glass of milk on hand. The casein molecules in milk surround the capsaicin and wash it away.

The Scoville Heat Scale


The Scoville heat scale is named after Wilbur Scoville, a pharmacist who created the scale in 1912. The Scoville rating depends on the capsaicin concentration. Pure capsaicin has a rating of 16 million Scoville Heat Units, or SHU. Bell peppers have a rating of 0 SHU. According to Guinness World Records, the hottest chili pepper at the moment is the Carolina Reaper, which was bred by the PuckerButt Pepper Company in the United States. The full name of the chili is Smokin Ed's Carolina Reaper. The fruit has an average rating of 1,569,300 SHU, but some specimens may have a rating as high as 2 million SHU.


Chili Peppers
Photo by Hans, public domain license

The Dragon's Breath Chili


Information about a new contender for the title of the world's hottest chile pepper has been sent to the Guinness Word Records organization. The Dragon's Breath chili was created as a joint project by a plant breeder in Wales and professors at Nottingham Trent University in the United Kingdom. It reportedly has a rating of 2.48 million SHU. The fruit is orange-red in colour and is about the size of a fingernail.

The new pepper is so hot that eating it might be dangerous as well as painful. The creators have suggested that it could cause anaphylactic shock in some people and block the airways, although this statement is a bit puzzling. Anaphylactic shock is an extreme and very dangerous type of allergic response that affects the whole body, including the airways. Someone would have to be allergic to capsaicin in order to develop this reaction. Still, the pepper has such a high Scoville rating that it might cause harmful effects when eaten. It wasn't created as food, however. The breeders of the chili think that the oil inside it—which contains capsaicin— could be useful as an anesthetic.

Capsaicin in Medicinal Creams


Capsaicin is used in creams to relieve pain from sore muscles and joints. Based on the reports that I've read, it seems to be quite effective for some conditions, including arthritis. It may cause a burning sensation to begin with, but this is often followed by pain relief. The most common explanation for its action is that it reduces the amount of substance P, a neurotransmitter that transmits pain signals. Neurotransmitters control the passage of nerve impulses from one neuron to another. It's interesting that capsaicin has benefits as well as disadvantages. The effects seem to depend on the method of application, the dose, and individual sensitivity to the chemical.

References 


Hot peppers from the American Chemical Society
Capsaicin information from HealthLinkBC (a British Columbia government organization)

Wednesday, 17 May 2017

Mussel Glue Mixture May Significantly Reduce Scarring

A group of researchers in South Korea has just made what could be an important discovery with respect to wound healing. They've used a mixture containing a protein from mussel glue to greatly reduce scarring in rats who experienced a serious skin injury. It's possible that the mixture may be helpful for reducing scarring in humans as well.


Mussels
Photo by stux, CC0 public domain license


Animal Testing


The experiment that was performed involved creating surface wounds in rats and then observing whether the test mixture reduced scar formation. As with many experiments with lab animals, the treatment of the animals could definitely be criticized. Using stem cells to create different types of human tissue and sections of organs may well reduce the use of animals in medical research in the future. It probably won't persuade researchers to abandon animal research altogether, though, because they sometimes want to look at whole-body effects.

Three classes of medical research are in vivo experiments (done in living things), in vitro experiments (done in lab equipment, and in silico experiments (done with computers or via computer simulations). I'm hoping that the last two types of experiments rapidly become more and more useful.



Collagen in Skin


Collagen is a fibrous protein that could be thought of as the scaffolding for our skin. It forms a network or mesh that helps to support the skin's structure and provide firmness. When we receive a significant wound, the skin that fills in the wound contains parallel strands of collagen in bundles instead of a fibrous network. This is a major contributor to the abnormal appearance of a scar.



Decorin


Decorin is a protein involved in the normal organization of collagen in the skin. It has been shown to reduce scarring when applied to wounds, but it isn't used therapeutically. It's a complex molecule that is too hard to make and too expensive to use. The Korean researchers used part of the decorin molecule in their experimental mixture, however. They also added a sticky substance from mussels and a collagen-binding molecule to the mixture. The mixture was then applied to the skin of rats with a major wound.



The Rat Experiment


The researchers say that the wounds in some of the animals were treated with the test mixture and then covered with plastic to keep the wound moist. In the other rats in the experiment (which formed the control group), the wound was covered with plastic but nothing else. The wounds on all of the rats had the same width and depth.


The New Scientist article referenced below shows pictures of the rats' wounds over time. Based on these photos, and assuming that there was no further change in skin appearance after day 28, it seems inaccurate to say that the experimental mixture prevented scarring as some headlines do (including the one in the referenced article). The mixture did reduce the size of the scar very significantly, however.

  • By Day 11, 99% of the wounds were closed in the test rats and 78% in the control group.
  • By Day 28, "treated rats had fully recovered" and there was very little scarring. The rats in the control group had thick purple scars.
The scientists found that the collagen in the healed wounds looked normal and that the skin contained oil glands, hair follicles, and blood vessels, structures that are absent from scars. 


Possible Application to Humans


Rats and humans are both mammals, so what applies to one often applies to the other. This isn't always the case, though. The researchers say that one factor which may be significant with respect to the scar experiment is that rats have looser skin than humans and tend to scar less. The scientists plan to experiment on pig skin next, which is more similar to human skin.



Research Reference


Mussel Gloop Can Be Used to Make Wounds Knit from New Scientist


Sunday, 14 May 2017

Sushi and Raw Fish, Parasitic Nematodes, and Anisakiasis

Sushi and sashimi can be delicious, but diners should know that eating a meal of raw fish is potentially dangerous. Unless the fish has been adequately frozen before use, it may harbour a parasitic nematode named Anisakis simplex. The nematode attaches itself to the lining of the gastrointestinal tract (or the digestive tract) and often stays alive for some time. It may cause severe pain as well as other unpleasant and sometimes serious problems.




Anisakiasis


Nematodes are also known as roundworms. Anisakis is a roundworm with a complex life cycle that involves marine mammals, crustaceans, and fish or squid. The basic steps in the cycle are as follows.
  • The parasite reproduces inside marine mammals such as seals and whales. 
  • The eggs of the parasite are released into the ocean in the animals' feces. 
  • The eggs become larvae, which are eaten by crustaceans.
  • The crustaceans are eaten by fish and squid. The larvae migrate to the muscles of these animals.
  • The fish and squid are eaten by marine mammals. Here the larvae mature and the cycle begins again.
  • If the fish and squid are eaten by humans instead of a marine mammal, a nematode infection may result. 

The parasite can only penetrate the outer layer of the lining of the human digestive tract and eventually dies. This may sound like a good outcome, but the problem is that the presence of the worm triggers a strong response by the immune system. Inflammation occurs and a mass of cells is formed in the tract.

Infection, Symptoms and Treatment


Until quite recently, cases of anisakiasis were generally restricted to countries such as Japan, where raw fish is very popular. In the last few years cases have appeared in other parts of the world as the popularity of raw seafood dishes has spread. The disease can develop after eating fish and squid that is raw and improperly prepared. Sushi and sashimi can both be problematic. Sushi consists of raw fish, vinegared rice, and sometimes additional ingredients such as seaweed or other vegetables. Sashimi consists of thin slices of raw fish.

Possible symptoms of the infection include abdominal pain and swelling, nausea, vomiting, diarrhea (which may be bloody or contain mucus) and a slight fever. Some people experience an allergic reaction when they are infected by the parasite. This reaction may involve a rash and itching. Rarely, anaphylaxis may develop. This is a severe and body-wide allergic response that is life threatening and a medical emergency. As with any symptoms and condition, a doctor is needed in order to diagnose the problem.

The treatment for the disorder is often removal of the parasite by endoscopy or surgery. Endoscopy is a process in which a flexible tube with a tiny camera and a light are inserted into the digestive tract so that a doctor can examine the area. Devices can be inserted into the tube to remove items from the tract if necessary. These items include a nematode attached to the lining of the digestive tract.

How to Kill the Parasite


A professional sushi chef will probably know how to prepare sushi and sashimi safely, at least in North America, where I live. Some communities have a law mandating the correct treatment of the fish. People who prepare the fish at home or without training are more likely to cause a problem.

Adequate cooking will kill parasitic worms. According to the CDC (Centers for Disease Control and Prevention), under specific conditions freezing raw fish will also kill the parasites. The CDC says that one of the following procedures for treating the fish should be used. Note that none of them can be obtained in a home freezer.
  • Freeze at -4 degrees Fahrenheit (-20 degrees Celsius) or below for 7 days.
  • Freeze at -31 degrees Fahrenheit (-35 degrees Celsius) until solid and then store at the same temperature or below for 15 hours.
  • Freeze at -31 degrees Fahrenheit (-35 degrees Celsius) until solid and then store at 4 degrees Fahrenheit (-20 degrees Celsius) or below for 24 hours.
It's important that a raw fish lover checks that their preferred source of sushi or sashimi prepares the food properly. If this is done, it should be possible to enjoy the food and stay safe.


References and Further Information


Information about anisakiasis from the CDC

A case report from the British Medical Journal