Dengue Virus Type 2 Modulates Endothelial Barrier Function through CD73

Dengue Virus Type 2 Modulates Endothelial Barrier Function through CD73
Chinmay Patkar, Kris Giaya and Daniel H. Libraty

Dengue hemorrhagic fever is characterized by a unique vascular leakage syndrome. The mechanisms of endothelial barrier dysfunction in dengue hemorrhagic fever are not well understood. We examined the modulation of endothelial barrier function in dengue virus type 2 (DENV2) infections using primary human umbilical vein endothelial cells. We demonstrated that the increase in endothelial barrier function within 72 hours after DENV2 infection is mediated by type I interferon–dependent CD73 up-regulation. After 72 hours, DENV2 slowed the recovery of endothelial barrier function in response to tumor necrosis factor-α or vascular endothelial growth factor. This phenomenon was likely caused by type I interferon receptor signaling inhibition and lower CD73 levels in DENV2-infected endothelial cells. Our findings suggest that during DENV2 infection, endothelial barrier homeostasis is maintained by a balance between pro-inflammatory and pro-angiogenic cytokines, and type I interferon–dependent CD73 expression and activity.

PROBIOTICS, PREBIOTICS, AND SYNBIOTICS. WHAT ARE THEY AND WHEN SHOULD THEY BE IMPLEMENTED?

PROBIOTICS, PREBIOTICS, AND  SYNBIOTICS. WHAT ARE THEY AND WHEN SHOULD THEY BE IMPLEMENTED? 

Stanley L. Marks, BVSc, PhD, DACVIM (Internal Medicine, Oncology), DACVN University of California, 

Davis, School of Veterinary Medicine, Davis, CA, USA 

Professor of Small Animal Medicine 

The mammalian intestinal tract contains a complex, dynamic, and diverse population of non-pathogenic bacteria.  Researchers have estimated that the human body contains 10.000.000.000.000 cells, only 10% of which are not bacteria, and belong to the human body proper. 1. There has been a plethora of research focusing on the mechanisms by which pathogenic bacteria influence intestinal function and induce disease; however, recent attention has focused on the indigenous non-pathogenic microorganisms and the ways in which they may benefit the host.  Initial colonization of the sterile newborn intestine occurs with maternal vaginal and fecal bacterial flora.  The first colonizers have a high reduction potential and include species such as enterobacter, streptococcus, and staphylococcus. These bacteria metabolize oxygen, favouring the growth of anaerobic bacteria, including lactobacilli and bifdobacteria.  Colonization with these bacteria is significantly delayed in caesarean deliveries, 2. leading to delayed activation of the efferent limb of the mucosal immune response. 3.Additional beneficial effects of developing a normal bacterial flora is seen in germ free mice that have small intestines that weigh less than their healthy counterparts.  This effect occurs partly due to underdevelopment of lymphoid constituents, with a lack of plasma cells in the lamina propria and Peyer’s patches, and subsequent reduction in IgA production.  Exposure to bacteria results in a reversal of this phenomenon within 28 days of exposure.

What is The Role Of An Antibody

Antibodies have the ability to fight infections that can leave us feeling run down, sick and achy. Whether created by the body's natural defense systems or acquired through vaccines, antibodies have the ability to protect against a range of illnesses caused by bacteria and viruses.

Definition

Antibodies are proteins created by the body's immune system (the organs and cells that help to fight infection) that attack foreign viruses and bacteria that can cause infection and illness.

Production

Antibodies are produced when the immune system's B cells (lymphocytes that recognize foreign bacteria or viruses and send out defense mechanisms to destroy them) detect these antigens (the foreign bodies) and send out antibodies to fight off infection.

Action

Antibodies fight these foreign bodies by attaching themselves directly to them. Antibodies do not single-handedly destroy the foreign bodies, but help to signal other cells, such as phagocytes, to attack the bacteria or viruses.

Types

There are five groups of antibodies, each with their own specific role or area of the body to protect. They are known as IgA, IgD, IgE, IgM and IgG.

Immunity

One of the benefits of antibodies is the body's ability to subsequently remember what the antigens looked like and keep the antibodies used to fight off that bacterium or virus in the body's memory. So if that particular virus or bacterium (such as chicken pox or measles) were to strike again, the antibodies would already be ready to fight off the infection. Because of the body's ability to remember the antibodies, chicken pox and other illnesses are much less likely to strike twice in a person's life.

Definition of Dengue Shock Syndrome

Dengue shock syndrome: A syndrome due to the dengue virus that tends to affect children under 10, causing abdominal pain, hemorrhage (bleeding) and circulatory collapse (shock). Known also as dengue hemorrhagic fever (DHF), it starts abruptly with high continuous fever and headache plus respiratory and intestinal symptoms with sore throat, cough, nausea, vomiting, and abdominal pain. Shock occurs after 2 to 6 days with sudden collapse, cool clammy extremities, weak thready pulse, and blueness around the mouth (circumoral cyanosis). There is bleeding with easy bruising, blood spots in the skin (petechiae), spitting up blood (hematemesis), blood in the stool (melena), bleeding gums and nosebleeds (epistaxis). Pneumonia and heart inflammation (myocarditis) may be present. The mortality is appreciable ranging from 6 to 30%. Most deaths occur in children. Infants under a year of age are especially at risk of death. It is also called Philippine or Southeast Asian hemorrhagic fever.

How is Varicocele Happened in Man?

nlm.nih.gov- A varicocele is a widening of the veins along the cord that holds up a man's testicles (spermatic cord).

Causes

A varicocele forms when valves inside the veins along the spermatic cord prevent blood from flowing properly. This causes the blood to back up, leading to swelling and widening of the veins. (This is essentially the same process that leads to varicose veins, which are common in the legs.)

Varicoceles usually develop slowly. They are more common in men ages 15 - 25 and are most often seen on the left side of the scrotum.

The sudden appearance of a varicocele in an older man may be caused by a kidney tumor, which can block blood flow to a vein. This is more common on the left side than the right.

Symptoms

Enlarged, twisted veins in the scrotum

Painless testicle lump, scrotal swelling, or bulge in the scrotum

There may not be symptoms.

Exams and Tests

The health care provider will examine the groin area, including the scrotum and testicles. The health care provider may feel a twisted growth along the spermatic cord. (It feels like a bag of worms.)

However, the growth may not be able to be seen or felt, especially when you are lying down.

The testicle on the side of the varicocele may be smaller than the one on the other side.

Treatment

A jock strap (scrotal support) or snug underwear may help relieve the pain or discomfort. If pain continues or other symptoms occur, you may need further treatment.

Surgery to correct a varicocele is called varicocelectomy. You will leave the hospital on the same day as your surgery. During this procedure, you will receive some type of numbing medication (anesthesia). The urologist will make a cut, usually in the lower abdomen, and tie off the abnormal veins. Blood will now flow around the area into normal veins. Keep an ice pack on the area for the first 24 hours after surgery to reduce swelling.

An alternative to surgery is varicocele embolization. This method is also done without an overnight hospital stay. It uses a much smaller cut than surgery, so you will heal faster. A small hollow tube called a catheter (tube) is placed into a vein in your groin or neck area.

Using x-rays as a guide, the health care provider moves the tube into the varicocele. A tiny coil passes through the tube into the varicocele. The coil blocks blood flow to the bad vein, and sends it to normal veins.

After the procedure, you will be told to place ice on the area and wear a scrotal support for a little while.

Outlook (Prognosis)

A varicocele is usually harmless and often does not need to be treated.

If you have surgery, your sperm count will likely increase but it will not improve your chances of getting a woman pregnant. In most cases, testicular wasting (atrophy) does not improve unless surgery is done early in adolescence.

Possible Complications

Infertility is a complication of varicocele.

Complications from treatment may include:

Atrophic testis

Blood clot formation

Infection

Injury to the scrotum or nearby blood vessel

When to Contact a Medical Professional

Call for an appointment with your health care provider if you discover a testicle lump or need to treat a diagnosed varicocele.

Alternative Names

Varicose veins - scrotum

References

Wampler SM, Llanes M. Common scrotal and testicular problems. Prim Care. 2010;37:613-626. 

Barthold JS. Abnormalities of the testes and scrotum and their surgical management. In: Wein AJ, ed. Campbell-Walsh Urology. 10th ed. Philadelphia, Pa: Saunders Elsevier; 2011:chap 132. 

Animal Fat Consumption Before Conception Linked To Gestational Diabetes Risk

medicalnewstoday.com- Women who consumed a diet high in animal fat and cholesterol before pregnancy were at higher risk for gestational diabetes than women whose diets were lower in animal fat and cholesterol, according to researchers at the National Institutes of Health and Harvard University.

Gestational diabetes is a form of diabetes seen during pregnancy. Gestational diabetes increases the risk for certain pregnancy complications and health problems in the newborn.

Women whose diets were high in total fat or other kinds of fats - but not in animal fat or cholesterol - did not have an increased risk.

Moreover, the increased risk for gestational diabetes seen with animal fat and cholesterol appeared to be independent of other, dietary and non-dietary, risk factors for gestational diabetes. For example, exercise is known to reduce the risk of gestational diabetes. Among women who exercised, however, those who consumed higher amounts of animal fat and cholesterol had a higher risk than those whose diets were lower in these types of fat.

"Our findings indicate that women who reduce the proportion of animal fat and cholesterol in their diets before pregnancy may lower their risk for gestational diabetes during pregnancy," said senior author Cuilin Zhang, M.D., M.P.H., Ph.D., of the Epidemiology Branch at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), one of three NIH institutes supporting the study.

The researchers concluded that changing the source of 5 percent of dietary calories from animal fat to plant-derived sources could decrease a woman's risk for gestational diabetes by 7 percent.

The U.S. Department of Agriculture website, ChooseMyPlate.gov*, contains information on healthy eating for children and adults, as well as health and nutrition information for pregnant and breast feeding women.

First author Katherine Bowers, Ph.D., conducted the research with NICHD colleagues Dr. Zhang and Edwina Yeung, Ph.D., and with Deirdre K. Tobias and Frank B. Hu, M.D., M.P.H., Ph.D., of Harvard University, in Boston.

Their findings appear online in the American Journal of Clinical Nutrition.

The research was also funded by the National Cancer Institute and the National Institute of Diabetes and Digestive and Kidney Diseases.

The researchers utilized information from more than 13,000 women participating in the Nurses' Health Study II. The women were 22 to 45 years old when they enrolled in the study. Every two years they responded to questions on their general health, pregnancy status, and lifestyle habits, such as consuming alcohol or smoking. In addition, every four years they completed a comprehensive survey about the kinds of food and drink they consumed.

About 6 percent of the participants reported having been diagnosed with gestational diabetes. The researchers calculated the amount of animal fat in participants' diets as a percentage of total calories and divided participants into five groups, or quintiles, based on those percentages. Then the researchers compared the risk for developing gestational diabetes for each group. Women in the highest quintile of intake had almost double the risk for gestational diabetes compared to women in the lowest quintile.

They also observed that women in the highest quintile for cholesterol consumption were 45 percent more likely to develop gestational diabetes than were women in the lowest quintile.

"This is the largest study to date of the effects of a pre-pregnancy diet on gestational diabetes," Dr. Bowers said. "Additional research may lead to increased understanding of how a mother's diet before and during pregnancy influences her metabolism during pregnancy, which may have important implications for the baby's health at birth and later in life."

There are Three Types of Diabetes?

medicalnewstoday.com- Diabetes, often referred to by doctors as diabetes mellitus, describes a group of metabolic diseases in which the person has high blood glucose (blood sugar), either because insulin production is inadequate, or because the body's cells do not respond properly to insulin, or both. Patients with high blood sugar will typically experience polyuria (frequent urination), they will become increasingly thirsty (polydipsia) and hungry (polyphagia).

There are three types of diabetes: 

1) Type 1 Diabetes

The body does not produce insulin. Some people may refer to this type as insulin-dependent diabetes, juvenile diabetes, or early-onset diabetes. People usually develop type 1 diabetes before their 40th year, often in early adulthood or teenage years.

Type 1 diabetes is nowhere near as common as type 2 diabetes. Approximately 10% of all diabetes cases are type 1.

Patients with type 1 diabetes will need to take insulin injections for the rest of their life. They must also ensure proper blood-glucose levels by carrying out regular blood tests and following a special diet.

Between 2001 and 2009, the prevalence of type 1 diabetes among the under 20s in the USA rose 23%, according to SEARCH for Diabetes in Youth data issued by the CDC (Centers for Disease Control and Prevention). (Link to article) 

2) Type 2 Diabetes

The body does not produce enough insulin for proper function, or the cells in the body do not react to insulin (insulin resistance).

Approximately 90% of all cases of diabetes worldwide are of this type.

Some people may be able to control their type 2 diabetes symptoms by losing weight, following a healthy diet, doing plenty of exercise, and monitoring their blood glucose levels. However, type 2 diabetes is typically a progressive disease - it gradually gets worse - and the patient will probably end up have to take insulin, usually in tablet form.

Overweight and obese people have a much higher risk of developing type 2 diabetes compared to those with a healthy body weight. People with a lot of visceral fat, also known as central obesity, belly fat, or abdominal obesity, are especially at risk. Being overweight/obese causes the body to release chemicals that can destabilize the body's cardiovascular and metabolic systems.

The risk of developing type 2 diabetes is also greater as we get older. Experts are not completely sure why, but say that as we age we tend to put on weight and become less physically active. Those with a close relative who had/had type 2 diabetes, people of Middle Eastern, African, or South Asian descent also have a higher risk of developing the disease.

Men whose testosterone levels are low have been found to have a higher risk of developing type 2 diabetes. Researchers from the University of Edinburgh, Scotland, say that low testosterone levels are linked to insulin resistance. (Link to article) 

Measuring the glucose level in blood

3) Gestational Diabetes

This type affects females during pregnancy. Some women have very high levels of glucose in their blood, and their bodies are unable to produce enough insulin to transport all of the glucose into their cells, resulting in progressively rising levels of glucose.

Diagnosis of gestational diabetes is made during pregnancy.

The majority of gestational diabetes patients can control their diabetes with exercise and diet. Between 10% to 20% of them will need to take some kind of blood-glucose-controlling medications. Undiagnosed or uncontrolled gestational diabetes can raise the risk of complications during childbirth. The baby may be bigger than he/she should be.

Scientists from the National Institutes of Health and Harvard University found that women whose diets before becoming pregnant were high in animal fat and cholesterol had a higher risk for gestational diabetes, compared to their counterparts whose diets were low in cholesterol and animal fats.