Baldness as a Signal of Heart Disease Risk

Baldness as a Signal of Heart Disease Risk

Courtesy : NY Times and BMJ online.

Baldness may indicate an increased risk for coronary heart disease.
The risk is associated only with male pattern baldness, the kind that starts at the top or back of the head, and not with a receding hairline, according to researchers who reviewed six studies that included 37,000 participants.
The analysis, published online in BMJ Open, found that baldness increased the risk for heart disease by between 30 and 40 percent compared with men with a full head of hair. They found the association among men 55 to 60 as well as among older men, and the more severe the baldness, the greater the risk.
The reason for the association is unclear, but the authors suggest that known risk factors for heart disease — hypertension, high cholesterol, smoking and others — may affect both conditions, and that baldness may be a marker of atherosclerosis. In previous studies, baldness has been linked to an increased risk of prostate cancer, diabetes and high blood pressure.
“It may be premature to confirm this relationship on the basis of only six studies,” said a co-author, Dr. Kazuo Hara, an associate professor of medicine at the University of Tokyo. “But the ultimate aim is to be able to predict the risk for heart disease more precisely in clinical practice.”

Liver Stem Cells Discovered in Mice

Share on emailShare on facebookShare on twitter

Scientists successfully identified and grew a renewable population of liver stem cells for the first time, a new study reported. Tissues derived from these stem cells slightly boosted liver function when implanted into mice with a liver disorder. The findings could eventually lead to approaches that help rejuvenate damaged livers in people.

A single cell was coaxed to mature into liver cells that produce common liver proteins (green and red). Image courtesy of Huch et al., Nature.

The liver is a large, versatile organ that has many jobs, including cleansing blood and digesting food. The liver also has a unique ability to quickly regenerate and regain its original size if partially removed by surgery. Scientists have long known that stem cells that have the potential to create more liver cells must exist in the adult liver. But until now, no one had found a way to detect and cultivate liver stem cells.

An international team led by Dr. Hans Clevers at the Hubrecht Institute, The Netherlands, sought to identify and grow mouse liver stem cells. Their work was funded in part by the European Union and NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Results were described in Nature on February 14, 2013.

In earlier studies, Clevers and colleagues discovered that a protein called Lgr5 is found on the surface of rapidly dividing stem cells in the intestine, stomach and hair follicles. In all of these tissues, growth is prompted by signaling molecules known as Wnt proteins, which regulate expression ofLgr5 and many other genes. Wnt signaling is known to play a role in tissue regeneration, embryo development and cancer.

To see if Lgr5 might also be a marker for liver stem cells, the scientists studied genetically engineered mice in which Lgr5 genes were tagged by “reporter” genes. The researchers found that the gene was not activated in healthy mouse livers. But in injured livers, small Lgr5-positive cells appeared near the bile ducts—a location where resting liver stem cells were thought to reside. The cells also showed signs of Wnt signaling.

The researchers traced Lgr5-positive liver cells in mice after liver injury. Within a week, they detected small, fast-growing Lgr5 offspring cells, which later evolved into bile duct cells and liver cells.

To grow Lgr5-positive liver cells, the researchers used a 3-D culture system they’d previously developed for growing stem cells into tiny clumps, or “organoids.” Some of the cultures were propagated from a single Lgr5-positive cell. All were grown in a special medium that enhances Wnt signaling.

The team was able to grow and propagate the resulting liver organoids for several months. In culture, the organoids could be coaxed into generating functional liver and bile duct cells. When the organoids were injected into mutant mice with a deadly liver enzyme deficiency, patches of enzyme-producing liver cells appeared in the livers of 5 of the 15 treated mice. Mice with successful organoid transplants survived significantly longer than untreated enzyme-deficient mice.

“This study raises the hope that the human equivalent of these mouse liver stem cells can be grown in a similar way and efficiently converted into functional liver cells,” says coauthor Dr. Markus Grompe of the Oregon Health and Science University School of Medicine. Going forward, the researchers plan to test other growth factors and conditions to improve the efficiency of the procedure.

Only 3 days left for BSMMU online application submission : ......

Protein in human blood platelets points to a new weapon against malaria

One of the world's most devastating diseases is malaria, responsible for at least a million deaths annually, despite global efforts to combat it. Researchers from the Perelman School of Medicine at the University of Pennsylvania, working with collaborators from Drexel University, The Children's Hospital of Philadelphia, and Johns Hopkins University, have identified a protein in human blood platelets that points to a powerful new weapon against the disease. Their work was published in this months' issue of Cell Host and Microbe.

Malaria is caused by parasitic microorganisms of the Plasmodium genus, which infect red blood cells. Recent research at other universities showed that blood platelets can bind to infected red blood cells and kill the parasite, but the exact mechanism was unclear. The investigators on the Cell Host and Microbe paper hypothesized that it might involve host defense peptides (HDP) secreted by the platelets.

"We eventually found that a single protein secreted when platelets are activated called human platelet factor 4 [hPF4] actually kills parasites that are inside red cells without harming the red cell itself," explains senior author Doron Greenbaum, PhD, assistant professor of Pharmacology, whose team studies innovative ways to fight malaria. The hPF4 targets a specific organelle of the Plasmodium falciparum parasite called the digestive vacuole, which essentially serves as its "stomach" for the digestion of hemoglobin. The investigators found that hPF4 destroys the vacuole with a deadly speed of minutes or even seconds, killing the parasite without affecting the host cell.

While host defense peptides appear to be attractive therapeutic agents, the expense of manufacturing this protein lessens its potential impact on the treatment of malaria. Greenbaum and colleagues set out to discover whether synthetic molecules mimicking the structure of HDPs could have similar beneficial effects against the Plasmodium parasite. After screening approximately 2000 small molecule HDP mimics (smHDPs) developed by biotech company PolyMedix, Inc. of Radnor, PA, Greenbaum and his team found that "all of the best hits had the same mechanism of action against Plasmodium parasites."

Like the natural hPF4 found in platelets, the most effective smHDPs tested targeted only infected red blood cells, attacking and destroying the parasite in exactly the same way, but with even greater potency and speed. "The smHDPs get into infected red cells and lyse or basically destroy the digestive vacuole or stomach of the parasite more rapidly than the hPF4 protein," Greenbaum notes. "The protein from platelets is about 25 times less potent, but the surprising thing is they act with the same mechanism. With ease, within seconds, they destroy the vacuole of the parasite."

Greenbaum's team settled on two compounds, PMX1207 and PMX207, for testing in mouse models of malaria. Both compounds significantly decreased parasitic growth and greatly improved survival rates, providing further confirmation of the potential of smHDPs as antimalarial agents. The work, Greenbaum says, shows that "we can translate a natural arm of the innate immune system in platelets to drug-like small molecules that we are honing to become potent, selective, potentially less toxic, and cheaper to make as an antimalarial."

 

Aside from their great effectiveness, smHDPs may have several other advantages over other antimalarial therapies. As Plasmodium inevitably adapts and becomes resistant to a particular drug therapy, the efficacy of that treatment decreases and survival rates drop. By mimicking the body's own natural defenses, the new HDP-centered approach could avoid that pitfall. "Certainly with malaria we've had a lot of problems in the last 20 years with resistance," Greenbaum explains. "One of the unique features of the synthetic HDPs is that studies show that pathogens have a difficult time generating resistance to them, because they attack membranes, not proteins. So they might be intrinsically more difficult to become resistant against."

Although Greenbaum's team focused mostly on the chronic red-blood-cell stage of malaria, their HDP-mimic also shows promise against other stages of the disease. "We think that the mimics would be useful as a transmission-blocking therapeutic," Greenbaum says. "In other words, you prevent transmission from human to mosquito and therefore back to human again. We have positive data for those two stages. It's becoming increasingly more important in antimalarial drug development that people think more and more about multistage inhibition."

The next step for Greenbaum's team is to further hone the selectivity and potency of the smHDP compounds, while developing them into drugs that can be orally administered. As Greenbaum explains, practical antimalarials need to be "taken as pills rather than having to be used intravenously, which is not going to be appropriate for treatment in endemic countries, especially in more rural environments."

Source Penn Medicine

Protein in human blood platelets points to a new weapon against malaria

One of the world's most devastating diseases is malaria, responsible for at least a million deaths annually, despite global efforts to combat it. Researchers from the Perelman School of Medicine at the University of Pennsylvania, working with collaborators from Drexel University, The Children's Hospital of Philadelphia, and Johns Hopkins University, have identified a protein in human blood platelets that points to a powerful new weapon against the disease. Their work was published in this months' issue of Cell Host and Microbe.

Malaria is caused by parasitic microorganisms of the Plasmodium genus, which infect red blood cells. Recent research at other universities showed that blood platelets can bind to infected red blood cells and kill the parasite, but the exact mechanism was unclear. The investigators on the Cell Host and Microbe paper hypothesized that it might involve host defense peptides (HDP) secreted by the platelets.

"We eventually found that a single protein secreted when platelets are activated called human platelet factor 4 [hPF4] actually kills parasites that are inside red cells without harming the red cell itself," explains senior author Doron Greenbaum, PhD, assistant professor of Pharmacology, whose team studies innovative ways to fight malaria. The hPF4 targets a specific organelle of the Plasmodium falciparum parasite called the digestive vacuole, which essentially serves as its "stomach" for the digestion of hemoglobin. The investigators found that hPF4 destroys the vacuole with a deadly speed of minutes or even seconds, killing the parasite without affecting the host cell.

While host defense peptides appear to be attractive therapeutic agents, the expense of manufacturing this protein lessens its potential impact on the treatment of malaria. Greenbaum and colleagues set out to discover whether synthetic molecules mimicking the structure of HDPs could have similar beneficial effects against the Plasmodium parasite. After screening approximately 2000 small molecule HDP mimics (smHDPs) developed by biotech company PolyMedix, Inc. of Radnor, PA, Greenbaum and his team found that "all of the best hits had the same mechanism of action against Plasmodium parasites."

Like the natural hPF4 found in platelets, the most effective smHDPs tested targeted only infected red blood cells, attacking and destroying the parasite in exactly the same way, but with even greater potency and speed. "The smHDPs get into infected red cells and lyse or basically destroy the digestive vacuole or stomach of the parasite more rapidly than the hPF4 protein," Greenbaum notes. "The protein from platelets is about 25 times less potent, but the surprising thing is they act with the same mechanism. With ease, within seconds, they destroy the vacuole of the parasite."

Greenbaum's team settled on two compounds, PMX1207 and PMX207, for testing in mouse models of malaria. Both compounds significantly decreased parasitic growth and greatly improved survival rates, providing further confirmation of the potential of smHDPs as antimalarial agents. The work, Greenbaum says, shows that "we can translate a natural arm of the innate immune system in platelets to drug-like small molecules that we are honing to become potent, selective, potentially less toxic, and cheaper to make as an antimalarial."

Water and fluid : The alternate fuel of our body.

We know that food is our body fuel. Specially, the Glucose. Glucose is the main fuel of our body. But, do we know that water is our alternate fuel ?..............

POSTPARTUM HEMORRHAGE

Postpartum Hemorrhage

Postpartum hemorrhage is blood loss of > 500 mL during or immediately after the 3rd stage of labor in a vaginal delivery or > 1000 mL in a cesarean delivery. Diagnosis is clinical. Treatment depends on etiology of the hemorrhage.

Causes of postpartum hemorrhage :

> Uterine atony (the most common)
> Lacerations of the genital tract
> Extension of an episiotomy
> Uterine rupture
> Bleeding disorders
> Retained placental tissues
> Hematoma
> Uterine inversion
>Subinvolution (incomplete involution) of the placental site (which usually occurs early but may occur as late as 1 mo after delivery)


Risk factors for uterine atony include uterine overdistention (caused by multifetal pregnancy, polyhydramnios, or an abnormally large fetus), prolonged or dysfunctional labor, grand multiparity (delivery of ≥ 5 viable fetuses), relaxant anesthetics, rapid labor, and chorioamnionitis.

Uterine fibroids may contribute to postpartum hemorrhage. A history of prior postpartum hemorrhage may indicate increased risk.



Treatment

Ø Removal of retained placental tissues and repair of genital lacerations Uterotonics (eg, oxytocin , prostaglandins)
Ø Sometimes surgical procedures


Ø Intravascular volume is replenished with 0.9% saline up to 2 L IV; blood transfusion is used if this volume of saline is inadequate. Hemostasis is attempted by bimanual uterine massage and IV oxytocin infusion, and the uterus is explored for lacerations and retained placental tissues. The cervix and vagina are also examined; lacerations are repaired. Bladder drainage via catheter can sometimes reduce uterine atony.

Ø 15-Methyl prostaglandin F2 α250 μg IM q 15 to 90 min up to 8 doses or methylergonovine 0.2 mg IM q 2 to 4 h (which may be followed by 0.2 mg po tid to qid for 1 wk) should be tried if excessive bleeding continues during oxytocin infusion; during cesarean delivery, these drugs may be injected directly into the myometrium. Prostaglandins should be avoided in women with asthma; methylergonovine should be avoided in women with hypertension. Sometimes misoprostol 800 to 1000 μg rectally can be used to increase uterine tone.

Ø Uterine packing or placement of a Bakri balloon can sometimes provide tamponade. This silicone balloon can hold up to 500 mL and withstand internal and external pressures of ≤ 300 mm Hg. If hemostasis cannot be achieved, surgical placement of a B-Lynch suture (a suture used to compress the lower uterine segment via multiple insertions), hypogastric artery ligation, or hysterectomy may be required. Uterine rupture requires surgical repair.

Blood products are transfused as necessary, depending on the degree of blood loss and clinical evidence of shock. Infusion of factor VIIa (50 to 100 μg/kg, as a slow IV bolus over 2 to 5 min) can produce hemostasis in women with severe life-threatening hemorrhage. The dose is given q 2 to 3 h until hemostasis occurs.


Prevention

Ø Predisposing conditions (eg, uterine fibroids, polyhydramnios, multifetal pregnancy, a maternal bleeding disorder, history of puerperal hemorrhage) are identified antepartum and, when possible, corrected. If women have an unusual blood type, that blood type is made available. Careful, unhurried delivery with a minimum of intervention is always wise.

Ø After placental separation, oxytocin 10 units IM or dilute oxytocin infusion (10 or 20 units in 1000 mL of an IV solution at 125 to 200 mL/h for 1 to 2 h) usually ensures uterine contraction and reduces blood loss. After the placenta is delivered, it is thoroughly examined for completeness; if it is incomplete, the uterus is manually explored and retained fragments are removed. Rarely, curettage is required. Uterine contraction and amount of vaginal bleeding must be observed for 1 h after completion of the 3rd stage of labor.

Prepared and modified by MD. Niamul Hasan , MBBS Final Year BMCH