Gene therapy can destroy HIV infected cells

Through gene therapy, researchers engineered blood-forming stem cells (hematopoietic stem/progenitor cells, or HSPCs) to carry chimeric antigen receptor (CAR) genes to make cells that can detect and destroy HIV-infected cells. These engineered cells not only destroyed the infected cells, they persisted for more than two years, suggesting the potential to create long-term immunity from the virus that causes AIDS.

Antiviral drugs can suppress the amount of HIV in the body to nearly undetectable levels, but only an effective immune response can eradicate the virus. Researchers have been seeking a way to improve the body's ability to combat the virus by engineering blood-forming stem cells to specifically target and kill HIV-infected cells for the life of the individual.

 Although chimeric antigen receptor (CAR) T-cells have emerged as a powerful immunotherapy for various forms of cancer -- and show promise in treating HIV-1 infection -- the therapy may not impart long-lasting immunity. Researchers, physicians and patients need T cell-based products that can respond to malignant or infected cells that may reappear months or years after treatment.

Because HIV uses CD4 to infect cells, the researchers used a CAR molecule that hijacks the essential interaction between HIV and the cell surface molecule CD4 to make stem cell-derived T-cells target infected cells. When the CD4 on the CAR molecule binds to HIV, other regions of the CAR molecule signal the cell to become activated and kill the HIV infected cell.

The researchers found that, in test animals, modification of the blood-forming stem cells resulted in more than two years of stable production of CAR-expressing cells without any adverse effects. In addition, these cells were widely distributed throughout the lymphoid tissues and gastrointestinal tract, which are major anatomic sites for HIV replication and persistence in infected people. Most important, engineered CAR T-cells showed efficacy in attacking and killing HIV-infected cells.
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Ebola virus inhibited in cell cultures

When the Ebola virus enters the human cell, its only purpose is to copy itself, fast. First it must copy all its proteins, then its genetic material. But by inhibiting a specific enzyme we rob the Ebola virus of its ability to copy itself. And that may potentially prevent an Ebola infection from spreading.

When Ebola virus ravaged West Africa, where thousands of people died from the extremely infectious Ebola infection. Once you are infected, all you can do is hope that your own immune system is able to kill the infection, because there is no treatment for Ebola presently.

However, the researchers behind the new study have found what is called a new host factor for Ebola virus. It can be described as a small part of the host's-for example the human body's-own cells, which the Ebola virus uses to copy itself and produce more infection. The virus uses the host factor enzyme PP2A-B56 to start producing proteins. So if the researchers switch off PP2A-B56, the virus' ability to copy itself and produce more infection is never 'switched on.

When we inhibit the PP2A-B56 enzyme, we remove the first link in a long process, which ends with Ebola spreading. The Ebola infection in cell cultures where we have inhibited the PP2A-B56 enzyme is 10 times smaller after 24 hours compared to infections where we have not inhibited this enzyme. But because the researchers have so far focused on cell cultures, there is still work to be done before their results can be used to treat people infected with Ebola.

 Initially the researchers hope to be able to test it on animals and, in the long term, develop a drug that inhibits the relevant enzyme.The potential of the new discovery may turn out to work on other viruses too, because the structure of Ebola virus is very similar to the other filoviruses.
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Lack of sleep increases the levels of Alzheimer's protein

Chronic poor sleep has been linked to cognitive decline, and a new study from Washington University School of Medicine in St. Louis explains why: As a wakeful brain churns away through the night, it produces more of the Alzheimer's protein amyloid beta than its waste-disposal system can handle. Levels of the protein rise, potentially setting off a sequence of changes to the brain that can end with dementia.

This study is the clearest demonstration in humans that sleep disruption leads to an increased risk of Alzheimer's disease through an amyloid beta mechanism, the study showed that it was due to overproduction of amyloid beta during sleep deprivation. Sleeping poorly increases levels of brain proteins such as amyloid beta that are linked to Alzheimer's disease. But it wasn't clear why amyloid beta levels rise in a tired brain.

Neurologist studied eight people ages 30 to 60 with no sleep or cognitive problems. The participants were assigned randomly to one of three scenarios: having a normal night's sleep without any sleep aids ; staying up all night; or sleeping after treatment with sodium oxybate, a prescription medication for sleep disorders. Sodium oxybate increases slow-wave sleep-the deep, dreamless phase of sleep that people need to wake up feeling refreshed.

Each scenario occurred during 36 hours of monitoring, starting in the morning and continuing through the afternoon of the following day. The researchers took samples of the fluid that surrounds the brain and spinal cord every two hours to monitor how amyloid beta levels change with time of day and tiredness. All eight participants returned four to six months later to undertake a second scenario, and four people completed all three. Studying the same people under different conditions provides the statistical power to detect changes in amyloid beta levels.

Amyloid beta levels in sleep-deprived people were 25 to 30 percent higher than in those who had slept the night through. After a sleepless night, amyloid beta levels were on par with the levels seen in people genetically predisposed to develop Alzheimer's at a young age. brain changes. The brains of people with Alzheimer's disease are dotted with such plaques. Amyloid beta is a byproduct of normal brain activity.

The researchers found that when people stay awake, their brains continue to produce amyloid beta through the night. A sleeping brain produces much less. Asleep or awake, however, the brain clears the protein away at the same rate, so the increased production during sleep deprivation leads to higher levels of the damaging protein.
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Berry boosts cervical cancer therapy

According to the Centers for Disease Control and Prevention many women are diagnosed with cervical cancer each year. One of the most common treatments for cervical cancer is radiation. While radiation therapy destroys cancer cells, it also destroys nearby healthy cells. University of Missouri School of Medicine researchers studied in vitro human cancer cells to show that combining blueberry extract with radiation can increase the treatment's effectiveness.

Radiosensitizers are non-toxic chemicals that make cancer cells more responsive to radiation therapy. In a previous study, Fang and his research team showed that resveratrol, a compound in red grapes, could be used as a radiosensitizer for treating prostate cancer. Blueberries also contain resveratrol. In addition to resveratrol, blueberries also contain flavonoids.

The researchers used human cervical cancer cell lines to mimic clinical treatment. The cell lines were divided into four groups that included a control group, a group that received only radiation, a group that received only blueberry extract, and a group that received both radiation and the extract. Researchers used three different measures to confirm results of the study.

 Radiation decreased cancer cells by approximately 20 percent. Interestingly, the cell group that received only blueberry extract had a 25 percent decrease in cancer. However, the biggest decline in cancer cells occurred in the radiation and extract group.
The mechanism that makes blueberry extract a radiosensitizer also reduces the abnormal explosion of cell growth. Cancer cells avoid death by remodeling themselves. Along with reducing cell proliferation, the extract also 'tricks' cancer cells into dying. So it inhibits the birth and promotes the death of cancer cells.
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Alternative therapies for antibiotic resistance

Drug development strategies have focused on replacing antibiotics in extreme infections, such as sepsis, where every minute without an effective drug increases the risk of death. But the evolutionary process that brings forth antibiotic resistance doesn't happen nearly as often in those big infections as it does in the multitude of small ones like sinusitis, tonsillitis, bronchitis, and bladder infections.

 Antibiotic prescriptions against those smaller ailments account for about 90 percent of antibiotic use, and so are likely to be the major driver of resistance evolution. Bacteria that survive these many small battles against antibiotics grow in strength and numbers to become formidable armies in big infections, like those that strike after surgery.  It is advisable to give antibiotics less often and preserve their effectiveness for when they're really needed.

E. coli is widespread in the human gut, and some strains secrete enzymes that thwart antibiotics, while other strains don't.
 A broad-spectrum antibiotic can kill off more of the vulnerable, less dangerous bacteria, leaving the more dangerous and robust bacteria to propagate. Much too often, superbugs have made their way into hospitals in someone's intestines, where they had evolved high resistance through years of occasional treatment with antibiotics for small infections. Then those bacteria have infected patients with weak immune systems.

Drug developers facing dwindling antibiotic effectiveness against evolved bacteria have looked for multiple alternate treatments. Developing non-antibiotic therapies for strep throat, bladder infections, and bronchitis could prove easier, thus encouraging pharmaceutical investment and research.

For example, one particular kind of strep bacteria , group A streptococci, is responsible for the vast majority of bacterial upper respiratory infections. People often carry it without it breaking out. Strep bacteria secrete compounds that promote inflammation and bacterial spread. If an anti-virulence drug could fight the secretions, the drug could knock back the strep into being present but not sickening.

Strep infection can lead to rheumatic heart disease, a deadly condition that is very rare in the industrialized world. Some push-back against virulent bacteria until the body's immune system can take care of it. Developing a spray-on treatment with bacteriophages, viruses that attack bacteria can prevent the resistance.
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How cancer spreads

A University of Hawai'i Cancer Center researcher has identified how some cancer cells are made to move during metastasis. The research provides a better understanding of how cancer spreads and may create new opportunities for cancer drug development. Metastasis causes the deaths of 90 percent of cancer patients.

The spread of cancer by metastasis is driven by a set of mutant proteins called oncogenes which cause cancer cells to multiply uncontrollably and promotes their ability to move. How oncogene activity specifically directs the increased movement and metastasis is highly complex and remains largely unknown.

 RSK2 protein forms a signaling hub that includes proteins called LARG and RhoA. They show that turning on this signaling hub activates the movement of the cancer cells. These results significantly advance understanding of how cancer cells are made to move during metastasis and may provide more precise targets for drugs to stop cancer metastasis in patients where there are oncogenic mutations.
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Kidney disease can cause diabetes

Urea plays a role in the two-way link between the two diseases. Urea comes from the breakdown of protein in food. Kidneys normally remove urea from the blood, but poor kidney function can lead to increased levels of urea.

The study involved the analysis of medical records of adults who did not have diabetes. About 9 percent had elevated urea levels, a sign of reduced kidney function. That's the same rate as in the general population, according to the researchers.

People with high urea levels were 23 percent more likely to develop diabetes than those with normal urea levels, the study found. Diabetes is a major risk factor for kidney disease, elevated levels of urea, also raises the risk of diabetes.

When urea builds up in the blood because of kidney dysfunction, increased insulin resistance and impaired insulin secretion often result.
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Topiramate increases the risk of oral clefts

The anti-epileptic drug topiramate has been increasingly prescribed over the last decade not only to prevent seizures, but also to treat bipolar disorder and migraine headaches. In addition, topiramate is a component of a recently FDA-approved drug for weight loss. Past studies have found that women taking topiramate during early pregnancy to prevent epileptic seizures had greater chance of giving birth to a baby with an oral cleft, but such studies did not focus on women taking the drug at a lower dose for non-seizure related conditions.

 A new study by investigators from Brigham and Women's Hospital and the Harvard T.H. Chan School of Public Health suggest that using topiramate in early pregnancy, particularly at the high doses used for epilepsy, increases the risk of oral clefts. The new work leverages nationwide Medicaid data on more than 1 million live births from between 2000 and 2010.

The team examined the risk of oral clefts -- including cleft palate or cleft lip -- among three groups: infants born to women who had taken topiramate in their first trimester; infants born to women who had taken the drug lamotrigine (an unrelated drug used to treat bipolar disorder and epilepsy); and infants who had not been exposed to anti-epileptic medications in utero.

They found that the risk of oral clefts was approximately three times higher for the topiramate group than for either the lamotrigine or the unexposed group. Approximately one out of every 1,000 infants are born with an oral cleft, but among infants exposed to low doses of topiramate (median 100-mg daily dose) in the first trimester, that risk was 2.1 out of every 1,000 live births.

Among women taking higher dose topiramate (median 200-mg daily dose), the risk was much higher -- 12.3 for every 1,000 live births. Women with epilepsy on topiramate have the highest relative risk of giving birth to a baby with cleft lip or cleft palate, likely due to the higher doses of topiramate when used for controlling seizures.
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Effects of obesity on bone marrow cells

According to new research, obesity causes durable and harmful changes to the hematopoietic stem cell compartment-the blood-making factory in human body. Blood stem cell compartment is made up of numerous cell subsets, age and environmental stresses can lessen the healthy diversity of cells in human blood-making machinery. This can include skewing blood cell formation toward myeloid cells and possibly promoting pre-leukemic fates.

Obesity related stresses alter the cellular architecture of the hematopoietic stem cell compartment and reduce its long-term functional fitness. Tests in obese mice show these effects are progressive and that some of the harmful manifestations persist even after researchers normalize the animals' weight through dietary controls. Alterations of the body's blood-making system appear to be linked to over- expression of a transcription factor called Gfi1- a regulatory gene that controls other genes. The researchers show that oxidative stresses in the body caused by obesity drive overexpression of Gfi1.

 This produces a lasting alteration of hematopoietic stem cell compartment and molecular mayhem. The study also provides groundwork to investigate how lifestyle choices, such as diet, can durably impact blood formation and may contribute to the development of blood cancer. Hematopoietic stem cells are an important tool for treating leukemia and other blood diseases.
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New treatment for tuberculosis

In search of new strategies against life-threatening tuberculosis infections, a team from the Technical University of Munich (TUM), as well as Harvard University and Texas A&M University in the USA have found a new ally. They discovered a substance that interferes with the mycomembrane formation of the bacterium. It is effective even in low concentrations and when combined with known antibiotics their effectiveness is improved by up to 100-fold.

Among the greatest challenges when treating life-threatening tuberculosis infections is the increasing resistance to antibiotics. But the pathogen itself also makes the life of doctors difficult: its dense mycomembrane hampers the effect of many medications. The mycomembrane of the tuberculosis pathogen Mycobacterium tuberculosis consists of a lipid double layer that encapsulates the cell wall, forming an exterior barrier.

 Structural hallmarks are mycolic acids, branched beta-hydroxy fatty acids with two long hydrocarbon chains. The team hypothesizes that similarly structured beta lactones could "mask" themselves as mycolic acid to enter the mycolic acid metabolic pathways and then block the decisive enzymes. In the context of an extensive search, the interdisciplinary team of scientists hit the bullseye with the beta lactone EZ120. It does indeed inhibit the biosynthesis of the mycomembrane and kills mycobacteria effectively.

Using enzyme assays and mass spectroscopy investigations, Dr. Johannes Lehmann, a researcher at the Chair of Organic Chemistry II at TU Munich, demonstrated during his doctoral work that the new inhibitor blocks especially the enzymes Pks13 and Ag85, which play a key role in the development of mycomembranes. EZ120 is effective even in low doses, easily passes the mycomembrane and exhibits only low toxicity to human cells.

The combined application of this substance with known antibiotics showed a synergistic effect leading to significantly increased effectiveness."Vancomycin, a common antibiotic, and EZ120 work together very well. When used together, the dose can be reduced over 100-fold. Disrupting the mycomembrane enables antibiotics to enter the bacteria more easily. This is a new mode of action and might be a starting point for novel tuberculosis therapies.
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Bacteria obtain resistance from competitor

Bacteria not only develop resistance to antibiotics, they also can pick it up from their rivals. In a recent publication in Cell Reports, Researchers from the Biozentrum of the University of Basel have demonstrated that some bacteria inject a toxic cocktail into their competitors causing cell lysis and death. Then, by integrating the released genetic material, which may also carry drug resistance genes, the predator cell can acquire antibiotic resistance.

The frequent and sometimes careless use of antibiotics leads to an increasingly rapid spread of resistance. Hospitals are a particular hot spot for this. Patients not only introduce a wide variety of pathogens, which may already be resistant but also, due to the use of antibiotics to combat infections, hospitals may be a place where anti-microbial resistance can develop and be transferred from pathogen to pathogen. One of these typical hospital germs is the bacterium Acinetobacter baumannii. It is also known as the "Iraq bug" because multidrug-resistant bacteria of this species caused severe wound infections in American soldiers during the Iraq war.

The emergence and spread of multidrug resistance could be attributed, among other things, to the special skills of certain bacteria: Firstly, they combat their competitors by injecting them with a cocktail of toxic proteins, so-called effectors, using the type VI secretion system (T6SS), a poison syringe. They are able to uptake and reuse the released genetic material. In the model organism Acinetobacter baylyi, a close relative of the Iraq bug, Prof. Marek Basler's team at the Biozentrum of the University of Basel, has now identified five differently acting effectors. Some of these toxic proteins kill the bacterial competition very effectively, but do not destroy the cells.

The predator bacteria take up the released DNA fragments. If these fragments carry certain drug resistance genes, the specific resistance can be conferred upon the new owner. As a result, the antibiotic is no longer effective and the bacterium can reproduce largely undisturbed. Pathogens with such abilities are a major problem in hospitals, as through contact with other resistant bacteria they may accumulate resistance to many antibiotics -- the bacteria become multidrug-resistant. In the worst case, antibiotic treatments are no longer effective, thus nosocomial infections with multidrug-resistant pathogens become a deadly threat to patients.

The T6SS, as well as a set of different effectors, can also be found in other pathogens such as those which cause pneumonia or cholera. Interestingly, not all effectors are sufficient to kill the target cell, as many bacteria have developed or acquired antitoxins -- so-called immunity proteins. Antibiotics and anti-microbial resistance have existed for a long time. They developed through the coexistence of microorganisms and enabled bacteria to defend themselves against enemies or to eliminate competitors. This is one of the ways in which bacteria can conquer and colonize new environmental niches. With the use of antibiotics in medicine, however, the natural ability to develop resistance has become a problem. This faces researchers with the challenge of continually developing new antibiotics and slowing down the spread of drug resistance.
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Cancer alters the circadian clock to survive

Tumor cells use the unfolded protein response to alter circadian rhythm, which contributes to more tumor growth, Hollings Cancer Center researchers at the Medical University of South Carolina (MUSC) find. A key part of the circadian clock opposes this process. For tumors to grow and spread, cancer cells must make larger than normal amounts of nucleic acids and protein, so they can replicate themselves. Yet in both normal and cancer cells that increase their synthesis of protein, a small percent of those proteins do not fold properly.

When that happens, the cell activates its unfolded protein response (UPR), which slows down the making of new proteins while the misfolded proteins are refolded. Eventually, the buildup of misfolded proteins becomes toxic and leads to cell death. However, cancer cells have learned to use the UPR to slow protein synthesis when needed, in order to handle the backlog of misfolded proteins. This helps them survive in conditions that would kill normal cells.

This pattern of adaptation is often seen in tumor cells. UPR and circadian rhythm are linked together to lead the clockwork of the cell and also that cancer cells use the UPR to manipulate the circadian clock in ways that allow them to survive conditions that are toxic to normal cells. Researchers formulated a new idea based on what was known about protein synthesis in the cell. The UPR is altered in tumors, and second, cells establish a circadian rhythm to regulate metabolism by producing levels of certain proteins that rise and fall in coordination with natural cycles of light and dark.

 Scientists had observed that circadian rhythm is altered in tumor cells. Since protein production is tied to circadian rhythm. Research team used chemicals to activate the UPR in osteosarcoma cells. They found that, when activated, the UPR changes levels of an important protein called Bmal1, which is a transcription factor that rises and falls with cycles of light and dark. As it does, it regulates the expression of major circadian rhythm genes.

When cells were exposed to cycles of light and dark, Bmal1 levels peaked during dark hours. But when the UPR was chemically activated, Bmal1 stayed low during both light and dark phases, which caused a phase shift in the expression of circadian genes. When one of the main parts of the UPR machinery was absent in cells, the phase shift did not happen.

Levels of the circadian protein Bmal1 continued to decrease, as the UPR was increasingly activated. In rodents that had their light-dark cycles suddenly reversed, Bmal1 stopped rising and falling - a clear sign that their circadian rhythms were disrupted. Shifts in light exposure activated the UPR in those rodents' cells.

 The team found that patients with breast, gastric or lung cancers survived longer when they had higher levels of Bmal1 protein. In myc-driven cancers, the UPR was causing the loss of Bmal1 protein, which caused the tumors to grow. Myc-driven tumors lost circadian rhythm, whereas normal cells maintained it. Conversely, high levels of Bmal1 overtook the UPR, thereby allowing protein synthesis to continue, which was toxic to tumor cells . In this way, Bmal1 directly encourages protein synthesis.

Human cancer suppresses circadian rhythm by controlling protein synthesis through Bmal1. Cancer cells survived longer by using the UPR to suppress Bmal1 and short-circuit their circadian rhythms. These results are important for human biology. Every single normal cell in human body has circadian oscillation, resetting the circadian rhythms in cancer cells slows down their proliferation.
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Skin patch for management of type 2 diabetes

Researchers with NIH's National Institute of Biomedical Imaging and Bioengineering (NIBIB) have devised an innovative biochemical formula of mineralized compounds that interacts in the bloodstream to regulate blood sugar for days at a time. In a proof-of-concept study performed with mice, the researchers showed that the biochemically formulated patch of dissolvable microneedles can respond to blood chemistry to manage glucose automatically.

Insulin is a hormone made in the pancreas and secreted into the bloodstream to regulate glucose in response to food intake. It is needed to move glucose from the bloodstream into cells where the sugar can be converted to energy or stored. In type 1 diabetes, usually diagnosed in children and young adults, the body does not make insulin at all. Type 2 diabetes, which can be diagnosed at any age but more commonly as an adult, progressively lessens the body's ability to make or use insulin.

Untreated, diabetes can result in both vascular and nerve damage throughout the body, with debilitating impacts on the eyes, feet, kidneys, and heart. The base of the experimental patch is material called alginate, a gum-like natural substance extracted from brown algae. It is mixed with therapeutic agents and poured into a microneedle form to make the patch. Alginate is a pliable material -- it is soft, it has to be able to poke the dermis, and while not a commonly used material for needles, it seems to work pretty well in this case.

Researchers infused the alginate with a formula of biochemical particles that stimulates the body's own insulin production when needed and curtails that stimulation when normal blood sugar concentration is reached. The responsive delivery system of the patch can meet the body's need for days instead of being used up all at once. Diabetes is a very serious disease and affects a lot of people. Researchers puts two drug compounds -- exendin-4 and glucose oxidase -- into one patch. The two compounds react with the blood chemistry to trigger insulin secretion. Each is matched with a phosphate mineral particle, which stabilizes the compound until it is needed. Acidity that occurs when sugar concentrations rise weakens the bond with the drug being held by one, but not the other mineral.

Exendin-4 is similar in genetic makeup to a molecule the body produces and secretes in the intestine in response to food intake. Though it is somewhat weaker than the naturally occurring molecule, the team chose exendin-4 for its application because exendin-4 does not degrade in the bloodstream for an hour or more, so can have long-lasting effect after being released. However, it can induce nausea when too much is absorbed. To control how quickly it is absorbed, the researchers combined exendin-4 with mineral particles of calcium phosphate, which stabilize it until another chemical reaction occurs. That chemical reaction is caused by the second drug compound in the patch -- glucose oxidase -- that is held in its mineral buffer of copper phosphate.

When blood sugar is elevated beyond a precise point, it triggers a reaction with copper phosphate and glucose oxidase to produce slight acidity, which causes calcium phosphate to release some exendin-4. Rising glucose levels trigger the release of exendin-4; but exendin-4 then gets insulin flowing to reduce the glucose level, which slows down and stops release of exendin-4. The researchers demonstrated that a patch about half an inch square contained sufficient drug to control blood sugar levels in mice for a week.

 For the approach to advance as an application that people with type-2 diabetes can use, the team will need to perform tests to treat larger animals with a patch that contains proportionately more therapeutic compound. In addition to its size, the patch would need to be altered for application on human skin, likely requiring longer needles.
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Effects of estrogen treatment in multiple sclerosis

A study by UCLA researchers reveals the cellular basis for how the hormone estrogen protects against damage to the central nervous system in people with multiple sclerosis (MS). The researchers found that estrogen treatment exerts positive effects on two types of cells during disease -immune cells in the brain and also cells called oligodendrocytes. Complementary actions on these two types provide protection from disease.

Multiple sclerosis is a chronic autoimmune, neurodegenerative disease marked by visual impairment, weakness and sensory loss, as well as cognitive decline. These symptoms emerge when inflammatory immune cells destroy the myelin sheath that surrounds nerve processes called axons. Loss of that protective insulation disrupts electrical communication between nerve cells. The third trimester of pregnancy has been previously shown to reduce relapse rates by approximately 70 percent as compared to before pregnancy, and other studies have shown benefit over the long term due to multiple pregnancies.

An estrogen unique to pregnancy that is made by the fetus and placenta has been proposed by Dr. Rhonda Voskuhl and colleagues to mediate this pregnancy protection in both the MS mouse model as well as in two successfully completed clinical trials of estriol treatment in MS patients. How that happens has remained a critical question. Voskuhl, who led the latest study, reported mouse studies showing that estrogen protected the brain from damage by activating a protein called estrogen receptor beta (ERb). Her new research identifies which cells within the brain are mediating this protective effect.

The researchers first genetically eliminated ERb in either immune cells of the brain or in oligodendrocytes, the cells that make the myelin sheath, as a way of making cells unresponsive to estrogen during the MS like disease in mice. They then treated mice without or with ERb in these cells to ask if disease protection was lost or not. Loss of protection during treatment meant that the treatment was acting on the cell that had the receptor removed. Results showed that the estrogen-like treatment was acting on both immune cells of the brain as well as on oligodendrocytes, together resulting in repair of myelin and less disability.

Drug developers often optimize therapies by targeting only one single cell type. By contrast, this study confirms that this estrogen-like compound can combat MS via complementary effects on two distinct cell types. Voskuhl and other UCLA researchers are in fact now developing a next-generation estrogen-like compound with robust biochemical effects on oligodendrocytes and immune cells in the brain.
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Segluromet for treating type 2 diabetes

FDA Approves Segluromet (ertugliflozin and metformin hydrochloride) for Type 2 Diabetes. Segluromet is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are not adequately controlled on a regimen containing ertugliflozin or metformin, or in patients who are already treated with both ertugliflozin and metformin.

Segluromet is not recommended in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. The labeling for Segluromet contains a boxed warning for lactic acidosis. Segluromet is contraindicated in patients with severe renal impairment, end-stage renal disease or on dialysis, acute or chronic metabolic acidosis, including diabetic ketoacidosis, or a history of a serious hypersensitivity reaction to Segluromet, ertugliflozin or metformin hydrochloride.

Segluromet combines 2.5 mg or 7.5 mg of ertugliflozin with 500 mg or 1,000 mg of metformin hydrochloride. Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment.

If metformin-associated lactic acidosis is suspected, immediately discontinue Segluromet (ertugliflozin and metformin hydrochloride) and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended. Ketoacidosis, a serious life-threatening condition requiring urgent hospitalization, has been reported in patients with type 1 and type 2 diabetes receiving SGLT2 inhibitors, including ertugliflozin. Some cases were fatal. Assess patients with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level. If ketoacidosis is suspected, Segluromet should be discontinued, patient should be evaluated, and prompt treatment should be instituted.

Before initiating Segluromet, consider risk factors for ketoacidosis, including pancreatic insulin deficiency from any cause, caloric restriction, and alcohol abuse. In patients treated with Segluromet, consider monitoring for ketoacidosis and temporarily discontinuing Segluromet in clinical situations known to predispose to ketoacidosis (e.g., prolonged fasting due to acute illness or surgery).
Segluromet causes intravascular volume contraction and can cause renal impairment.

There have been reports of acute kidney injury, some requiring hospitalization and dialysis, in patients receiving SGLT2 inhibitors. Before initiating Segluromet, consider factors that may predispose patients to acute kidney injury. Consider temporarily discontinuing Segluromet in any setting of reduced oral intake or fluid losses; monitor patients for signs and symptoms of acute kidney injury. If acute kidney injury occurs, discontinue Segluromet promptly and institute treatment.
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Macrilen for treating growth hormone deficiency

Macrilen (macimorelin) stimulates the secretion of growth hormone from the pituitary gland into the circulatory system. Stimulated growth hormone levels are measured in four blood samples over ninety minutes after oral administration of Macrilen (macimorelin) for the assessment of growth hormone deficiency (“GHD”).

 Prior to the approval of Macrilen (macimorelin), the historical gold standard for evaluation of AGHD was the insulin tolerance test (“ITT”), an intravenous test requiring many blood draws over several hours. The ITT procedure is inconvenient for patients and medical practitioners and may contraindicate in patients, such as those with coronary heart disease or seizure disorder, because it requires the patient to experience hypoglycemia to obtain an accurate result.

Clinical studies have demonstrated that growth hormone stimulation testing for AGHD with oral Macrilen (macimorelin) is reliable, well-tolerated, reproducible, safe and a much simpler test to conduct than currently available options. The availability of Macrilen (macimorelin) will greatly relieve the burden of endocrinologists in reliably and accurately diagnosing AGHD.
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Giapreza for treating low blood pressure

FDA Approves Giapreza (angiotensin II) to treat dangerously low blood pressure. Giapreza (angiotensin II) injection for intravenous infusion to increase blood pressure in adults with septic or other distributive shock. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Hypotension is abnormally low blood pressure.

 Shock is a critical condition in which blood pressure drops so low that the brain, kidneys and other vital organs can't receive enough blood flow to function properly. In a clinical trial patients with shock and a critically low blood pressure, significantly more patients responded to treatment with Giapreza compared to those treated with placebo.

 Giapreza effectively increased blood pressure when added to conventional treatments used to raise blood pressure. The drug can cause dangerous blood clots with serious consequences (clots in arteries and veins, including deep venous thrombosis); prophylactic treatment for blood clots should be used.
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Lumify for treating eye redness

Ocular redness is a common condition that can be caused by inflammation of almost any part of the eye. With frequent use, non-selective redness relieving eye drops that constrict blood vessels in the eye can result in users developing a tolerance or loss of effectiveness, as well as rebound redness.

 In contrast, low-dose brimonidine, the active ingredient in Lumify, selectively constricts veins in the eye, increasing the availability of oxygen to surrounding tissue, thereby reducing the potential risk of these side effects.

Patients with eye redness and irritation can experience negative social connotations, which may impact daily life, having a drop that reduces redness without the side effects of rebound hyperemia or tachyphylaxis, which may lead to overuse and potential corneal toxicity, Lumify is adequate and accurate for treating the condition without side effects.
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Exercise improves memory and thinking

Mild cognitive impairment is an intermediate stage between the expected cognitive decline of normal aging and the more serious decline of dementia. Symptoms can involve problems with memory, language, thinking and judgment that are greater than normal age-related changes. Generally, these changes aren't severe enough to significantly interfere with day-to-day life and usual activities.

 A new guideline for medical practitioners says they should recommend twice-weekly exercise to people with mild cognitive impairment to improve memory and thinking. However, mild cognitive impairment may increase the risk of later progressing to dementia caused by Alzheimer's disease or other neurological conditions.

But some people with mild cognitive impairment never get worse, and a few eventually get better. Engaging in aerobic exercise like walking briskly, jogging, whatever you like for more than 100 minutes a week can improve memory. The level of exertion should be enough to work up a bit of a sweat but doesn't need to be so rigorous that you can't hold a conversation. Exercising might slow down the rate at which you would progress from mild cognitive impairment to dementia.
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DNA test for breast cancer

Scientists have developed a DNA test that may diagnose fatal breast cancer one year earlier than current methods. Changes in a part of DNA, which the researchers named EFC#93, suggests early warning signs of life-threatening breast cancer. These changes occur in patients' blood before their cancer becomes detectable in their breast tissue.

 A study revealed among women who have EFC#93 in their blood, 43 per cent were diagnosed with a life-threatening form of breast cancer three-to-six months later, while 25 per cent were diagnosed within six-to-12 months.

Markers such as EFC#93 provide a highly specific indicator that could diagnose fatal breast cancers up to one year in advance of current diagnosis.  This may enable individualised treatment, which could even begin in the absence of radiological evidence in the breast.

The researchers analysed EFC#93 in blood samples from breast cancer patients taken both after surgery but before chemotherapy and once chemotherapy was complete. They demonstrated DNA change in samples taken before chemotherapy as a marker for poor prognosis even if cancer cells are not yet circulating in the body.

 To assess whether EFC#93 can diagnose women with a poor prognosis earlier, the researchers then analysed samples of 925 healthy women, of which 229 went on to develop life-threatening breast cancer, while 231 got non-fatal forms of the disease within three years.
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Don't urinate before sex

New York City urologist David Kaufman explained the idea females should pee before intercourse is one of the biggest misconceptions he has to address with patients in his clinic. He stresses that urinating after sex is important, but warns going to the bathroom beforehand is not advisable. Urinating and consequently having enough urine stored up to create a strong stream, increases the odds of pushing bacteria out after sex.

Holding on will ensure full bladder to produce a stream strong enough to clear any bacteria in the urethra. Without any urine in the bladder, the bacteria can cause an infection. Not urinating after sex  can make cause bacterial to make its way into the bladder and develop into an infection. Women are far more susceptible to UTIs than men because of their anatomy. The female urethra is separated from the vagina and anus by just a small distance, making it easy for bacteria from either the vagina or bottom to reach it.

According to the NHS, using a diaphragm as contraception can increase your risk of getting a UTI, as the diaphragm may press on the bladder and prevent it emptying completely. You can do this to prevent UTI. Avoiding perfumed bubble bath, soap or talcum powder around your genitals-use plain, unperfumed varieties, and have a shower rather than a bath.

Going to the toilet as soon as you need to pee and always emptying your bladder fully. Staying hydrated,wiping your bottom from front to back when you go to the toilet, emptying your bladder as soon as possible after having sex,  not using a contraceptive diaphragm or condoms with spermicidal lubricant on them.Wearing underwear made from cotton, rather than synthetic material such as nylon, and avoiding tight jeans and trousers
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Valsartan for treating high blood pressure

Valsartan is an angiotensin II receptor antagonist. Valsartan keeps blood vessels from narrowing, which lowers blood pressure and improves blood flow. It is used to treat high blood pressure (hypertension) in adults and children who are at least 6 years old. Valsartan is also used in adults to treat heart failure, and to lower the risk of death after a heart attack. It is sometimes given together with other blood pressure medications.

If you have diabetes, do not use valsartan together with any medication that contains aliskiren (Amturnide, Tekturna, Tekamlo, Valturna). Before taking this medicine. Do not use valsartan if you are allergic to it. You may take valsartan with or without food. Take the medicine at the same time each day. If a child taking valsartan cannot swallow a capsule whole, your pharmacist can mix the medicine into a liquid. Shake this liquid well just before you measure a dose.

Measure the liquid with a special dose-measuring spoon or medicine cup, not with a regular table spoon. You may have very low blood pressure while taking valsartan. Call your doctor if you are sick with vomiting or diarrhea, or if you are sweating more than usual. Drinking alcohol can further lower your blood pressure and may increase certain side effects of valsartan. Do not use potassium supplements or salt substitutes while you are taking valsartan, unless your doctor has told you to.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall. Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. In rare cases, valsartan can cause a condition that results in the breakdown of skeletal muscle tissue, leading to kidney failure. Call your doctor right away if you have unexplained muscle pain, tenderness, or weakness especially if you also have fever, unusual tiredness, and dark colored urine.
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Links between personality trait and depression

Scientists analysed the DNA of over 300,000 people and found many genes linked to neuroticism- characterised by feelings of anxiety, worry and guilt. The genes are also linked to depression. The findings shed light on the causes of depression-which affects one in five people and could provide information to help better diagnosis and treatment for individuals.

Researchers analysed genetic information from a group of people aged from 39 to 73, whose levels of neuroticism had been measured by a personality questionnaire. DNA analysis combined with the personality data uncovered 116 gene variations linked to neuroticism.

Researchers from the University found that genes associated with neuroticism had some overlap with genes linked to a susceptibility to depression and some other psychiatric conditions. More than half of the genetic variations associated with neuroticism are expressed in the brain.
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Fish consumption linked to higher IQ

Children who eat fish at least once a week sleep better and have IQ scores that are 4 points higher, on average, than those who consume fish less frequently or not at all. Previous studies showed a relationship between omega-3s, the fatty acids in many types of fish and improved intelligence, as well as omega-3s and better sleep. But they've never all been connected before.

This work, conducted by Jianghong Liu, Jennifer Pinto-Martin and Alexandra Hanlon of the School of Nursing and Penn Integrates Knowledge Professor Adrian Raine, reveals sleep as a possible mediating pathway, the potential missing link between fish and intelligence.

For the work, a cohort of 541 9- to 11-year-olds in China, 54 percent boys and 46 percent girls, completed a questionnaire about how often they consumed fish in the past month, with options ranging from "never" to "at least once per week." They also took the Chinese version of an IQ test called the Wechsler Intelligence Scale for Children-Revised, which examines verbal and non-verbal skills such as vocabulary and coding.

Their parents then answered questions about sleep quality using the standardized Children Sleep Habits Questionnaire, which included topics such as sleep duration and frequency of night waking or daytime sleepiness. Finally, the researchers controlled for demographic information, including parental education, occupation and marital status and number of
children in the home.

Analyzing these data points, the Penn team found that children who reported eating fish weekly scored 4.8 points higher on the IQ exams than those who said they "seldom" or "never" consumed fish. Those whose meals sometimes included fish scored 3.3 points higher. In addition, increased fish consumption was associated with fewer disturbances of sleep, which the researchers say indicates better overall sleep quality. Lack of sleep is associated with antisocial behavior; poor cognition is associated with antisocial behavior, fish consumption has positive health benefits. Children should be introduced to it early on.
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Rhopressa for treating glaucoma

Rhopressa (netarsudil ophthalmic solution) 0.02%, is a novel once-daily eye drop for the lowering of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Rhopressa is believed to reduce IOP by increasing the outflow of aqueous humor (the fluid inside the eye) through the trabecular meshwork, the main fluid drain of the eye.

Rhopressa (netarsudil ophthalmic solution) is a Rho kinase inhibitor for the treatment of open-angle glaucoma or ocular hypertension. Use one drop in the affected eye(s) once daily in the evening. If a dose is missed, treatment should continue with the next dose in the evening. Avoid allowing the tip of the dropper to contact the eye, surrounding structures, fingers, or any other surface in order to minimize contamination of the solution.

 Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions. Rhopressa contains benzalkonium chloride, which may be absorbed by soft contact lenses. Contact lenses should be removed prior to instillation of Rhopressa and may be reinserted 15 minutes following its administration.

If more than one topical ophthalmic drug is being used, the drugs should be administered at least 5 minutes between applications. The most common side effect is eye redness. Other common side effects include corneal verticillata, pain at the instillation site, and conjunctival hemorrhage.
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Luxturna for treating inherited retinal disease

Luxturna (voretigene neparvovec) is an adeno-associated viral (AAV) vector gene therapy for the treatment of patients with vision loss due to confirmed biallelic RPE65-mediated inherited retinal disease (IRD). Luxturna is approved for the treatment of patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy that leads to vision loss and may cause complete blindness in certain patients.

Hereditary retinal dystrophies are a broad group of genetic retinal disorders that are associated with progressive visual dysfunction and are caused by mutations in any one of more than 220 different genes. Biallelic mutation carriers have a mutation (not necessarily the same mutation) in both copies of a particular gene (a paternal and a maternal mutation). The RPE65 gene provides instructions for making an enzyme (a protein that facilitates chemical reactions) that is essential for normal vision.

 Mutations in the RPE65 gene lead to reduced or absent levels of RPE65 activity, blocking the visual cycle and resulting in impaired vision. Individuals with biallelic RPE65 mutation-associated retinal dystrophy experience progressive deterioration of vision over time. This loss of vision, often during childhood or adolescence, ultimately progresses to complete blindness.

Luxturna works by delivering a normal copy of the RPE65 gene directly to retinal cells. These retinal cells then produce the normal protein that converts light to an electrical signal in the retina to restore patient’s vision loss. Luxturna uses a naturally occurring adeno-associated virus, which has been modified using recombinant DNA techniques, as a vehicle to deliver the normal human RPE65 gene to the retinal cells to restore vision. Luxturna should be given only to patients who have viable retinal cells as determined by the treating physician(s).

 Treatment with Luxturna must be done separately in each eye on separate days, with at least six days between surgical procedures. It is administered via subretinal injection by a surgeon experienced in performing intraocular surgery. Patients should be treated with a short course of oral prednisone to limit the potential immune reaction to Luxturna. The most common adverse reactions from treatment with Luxturna included eye redness (conjunctival hyperemia), cataract, increased intraocular pressure and retinal tear.
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Using viruses to fight viruses

Researchers at The Ottawa Hospital and the University of Ottawa have discovered that the Maraba virus, or MG1, can target and destroy the kind of HIV-infected cells that standard antiretroviral therapies can't reach. Daily medications keep the level of HIV virus in the blood low, there is currently no way to totally eliminate dormant HIV-infected cells from the body. If a person living with HIV stops taking antiretroviral medications, these hidden viruses rapidly rebound.

These latently HIV-infected cells are hard to target because they are not distinguishable from normal cells. Dr. Jonathan Angel and his team tried a new approach of identifying these dormant cells by using the MG1 virus. This virus attacks cancer cells that have defects in their interferon pathway, which makes the cells more vulnerable to viruses. Dr. Angel and his team previously found that latently HIV-infected cells also have defects in this pathway.

Using a number of laboratory models of latently HIV-infected cells, the researchers found that the MG1 virus targeted and eliminated the infected cells, and left healthy cells unharmed.
While most of these cells in patients are in the lymph nodes and other organs, a tiny number are found in the blood. When the researchers added MG1 to relevant blood cells taken from HIV-positive individuals, the levels of HIV DNA in the sample dropped. This indicated that the HIV-infected cells had been eliminated.
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Heart burn pills increases the risk of stomach cancer

Chronic heartburn, caused by stomach acid splashing into the gullet, also known as acid reflux, affects many people. Proton pump inhibitors (PPIs)  is popularly used to treat the condition. Available both on prescription and over-the-counter at lower doses, PPIs are among the top ten most regularly taken drugs. A study this year by University College London (UCL) involving 63,000 patients, found those taking PPIs for two weeks were twice as likely as those not on the drugs to develop stomach cancer in the following seven years.

If they stayed on them for a year, they were five times more at risk of cancer. And after three years of taking the drugs daily, the risk rose eight-fold. Scientists think PPIs may linked to cancer by stimulating a hormone called gastrin, known to play a part in triggering the growth of cancerous cells in the stomach. It is important to clarify that the UCL findings do not prove these drugs cause cancer, and researchers stressed the risk of stomach cancer in patients on the drugs is still small.

Chronic reflux can cause cells in the gullet to grow abnormally, a condition known as Barrett’s oesophagus that’s thought to affect one in ten people with reflux. Left untreated, this can develop into oesophageal cancer. PPIs such as Nexium, Zanprol, Prevacid and Prilosec, work by suppressing the release of stomach acid by cells, called proton pumps, in the stomach lining. In theory, PPIs should reduce oesophageal cancer rates by treating acid reflux.

An investigation in 2016 by Erasmus University Rotterdam in the Netherlands revealed men who regularly took PPIs were three times more likely to have low sperm counts. Meanwhile, research from Johns Hopkins University in the U.S. in 2015 found that those on PPIs were 90 per cent more likely to develop kidney failure, while a study conducted by McGill University in Canada in 2015 found that they raised the risk of hip fractures by 44 per cent. In all the studies, the longer people stay on them, the bigger the risk. In the U.S., the Food and Drug Administration (FDA) has already acted on PPI safety fears and nearly 300 patients in New Jersey have filed lawsuits in the past year or so claiming the drugs left them with kidney damage and that manufacturers knew about the risks but failed to warn them.

Stomach acid protects against infection by destroying the spores containing the C.difficile bacterium before they infect the gut. But if the stomach is producing very little acid because PPIs are being taken every day, it boosts the bug’s chances of thriving. Lab research at Stanford University in the U.S. showed that the drugs don’t just turn off acid pumps in the stomach-they also block production of acid in every cell in the body. Each cell has an area called a lysosome, which contains enzymes that help to break down damaged or defective proteins, the debris from the ageing process. But these enzymes only work properly in acidic conditions.

If the lysosome is unable to release acid to help with this process (because PPIs have blocked the mechanism), waste material builds up and cells age quicker. People with acid reflux should be able to control it by quitting smoking (a big risk factor), losing weight or raising the head of the bed by six to eight inches (which stops gravity pulling acid out of the stomach during sleep). A study this year by University College London (UCL) involving 63,000 patients, found those taking PPIs for two weeks were twice as likely as those not on the drugs to develop stomach cancer in the following seven years. If they stayed on them for a year, they were five times more at risk of cancer.
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Cancer survivors age faster and die younger

Childhood cancer survivors naturally age faster and are more likely to die sooner than those who have not had the disease, according to a new study. The research also showed that survivors are three to six times more likely to develop cancer again. Researchers from the Mayo Clinic in Rochester, Minnesota, found that hormonal/gland disorders (endocrinopathies), heart problems, lower bone mineral density, lung scarring (pulmonary fibrosis) and secondary cancers are more likely to occur in childhood cancer survivors later in life.

Frailty to bones and joints may also occur at an earlier age than the general population due to the damage caused by chemotherapy and radiotherapy to normal healthy tissues. The cancer and harsh treatments diminishes 'physiological reserve', the capacity in organs and biological body systems given to us at birth. These are the body's natural resilience to overcome internal and external biological stressors.

Other findings showed that childhood cancer survivors' estimated life expectancy is 30 percent lower than that of the general population. Also, the risk of frailty among bone marrow transplant recipients is around eight times as high as that of their siblings. Radiation therapy is associated with dementia, memory loss and secondary bone marrow cell and blood cancers, while long-term steroid treatment is linked to a higher risk of cataracts, osteoporosis, nerve damage and infection.
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Xepi for treating Impetigo

Xepi (ozenoxacin) is a topical non-fluorinated quinolone for the treatment of impetigo due to Staphylococcus aureus or Streptococcus pyogenes. Xepi is usually applied as a thin layer to the affected area twice daily for five days.

Impetigo is a highly contagious bacterial skin infection. Always use Xepi as directed by your healthcare practitioner. Wash your hands after applying the cream if the hands are not the area for treatment.

Xepi is for external use only. Do not swallow the cream, or use it in the eyes, on the mouth or lips, inside the nose, or inside the female genital area. The treated area may be covered by a sterile bandage or gauze dressing.

Use Xepi for the entire time as recommended by your healthcare practitioner, even though your symptoms may have improved. Notify your healthcare practitioner if there is no improvement in symptoms within three days of starting treatment.
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Eskata for treating Keratoses

Eskata (hydrogen peroxide) 40% (w/w) topical solution is a high-concentration hydrogen peroxide formulation for the treatment of raised seborrheic keratoses.

Seborrheic keratoses (SKs) are non-cancerous skin growths. SKs vary in color from flesh-colored to pink, yellow, gray, tan, brown, or black; can range in size from a millimeter to a few centimeters wide; and typically have a slightly elevated, waxy or scaly appearance.

The number and size of SKs tends to increase with advancing age. SKs frequently appear in highly visible locations, such as the face or neck, but can also appear anywhere on the body, except the palms, soles and mucous membranes.

Eskata is applied by healthcare provider as an in-office treatment and is not for use at home. Serious eye problems can happen if Eskata gets into your eyes. If Eskata accidentally gets into your eyes, flush them well with water for 15 to 30 minutes.

Skin reactions have occurred in and around the treatment area after application of Eskata. Reactions can be severe, including breakdown of the outer layer of the skin (erosion), ulcers, blisters and scarring. The most common side effects of Eskata include itching, stinging, crusting, swelling, redness and scaling.
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Genetic mutation causes low sensitivity to pain

A UCL-led research team has identified a rare mutation that causes one family to have unusually low sensitivity to pain. They studied an Italian family, the Marsilis, which includes six people who have a distinctive pain response that has not been identified in any other people. "The members of this family can burn themselves or experience pain-free bone fractures without feeling any pain. But they have a normal intraepidermal nerve fibre density, which means their nerves are all there, they're just not working how they should be. We're working to gain a better understanding of exactly why they don't feel much pain, to see if that could help us find new pain relief treatments," said the study's lead author, Dr James Cox (UCL Wolfson Institute for Biomedical Research).

One in ten people experience moderately to severely disabling chronic pain, but treatments beyond common painkillers remain elusive. Understanding the causes of congenital analgesia, a rare inherited condition that reduces the capacity to feel physical pain, is one of the main areas of research that could lead to new pain relief therapies. Two other mutations causing congenital analgesia are being actively explored by researchers alongside pharmaceutical firms, but have yet to yield any breakthrough drugs.

The research team added to previous work with the Italian family to clarify the nature of their phenotype (the observable characteristics caused by their genetics) - named the Marsili syndrome after their surname - finding that they're hyposensitive to noxious heat, hyposensitive to capsaicin (in chilli peppers) and have experienced pain-free bone fractures. Using DNA from blood samples, the researchers conducted a whole exome sequencing - mapping out the protein-coding genes in the genome of each family member.

 They identified a novel point mutation in the ZFHX2 gene. The mutation alters a part of the gene's protein sequence that is normally consistent across species as variable as mice and frogs. The researchers then conducted two animal studies to understand how the gene affects pain sensations in mice. They initially used mice that had been bred with the ZFHX2 gene entirely absent, and found them to have altered pain thresholds. They then bred a new line of mice that had the relevant mutation, and those mice were notably insensitive to high temperatures.

Further analysis of the mice bearing the mutation clarified that the gene regulates a number of other genes that have previously-established connections to pain signalling. By identifying this mutation and clarifying that it contributes to the family's pain insensitivity, we have opened up a whole new route to drug discovery for pain relief. With more research to understand exactly how the mutation impacts pain sensitivity, and to see what other genes might be involved.
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How to cure a burned mouth

Burns on the tongue heal faster than on the roof of the mouth, since the tongue has the most blood vessel supply in the entire body.

However, the pain can be searing since the skin here is more sensitive than other parts of the body, and it doesn't have any fat between the skin and the bones. As a result, it usually lingers two to three days.

Burned mouth can be healed quickly by sticking to a soft diet like yogurt and sushi, avoiding spice,noodles,soup, iced drink and hot foods eat lukewarm food - room temperature.

Coffee, wine and soda should all be off the menu for days. These foods are acidic, they will irritate skin as it's healing, potentially delaying the healing process.

Bacteria in an open wound can lead to infection and prevent healing. After a burn, brush your teeth thoroughly, use mouthwash, and drink plenty of water to wash out any built-up food or bacteria from your mouth.
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Infliximab for reducing inflammation

Infliximab reduces the effects of a substance in the body that can cause inflammation. Infliximab is used to treat rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, Crohn's disease, and ankylosing spondylitis. Infliximab is also used to treat severe or disabling plaque psoriasis. Infliximab is often used when other medicines have not been effective.

Using infliximab may increase the risk of developing certain types of cancer, including a rare fast-growing type of lymphoma that can be fatal. Infliximab can lower blood cells that help the body fight infections. Serious and sometimes fatal infections may occur.  However, people with autoimmune disorders (including rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, and psoriasis) may have a higher risk of lymphoma.

Using infliximab may increase the risk of developing other types of cancer, including skin cancer. Before you start treatment with infliximab, your doctor may perform tests to make sure you do not have tuberculosis (TB) or other infections. Infliximab is injected into a vein through an IV. A healthcare provider will give you this injection. You may be watched closely after receiving infliximab, to make sure the medicine has not caused any serious side effects.

Infliximab can lower blood cells that help your body fight infections and help your blood to clot. Do not receive a "live" vaccine while using infliximab, or you could develop a serious infection. Live vaccines include measles, mumps, rubella (MMR), polio, rotavirus, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.

Some side effects may occur during the injection. Tell your caregiver right away if you feel dizzy, nauseated, light-headed, itchy or tingly, swollen, short of breath, or have a headache, fever, chills, muscle or joint pain, pain or tightness in your throat, chest pain, or trouble swallowing during the injection. Infusion reactions may also occur within 1 or 2 hours after injection.

Get emergency medical help if you have signs of an allergic reaction: hives; chest pain, difficult breathing; fever, chills, severe dizziness; swelling of your face, lips, tongue, or throat. Serious and sometimes fatal infections may occur during treatment with infliximab. Call your doctor right away if you have signs of infection such as: fever, extreme tiredness, flu symptoms, cough, or skin symptoms (pain, warmth, or redness).
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Habits that increase the risk of cancer

Forty per cent of cancer deaths could be prevented with simple lifestyle changes. Quitting smoking, eating healthier and boozing less would stop the disease. Scientists suggest habits responsible for cancer with tobacco proving the biggest burden. Other habits, includes excessive UV radiation, obesity and not exercising enough can be blamed.

Researchers at the QIMR Berghofer Medical Research Institute, Brisbane, said the total amount is greater than 38 per cent because many deaths involved two factors. Even 'small improvements' would reduce the risk of dying prematurely from cancer, the Australian researchers claimed. Their findings, which also highlighted irresponsible sun tanning as a cause, were derived from an analysis of cancer deaths.

Obesity and infections were responsible for five per cent of the deaths while not exercising enough was blamed for 0.8 per cent.Dr David Whiteman, lead researcher of the study published in the International Journal of Cancer, found that the bad habits fueled 41 per cent of cancer deaths in men and 34 per cent in women because men smoke and drink more, spend more time in the sun and don't eat healthy foods.

The researchers concluded that the following eight habits are responsible for 38 per cent of cancer deaths. Researchers at the QIMR Berghofer Medical Research Institute, Brisbane, said the total amount is greater than 38 per cent because many deaths involved two factors. The habits are-Smoking, Poor diet, Boozing, UV radiation, Obesity, Infections, Inactivity and Hormones.
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Ketamine reduces suicidal thoughts

Ketamine was significantly more effective than a commonly used sedative in reducing suicidal thoughts in depressed patients, according to researchers at Columbia University Medical Center (CUMC). They also found that ketamine's anti-suicidal effects occurred within hours after its administration.

"There is a critical window in which depressed patients who are suicidal need rapid relief to prevent self-harm," said Michael Grunebaum, MD, a research psychiatrist at CUMC, who led the study. "Currently available antidepressants can be effective in reducing suicidal thoughts in patients with depression, but they can take weeks to have an effect. Suicidal, depressed patients need treatments that are rapidly effective in reducing suicidal thoughts when they are at highest risk.

 Currently, there is no such treatment for rapid relief of suicidal thoughts in depressed patients. Most antidepressant trials have excluded patients with suicidal thoughts and behavior, limiting data on the effectiveness of antidepressants in this population. However, previous studies have shown that low doses of ketamine, an anesthetic drug, causes a rapid reduction in depression symptoms and may be accompanied by a decrease in suicidal thoughts.

The 80 depressed adults with clinically significant suicidal thoughts who enrolled in this study were randomly assigned to receive an infusion of low-dose ketamine or midazolam, a sedative. Within 24 hours, the ketamine group had a clinically significant reduction in suicidal thoughts that was greater than with the midazolam group. The improvement in suicidal thoughts and depression in the ketamine group appeared to persist for up to six weeks.

Those in the ketamine group also had greater improvement in overall mood, depression, and fatigue compared with the midazolam group. Ketamine's effect on depression accounted for approximately one-third of its effect on suicidal thoughts, suggesting the treatment has a specific anti-suicidal effect.Side effects, mainly dissociation (feeling spacey) and an increase in blood pressure during the infusion, were mild to moderate and typically resolved within minutes to hours after receiving ketamine. This study shows that ketamine offers promise as a rapidly acting treatment for reducing suicidal thoughts in patients with depression.
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