Scientists Develop Oral Vaccine Against Salmonella Infection

December 20, 2016

Houston, Dec 20: Scientists, including one of Indian origin, have developed an oral vaccine against Salmonella - the deadly bacteria responsible for one of the most common food-borne illnesses in the world.

5-teamdevelopsOral vaccination is simplest and least invasive way to protect people against salmonella infection, researchers said.

Taking this vaccine by mouth also has the added advantage of using the same pathway that salmonella uses to wreak havoc on the digestive system, they said.

"In the current study, we analysed the immune responses of mice that received the vaccination by mouth as well as how they responded to a lethal dose of salmonella," said Ashok Chopra, professor at The University of Texas Medical Branch at Galveston (UTMB) in the US.

"We found that the orally administered vaccines produced strong immunity against salmonella, showing their potential for future use in people," said Mr Chopra.

There is no vaccine currently available for salmonella poisoning. Antibiotics are the first choice in treating salmonella infections, but the fact that some strains of salmonella are quickly developing antibiotic resistance is a serious concern.

"Another dangerous aspect of salmonella is that it can be used as a bioweapon - this happened in Oregon when a religious cult intentionally contaminated restaurant salad bars and sickened 1,000 people," researchers said.

Salmonella is responsible for one of the most common food-borne illnesses in the world. In the US alone, the Centres for Disease Control and Prevention estimates that there are about 1.4 million cases with 15,000 hospitalisations and 400 deaths each year.

It is thought that for every reported case, there are about 39 undiagnosed infections. Overall, the number of salmonella cases in the US has not changed since 1996.

Salmonella infection in people with compromised immune systems and children under the age of three are at increased risk of invasive non-typhoidal salmonellosis, which causes systemic infection. There are about one million cases globally per year, with a 25 per cent fatality rate.

In earlier studies, the UTMB researchers developed potential vaccines from three genetically mutated versions of the salmonella bacteria, that is Salmonella Typhimurium, that were shown to protect mice against a lethal dose of salmonella. In these studies, the vaccines were given as an injection.

The findings were published in the journal Frontiers in Cellular and Infection Microbiology.

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Agencies
June 10,2020

Early treatment with the antiviral drug remdesivir has been found to reduce viral load and prevent lung disease in macaques infected with SARS-CoV-2 that causes COVID-19, according to a study.

The findings, published in the journal Nature on Tuesday, support the early use of remdesivir treatment in patients with COVID-19 to prevent progression to pneumonia.

Researchers from the National Institutes of Health in the US noted that remdesivir has broad antiviral activity and has been shown to be effective against infections with SARS-CoV and MERS-CoV in animal models.

The drug is being tested in human clinical trials for the treatment of COVID-19, they said.

Researcher Emmie de Wit and colleagues investigated the effects of remdesivir treatment in rhesus macaques, a recently established model of SARS-CoV-2 infection.

Two sets of six macaques were inoculated with SARS-CoV-2.

One group was treated with remdesivir 12 hours later -- close to the peak of virus reproduction in the lungs -- and these macaques received treatment every 24 hours until six days after inoculation.

In contrast to the control group, the researchers found that macaques that received remdesivir did not show signs of respiratory disease, and had reduced damage to the lungs.

Viral loads in the lower respiratory tract were also reduced in the treated animals; viral levels were around 100 times lower in the lower-respiratory tract of remdesivir-treated macaques 12 hours after the first dose, they said.

The researchers said that infectious virus could no longer be detected in the treatment group three days after initial infection, but was still detectable in four out of six control animals.

Despite this virus reduction in the lower respiratory tract, no reduction in virus shedding was observed, which indicates that clinical improvement may not equate to a lack of infectiousness, they said.

Dosing of remdesivir in the rhesus macaques is equivalent to that used in humans, the researchers noted.

They cautioned that it is difficult to directly translate the timing of treatment used in corresponding disease stages in humans, because rhesus macaques normally develop only mild disease.

However, researchers said the results indicate that remdesivir treatment of COVID-19 should be initiated as early as possible to achieve the maximum treatment effect.

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News Network
February 21,2020

Washington, Feb 21: The fat around arteries may play an important role in keeping the blood vessels healthy, according to a study in rats that may affect how researchers test for treatments related to plaque buildup, as seen in conditions leading to heart attack.

The study, published in the journal Scientific Reports, noted that the fat, known as perivascular adipose tissue, or PVAT, helps arteries let go of muscular tension while under constant strain.

According to the researchers, including Stephanie W. Watts from the Michigan State University in the US, this feature is similar to how the bladder expands to accommodate more liquid, while at the same time keeping it from spilling out.

"In our study, PVAT reduced the tension that blood vessels experience when stretched," Watts said.

"And that's a good thing, because the vessel then expends less energy. It's not under as much stress," she added.

According to Watts and her team, PVAT has largely been ignored by researchers believing its main job was to store lipids and do little more.

Until now, she said, scientists only divided blood vessels into three parts, the innermost layer called the tunica intima, the middle layer called the tunica media, and the outermost layer called the tunica adventitia.

Watts believes PVAT is the fourth layer, which others have called tunica adiposa.

Tunica, she said, meant a membranous sheath enveloping or lining an organ, and adiposa is a synonym for fat.

"For years, we ignored this layer -- in the lab it was thrown out. In the clinic it wasn't imaged. But now we're discovering it may be integral to our blood vessels," Watts said.

"Our finding redefines what the functional blood vessels are, and is part of what can be dysfunctional in diseases that afflict us, including hypertension. We need to pay attention to this layer of a blood vessel because it does far more than we originally thought," she added.

Earlier studies, Watts said, had shown that PVAT plays a role in the functioning of blood vessels, finding that it secretes substances that can cause blood vessels to relax as well as substances that can cause it to contract.

In the current study, the researchers decided to test whether PVAT provides a structural benefit to arteries by assisting the function of stress relaxation.

They tested the thoracic aorta in rats, and found those with intact PVAT had more stress relaxation than those without.

The study revealed that the pieces of artery with surrounding fat had measurably relaxed more than those without.

Watts and her colleagues then tested other arteries, and were able to duplicate the same response.

"It's not something you see only in this particular vessel or this particular species or this particular strain. But that maybe it's a general phenomenon," she said.

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Dr G K Sudhakar Reddy
August 4,2020

Being overweight or obese is now recognised as a serious cause of ill health and disability. There is a significant positive association between orthopaedic disorders and the level of obesity causing pain, deformity and difficulty in walking.

Excess body weight accumulation increases pressure on joints, particularly the hips, knees and ankles.

Here are a few type of  arthritis:

Osteoarthritis

It is a condition of damage/ wear and tear of the joint lining or cartilage. Obesity triggers this by loading excessive weight on the weight bearing joints like the knee and the hip. 

Knee Osteoarthritis

This is the most common arthritis especially in the Indian subcontinent.

While walking, an individual exerts 3 to 6 times pressure that of the body weight on the weight-bearing knee joint, which means in an obese with excess body weight, larger forces are exerted, which lead to higher risk of deterioration of cartilage.

In addition, there are excessive fat tissues that produce hormones and other factors that affect the joint cartilage metabolism and cause inflammation of the joints giving rise to joint pathology.  Leptin is one of the hormones causing knee osteoarthritis. 

Hip osteoarthritis

The force exerted across the hip is 3 times that of body weight. Hip osteoarthritis is caused by factors such as joint injury, increasing age and being overweight.    

Hand osteoarthritis

The observation that obese individual has a higher risk in having hand osteoarthritis has led to a hypothesis that the metabolic effect produced by fat tissue is the underlying factor. 

Osteoporosis

It is a progressive bone condition of decrease in bone mass and density (Bone Mineral Density or BMD) which can lead to an increased risk of fracture. Recent research suggests that obesity may accelerate bone loss. It is the amount of muscle mass which is seen in an active person, which accounts for bone strengthening effects and not due to the fat seen in a heavy person.

Low back pain

Low back pain from degenerative disc disease of the lumbar spine is one of the most disabling conditions in the community and overweight and obesity have the strongest association with seeking care for low back pain.

Managing Hip and Knee Osteoarthritis

Life style changes

If one is overweight, try to lose weight by doing more physical activity and eating a healthier diet. Regular exercise keeps you active and mobile and builds up muscle, thereby strengthening the joints and can improve symptoms. 

Pain Killers

Painkillers help with pain and stiffness for short term. They don’t affect the arthritis itself and won’t repair the damage to your joint. Creams and gels can be applied directly onto painful joints.

Nutritional Supplements

Glucosamine and chondroitin are nutritional supplements. Animal studies have found that glucosamine can both delay the breakdown of and repair damaged cartilage. However, there is insufficient evidence to support the use of glucosamine in humans and one can expect only a mild-to-moderate reduction in pain

Joint injections

If pain from osteoarthritis is severe joint steroid injections are injected into the joints that can reduces swelling and pain. The injections can start working within a day or so and may improve pain for several weeks or months. 

Hyaluronic acid injections, which help to lubricate your knee joint also give short term relief. In early stages. Stem cell treatment or cartilage regeneration procedures are being tried in young people with small defects, however it is still experimental and lacks long term evidence.

Surgery

May be recommended if you have severe pain or mobility problems.

Arthroscopy

If one has frequent painful locking/stiffening episodes especially in the knee joint, an operation to wash out loose fragments of bone and other tissue as joint can be performed by a minimally invasive key hole procedure called Arthroscopy.

Arthrodesis

If hip or knee replacement is not suitable, especially in young people who do heavy manual work, one can consider an operation known as an arthrodesis, which fuses your joint in a permanent position. This means that your joint will be stronger and much less painful, although you will no longer be able to move it.

Osteotomy

In young, active people in whom a knee joint replacement would fail due to excessive use one can consider an operation called an osteotomy. This involves adding or removing a small section of bone either above or below your knee joint.  This helps realign your knee so your weight is no longer focused on the damaged part of your knee. An osteotomy can relieve your symptoms of osteoarthritis, although you may still need knee replacement surgery eventually as you grow old

Joint replacement surgery

Joint replacement therapy is most commonly carried out to replace hip and knee joints. It involves replacing a damaged, worn or diseased joint with an artificial joint made of special plastics and metal.

For most people, a replacement hip or knee will last for at least 20 years, especially if it is cared for properly and not put under too much strain.

Dr G K Sudhakar Reddy is a Sr Consultant Orthopaedic Surgeon at Citizens Speciality Hospitals, Hyderabad

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