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Too much of calcium in brain may cause Parkison's disease, says study

Agencies
February 21, 2018

Washington, Feb 21: A new study has found excessive calcium levels in the brain are behind Parkinson's disease.

The findings of the international team, led by the University of Cambridge, represent another step towards understanding how and why people develop Parkinson's.

They found that calcium can mediate the interaction between small membranous structures inside nerve endings, which are important for neuronal signalling in the brain, and alpha-synuclein, the protein associated with Parkinson's disease.

Excess levels of either calcium or alpha-synuclein may be what starts the chain reaction that leads to the death of brain cells.

Parkinson's disease is one of a number of neurodegenerative diseases caused when naturally occurring proteins fold into the wrong shape and stick together with other proteins, eventually forming thin filament-like structures called amyloid fibrils. These amyloid deposits of aggregated alpha-synuclein, also known as Lewy bodies, are the sign of Parkinson's disease.

Curiously, it hasn't been clear until now what alpha-synuclein actually does in the cell: why it's there and what it's meant to do. It is implicated in various processes, such as the smooth flow of chemical signals in the brain and the movement of molecules in and out of nerve endings, but exactly how it behaves is unclear.

"Alpha-synuclein is a very small protein with very little structure, and it needs to interact with other proteins or structures in order to become functional, which has made it difficult to study," said senior author Dr Gabriele Kaminski Schierle from Cambridge's Department of Chemical Engineering and Biotechnology.

Thanks to super-resolution microscopy techniques, it is now possible to look inside cells to observe the behaviour of alpha-synuclein. To do so, Kaminski Schierle and her colleagues isolated synaptic vesicles, part of the nerve cells that store the neurotransmitters which send signals from one nerve cell to another.

In neurons, calcium plays a role in the release of neurotransmitters. The researchers observed that when calcium levels in the nerve cell increase, such as upon neuronal signalling, the alpha-synuclein binds to synaptic vesicles at multiple points causing the vesicles to come together. This may indicate that the normal role of alpha-synuclein is to help the chemical transmission of information across nerve cells.

"This is the first time we've seen that calcium influences the way alpha-synuclein interacts with synaptic vesicles," said Dr Janin Lautenschlger, the paper's first author. "We think that alpha-synuclein is almost like a calcium sensor. In the presence of calcium, it changes its structure and how it interacts with its environment, which is likely very important for its normal function."

"There is a fine balance of calcium and alpha-synuclein in the cell, and when there is too much of one or the other, the balance is tipped and aggregation begins, leading to Parkinson's disease," said co-first author Dr Amberley Stephens.

The imbalance can be caused by a genetic doubling of the amount of alpha-synuclein (gene duplication), by an age-related slowing of the breakdown of excess protein, by an increased level of calcium in neurons that are sensitive to Parkinson's, or an associated lack of calcium buffering capacity in these neurons.

Understanding the role of alpha-synuclein in physiological or pathological processes may aid in the development of new treatments for Parkinson's disease. One possibility is that drug candidates developed to block calcium, for use in heart disease for instance, might also have potential against Parkinson's disease.

The findings have been reported in the journal Nature Communications.

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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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Agencies
March 15,2020

Should you let your babies "cry it out" or rush to their side? Researchers have found that leaving an infant to 'cry it out' from birth up to 18 months does not adversely affect their behaviour development or attachment.

The study, published in the Journal of Child Psychology and Psychiatry, found that an infant's development and attachment to their parents is not affected by being left to "cry it out" and can actually decrease the amount of crying and duration.

"Only two previous studies nearly 50 or 20 years ago had investigated whether letting babies 'cry it out' affects babies' development. Our study documents contemporary parenting in the UK and the different approaches to crying used," said the study's researcher Ayten Bilgin from the University of Warwick in the UK.

For the study, the researchers followed 178 infants and their mums over 18 months and repeatedly assessed whether parents intervened immediately when a baby cried or let the baby let it cry out a few times or often.

They found that it made little difference to the baby’s development by 18 months.

The use of parent’s leaving their baby to ‘cry it out’ was assessed via maternal report at term, 3, 6 and 18 months and cry duration at term, 3 and 18 months.

Duration and frequency of fussing and crying was assessed at the same ages with the Crying Pattern Questionnaire.

According to the researchers, how sensitive the mother is in interaction with their baby was video-recorded and rated at 3 and 18 months of age.

Attachment was assessed at 18 months using a gold standard experimental procedure, the strange situation test, which assesses how securely an infant is attached to the major caregiver during separation and reunion episodes.

Behavioural development was assessed by direct observation in play with the mother and during assessment by a psychologist and a parent-report questionnaire at 18 months.

Researchers found that whether contemporary parents respond immediately or leave their infant to cry it out a few times to often makes no difference on the short - or longer term relationship with the mother or the infants behaviour.

This study shows that 2/3 of mum's parent intuitively and learn from their infant, meaning they intervene when they were just born immediately, but as they get older the mother waits a bit to see whether the baby can calm themselves, so babies learn self-regulation.

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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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