To ramp up India’s fight against Covid-19, pharmaceutical company Cipla and CSIR-Indian Institute of Chemical Technology (IICT) have developed Ciplenza (indigenous version of Favipiravir drug) — a convenient and cost-effective drug for Covid treatment. While speaking exclusively to The Daily Guardian, S. Chandrasekhar, director, CSIRIICT, said that the medicine would hit the market next week. He also added that since discovering a drug in such a short time during the pandemic was not possible, they went for “repurposing” an existing drug, which would be cheaper and thus not out of the reach for common people. Excerpts:
Q. When do you think indigenous versions of Favipiravir will be available in the market?
A. The Favipiravir by Glenmark is already in the market. Our collaborator Cipla will make Ciplenza available next week.
Q. What is the concept of repurposing the drug? How is it useful in making Ciplenza?
A. Repurposing means using a drug which was initially discovered for a disease for another disease if symptoms and mode of action are the same. Favipiravir was initially discovered for influenza virus in Japan.
Q. What would be the cost of Ciplenza?
A. Now it is priced at Rs 68 per tablet but it will reduce further depending on the demand and supply.
Q. How much dosage has to be given to the patient?
A. It depends on the patient’s condition but the course is for 14 days: 3.6 gm for the first day and 1.6 gm from the second day.
Q. How did you source the chemicals and reduce the price of the drug?
A. The indigenous chemicals are completely sourced from Indian companies which have helped in bringing down the import dependency so that an affordable version of the drug could be made available for the country.
Q. What was the first thought in your mind about a drug when the pandemic broke out?
A . We had multiple thoughts like discovering a new drug which was not possible quickly; repurpose existing drugs which helped us to work on Favipiravir and Umifenovir and vaccine development which luckily has progressed very well.
Q. What are the challenges you are facing in drug supply during Covid-19 pandemic?
A. There are many challenges including supply chain disruption. Students and faculties had to work at odd conditions because of social distancing. Suddenly the workforce was required to be in isolation to protect them from getting Covid-positive. Also, several students and project staff were stuck at various places but now slowly they are joining.
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BLOOD PROTEINS COULD BE THE KEY TO A LONG AND HEALTHY LIFE: STUDY
As people age, their bodies begin to decline after they reach adulthood, which results in age-related diseases and death. A new research investigated which proteins could influence the ageing process.
Two blood proteins have been shown by scientists to influence how long and healthy a life people live. The findings have been published in the journal ‘Nature Aging’. Developing drugs that target these proteins could be one way of slowing the ageing process, according to the largest genetic study of ageing.
Many complex and related factors determined the rate at which people age and die, and these included genetics, lifestyle, environment and chance. Some people naturally had higher or lower levels of certain proteins because of the DNA they inherit from their parents. These protein levels could, in turn, affect a person’s health.
University of Edinburgh researchers combined the results of six large genetic studies into human ageing – each containing genetic information on hundreds of thousands of people,
Among 857 proteins studied, researchers identified two that had significant negative effects across various ageing measures.
People who inherited DNA that caused raised levels of these proteins were frailer, had poorer self-rated health and were less likely to live an exceptionally long life than those who did not.
The first protein, called apolipoprotein(a) (LPA), is made in the liver and has been thought to play a role in clotting. High levels of LPA can increase the risk of atherosclerosis—a condition in which arteries become clogged with fatty substances. Heart disease and stroke are also a possible outcome.
The second protein, vascular cell adhesion molecule 1 (VCAM1), is primarily found on the surfaces of endothelial cells – a single-cell layer that lines blood vessels. This protein, controlled vessels’ expansion and retraction – and function in blood clotting and the immune response.
Levels of VCAM1 increased when the body sent signals to indicate it has detected an infection, VCAM1 then allows immune cells to cross the endothelial layer, as seen for people who have naturally low levels of these proteins.
The researchers said that drugs used to treat diseases by reducing levels of LPA and VCAM1 could have the added benefit of improving quality and length of life.
One such example is a clinical trial that is testing a drug to lower LPA as a way of reducing the risk of heart disease. There were currently no clinical trials involving VCAM1, but studies in mice have shown how antibodies lowering this protein’s level improved cognition during old age.
Dr Paul Timmers, lead researcher at the MRC Human Genetics Unit at University of Edinburgh, said: “The identification of these two key proteins could help extend the healthy years of life. Drugs that lower these protein levels in our blood could allow the average person to live as healthy and as long as individuals who have won the genetic lottery and are born with genetically low LPA and VCAM1 levels.”
Professor Jim Wilson, Chair of Human Genetics at the University of Edinburgh’s Usher Institute, said: “This study showcases the power of modern genetics to identify two potential targets for future drugs to extend lifespan.
Study finds how the timing of dinner and genetics affect blood sugar control
We live in a day and age where very young children also get diagnosed with diabetes, despite being perfectly healthy. Blood sugar control, which is impaired in people with diabetes, is affected by factors like timing of meals relative to sleep and levels of melatonin, a hormone released at night that helps control sleep-wake cycles.
In research published in ‘Diabetes Care’, a team led by investigators at Massachusetts General Hospital (MGH), Brigham and Women’s Hospital (BWH) and the University of Murcia in Spain conducted a clinical trial to look for connections between these two factors. “We decided to test if late eating that usually occurs with elevated melatonin levels results in disturbed blood sugar control,” said senior author Richa Saxena, PhD, a principal investigator at the Center for Genomic Medicine at MGH.
For the randomised crossover study that included 845 adults from Spain, each participant fasted for eight hours and then for the next two evenings had first an early meal and then a late meal relative to their typical bedtime. The investigators also analyzed each participant’s genetic code within the melatonin receptor-1b gene (MTNR1B) because previous research had linked a variant (called the G-allele) in MTNR1B with an elevated risk of type 2 diabetes.
“In natural late eaters, we simulated early and late dinner timing by administering a glucose drink and compared effects on blood sugar control over two hours,” explained Saxena. “We also examined differences between individuals who were carriers or not carriers of the genetic variant in the melatonin receptor.”
The team found that melatonin levels in participants’ blood were 3.5-fold higher after the late dinner. The late dinner timing also resulted in lower insulin levels and higher blood sugar levels. (This connection made sense because insulin acted to decrease blood sugar levels.) In the late dinner timing, participants with the MTNR1B G-allele had higher blood sugar levels than those without this genetic variant.
“We found that late eating disturbed blood sugar control in the whole group. Furthermore, this impaired glucose control was predominantly seen in genetic risk variant carriers, representing about half of the cohort,” said lead author Marta Garaulet, PhD, a professor of physiology and nutrition in the Department of Physiology at the University of Murcia.
Experiments revealed that the high melatonin levels and carbohydrate intake associated with late eating impairs blood sugar control through a defect in insulin secretion.
“Our study results may be important in the effort towards prevention of type 2 diabetes,” said co-senior author Frank A.J.L. Scheer, PhD, MSc, director of the Medical Chronobiology Program at BWH. “Our findings are applicable to about a third of the population in the industrialised world who consume food close to bedtime, as well as other populations who eat at night, including shift workers, or those experiencing jetlag or night eating disorders, as well as those who routinely use melatonin supplements close to food intake.”
The authors noted that for the general population, it may be advisable to abstain from eating for at least a couple of hours before bedtime. “Genotype information for the melatonin receptor variant may further aid in developing personalised behavioral recommendations,” said Saxena. “Notably, our study does not include patients with diabetes, so additional studies are needed to examine the impact of food timing and its link with melatonin and receptor variation in patients with diabetes,” he concluded.
Food intervention as good as medications for lowering cholesterol
A new study has found that for many individuals a “food as medicine” approach can be as effective as medications for cholesterol-lowering, without the need for drastic lifestyle changes.
“Based on the outcomes seen in our study, using this type of food as medicine approach expands the options for medical professionals and patients,” said Stephen Kopecky, M.D, FACC, cardiologist and Director of the Statin Intolerance Clinic at Mayo Clinic.
“Many patients who are unwilling or unable to take statin drugs may be able to help manage their high cholesterol, or hyperlipidemia with a realistic food-based intervention,” he added.
Substituting only a small portion of what hyperlipidemic patients were eating with Step One Foods (a twice per day dosed eating system with products precisely formulated to help lower LDL cholesterol), researchers found rapid and highly significant cholesterol reductions. Ultimately, participants saw an average 9 per cent decrease in LDL (bad) cholesterol within 30 days, with some experiencing more than 30 per cent LDL cholesterol reductions.
This first of its kind free-living multicenter international study was conducted at Mayo Clinic in Rochester, Minnesota and Richardson Centre at the University of Manitoba in Winnipeg, Manitoba. The study which followed a randomized, double-blind crossover design, was conducted by Soumya Alias, University of Manitoba; Peter J. H. Jones, Richardson Centre for Functional Foods and Nutraceuticals; Elizabeth Klodas, M.D., founder and Chief Medical Officer of Step One Foods and Stephen L. Kopecky, M.D, Mayo Clinic.
During the intervention phase, participants ate an assortment of whole food based snacks from Step One Foods – ranging from chocolate bars to strawberry-banana smoothies – that were made entirely from real ingredients, such as walnuts, and are known to positively impact cholesterol profiles. These study foods were specifically formulated to deliver a nutrient compendium of whole food fiber, plant sterols, ALA omega 3 fatty acids and antioxidants. Participants were instructed to consume these snacks in exchange for similar foods they were consuming already.
The researchers also compared the results of Step One Foods with comparable leading grocery stores brands that are considered “better for you” foods. Each participant consumed these leading brands for 30 days. No cholesterol reductions were seen during this phase of the study.
“Nutrition contributes to 5 of the 7 modifiable risk factors for heart disease, but getting patients to change diet is incredibly challenging,” said Elizabeth Klodas MD, FACC.
“This study underscores what’s possible when we succeed. The implications of attaining such a significant cholesterol impact from a small food based intervention are profound. We could change the health of our country in 30 days,” she added.
The Study has been published in the ‘Journal of Nutrition ‘.
ULTRASOUND STIMULATION IS EFFECTIVE THERAPY FOR ALZHEIMER’S DISEASE: STUDY
An increase in average life expectancy in many parts of the world has made certain age-related diseases more common. Alzheimer’s disease (AD), is one of them, being extremely prevalent within ageing societies in Japan, Korea, and various European countries. Currently, there is no cure or an effective strategy to slow down the progression of AD.
Fortunately, a recent study, published in ‘Translational Neurodegeneration’ by a team of scientists has shown a ray of hope.
The scientists at the Gwangju Institute of Science and Technology (GIST) in Korea demonstrated that there might be a way to combat AD by using “ultrasound-based gamma entrainment,” a technique that involved syncing up a person’s (or an animal’s) brain waves above 30 Hz (called “gamma waves”) with an external oscillation of a given frequency. The process happens naturally by exposing a subject to a repetitive stimulus, such as sound, light, or mechanical vibrations.
Previous studies on mice showed that gamma entrainment could fight off the formation of b-amyloid plaques and tau protein accumulations — a standard hallmark of the onset of AD. In this recent paper, the GIST team demonstrated that it is possible to realize gamma entrainment by applying ultrasound pulses at 40 Hz, i.e., in the gamma frequency band, into the brain of an AD-model mice.
One of the main benefits of this approach was in the way it was administered. Associate Professor Jae Gwan Kim, who led the study alongside Assistant Professor Tae Kim, explained: “Compared with other gamma entrainment methods that rely on sounds or flickering lights, ultrasound can reach the brain non-invasively without disturbing our sensory system. This makes ultrasound-based approaches more comfortable for the patients.”
As their experiments showed, mice exposed to ultrasound pulses for two hours daily for two weeks had reduced b-amyloid plaque concentration and tau protein levels in their brain. Furthermore, electroencephalographic analyses of these mice also revealed functional improvements, suggesting that brain connectivity also benefited from this treatment. Moreover, the procedure did not cause any type of microbleeding (brain hemorrhages), indicating that it was not mechanically harmful to brain tissue.
Overall, the promising results of this study could pave the way to innovative, non-invasive therapeutic strategies for AD without side effects, as well as help treat other conditions besides AD. Dr. Tae Kim remarked: “While our approach can significantly improve the quality of life of patients by slowing the progression of AD, it could also offer a new solution to other neurodegenerative diseases, such as Parkinson’s disease.”
WHAT IS THE RIGHT TIME FOR BOOSTER DOSE OF COVID VACCINE?
Opening the third or booster dose for the healthcare and frontline workers as well as senior citizens with comorbidities will help the country protect its high-risk population, given the rising concerns of a third wave due to a variant of concern, Omicron.
India has achieved the landmark of administering over 140 crores COVID-19 vaccination to its population, which has been globally acclaimed as a phenomenal achievement. India’s vaccination programme had started on 16 January 2021, and all vulnerable groups of the population received both doses in the first half of 2021. As a result of this, a significant majority of the population have developed antibodies, combined with those who have recovered from naturally acquired infection.
However, there is uncertainty regarding the duration of protection being offered as a result of the probable waning away of antibodies. Also, there have been instances of individuals being diagnosed with COVID despite having had two doses of COVID-19 vaccination. It is promising to note that the Indian government has considered the recommendation of the scientific committee of AHPI to introduce booster dose, to at least the vulnerable group, to begin with. The recommendation was made by the AHPI scientific committee, which deliberated on the subject in November 2021. The government is considering enabling the booster dose to be given to eligible people voluntarily. Ample stock of COVID-19 vaccine is available with the private sector also, and these may be effectively utilised for this purpose.
Prime Minister Narendra Modi recently announced the launch of the vaccination campaign for children in the age group of 15-18 years who form a major part of the unvaccinated, susceptible population in India. Moreover, opening the third or Booster dose for the healthcare and frontline workers as well as the senior citizens with comorbidities will help the country to protect its high-risk population, given the rising concerns of a third wave due to a variant of concern- Omicron.
The third or booster dose will help India to fight against the COVID-19 pandemic and will aid in checking the severity of Omicron. Unfortunately, the second wave had resulted in unprecedented death and destruction in its wake all over the country. It is time to take urgent action to enable the nation to be in a better position to face or avoid future waves. Apart from social distancing and masking, universal vaccination is a viable answer to prevent future waves. While the majority of the people in metro areas have relatively easy access to immunisation, a more focused effort for rural areas of the country is also urgently needed.
AHPI has been at the forefront, supporting the government at every stage during the pandemic. The private sector provides over 70% of healthcare, and in both the first and second waves, private healthcare has been a strong supporter, treating the majority of patients across the country. The private sector has also been partnering with the Government to ensure that as many possible adults are vaccinated before any future waves.
The scientific committee of AHPI has also suggested that the gap between the second dose and this third dose should be between 6 to 12 months.
With the emergence of new variants, the need for a third dose that may operate as a booster to the body’s immune system was felt all across the world, and numerous countries began delivering this third dose, also known as a booster dose.
Finally, studies have shown that immunity is protecting people against the effects of COVID-19. Hence, the priority should be universal vaccination. The virus thrives due to a lack of adequate vaccine coverage. When a virus infects and reproduces in tens of thousands of people, it has the potential to mutate, leading to the emergence of new variants. To prevent more VOCs from appearing, India needs to get ahead of the virus. If India achieves Universal Vaccination, it can hope to lessen the impact of the pandemic. The booster dose is one step forward towards safeguarding vulnerable and other groups.
The writer is President, Association of Healthcare Providers-India (AHPI).
SOCIALLY ISOLATED OLDER ADULTS MAY HAVE FEWER TEETH: STUDY
Researchers have found that older people who are socially isolated tend to lose their teeth more quickly than those with more social interaction.
The study involved observing older Chinese adults and was led by researchers at NYU Rory Meyers College of Nursing. The findings were published in ‘Community Dentistry and Oral Epidemiology.
“Our study suggests that maintaining and improving social connections may benefit the oral health of older adults,” said Xiang Qi, a PhD student at NYU Meyers and the study’s first author. “The findings align with previous studies demonstrating that structural indicators of social disconnection can have powerful effects on indicators of health and well-being,” he said.
Social isolation and loneliness in older adults have been major public health concerns around the world and are risk factors for heart disease, mental health disorders, cognitive decline, and premature death. In some countries, including the United States and China, up to one in three older adults were lonely, according to the World Health Organization. The COVID-19 pandemic had exacerbated these issues among older adults, as many in-person interactions had been interrupted to protect older adults from infection.
Social isolation and loneliness are related but different. Social isolation has been defined as having few social relationships or infrequent social contact with others, while loneliness referred to the feeling created by a lack of social connection.
“While social isolation and loneliness often go hand in hand, it’s possible to live alone and be socially isolated but to not feel lonely, or to be surrounded by people but still feel lonely,” said Bei Wu, Dean’s Professor in Global Health at NYU Meyers and the study’s senior author.
Older adults are also at risk for another health concern: losing teeth. In China, older adults aged 65 to 74 had fewer than 23 teeth on average (adults typically have 32 teeth, or 28 if wisdom teeth have been removed) and 4.5 per cent of this age group had lost all of their teeth.
Gum disease, smoking, lack of access to dental care, and chronic illnesses like diabetes and heart disease increase the risks of tooth loss. Missing teeth could have a significant impact on one’s quality of life, affecting nutrition, speech, and self-esteem.
To understand the relationship between social isolation, loneliness, and tooth loss in older adults in China, the researchers used the Chinese Longitudinal Healthy Longevity Survey to analyse data from 4,268 adults aged 65 and up. The participants completed surveys at three different time points (2011-12, 2014, and 2018), which captured measures of social isolation and loneliness, how many teeth people had and lost over the 7-year study, and other factors. More than a quarter (27.5 per cent) of the study participants were socially isolated, and 26.5 per cent reported feeling lonely.
The researchers found that higher levels of social isolation were associated with having fewer teeth and losing teeth more quickly over time, even when controlling for other factors such as oral hygiene, health status, smoking and drinking, and loneliness. Older adults who were socially isolated had, on average, 2.1 fewer natural teeth and 1.4 times the rate of losing their teeth than those with stronger social ties.
“Socially isolated older adults tend to be less engaged in social and health-promoting behaviours like physical activity, which could have a negative impact on their overall functioning and oral hygiene, as well as increase their risk for systemic inflammation,” said Wu. “This functional impairment seems to be a major pathway linking social isolation to tooth loss.”
Surprisingly, loneliness was not associated with the number of remaining teeth, nor with the rate of tooth loss.
“While social isolation can result in a lack of support that can affect health behaviours, for older adults who feel lonely, it’s possible that their social networks are still in place and can help them to keep up healthy behaviours,” said Qi.
The findings highlighted the importance of developing interventions to reduce social isolation.
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