A new study has found that chemotherapy may also affect the way the body builds new muscle.The findings of the study were published in the ‘American Journal of Physiology-Cell Physiology’. According to the researchers, it was previously known that chemotherapy drugs can affect the mitochondria within cells, which can cause the loss of muscle tissue via a process called oxidative stress.
In their new study, the researchers studied three different chemotherapy drugs in cultured muscle cells at levels too low to trigger oxidative stress. They found that the muscle cells were still affected by the lower levels of drugs — this time by interfering with the process that builds muscle, called protein synthesis.
Gustavo Nader, associate professor of kinesiology, said that while the findings need to be confirmed in humans, they could have implications for cancer treatment in the future.
“Eventually, it may be that the implementation of cancer treatments should consider that even at low doses that do not cause oxidative stress, some chemotherapy drugs may still promote the loss of muscle tissue. The tumour is already making you weak, it’s contributing to the loss of muscle mass, and the chemo drugs are helping the tumour to accomplish that,” Nader said.
Additionally, Nader said the results also have the potential to change how health care professionals think about the ways chemotherapy affects the body.
“For a long time, people thought the problem with chemo and muscle loss was an issue with degrading the proteins that already existed in the muscle. So, a lot of research and treatments in the past had the goal of preventing protein degradation. But our study points to there also being a problem with protein synthesis, or the building of new muscle proteins, as well,” Nader said.
Nader said that in addition to having implications for chemotherapy treatment, the findings could also ultimately change the way health care professionals think about other, nonpharmaceutical cancer treatments and programs.
According to Nader, people with cancer are often recommended to exercise as a way to build up muscle they’ve lost due to their illness and treatment. But if chemotherapy also affects the way the body builds new muscle, that will have to be taken into consideration when designing exercise programs.
“If you’re still receiving chemotherapy while going through an exercise rehabilitation program, it’s possible that chemo could impede your progress. During exercise interventions, the muscles need to make ribosomes, which then build new proteins. But if the drug is blocking that, the rehab might not be successful. The implications of this work could be huge, and I think we’re beginning to see the tip of the iceberg,” Nader explained.
For the study, the researchers looked at the effects of three commonly used chemotherapy drugs — paclitaxel, doxorubicin and marizomib — on muscle cells grown in their lab. They applied enough of each drug to affect the cells without triggering oxidative stress, a process already known to affect muscle cells.
The drugs were applied to the cells for up to 48 hours, and in all three cases, the process of making new ribosomes was affected. Because ribosomes are essential for protein synthesis, these new findings uncover one way in which chemotherapy affects the making of muscle proteins.
“We chose to do this study in cultured cells because in a living organism, chemotherapy also affects nonmuscle cells like those in the pancreas and liver, which can then trigger their own processes that can also affect muscle cells,” Nader said.
“We wanted a very controlled environment with only the muscle cells and chemotherapy drugs so we can examine very precisely how they interact,” Nader concluded.
The National Institutes of Health helped support this research.
In their new study, the researchers studied three different chemotherapy drugs in cultured muscle cells at levels too low to trigger oxidative stress. They found that the muscle cells were still affected by the lower levels of drugs, this time by interfering with the process that builds muscle, called protein synthesis.
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DIABETES MEDICATION THAT MAY REVOLUTIONISE HEART FAILURE TREATMENT
A study conducted by the University of East Anglia has found a diabetes medication that is the first to help people with heart failure and could revolutionize its treatment.
The research has been published in the ‘European Journal of Preventive Cardiology’. Early research had shown that Sodium-glucose co-transporter-2 (SGLT2) inhibitors could help around half of heart failure patients—those with a condition known as reduction ejection fraction.
But new findings have shown that the medication could be beneficial for all heart failure patients — including those with the second type of heart failure called the preserved ejection fraction. It is the first drug to provide a real benefit in terms of improving outcomes for these patients. And the research team said that it will revolutionise treatment options.
Lead researcher Prof Vass Vassiliou, from UEA’s Norwich Medical School and an Honorary Consultant Cardiologist at the Norfolk and Norwich University Hospital, said, “Heart failure is a condition where the heart is not pumping as well as it should, and it affects about one million people in the UK. There are two types of heart failure. Heart Failure with a reduction in ejection fraction happens when the heart is unable to pump blood around the body due to a mechanical issue. And heart failure with preserved ejection fraction happens when, despite the heart pumping out blood well, it is not sufficient to provide oxygen to all the parts of the body.”
“Patients are equally split between the two types of heart failure. For many years there was not a single medicine that could improve the outcome in patients with the second type of heart failure — those patients with preserved ejection fraction,” Vass added.
This type of heart failure had puzzled doctors, as every medicine tested showed no benefit.
“One class of heart medication, called SGLT2 inhibitors, was initially used for patients with diabetes. However, it was noticed that it also helped patients who had heart failure. Previous studies had shown that this medication would be beneficial in heart failure with reduced ejection fraction. But we found that it can also help heart failure patients with preserved ejection fraction,” Vass said.
SGLT2 inhibitors are more commonly known under their trade-names Forxiga (Dapagliflozin), Invokana (Canagliflozin), and Jardiance (Empagliflozin).
The research team undertook a meta-analysis of all studies published in the field and brought together data from almost 10,000 patients. They used statistical modelling to show the specific effect of these medicines. Prof Vassiliou said, “We found that patients taking SGLT2 inhibitors were 22 per cent less likely to die from heart-related causes or be hospitalised for heart failure exacerbation than those taking placebo.”
“This is very important because this is the first medication that can provide a benefit to this previously untreatable group of patients — in terms of heart-related deaths or hospitalisation. This is the first medication that can really improve the outcomes for this patient group and it will revolutionize the treatment offered to heart failure patients,” he added.
Study finds de-cluttering might not help dementia patients
According to a study conducted by the University of East Anglia, a clutter-free environment may not help people with dementia in carrying out daily tasks.
The research has been published in the ‘Alzheimer Disease & Associated Disorders Journal’. Researchers studied whether people with dementia were better able to carry out tasks, such as making a cup of tea, at home—surrounded by their usual clutter—or in a clutter-free environment.
They were surprised to find that participants with moderate dementia performed better when surrounded by their usual clutter. But the different environments made no difference to people with mild and severe dementia, who were able to perform at the same level in both settings. Prof Eneida Mioshi, from UEA’s School of Health Sciences, said, “The majority of people with dementia live in their own home and usually want to remain living at home for as long as possible. So it’s really important to know how people with dementia can be best supported at home — one possible route would be by adapting the physical environment to best suit their needs.”
“As dementia progresses, people gradually lose their ability to carry out daily tasks due to changes in their cognitive, perceptual and physical abilities. Participation in daily tasks could then be improved by adapting the person’s environment,” Mioshi added.
“To this end, we wanted to investigate the role of clutter in activity participation, given the potential to use de-cluttering to support people with dementia to continue to be independent. Environmental clutter has been defined as the presence of an excessive number of objects on a surface or the presence of items that are not required for a task,” Mioshi continued.
“It is generally assumed that a person with dementia will be better able to carry out daily tasks when their home space is tidy and clutter-free. However there has been very little research to really test this hypothesis,” Mioshi said.
“We wanted to see whether clutter was negatively affecting people with dementia. So we studied how people at different stages of dementia coped with carrying out daily tasks at home, surrounded by their usual clutter, compared to in a clutter-free setting — a specially designed home research lab.” Mioshi explained.
Occupational therapist and PhD student Julieta Camino carried out the study with 65 participants who were grouped into those with mild, moderate and severe dementia. They were asked to carry out daily tasks including making a cup of tea and making a simple meal, both at their own home and at UEA’s specially designed NEAT research bungalow —a fully furnished research facility that felt just like a domestic bungalow.
The researchers evaluated the performance of activities in both settings, and also measured the amount of clutter in the participants’ homes. Meanwhile, the NEAT home setting was completely clutter-free. Julieta Camino, also from UEA’s School of Health Sciences, said, “We thought that the complete absence of clutter in our research bungalow would play a beneficial role in helping people with dementia with daily living activities. But we were wrong.”
“We were surprised to find that overall, people with moderate dementia, in particular, performed daily tasks better at home — even though their homes were significantly more cluttered than our research bungalow,” Camino added.
“And it didn’t seem to make any difference how cluttered the participant’s home was. The only factor that contributed to how well they could carry out tasks at home was their level of cognition—with those with severe dementia encountering the same difficulties to perform the tasks at home and in the research bungalow,” Camino explained. Sian Gregory, Research Information Manager at Alzheimer’s Society, said, “We can sometimes make assumptions about what might help someone with dementia who’s living at home, like de-cluttering so they can concentrate on tasks like making a cup of tea. But, as this study shows, our ideas might not always be right.”
“Challenging assumptions is so important for carers to understand how to help someone with dementia to live well in their environment.” Gregory concluded.
WHAT IS OBSTRUCTIVE SLEEP APNEA (OSA)?
Sleep apnea and hypopnea is a sleep disorder in which cessation or reduction of respiratory effort at the nostril level for a few seconds to a few minutes. It is subdivided into central, obstructive and mixed types. Obstructive sleep apnea (OSA) is the commonest subtype. A sedentary lifestyle, faulty eating habits and lack of physical activities are the predisposing factors for obesity. The collection of fat within and around the upper aerodigestive tract reduces the dimensions of airway lumen which increases the turbulence in the air current. Snoring is induced by turbulent airflow during sleep. The snoring loudness increases with severity of airway narrowing. The anatomical abnormalities (nasal, nasopharyngeal, oropharyngeal, hypopharyngeal and laryngeal) are generally responsible for OSA in young patients. Abnormal anatomy can worsen the symptoms of obesity-related OSA. The commonly found anatomical abnormalities are deviation of the nasal septum, hypertrophy of inferior turbinates, adeno-tonsillar hypertrophy, retrognathia, weak epiglottis & mass lesions of upper aerodigestive tract (nasal polyposis, bulky tongue). The reduced muscle strength secondary to the fat deposition in and around the upper aerodigestive tract is unable to maintain the adequate airway lumen required for healthy sleep. The moderate to excessive narrowing of airway lumen, easy collapsibility pharyngeal part of airway and induced negative pressure distal to the site of obstruction generates partial to complete blockage of the airway. The oxygen level in blood decreases in OSA due to reduced volume of available air for gas exchange at lung alveoli level. The arousal episodes occur during sleep due to induced signals from the brain when blood oxygen level reaches below a threshold level. Poor sleep induces excessive daytime sleepiness, morning headache, dry mouth, inattentiveness and irritability are the common presenting symptoms. OSA has a great impact on quality of life at school, working place and at home. Day time sleepiness increases the chances of road traffic and household accidents. The induced negative pressure in the airway, episodic fall in blood oxygen level affects almost all of the body systems. OSA increases the risk of stroke, and heart attack by many folds. Polysomnography helps in differentiating OSA from other mimicking diseases.
The multidisciplinary approach is required to manage the OSA. The detailed airway assessment is required from the ENT doctor for anatomical features. The site of airway narrowing is determined by a combination of clinical assessment with site localizing investigations. Apneograph, sleep MRI and DISE are investigations used by ENT surgeons to localise the site of obstruction. Site-directed surgery increases the long-term effectiveness of surgery. The majority of anatomical abnormalities are correctable by surgical intervention. Young age OSA can be completely reversed by surgical correction in abnormal anatomy patients. The severity of obesity related to OSA can be reduced by a healthy lifestyle, regular exercise, a balanced diet and correction of the sleeping position. PAP therapy is mostly followed treatment for obesity related OSA. The machine maintains the blood oxygen level during obstructive episodes but the long term compliance falls around 50 percent. The correction of abnormal anatomy can remove and/or increase the compliance of PAP therapy. Surgical success is persistent if an OSA patient follows a healthy lifestyle.
The author is Additional Professor (ENT), at AIIMS, New Delhi.
RESEARCHERS DEVELOP CHEWING GUM TO REDUCE SARS-COV-2 TRANSMISSION
The research team is currently working toward obtaining permission to conduct a clinical trial to evaluate whether the approach is safe and effective when tested in people infected with SARS-CoV-2.
A team of researchers has developed a chewing gum that is laced with a plant-grown protein serving as a “trap” for the SARS-CoV-2 virus and could reduce its transmission.
The study has been published in the ‘Molecular Therapy Journal’. The work, led by Henry Daniell at Penn’s School of Dental Medicine and performed in collaboration with scientists at the Perelman School of Medicine and School of Veterinary Medicine, as well as at The Wistar Institute and Fraunhofer USA, could lead to a low-cost tool in the arsenal against the Covid-19 pandemic.
“SARS-CoV-2 replicates in the salivary glands, and we know that when someone who is infected sneezes, coughs or speaks some of that virus can be expelled and reach others,” said Daniell.
“This gum offers an opportunity to neutralise the virus in the saliva, giving us a simple way to possibly cut down on a source of disease transmission,” he added.
Vaccinations for Covid-19 have helped change the course of the pandemic but haven’t stamped out transmission. Even people who are fully vaccinated can still become infected with SARS-CoV-2 and, according to recent research, can carry a viral load similar to those who are unvaccinated.
Prior to the pandemic, Daniell had been studying the angiotensin-converting enzyme 2 (ACE2) protein in the context of treating hypertension. His lab had grown this protein, as well as many others that may have therapeutic potential, using a patented plant-based production system. By bombarding plant material with the DNA of target proteins, they coaxed plant chloroplasts to take up the DNA and begin growing the proteins. The plant material, freeze-dried and ground-up, could be used as a means of delivering the protein. This system has the potential to avoid the usual obstacles to protein drug synthesis: namely, an expensive production and purification process.
Daniell’s past work on ACE2 proved fortuitous in the context of the Covid-19 pandemic. The receptor for ACE2 on human cells also happened to bind the SARS-CoV-2 spike protein. Other research groups had shown that injections of ACE2 could reduce viral load in people with severe infections.
Meanwhile, another line of work by Daniell and Penn Dental Medicine colleague Hyun (Michel) Koo had involved research to develop a chewing gum infused with plant-grown proteins to disrupt dental plaque. Pairing his insights about ACE2 with this technology, Daniell wondered if such a gum, infused with plant-grown ACE2 proteins, could neutralize SARS-CoV-2 in the oral cavity.
To find out, he reached out to Ronald Collman at Penn Medicine, a virologist and pulmonary and critical care doctor whose team, since the early stages of the pandemic, had been collecting blood, nasal swabs, saliva, and other biospecimens from Covid patients for scientific research.
“Henry contacted me and asked if we had samples to test his approach, what kind of samples would be appropriate to test, and whether we could internally validate the level of SARS-CoV-2 virus in the saliva samples,” Collman said.
“That led to a cross-school collaboration building on our microbiome studies,” he added.
To test the chewing gum, the team grew ACE2 in plants, paired with another compound that enabled the protein to cross mucosal barriers and facilitated binding, and incorporated the resulting plant material into cinnamon-flavoured gum tablets. Incubating samples obtained from nasopharyngeal swabs from Covid-positive patients with the gum showed that the ACE2 present could neutralise SARS-CoV-2 viruses.
Those initial investigations were followed by others at The Wistar Institute and Penn Vet, in which viruses, less-pathogenic than SARS-CoV-2, were modified to express the SARS-CoV-2 spike protein. The scientists observed that the gum largely prevented the viruses or viral particles from entering cells, either by blocking the ACE2 receptor on the cells or by binding directly to the spike protein.Finally, the team exposed saliva samples from Covid-19 patients to the ACE2 gum and found that levels of viral RNA fell so dramatically to be almost undetectable. The research team is currently working toward obtaining permission to conduct a clinical trial to evaluate whether the approach is safe and effective when tested in people infected with SARS-CoV-2. “Henry’s approach of making the proteins in plants and using them orally is inexpensive, hopefully scalable; it really is clever,” Collman said.
Though the research is still in the early stages of development, if the clinical trials prove that the gum is safe and effective, it could be given to patients whose infection status is unknown or even for dental check-ups when masks must be removed, to reduce the likelihood of passing the virus to caregivers. “We are already using masks and other physical barriers to reduce the chance of transmission,” said Daniell.
Bowel cancer patients at higher risk of clinical depression
According to a new study, the prevalence of depression in bowel cancer patients is up to five years after surgery to treat their cancer.
The findings have been published in the ‘Colorectal Disease Journal’. A research team, led by the University of Southampton and funded by Macmillan Cancer Support, surveyed 872 adult patients with non-metastatic colorectal cancer before surgery and conducted follow-up surveys at regular intervals until 60 months post-surgery.
Lead author Dr Lynn Calman, Associate Professor in Nursing at the University of Southampton, said, “Depression in people living with colorectal cancer is an important clinical problem. Our study shows that the level of depression exceeds that of the general population over time. The research has also helped us to identify important time points where certain patients are at a high risk of depression which can inform strategies for recognition and referral for appropriate support.”
The results of the survey showed that before surgery over a fifth of participants (21 percent) reported clinically significant levels of depression, which reduced to 14 percent at 5 years. Risk factors identified before surgery that predicted subsequent depression were pre-existing clinically significant depression and anxiety, previous mental health service use, low confidence to manage illness-related problems, poor health, and low social support.
Further analysis of the findings suggested that people with bowel cancer who had reduced levels of social support are nearly 2.5 times more likely to also have depression. Among participants with the highest levels of social support at diagnosis, 16 percent developed clinical levels of depression within five years of their cancer treatment, compared with 37 percent of those with lower levels of social support.
While the above results are based on people’s experiences pre-Covid, evidence suggested the social isolation linked to the pandemic could be further worsening the mental health of people with cancer. The research team are currently carrying out another study into the impact of Covid-19, also funded by Macmillan Cancer Support; interim results from this have found that four in five (81 percent) cancer patients surveyed remained at home at all times in the pandemic, and nearly half (45 percent) of these have experienced at least two serious psychological impacts from the pandemic, such as feeling afraid, depressed or helpless.
Dany Bell, Strategic Advisor for Treatment, Medicines and Genomics at Macmillan Cancer Support said, “We know that for many people, being diagnosed with cancer and going through treatment is one of the scariest things they have ever faced, and this can often have a serious impact on people’s mental health.”
“Cancer affects people differently and at Macmillan, we’re here to ensure everyone living with cancer gets the support that’s right for them. We’re urging anyone in need of help – or simply someone to talk to – to get in touch with the trained nurses and advisors on our Support Line who are available at the end of the phone, seven days a week,” Bell added.
The new findings also showed that people with bowel cancer who had undergone neoadjuvant chemotherapy were also more likely to experience depression, perhaps explained by the fact these patients usually face more complex treatment, side effects and increased treatment time.
Dr Calman continued, “in this study, we investigated risk factors of depression at two key time points: close to diagnosis before surgery and two years after surgery, when routine oncological check-ups end.”
“Depression in people living with cancer can lead to poor health and wellbeing and this has an impact on long-term outcomes. Recognising those colorectal cancer patients who are at a higher risk and referring them to the right support services could therefore lead to overall improved outcomes for patients,” Calman concluded.
THE SIGNIFICANCE OF MAINTAINING DENTAL HEALTH DURING DIABETES
Diabetes is the most common lifestyle disease in today’s world both in India and abroad in children and adults in men and women.
Diabetes is a disease that occurs when your blood glucose, also called blood sugar, is too high. Blood glucose is your main source of energy and comes from the food you eat. Insulin, a hormone made by the pancreas, helps glucose from food get into your cells to be used for energy. Sometimes your body doesn’t make enough—or any—insulin or doesn’t use insulin well. Glucose then stays in your blood and doesn’t reach your cells.
Over time, having too much glucose in your blood can cause health problems. Although diabetes has no cure, you can take steps to manage your diabetes and stay healthy. The most common types of diabetes are type 1, type 2, and gestational diabetes.
Too much glucose, also called sugar, in your blood from diabetes can cause pain, infection, and other problems in your mouth. Glucose is present in your saliva—the ﬂuid in your mouth that makes it wet. When diabetes is not controlled, high glucose levels in your saliva help harmful bacteria grow.
These bacteria combine with food to form a soft, sticky ﬁlm called plaque. Plaque also comes from eating foods that contain sugars or starches. Some types of plaque cause tooth decay or cavities. Other types of plaque cause gum disease and bad breath.
Gum disease can be more severe and take longer to heal if you have diabetes. In turn, having gum disease can make your blood glucose hard to control.
SOME COMMON PROBLEMS IN DIABETES
Tooth decay (cavities): Your mouth naturally contains many types of bacteria. When starches and sugars in foods and beverages interact with these bacteria, a sticky film known as plaque forms on your teeth. The acids in plaque attack the surfaces of your teeth (enamel and dentin). This can lead to cavities and gum disease. The higher your blood sugar level, the greater the supply of sugars and starches — and the more acid wears away at your teeth.
Early gum disease (gingivitis): Diabetes reduces your ability to fight bacteria. If you don’t remove plaque with regular brushing and flossing, it’ll harden under your gum line into a substance called tartar (dental calculus). The longer plaque and tartar remain on your teeth, the more they irritate the part of your gums around the base of your teeth, called the gingiva. In time, your gums become swollen and bleed easily. This is known as gingivitis.
Advanced gum disease (periodontitis): Left untreated, gingivitis can lead to a more serious infection called periodontitis, which destroys the soft tissue and bone that support your teeth. Eventually, periodontitis causes your gums and jawbone to pull away from your teeth, which in turn causes your teeth to loosen and possibly fall out. Periodontitis tends to be more severe among people who have diabetes because diabetes lowers the ability to resist infection and slows healing.
Thrush: People with diabetes may be more likely to develop thrush, which is a fungal infection caused by the yeast Candida albicans. Signs of thrush include painful white or red patches inside your mouth. Practicing good oral hygiene can help you avoid thrush.
Dry mouth (xerostomia): Some people with diabetes also experience a lack of saliva, a condition known as dry mouth. Without saliva to keep your mouth moist and bathe your teeth, you could be at risk of tooth decay, gum disease, and thrush.
It is important to take proper dental care to help prevent damage to your teeth and gums, and its very important to take diabetes and dental care seriously and there are some ways by following which you can take care of yourselves.
Make a commitment to manage your diabetes. Monitor your blood sugar level, and follow your doctor’s instructions for keeping your blood sugar level within your target range. The better you control your blood sugars, the less likely you are to develop gingivitis and other dental problems.
Brush your teeth at least twice a day. Brush in the morning, at night, and, ideally, after meals and snacks. Use a soft-bristled toothbrush and toothpaste that contains fluoride. Avoid vigorous or harsh scrubbing, which can irritate your gums.
Schedule regular dental visits. Visit your dentist at least twice a year for professional cleanings, X-rays, and checkups. Look for early signs of gum disease. Report any signs of gum disease — including redness, swelling, and bleeding gums — to your dentist. Also mention any other signs and symptoms, such as dry mouth, loose teeth, or mouth pain.
Smoking increases the risk of serious diabetes complications, including gum disease and ultimately, loss of your teeth. If you smoke, ask your doctor about options to help you quit.
The author is practising Cosmetic and Laser dental surgeon for 20 years. BDS MD Dental Lasers, Director Dentem & Associate Consultant Sir Ganga Ram Hospital.
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