esearch has shown that having the right gut microbes can reduce the risk of heart disease – if you’re a mouse. Now, our latest study, published in the European Heart Journal, shows that this might be true for humans, too.
Most people know that the risk factors for heart disease are high blood pressure, high cholesterol and smoking. But these factors are not very good at predicting heart disease in younger people, in women and in some ethnic groups.
A poor gut microbiome could be the missing risk factor we’ve been looking for.
One of the ways that the risk of heart attack or stroke is assessed is by measuring the hardening of the arteries. This measure, called arterial stiffness, is not strongly associated with high cholesterol or smoking, but it is closely related to inflammation.
Inflammation is our body’s normal response to injury, but when it is too high, in a way that is not a response to injury, it can cause many diseases, such as arthritis and eczema.
Studies have shown that the more inflammation a person has, the higher their risk of heart disease and of having artherosclerotic arteries.
Recently, several large clinical studies have shown that inflammation is a key factor in the development of heart disease and stiffening of the arteries.
But how can we reduce inflammation without fancy drugs? Avoiding obesity and smoking are a good start, but the good bacteria that live in our gut can also help.
We can improve our gut bacteria
The microbes that live in our gut seem to be important in preventing a number of diseases caused by inflammation such as psoriatic arthritis, diabetes and gut conditions like inflammatory bowel disease.
In all of these diseases, it has been found that there is a lack of diversity of healthy gut bacteria, which means there are fewer kinds of microbes.
In our study, we found that women with more hardening of the arteries have lower microbial diversity in their gut, and that the women with healthier arteries have more diversity.
Not only that, certain beneficial substances produced by microbes were also seen at higher levels in the blood of people with healthier arteries. This substance, indoleproprionic acid, has previously been shown to predict a lower risk of developing diabetes. Bacteria in the gut produce more indoleproprionic acid when a person eats a diet high in fibre.
Overall, we found that almost 10% of the amount arterial hardening was explained by the gut microbes and substances produced by the microbes. In comparison, cholesterol levels, smoking, diabetes and middle obesity explained less than 2% of this measure of risk of heart disease.
This is very exciting because, unlike genetic risks, which we can’t do much about, the microbes in the gut and the substances they produce can be changed.
One way to influence the gut microbes is to eat good bacteria. This can be done by eating probiotic foods or supplements, or by having a faecal transplant.
This method has worked for diabetes in a pilot study. Scientists gave gut microbes from healthy people to people with diabetes. After a few weeks, the diabetes improved and the microbes in the gut were changed. These type of studies could also be done for heart disease and other conditions.
Another way is to change what we eat. The good bacteria in our gut grow better when we eat a diet rich omega-3 (found in fish oil) or in dietary fibre, which is found in fruit and veg and is also particularly high in foods such as wholemeal bread, nuts, oats, beans and dark chocolate.
The links between gut microbes and our health are good news because we can do something to increase their diversity.
The Central government’s hesitance to introduce human papillomavirus (HPV) vaccine in the Universal Immunisation Programme (UIP) despite the recommendation of a high-level technical advisory group is resulting in thousands of cervical cancer deaths every year, statistics show. While healthcare professionals and vaccine advocacy groups rap policymakers for dilly-dallying on the issue, the number of potentially preventable deaths from HPV infections is surging at a quick pace.
According to data compiled by HPV Information Centre, a collaboration of The Catalan Institute of Oncology and the International Agency for Research on Cancer, India has one of the world’s highest burdens of HPV-related cancer. Cervical cancer is the second leading cause of cancer deaths among women here. More than 122,000 Indian women are diagnosed with cervical cancer and around 67,000 die from this disease each year, more than the country’s maternal mortality burden of 45,000. The National Technical Advisory Group on Immunisation (NTAGI), an advisory body that recommends vaccines for the country’s UIP, gave the green signal for the introduction of the HPV vaccine in the programme in December last year. But the proposal is yet to see the light of day.
“In spite of multiple warnings, the government remains unconvinced and many still doubt its efficacy. There are also concerns about the high cost factor. Recent reviews of vaccines have showed that they have high efficacy. It should be part of the immunisation programme regardless of current costs,” says Dr Meenakshi Ahuja, a leading gynecologist and obstetrician and a vocal supporter of HPV vaccination.
Two kinds of cervical cancer vaccines are currently available. Cervarix, manufactured by GlaxoSmithKline, is a bivalent vaccine that protects against infection by two HPV strains – type 16 and type 18. The other vaccine is Gardasil, manufactured by Merck Sharp and Dohme (MSD), which is a quadrivalent vaccine that provides protection against four HPV strains types 16, 18, 6 and 11. Types 6 and 11 cause genital warts that are additional risk factors for cervical cancer. India approved these two vaccines in 2008 and they have been available in the market. But the vaccines are priced at around Rs 3,000 for a single dose and are not affordable for the target population.
HPV vaccines sparked a furore in India in 2008 when 8 girls died after taking part in a clinical trial conducted by an American non-profit organisation with the Andhra Pradesh and Gujarat governments. A government enquiry later concluded that the deaths were unrelated to the vaccines. The Supreme Court is currently hearing a public interest litigation filed in 2012 raising questions about this trial and the vaccine. According to the ministry of health, the decision on who will make the HPV vaccines will depend on the verdict in this case.
The World Health Organisation issued an update on HPV vaccine safety last year, recording the findings of the Global Advisory Committee on Vaccine Safety that probed adverse events. The committee found that there was no evidence to suggest an association between HPV vaccine and the neurological and chronic fatigue disorders.
Health experts say that high cost, rather than doubts about its efficacy and safety, is acting as an impediment to HPV vaccination drive in the country. From 2006 to 2014, as many as 64 countries nationally, four countries sub-nationally and 12 overseas territories implemented HPV immunisation programmes. An estimated 118 million women had been targeted through those initiatives, but only 1 per cent were from low-income or lower-middle-income countries.
The HPV vaccine will soon have an Indian manufacturer which might reduce its cost substantially. Serum Institute of India is already conducting phase-III trials. Other domestic companies are also trying to develop similar vaccines.
But it is all a matter of political will, say health professionals. Delhi and Punjab have already incorporated the HPV vaccine into their public health programmes. “Women’s health issues should get more policy attention. If a vaccine is useful, the government should find resources for the expenses. It should be part of the routine childhood immunisation programme,” said Dr Arun Wadhwa, a well-known Delhi-based paediatrician who has more than 35 years of experience in the field.
Experts are of the view that all medicines have a certain amount of risks as well as benefits and the cost of the vaccine will come down once it is included in the immunisation drive. “In the case of HPV vaccine, the benefits outweigh the risks. It can save thousands of lives,” Dr Ahuja opined.
We’re not wired to feel safe all the time, but maybe one day we could be.
A recent study investigating the neurological basis of anxiety in the brain has identified ‘anxiety cells’ located in the hippocampus – which not only regulate anxious behaviour but can be controlled by a beam of light.
The findings, so far demonstrated in experiments with lab mice, could offer a ray of hope for the millions of people worldwide who experience anxiety disorders (including almost one in five adults in the US), by leading to new drugs that silence these anxiety-controlling neurons.
“We wanted to understand where the emotional information that goes into the feeling of anxiety is encoded within the brain,” says one of the researchers, neuroscientist Mazen Kheirbek from the University of California, San Francisco.
To find out, the team used a technique called calcium imaging, inserting miniature microscopes into the brains of lab mice to record the activity of cells in the hippocampus as the animals made their way around their enclosures.
These weren’t just any ordinary cages, either.
The team built special mazes where some paths led to open spaces and elevated platforms – exposed environments known to induce anxiety in mice, due to increased vulnerability to predators.
Away from the safety of walls, something went off in the mice’s heads – with the researchers observing cells in a part of the hippocampus called ventral CA1 (vCA1) firing up, and the more anxious the mice behaved, the greater the neuron activity became.
“We call these anxiety cells because they only fire when the animals are in places that are innately frightening to them,” explains senior researcher Rene Hen from Columbia University.
The output of these cells was traced to the hypothalamus, a region of the brain that – among other things – regulates the hormones that controls emotions.
Because this same regulation process operates in people, too – not just lab mice exposed to anxiety-inducing labyrinths – the researchers hypothesise that the anxiety neurons themselves could be a part of human biology, too.
“Now that we’ve found these cells in the hippocampus, it opens up new areas for exploring treatment ideas that we didn’t know existed before,” says one of the team, Jessica Jimenez from Columbia University’s Vagelos College of Physicians & Surgeons.
Even more exciting is that we’ve already figured out a way of controlling these anxiety cells – in mice at least – to the extent it actually changes the animals’ observable behaviour.
Using a technique called optogenetics to shine a beam of light onto the cells in the vCA1 region, the researchers were able to effectively silence the anxiety cells and prompt confident, anxiety-free activity in the mice.
“If we turn down this activity, will the animals become less anxious?” Kheirbek told NPR.
“What we found was that they did become less anxious. They actually tended to want to explore the open arms of the maze even more.”
This control switch didn’t just work one way.
By changing the light settings, the researchers were also able to enhance the activity of the anxiety cells, making the animals quiver even when safely ensconced in enclosed, walled surroundings – not that the team necessarily thinks vCA1 is the only brain region involved here.
“These cells are probably just one part of an extended circuit by which the animal learns about anxiety-related information,” Kheirbek told NPR, highlighting other neural cells justify additional study too.
In any case, the next steps will be to find out whether the same control switch is what regulates human anxiety – and based on what we know about the brain similarities with mice, it seems plausible.
If that pans out, these results could open a big new research lead into ways to treat various anxiety conditions.
And that’s something we should all be grateful for.
“We have a target,” Kheirbek explained to The Mercury News. “A very early way to think about new drugs.”
The findings were reported in Neuron.
The original version of this story was published in February 2018.
Indian Pharmaceutical Market (IPM) has registered a growth of 7.8 per cent during the month of April 2018 and reached at Rs.10,402 crore. However, this growth is slower than the growth of 9.3 per cent registered in March 2018. Though the volumes have posted a positive growth, the price component is dragging the market. As per the AIOCD AWACS report during the quarter ended April 2018, volume growth was at 6.8 per cent, but price growth was at negative 1.1 per cent. New products fared comparatively better at 2.5 per cent.
Fixed dose combination (FDC) related market showed growth of 14.8 per cent while the non FDC market showed a growth of 7.9 per cent. Single molecules grew at 7.5 per cent. Price component of GD for the FDCs for April 18 is 0.6 per cent, other GDs in terms of volumes are at 13.6 per cent while new products are growing at 0.6 per cent. The single molecules are driven by volumes at 6.4 per cent, however the prices are pulling down at negative 1.4 per cent. MNC are growing faster at 9.1 per cent at Rs.2,145 crore as compared to Indian companies growth of 7.5 per cent to Rs.8,256 crore..
Lupin has registered highest growth of 15.7 per cent among top 10 corporates followed by Abbott at 13.8 per cent and Alkem at 13.2 per cent. Amongst the top 50 corporates, 43 corporate registered positive growth of IPM during April 2018. AstraZeneca has the highest growth of 29.2 per cent among top 50 corporates followed by Win Medicare growing at 21.6 per cent and Hetero at 19.1 per cent. Sun Pharma portfolio has shown a growth of 7.2 per cent, Ranbaxy has slowed down at 2.1 per cent. There were 17 new companies during the last 36 months, of which only one company registered revenue of Rs.10 crore.
Amongst the top 60 MNCs, AstraZeneca was the fastest growing at 29.2 per cent followed by Boehringer Ingelheim growing at 24 per cent and Danone which grew at 22.4 per cent during April 2018. The NLEM 2013 containing molecules market showed growth at 5 per cent whereas the non NLEM market grew at 8.2 per cent. Resulting in an overall growth of 7.8 per cent in April 2018.
From therapy perspective, 19 therapies are showing a positive growth. Respiratory market posted a double growth of 16.1 per cent, gastrointestinal showed an improved growth of 9.1 per cent and pain and analgesic market showed a growth of 5.2 per cent. Anti-diabetic market has posted a double digit growth of 10.3 per cent and cardia is almost at double digit at 9.7 per cent, neuro/CNS showed a growth of 7.1 per cent. Anti infectives posted a positive growth of 5.3 per cent and VMS market achieved growth of 7 per cent. Derma is growing at 6.8 per cent.
Total 28 regions have posted positive growth during April 2018. North AP market grew the highest at 17.49 per cent followed by Bihar growing at 16.67 per cent and Madhya Pradesh at 16.24 per cent.
Amoxycillin plus clavulanic acid market has shown a recovery of 9.3 per cent at Rs.142.8 crore and glimepiride plus metformin market achieved stagnant growth of 0.9 per cent at Rs.177.6 crore. Azilsartan plan market reached at Rs.65.9 crore on MAT basis. Sofosbuvir and its combination market has reached Rs.607.8 crore on MAT basis. The luliconazole market reached at Rs.284.8 crore, while tenegliptin and its combinations have crossed 664 crore mark on MAT basis. The market of paracetamol plain is growing double digit rate at 13.2 per cent on monthly basis, plan atorvastatin has posted a growth of 1.3 per cent and probiotic microbes moved up by 12.4 per cent.
Among the leading brands, Mixtard has posted monthly sales of Rs.44 crore while Spasmoproxivon plus has registered sales of Rs.39 crore. Glycomet GP is at Rs.37 crore, Lantus is at Rs.35 crore and Galvus Met at Rs.36 crore and Liv 52 at Rs.26 crore. The performance of new molecule launched dominated by Azilsartan and combinations with value of Rs.68 crore. On MAT basis Zilarbi (Emcure) leading followed by Aztric (Intas) and Abel (Lupin). Luliconazole segment is worth Rs.285 crore on MAT basis and there are already 54 brands in the foray. Overall 79 brands were launched in last 24 months in Itraconazole. The new launches are valued at Rs.169 crore on MAT basis.
Schizophrenia is considered a disorder of the mind, influencing the way a person thinks, feels and behaves. But our latest research shows that organs, other than the brain, also change at the onset of the disease.
Scientists have known for a long time that people with schizophrenia have much higher rates of physical illness compared with the general population, and this contributes to startlingly high rates of premature death.
People with the disorder die 15 to 20 years earlier than the average person.
This poor physical health has often been seen as a secondary effect of illness. Antipsychotic drugs, for example, are associated with an increased risk of weight gain and type 2 diabetes.
Lifestyle factors have been thought to play a part, too. A person with debilitating mental symptoms is more likely to forgo exercise and have a poor diet.
However, in recent years, scientists have observed that people who have recently been diagnosed with schizophrenia and who aren’t on any medication yet show evidence of physiological changes, such as an overactive immune system.
Could it be that schizophrenia is in fact a body-wide disorder?
My colleagues and I examined evidence of physiological changes around the body at the onset of schizophrenia and compared it with evidence of changes within the brain in the same group of people.
We pooled data from multiple studies, examining markers of inflammation, hormone levels and heart disease risk factors, including glucose and cholesterol levels.
We also pooled data from studies examining brain structure, levels of different chemicals within the brain, and markers of brain activity.
We showed that compared with the general population, early schizophrenia is associated with changes in brain structure and function. We also showed that early schizophrenia is associated with various changes around the body.
We calculated the magnitude of these changes using a statistical measure known as the effect size.
At the onset of schizophrenia, we observed that there was no difference in the effect size for changes within the brain compared with the effect size for changes around the body, suggesting that schizophrenia might indeed be a whole-body disorder, and one that should be treated as such.
Three possible explanations
There are three theories which might explain how alterations within the brain might be associated with alterations around the body in schizophrenia.
First, dysfunction around the body may cause changes in the brain, ultimately leading to schizophrenia. This process has been seen in certain rare cancers that produce antibodies that target the brain and trigger psychosis.
If the tumour is removed, the psychotic experiences improve.
Second, symptoms of schizophrenia may result in physical health disorders. An example of this is the stress of psychosis resulting in raised levels of the steroid hormone cortisol. High levels of cortisol are associated with weight gain, diabetes and raised blood pressure.
Third, symptoms of schizophrenia and physical health disorders may arise via different mechanisms but from a common risk factor.
An example of this is how famine experienced by a pregnant mother increases the chances of her child developing both diabetes and schizophrenia in adult life.
The increased risk of schizophrenia may be due to impaired development of the child’s brain as a result of the mother’s malnutrition. The increased risk of diabetes may be due to changes in the child’s ability to metabolise glucose, again a result of the mother’s malnutrition.
Work still to be done
We need to do more work to figure out whether changes around the body are a cause or a consequence of schizophrenia.
One approach is to look at those people who are at risk of developing schizophrenia to see how changes around the body evolve in the ones who develop schizophrenia compared with those who don’t.
More work is also needed to see how changes around the body respond to changes in the severity of symptoms of schizophrenia.
Finally, most premature deaths seen in schizophrenia are due to cardiovascular disease. Life expectancy in schizophrenia has failed to improve over recent decades. Studies are needed to determine if addressing physical health early on will reduce mortality in schizophrenia.