Healthcare online Keeping you up-to-date
VOL.  19     ISSUE:  10    October  2021 Medical Services Department

SQUARE Pharmaceuticals Ltd.





P G Dip. Business Management









Dear Doctor,

Welcome to our healthcare bulletin 'e-SQUARE' !

In this issue, we focused on some interesting features like -

"Magnetic Seizure Therapy !", "Broken Heart Syndrome !", "Sense of Smell !",  "Novel Migraine Therapy !",  "Air Linked Healthy Brain !", "Stem Cell Therapy !".

In our regular feature, we have some new products information of SQUARE Pharmaceuticals Ltd. as well.


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Yours sincerely,


Editorial Team

Reply Mode      : e-square@squaregroup.com

The views expressed in this publication do not necessarily reflect those of its editor or SQUARE Pharmaceuticals Ltd.

Magnetic Seizure Therapy !

Magnetic seizure therapy may be attractive alternative to electroconvulsive therapy

In a study, it has been investigated whether continued magnetic seizure therapy (MST) might effectively prevent the relapse of Treatment-resistant depression (TRD), particularly in comparison to what is known about electroconvulsive therapy (ECT), the current standard of care but a method with mixed results and a controversial history. ECT is a procedure, performed under general anesthesia, in which small electric currents are passed through the brain, triggering a brief seizure and changes in brain chemistry that reverse symptoms of some mental health conditions, most notably depression and mania. ECT dates back to the 1930s. Early treatments involved high doses of electricity administered without anesthesia, resulting in memory loss, fractured bones and other serious side effects. Contemporary ECT uses much lower levels of electric stimulus in combination with anesthesia to avoid pain and muscle relaxants to reduce the physical dangers of a seizure. ECT often works when other treatments are unsuccessful, but it does not work for everyone, and some side effects may still occur, such as confusion and memory loss. These concerns, and a lingering public stigma, have limited its widespread use. MST is a different form of electrical brain stimulation, debuting in the late-1990s. It induces a seizure in the brain by delivering high intensity magnetic field impulses through a magnetic coil. Stimulation can be tightly focused to a region of the brain, with minimal effect on surrounding tissues and fewer cognitive side effects. Like ECT, MST is being studied for treating depression, psychosis and obsessive-compulsive disorder. While ECT and, to a lesser degree MST, have both been shown in previous research to produce immediate benefit in treating at least some cases of acute or treatment-resistant depression, much less is known about whether continued MST might prevent relapse of mental illness.

SOURCE: Science Daily News, October 2021

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Broken Heart Syndrome !

Broken heart syndrome is on the rise in women

Researchers have discovered two alarming trends in Takotsubo cardiomyopathy, also known as 'broken heart' syndrome. It is a condition that is often triggered by stress or loss and can lead to long-term heart injury and impaired heart function. The study suggests middle-aged and older women are being diagnosed with broken heart syndrome more frequently up to 10 times more often than younger women or men of any age. The research also suggests that the rare condition has become more common, and the incidence has been rising steadily since well before the COVID-19 pandemic. Although the global COVID-19 pandemic has posed many challenges and stressors for women, this research suggests the increase in Takotsubo diagnoses was rising well before the public health outbreak. This study further validates the vital role the heart-brain connection plays in overall health, especially for women. Research team used national hospital data collected from more than 135,000 women and men who were diagnosed with Takotsubo syndrome between 2006 and 2017. While confirming that women are diagnosed more frequently than men, the results also revealed that diagnoses have been increasing at least six to 10 times more rapidly for women ages 50 to 74 than for any other demographic. Of the 135,463 documented cases of Takotsubo cardiomyopathy, the annual incidence increased steadily in both sexes, with women contributing most cases (83.3%), especially those over 50. In particular, researchers observed a significantly greater increase in incidence among middle-aged women and older women, compared to younger women. For every additional diagnosis of Takotsubo in younger women or men of all age groups there were 10 additional cases diagnosed for middle-aged women and six additional diagnoses for older women. Prior to this study, researchers only knew that women are more prone than men to developing Takotsubo syndrome. This latest study is the first to ask whether there are age-based sex differences and if case rates may be changing over time. There is likely a tipping point, just beyond midlife, where an excess response to stress can impact the heart. The researchers are next investigating the longer-term implications of a Takotsubo diagnosis, molecular markers of risk, and the factors that may be contributing to rising case rates.

SOURCE:  Science Daily News, October 2021                                           

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Sense of Smell !

Sense of smell is our most rapid warning system

The ability to detect and react to the smell of a potential threat is a precondition of our and other mammal’s survival. Using a novel technique, researchers able to study what happens in the brain when the central nervous system judges a smell to represent danger. The human avoidance response to unpleasant smells associated with danger has long been seen as a conscious cognitive process. The olfactory organ takes up about five per cent of the human brain and enables us to distinguish between many million different smells. A large proportion of these smells are associated with a threat to our health and survival, such as that of chemicals and rotten food. Odor signals reach the brain within 100 to 150 milliseconds after being inhaled through the nose. The survival of all living organisms depends on their ability to avoid danger and seek rewards. One reason for this is the lack of non-invasive methods of measuring signals from the olfactory bulb, the first part of the rhinencephalon (literally "nose brain") with direct (monosynaptic) connections to the important central parts of the nervous system that helps us detect and remember threatening and dangerous situations and substances. Researchers now developed a method that for the first time has made it possible to measure signals from the human olfactory bulb, which processes smells and in turn can transmits signals to parts of the brain that control movement and avoidance behavior. Their results are based on three experiments in which participants were asked to rate their experience of six different smells, some positive, some negative, while the electrophysiological activity of the olfactory bulb when responding to each of the smells was measured. It was clear that the bulb reacts specifically and rapidly to negative smells and sends a direct signal to the motor cortex within about 300 ms said by researcher. The results suggest that our sense of smell is important to our ability to detect dangers in our vicinity, and much of this ability is more unconscious than our response to danger mediated by our senses of vision and hearing.

SOURCE: Science Daily News, October 2021

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Novel Migraine Therapy !

Potential new cellular mechanism to treat chronic migraine

Researchers explained that the dynamic process of routing and rerouting connections among nerve cells, called neural plasticity, is critical to both the causes and cures for disorders of the central nervous system such as depression, chronic pain, and addiction. The structure of the cell is maintained by its cytoskeleton which is made up of the protein, tubulin. Tubulin is in a constant state of flux, waxing and waning to change the size and shape of the cell. This dynamic property of the cell allows the nervous system to change in response to its environment. Tubulin is modified in the body through a chemical process called acetylation. When tubulin is acetylated, it encourages flexible, stable cytoskeleton; while tubulin deacetylation induced by histone deacetylase 6, or HDAC6, promotes cytoskeletal instability. Studies show that decreased neuronal complexity may be a feature, or mechanism of chronic migraine. When HDAC6 is inhibited, tubulin acetylation and cytoskeletal flexibility is restored. Additionally, HDAC6 reversed the cellular correlates of migraine and relieved migraine-associated pain. This work suggests that the chronic migraine state may be characterized by decreased neuronal complexity, and that restoration of this complexity could be a hallmark of anti-migraine treatments. This work also forms the basis for development of HDAC6 inhibitors as a novel therapeutic strategy for migraine. Blocking HDAC6 would allow neurons to restore its flexibility so the brain would be more receptive to other types of treatment. In this model, maybe chronic migraine sufferers have decreased neuronal flexibility. If we can restore that complexity maybe we could get them out of that cycle. Once out of the cycle of decreased neuronal complexity, the brain may become more responsive to pain management therapies. HDAC6 inhibitors are currently in development for cancer, and HDCA6 as a target has been identified for other types of pain.

SOURCE: Science Daily News, October 2021

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Air Linked Healthy Brain !
Cleaner air may reduce risk for Alzheimer’s and other dementias

Cars and factories produce a fine particulate known as PM2.5. Some studies have linked this particulate to memory loss and Alzheimer's disease. Smaller than the width of a human hair, these tiny particles pose a big problem. Once inhaled, they pass directly from the nose up and into the brain, beyond the blood-brain barrier that normally protects the brain from dust or other invaders. Long-term exposure to PM2.5 has been linked to premature death, particularly in people with chronic heart or lung diseases. Notably in 2014, very few of the study participants lived in places with annual average PM2.5 that exceeded U.S. Environmental Protection Agency air quality standards. This further suggested that the improvements with cognitive decline were linked to a drop in exposure to high pollution among older adults. From 2000 to 2020, PM2.5 levels declined nationwide by 41%, according to the EPA. In contrast, urban PM2.5 in Los Angeles declined only slightly from 2009 to 2019. Based on data from the nationwide Health and Retirement Study, data showed that when exposed to PM2.5, adults of 65 and older faced a greater risk of cognitive impairment. While nationwide ozone levels decreased, Los Angeles County ozone reversed the prior trends by increasing after 2015. Researchers emphasize that their findings can evaluate potential benefits of air pollution improvements to the risk of cognitive decline and dementia. Although PM2.5 levels declined nationally from 2009 to 2016, the year-over-year increases that have been observed since 2017 show that improvements in air quality can be reversed, as they were in Los Angeles. These findings underscore the importance of efforts to improve air quality as well as the continued importance of demographic and experimental evaluation of air pollution neurotoxicity.

SOURCE: Science Daily News , October 2021

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Stem Cell Therapy !

Functional sperm cells can be made in a dish using primate embryonic stem cells

With global rates of male infertility continuing to rise, a new study in spermatogonial stem cell research, researchers brings new hope for future clinical therapies. This is a major breakthrough towards producing stem cell-based therapies to treat male infertility in cases where the men do not produce any viable sperm cells. Researchers used embryonic stem cells from rhesus macaque monkeys to generate immature sperm cells known as round spermatids, which they showed to be capable of fertilizing a rhesus macaque egg. Scientists have been able to produce sperm-like cells using mouse stem cells but rodent sperm production is distinctly different than humans. Until this work, it wasn't clear that this technology could ever work in humans. This is the first step that shows this technology is potentially translatable. Rhesus macaques share similar reproductive mechanisms to humans, making them an ideal and necessary model for exploring stem cell-based therapies for male infertility. Using a novel method, the researchers differentiated the cells into immature sperm cells known as round spermatids. Like immature spermatids in vivo, fertilization with in vitro spermatids requires activating the egg and the addition of other factors to enable the fertilized egg to develop into a healthy embryo. This fall, the researchers plan to take the next critical step of implanting these embryos into a surrogate rhesus macaque to examine whether these embryos from in vitro spermatids can produce a healthy baby. If that step is successful, the team will carry out the same process using spermatid-like cells derived from macaque skin cells.

SOURCE: Science Daily News, October 2021

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New Products of SQUARE Pharmaceuticals Ltd.

  Product Toco™ Soft
  Generic Name Tocotrienol & Tocopherol
  Strength 50 mg (74.5 IU) & 13.5 mg (20 IU)
  Dosage form Soft capsule
  Therapeutic Category Vitamin (Herbal & Nutraceuticals)
  Product Livacol™
Generic Name

Obeticholic Acid


5 mg & 10 mg

Dosage form Tablet
Therapeutic Category Bile Therapy (Hepatobilliary Disorder)
Product Peranel TabletTM
  Generic Name Perampanel
Strength 2 mg & 4 mg
  Dosage form Tablet
  Therapeutic Category Antiepileptic

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