Healthcare online Keeping you up-to-date
VOL.  21     ISSUE:  10    October  2023 Medical Services Department

SQUARE Pharmaceuticals Ltd.



MBBS, FCGP, FIAGP, P G Dip. Business Management


Dear Doctor,

Welcome to our healthcare bulletin 'e-SQUARE' !

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

"Pregnancy & CVD !", "Explore Immune System !", "Sleep Benefits !", "Degenerative Mitral Regurgitation !",  "Joint Replacement  !", "Small Cell Lung Cancer !".

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


We always value your feedback !

Click on to reply mode.

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.

Pregnancy & CVD !

 Complications in pregnancy linked to risk of CVD 

A large new study shows that narrowing and calcification of the blood vessels of the heart are more common in women previously affected by pregnancy complications. Despite complications in pregnancy having increasingly been acknowledged as a new type of risk factor for heart disease, it is yet to be determined how this information can best be used within healthcare. The results suggest that the correlation exists even among women with a low expected risk of cardiovascular disease. The study is an important piece of the puzzle in understanding how women with pregnancy complications should be followed-up by their healthcare provider after pregnancy. Researchers included 10,528 women at age 50-65 years. All the women underwent CT scanning of the coronary arteries in order to detect calcification of blood vessels, narrowing, and other signs of heart disease. The researchers investigated signs of heart disease by history of five common complications in pregnancy: pre-eclampsia, high blood pressure during pregnancy, preterm delivery, gestational diabetes and infants born small for gestational age. Four percent more of the women with pregnancy complications had visible atherosclerosis of the coronary arteries, compared to the group who had not had complications in pregnancy. The greatest link was for pre-eclampsia and gestational hypertension. Among women who had not experienced any complications in pregnancy, two percent had narrowing in coronary arteries while the corresponding number among women who previously suffered from pre-eclampsia or pregnancy-induced hypertension was five percent. To reduce the risk of these women developing coronary heart disease in the future, it is important that they check risk factors such as blood pressure, blood sugar and cholesterol regularly. In this study, researcher have investigated many different associations between complications in pregnancy and heart disease all at once. Yet the pattern is relatively consistent, which makes it easier to draw conclusions including that women with prior pre-eclampsia have changes in the coronary arteries that are equivalent to the changes seen in women who have not experienced complications in pregnancy but are five to ten years older. According to CT scans of the coronary arteries are increasingly used in patients presenting with symptoms, but there is still a lack of large studies into the significance over time of some of the studied changes among women without current symptoms. Even if the study provides new knowledge on the development of coronary heart disease among middle-aged women who have previously suffered complications in pregnancy, there is a need for long-term studies in order to understand the true meaning that our discoveries have for symptomatic disease.

SOURCE: Science Daily, October 2023

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 Explore Immune System !

Immune system aging can be revealed by CT scan

Thymus, a small and relatively unknown organ, may play a bigger role in the immune system of adults. With age, the glandular tissue in the thymus is replaced by fat, but, according to a new study, the rate at which this happens is linked to sex, age and lifestyle factors. These findings also indicate that the appearance of the thymus reflects the ageing of the immune system. Doctors can assess the appearance of the thymus from largely all chest CT scans, but tend to not see this as very important. But now it turns out that the appearance of the thymus can actually provide a lot of valuable information that we could benefit from and learn more. The thymus is a gland located in the upper part of the chest. It has been long known that this small organ is important for immune defense development in children. After puberty, the thymus decreases in size and is eventually replaced by fat, in a process known as fatty degeneration. This has been taken to mean that it loses its function, which is why the thymus has for a long time been considered as being not important in adult life. This view has however been challenged in some minor research studies, mainly on animals, that indicate that having an active thymus as an adult may be an advantage and could provide increased resilience against infectious disease and cancer. Only very few studies so far have examined the thymus in adults. In the present study, published in Immunity & Ageing, the researchers have examined thymus appearance in chest CT scans of more than 1,000 individuals aged 50 to 64, who participated in the large study .It includes both extensive imaging and comprehensive health assessments including lifestyle factors, such as dietary habits and physical activity. In their sub-study of SCAPIS, the researchers also analyzed immune cells in the blood. There is a huge variation in thymus appearance. Six out of ten participants had complete fatty degeneration of thymus, which was much more common in men than in women, and in people with abdominal obesity. The researchers study provides new knowledge by associating thymus appearance with lifestyle and health factors, and the immune system. In the development of the immune system, the thymus acts like a school for a type of immune cells known as T-cells (where the T stands for "thymus"). This is where the T-cells learn to recognize bacteria, viruses and other things that are alien to the body. It also learns to be tolerant and not to attack anything that is part of the person's own body, which could otherwise lead to various autoimmune diseases. In their study, the researchers saw that individuals with fatty degeneration of the thymus showed lower T-cell regeneration.It indicates that what see in CT scans is not only an image but also reflects the functionality of the thymus. It might be possible to influence immune system ageing. But more research is needed before it will be possible to know whether thymus appearance, and thereby immune defense ageing, will have any implications for our health. The researchers are now moving on to follow-up studies of the thymus of all 5,000 participants in SCAPIS to see whether CT scan thymus images can provide information on future risk of disease.

SOURCE: Science Daily, October 2023                                           

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Sleep Benefits!

Increased deep sleep benefits Heart 

Researchers play ultra-brief tones to stimulate the brain during deep sleep. This stimulation improves cardiac output and relaxation of the left ventricle. Such technology to improve cardiovascular function could be relevant both in disease treatment and competitive sports. Sleep is a vital aspect of human life, with deep sleep being particularly crucial for overall health. The brain recovers during this sleep stage, and the rest of the body seems to regenerate then as well. Recently, Researchers have shown that increased deep sleep is of particular benefit to the cardiovascular system: targeted stimulation with brief tones during deep sleep causes the heart. In particular the left ventricle to contract and relax more vigorously. As a result, it pumps blood into the circulatory system and draws it out again more efficiently. The left ventricle supplies most organs, the extremities, and the brain with oxygen-rich arterial blood. When the heart contracts, the left ventricle is squeezed and wrung out like a wet sponge. The more immediate and more powerful this wringing action, the more blood enters the circulation and the less remains in the heart. This increases blood flow, which has a positive effect on the cardiovascular system. Researchers demonstrate that the left ventricle undergoes more intense deformation after nocturnal stimulation. This is the first time anyone has shown that an increase in brain waves during deep sleep (slow waves) improves cardiac function. Researchers were expecting that stimulation with tones during deep sleep would impact the cardiovascular system. But the fact that this effect was so clearly measurable after just one night of stimulation surprised them. They clearly saw that both the heart's pumping force and its relaxation were greater after nights with stimulation compared to nights without stimulation. The study involved 18 healthy men aged 30 to 57, who spent three non-consecutive nights in the sleep laboratory. On two nights, the researchers stimulated the subjects with sounds; on one night, they did not. While the subjects slept, the scientists continuously measured their brain activity, blood pressure and heart activity. As soon as the readings indicated that the subject had fallen into deep sleep, the computer played a series of very brief tones at certain frequencies, called pink noise, which sound like static. Ten seconds of such tones were followed by 10 seconds of silence, and then the same procedure could be repeated. A feedback mechanism ensured that the noise was played at the right time and depending on the brain wave pattern stopped again. This experimental setup allowed the researchers to directly monitor whether the sound simulation enhanced deep sleep and whether it influenced the subjects' heart rate and blood pressure. During stimulation, an increase in slow waves as well as a response from the cardiovascular system has been seen that is reminiscent of cardiovascular pulsation. The next morning, cardiologists examined the subjects' cardiac function using echocardiography (ultrasound). The researchers are now looking for further, more powerful stimulation methods to positively impact the cardiovascular system.

SOURCE: Science Daily, October 2023

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 Degenerative Mitral Regurgitation!

Heart valve disease linked to high dose antidepressant 

According to a new study, Serotonin can impact the mitral valve of the heart and potentially accelerate a cardiac condition known as degenerative mitral regurgitation. Serotonin can impact the mitral valve of the heart and potentially accelerate a cardiac condition known as degenerative mitral regurgitation. Degenerative mitral regurgitation (DMR) is one of the most common types of heart valve disease. The mitral valve is located between the left atrium and left ventricle of the heart. It closes tightly when the heart contracts to prevent blood from leaking back into the left atrium. In DMR, the shape of the mitral valve becomes distorted, preventing the valve from closing completely. This allows blood to leak back toward the lungs (regurgitation), limiting the amount of oxygen-rich blood moving through the heart to the rest of the body. As a result, DMR can bring about symptoms like fatigue and shortness of breath. Because of the reduced efficiency in circulation, the heart has to work harder, which over time causes permanent damage. This may result in atrial fibrillation and heart failure. Currently, there is no treatment for mitral valve degeneration. Certain medications can ease the symptoms and prevent complications, but they do not treat the mitral valve. If the degeneration of the mitral valve becomes severe, surgery to repair or replace the valve is needed. Serotonin plays a part in a wide range of body functions, including emotional state, digestion, sleep, memory, and blood-clotting. Serotonin's role as a neurotransmitter helps the brain regulate mood, lower levels of serotonin are associated with anxiety and depression. Serotonin binds to specific receptors on the surface of a cell, sending a signal to the cell to act accordingly. A protein known as the serotonin transporter (SERT or 5-HTT) moves serotonin into the cell to be reabsorbed and recycled, a process known as serotonin reuptake. Medications called selective serotonin reuptake inhibitors (SSRIs) bind to the SERT to reduce serotonin reuptake, allowing serotonin to remain available for longer periods. This increased serotonin availability can help improve symptoms of mood disorders. SSRIs are some of the most widely prescribed types of antidepressants and include well-known medications like fluoxetine and sertraline. The study examined clinical data from more than 9,000 patients who had undergone valve repair or replacement surgery for DMR and evaluated 100 mitral valve biopsies. Studying the data of these patients, found that taking SSRIs was associated with severe mitral regurgitation that needed to be treated with surgery at a younger age than for patients not taking SSRIs. The researchers also studied in vivo mouse models using transgenic mice lacking the SERT gene and normal mice. It was discovered that mice without a SERT gene developed thicker mitral valves and that normal mice treated with high doses of SSRIs also developed thickened mitral valves. Additional research may help determine if DMR patients who respond well to SSRIs should be regularly seen to assess progression of mitral degeneration, and whether DMR patients who are not responding well to SSRIs should consider switching to a non-SSRI antidepressant rather than raising the dose of the SSRI.

SOURCE:Science Daily , October 2023

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Joint Replacement !
A new approach for testing treatments for osteoarthritis 

Osteoarthritis (OA) is the most common form of arthritis and is among the top 10 conditions contributing to Years Lived with Disability a measure reflecting the impact an illness has on quality of life before it resolves or leads to death. To date, no treatments are approved that slow disease progression. Treatment development has been frustrating in part because animal models of disease caused by joint trauma poorly reflect human disease which usually occurs over many years and without preceding trauma. Researchers suggest studying persons after they sustain knee trauma such as anterior cruciate ligament tears (ACL). Given the repeated, expensive and discouraging past failures in the development of effective treatments for OA, a new approach is needed that focuses research into effective treatment on those with early disease. While most patients recover after sustaining a major joint injury like an ACL tear, a few experience persistent pain and develop OA. Researchers suggests that sufficient numbers of such patients exist and could be identified in advance to form a high-risk group in which treatments to prevent disease could be tested. Current options for treatments that reduce joint pain such as nonsteroidal anti-inflammatory drugs (NSAIDs) are successful in some patients but their use is limited by their toxicity. Exercise or weight loss are effective but long-term adherence is poor. Rates of total knee replacement surgeries are rising rapidly suggesting that nonsurgical treatments have not successfully alleviated patients' pain and disability. By using the MOON risk factors incorporating pain and structural changes in all joint tissues, especially cartilage loss to select persons at high risk of later pain, they could assemble a cohort at high risk of substantial post ACLR pain. This approach offers the opportunity to prevent disease and is especially valuable in targeting young adults who, after a knee injury, may have significant joint pain and disability for many years before they become eligible for joint replacement. Funding for this study was provided by the Arthritis Foundation and by the national Institutes of Health.

SOURCE:Science Daily , October 2023

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Small Cell Lung Cancer !

Overcoming small cell lung cancer chemo-resistance

Small cell lung cancer (SCLC) accounts for about 15 percent of all diagnosed lung cancers and is still associated with a high mortality rate. SCLC tumours often develop resistance to chemotherapy and thus poor prognosis is due to tumour recurrence which occurs within only five to 14 months after initial diagnosis. As a recent research study shows resistant cell lines can be successfully fought with a combination of two already available therapeutic agents. The study follows on from earlier, small cell lung cancer (SCLC) can be divided into subtypes that respond differently to chemotherapeutic agents and targeted drugs. In this context, histone deaceylase inhibitors (HDACi) have been shown to be effective in two SCLC subtypes (known as SCLC-A and SCLC-N). HDACi are drugs that have already been shown in trials to be effective in fighting cells of different tumour types and have now been further investigated for their use in SCLC.SCLC affects about 15 percent of lung cancer patients. This particularly aggressive tumour, which usually occurs in smokers, grows rapidly and has a high tendency to metastasize. About 70 per cent of advanced cases are fatal within a year. The high mortality rate is due to the rapid and virtually inevitable recurrence of the disease, which is often accompanied by resistance to treatment. HDACi in combination with standard chemotherapeutic agents turned out to be a possible solution during the studies. This significantly slowed down the growth of tumour cells that were resistant to individual therapy.In further analyses, the molecular mechanism underlying therapy resistance was also revealed. The findings of the research group thus contribute significantly to a better understanding of the biology of SCLC, a disease in which promising progress in the development of therapeutic innovations has been decades in waiting. "Our findings can provide the basis for research into successful new therapies that are superior to the resistance mechanisms of SCLC.

SOURCE:Science Daily, October  2023

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Products of SQUARE Pharmaceuticals Ltd.

  Product Magnide™
  Generic Name Magnesium Oxide
  Strength 365 mg
  Dosage form Tablet
  Therapeutic Category Mineral
  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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