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Healthcare online Keeping you up-to-date
VOL.  19     ISSUE:  12  December   2021 Medical Services Department

SQUARE Pharmaceuticals Ltd.

Features

EDITORIAL TEAM

OMAR AKRAMUR RAB

MBBS, FCGP, FIAGP,

P G Dip. Business Management

MAHFUZUR RAHMAN

MBBS, MBA

Rubyeat Adnan

MBBS, MPH

EDITORIAL

Dear Doctor,

Hope that you are enjoying this online healthcare bulletin.
Our current issue focused on some interesting features like -

"Future COVID-19 Virus !", "Stem Cell !", "Visuals Increase Attention !", "Cardio Health !",  "Children Overweight Risk !", "Star Cells !".

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

Please send your feedback !  We always value your comments !

Click on to reply mode.

On behalf of the management of SQUARE, we wish you all a very happy, healthy and prosperous life.

 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.


  Future COVID-19 Virus !

    Shark antibody-like proteins neutralize COVID-19 virus

Small, unique antibody-like proteins known as VNARs derived from the immune systems of sharks can prevent the virus that causes COVID-19, its variants, and related coronaviruses from infecting human cells. The new VNARs will not be immediately available as a treatment in people, but they can help prepare for future coronavirus outbreaks. The shark VNARs were able to neutralize WIV1-CoV, a coronavirus that is capable of infecting human cells but currently circulates only in bats, where SARS-CoV-2, the virus that causes COVID-19, likely originated. Developing treatments for such animal-borne viruses ahead of time can prove useful if those viruses make the jump to people. The anti-SARS-CoV-2 VNARs were isolated from Elasmogen's large synthetic VNAR libraries. One-tenth the size of human antibodies, the shark VNARs can bind to infectious proteins in unique ways that bolster their ability to halt infection. These small antibody-like proteins can get into nooks and crannies that human antibodies cannot access. They can form these very unique geometries. This allows them to recognize structures in proteins that our human antibodies cannot. The researchers tested the shark VNARs against both infectious SARS-CoV-2 and a "pseudotype," a version of the virus that can't replicate in cells. Researchers identified three candidate VNARs from a pool of billions that effectively stopped the virus from infecting human cells. The three shark VNARs were also effective against SARS-CoV-1, which caused the first SARS outbreak in 2003. The second most powerful shark VNAR, 2C02, seems to lock the spike protein into an inactive form. However, this VNAR's binding site is altered in some SARS-CoV-2 variants, which likely decreases its potency. What is exciting is that these new potential drug molecules against SARS-CoV-2 differ in their mechanism of action compared to other biologics and antibodies targeting this virus. Future therapies would likely include a cocktail of multiple shark VNARs to maximize their effectiveness against diverse and mutating viruses. This new class of drug is cheaper and easier to manufacture than human antibodies, and can be delivered into the body through various routes, but has yet to be tested in humans.

SOURCE: Science Daily News, December 2021

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 Stem Cell !

     Stem cell-based implants successfully secrete insulin in patients with type 1-DM

Interim results from a multicenter clinical trial demonstrate insulin secretion from engrafted cells in patients with type 1 diabetes. The safety, tolerability, and efficacy of the implants, which consisted of pancreatic endoderm cells derived from human pluripotent stem cells (PSCs), were tested in several patients. The possibility of an unlimited supply of insulin-producing cells gives hope to people living with type 1 diabetes. Despite the absence of relevant clinical effects, this study will remain an important milestone for the field of human PSC-derived cell replacement therapies as it is one of the first to report cell survival and functionality one year after transplantation. The use of human PSCs has made significant progress toward becoming a viable clinical option for the mass production of insulin-producing cells. Researchers reported a multi-stage protocol directing the differentiation of human embryonic stem cells into immature pancreatic endoderm cells. This stepwise protocol manipulating key signaling pathways was based on embryonic development of the pancreas. Follow-up studies showed that these pancreatic endoderm cells were able to mature further and become fully functional when implanted in animal models. Based on these results, clinical trials were started using these pancreatic endoderm cells. On a phase I/II clinical trial pancreatic endoderm cells were placed in non-immunoprotective ("open") macroencapsulation devices, which allowed for direct vascularization of the cells, and implanted under the skin in patients with type 1 diabetes. The use of third-party off-the-shelf cells in this stem cell-based islet replacement strategy required immunosuppressive agents, which protect against graft rejection but can cause major side effects, such as cancer and infections. The participants underwent an immunosuppressive treatment regimen that is commonly used in donor islet transplantation procedures. Both the clinical trials provided compelling evidence of functional insulin-secreting cells after implantation. PEC-01s -- the drug candidate pancreatic endoderm cells survived and matured into glucose-responsive, insulin-secreting cells within 26 weeks after implantation. Over the up to one year of follow-up, patients had 20% reduced insulin requirements, and spent 13% more time in target blood glucose range. Overall, the implants were well tolerated with no severe graft-related adverse events.

SOURCE: Science Daily News, December 2021

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 Visuals Increase Attention !

                           Chemicalís release in brain tied to processing of imagery, cellsí activation

"Look at me!" we might say while attempting to engage our children. It turns out there is a neurochemical explanation for why looking at mom or dad actually helps kiddoes pay better attention. Researcher report that norepinephrine, a fundamental chemical for brain performance, is locally regulated in a brain region called the visual cortex. Before this study, research suggested the possibility of local regulation of norepinephrine release, but it had never been directly demonstrated. Norepinephrine is known to be involved in paying attention. A certain amount of this chemical needs to be released for optimum brain performance and ability to pay attention. So, if there is either too much of it or too little of it, it may affect how we process information. Disease states in which norepinephrine is known to be altered include substance use disorders, Alzheimer's disease, post-traumatic stress disorder (PTSD) and attention-deficit/hyperactivity disorder (ADHD). In some substance use, Alzheimer's and ADHD, the release of norepinephrine is reduced, resulting in lower attention. In other substance use and PTSD, the level is too high. The researcherís findings also extend to cells called astrocytes that function as helper cells in the brain and central nervous system. When a person makes a movement, such as turning the head to listen to a parent, and that is combined with visual stimulation, then more norepinephrine is released where visual information is processed and another important, thing is that astrocytes can reliably detect the rate of norepinephrine release. They are sensitive to it, in other words. Astrocytes alter their response accordingly, which is expected to change brain performance. The researcher said that Understanding norepinephrine release, its local regulation, and the astrocyte response may represent a mechanism by which one could enhance sensory-specific attention.

SOURCE: Science Daily News, December 2021

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 Cardio Health !

                                 The sunshine vitamin that ĎDíelivers on cardio health

Free from the sun, vitamin D delivers a natural source for one of the hormones essential to our bodies, especially the bones. But when down on this essential nutrient, it's not only bones that could suffer, but also cardio health, according to new research. In the first study of its kind, researchers have identified genetic evidence for the role of vitamin D deficiency in causing cardiovascular disease. The study shows that people with vitamin D deficiency are more likely to suffer from heart disease and higher blood pressure than those with normal levels of vitamin D. For participants with the lowest concentrations, the risk of heart disease was more than double that seen for those with sufficient concentrations. The lead researcher said that appreciating the role of vitamin D deficiency for heart health could help reduce the global burden of cardiovascular disease. Severe deficiency is relatively rare, but in settings where this does occur it is very important to be proactive and avoid negative effects on the heart. Food is, unfortunately, a relatively poor source of vitamin D, and even an otherwise healthy diet does not typically contain enough. Understanding the connection between low levels of vitamin D and CVD is especially important, given the global prevalence of this deadly condition. This large-scale Mendelian study used a new genetic approach that allowed the team to assess how increasing levels can affect CVD risk based on how high the participantís actual vitamin D levels were. The study used information from up to 267,980 individuals which allowed the team to provide robust statistical evidence for the link between vitamin D deficiency and CVD. It is not ethical to recruit people with vitamin D deficiency to a randomized controlled trial and to leave them without treatment for long periods. It is exactly this type of difficulty setting which demonstrates the power of our genetic approach, given we can show how improving concentrations affect the risk in those most in need, without exposing participants to any harm.

SOURCE: Science Daily News, December 2021

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 Children Overweight Risk !

                          Overweight children are developing heart complications

The percentage of obese children and teens jumped from 19% pre-pandemic to 22%, according to a study from the Centers for Disease Control and Prevention. And the rate at which body mass index (BMI) increased doubled. New research suggests that could spell bad news for children's cardiovascular systems both now and down the line. The researchers found significantly higher levels of visceral fat and arterial stiffness in the overweight youth, suggesting that abdominal fat likely contributes to cardiovascular problems in kids. Studies of cardiovascular risks in youth are limited, but researchers believe the negative changes to the cardiovascular system that lead to disease and heart attacks likely begin in childhood and adolescence. The researchers used technology known as dual energy X-ray absorptiometry, or DXA, to measure levels of body fat in the children. It's a technique commonly used in the fields of bone and hormone research. And it's becoming more common in body fat research because it gives scientists the same information as traditional scans. But it's faster, less expensive and doesn't require large doses of radiation like other scans do. They also measured how long it took for participants' blood to make it from the central part of the body to the lower limbs, a standard way of assessing arterial stiffness. Another concern is that children are increasingly being diagnosed with Type 2 diabetes, a condition previously only seen in adults. Being overweight is a big risk factor. Of the study's participants, 145 had been diagnosed with the disease. Researcher said, It's a very pervasive, scary condition in youth, even more so than in adults. Many body systems tend to degrade at a more accelerated rate if the disease occurs during the growing years than in adulthood. This disease attacks the brain, the kidneys, the bones, the liver. It really heightens the need for understanding ways we can prevent disease.

SOURCE: Science Daily News, December 2021

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 Star Cells !

                                                                               Star cells in the brain render memory flexible

As we live in a dynamically changing environment, it is important for our brain to not only learn new things but also to modify existing memories. This is commonly referred to as "cognitive flexibility." Without this ability, we would not be able to adapt to the altered environment and be vulnerable to making wrong choices from relying only on past memories. It is thought that lower cognitive flexibility in brain disorders such as autism, schizophrenia, and early stages of Alzheimer's disease is caused by the reduced function of N-methyl-D-aspartate receptors (NMDARs). While NMDARs are important receptors for synaptic plasticity and are activated by a number of agonists and co-agonists, the source of one of the co-agonists, D-serine, has been controversial. Using astrocyte-specific gene regulation, the researchers showed that astrocytes can actually synthesize D-serine and release it through the calcium-activated channel called Best1. Combined with the previous knowledge that astrocytes can release glutamate through Best1, the co-release of D-serine and glutamate indicates that astrocytes are ideal regulators of NMDAR activity and synaptic plasticity. Researchers showed that heterosynaptic long-term depression (LTD), a phenomenon in which inactive synapses weaken when nearby synapses become active, is mediated by astrocytes and is critical for cognitive flexibility. In the report, they studied the Best1 knockout (Best1 KO) mouse model that lacks heterosynaptic LTD due to reduced NMDAR tone. Interestingly, when the NMDAR tone was improved in Best1 KO mice by D-serine injection during the initial learning period, their memory modification problem was restored in the subsequent experiment. This discovery shows that memory flexibility is determined from the time of initial learning, which is different from the previously proposed theory that synaptic plasticity only occurs when memory modification is needed. Additionally, the researchers discovered that norepinephrine and its receptor α1-AR can activate astrocytes and cause co-release of D-serine and glutamate. This implies that the flexibility of memory can be determined by the degree of concentration and arousal during the learning period. This study will provide valuable insights on how to relieve or treat symptoms of autism, schizophrenia, and early dementia, which are known to reduce cognitive flexibility.

SOURCE: Science Daily News, December 2021

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New Products of SQUARE Pharmaceuticals Ltd.

  Product GleazyTM   
  Generic Name Hydroxyethyl Cellulose USP & Glycerol BP
  Strength 50 mg
  Dosage form Tablet
  Therapeutic Category Personal Lubricant
  Product MolvirTM
Generic Name

Molnupiravir INN

Strength 200 mg
Dosage form Capsule
Therapeutic Category Anti Viral
  Product GlycoventTM 
  Generic Name Glycopyrronium Bromide
  Strength 25 mcg/ml
  Dosage form Nebuliser Solution
  Therapeutic Category Long acting muscarinic antagonist (LAMA)

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