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VOL.  16     ISSUE:  7    July 2018 Medical Services Department

SQUARE Pharmaceuticals Ltd.





P G Dip. Business Management






Dear Doctor:

Welcome to our healthcare bulletin 'e-SQUARE' !

Our current issue focused on some interesting features like

"Tumor Neutralizes !", "MTB & Macrophage !", "Peanut Allergies !", "Breast Milk & Allergies !", "Red Meat & Heart Diseases !", "Blood Diseases !".

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

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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.

 Tumor Neutralizes !

Biologists discover process that neutralizes tumors

Immune system identifies tumors as threatening elements and deploys immune cells (T cells) to find and kill them. However, tumor cells have evolved to employ a protein called PD-L1 to blind T cells from carrying out their functions and evade immune defenses. PD-L1 protects tumor cells by activating a "molecular brake" known as PD-1 to stop T cells. In important therapeutic progress, antibodies developed to block PD-L1/PD-1 have been clinically proven to benefit certain cancer patients. Yet why some patients don't respond to such therapy has remained a mystery. The lead researchers discovered an unexpected twist in the tumor versus T cell battle. Some tumor cells display not only their PD-L1 weapon, but also the PD-1 "brake." This simultaneous expression leads PD-1 to bind and neutralize PD-L1 on the same tumor cell. Thus, the PD-L1 on these tumor cells can no longer engage the PD-1 brake on T cells. The lead researcher said this study uncovered an unexpected role of PD-1 and another dimension of PD-1 regulation with important therapeutic implications. This study suggests that patients with high levels of PD-1 on tumor cells may not respond well to the blocking antibodies because the PD-1 pathway is self-canceled. In these patients, mechanisms other than PD-L1/PD-1 are likely employed by the tumors to escape from immune destruction. Lead researcher think that this finding is the tip of the iceberg. Lead researcher said that self-cancellation is a general mechanism to regulate immune cell function. Understanding these processes more clearly will help develop better immunotherapy strategies and more reliably predict whether a patient will respond or not.

SOURCE: HealthDay News, July 2018

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 MTB & Macrophage !

Mycobacterium tuberculosis (MTB) escapes death in macrophages

The bacteria that cause the devastating disease tuberculosis have the ability to escape destruction and grow after they are engulfed by lung macrophages, the immune cells that are supposed to destroy pathogens. Lead researcher said, reveals patient-targeted strategies to treat tuberculosis, which kills 1.4 million people and infects another 10 million each year. The toxin tuberculosis necrotizing toxin, or TNT, and showed that TNT is the founding member of a novel class of previously unrecognized toxins present in more than 600 bacterial and fungal species. These include Yersinia pestis, the bacteria that caused the Black Death bubonic plague in Medieval Europe. The researcher found that TNT enzymatically hydrolyzes NAD+, a vital coenzyme in all living cells, and this loss of NAD+ inside the macrophages somehow leads to necrotic cell death of the macrophage, which releases the M. tuberculosis bacteria to infect more cells. This necrotic death hijacked the macrophage away from its normal route to destroy engulfed bacteria -- lysosomal degradation of the bacteria inside the macrophage and programmed cell death, or apoptosis, of the macrophage. The present study shows how TNT helps win the battle between M. tuberculosis and the human immune system to control the fate of infected macrophages a critical fight that determines the outcome of the infection. Macrophages have genes for a canonical pathway to programed necrosis, known as necroptosis, that can be activated by the immune system. Surprisingly, when the researchers depleted NAD+ levels in uninfected macrophages by inhibiting an enzyme in the NAD+ salvage pathway, necrosis through the RIPK3 and MLKL pathway was also activated. This showed that NAD+ depletion alone, even when TNT and M. tuberculosis were not present, was sufficient to induce necroptosis. Lead researcher said that the finding that NAD+ depletion triggers programmed cell death to kill macrophages infected with M. tuberculosis. These could include use of FDA-approved drugs that decrease necroptosis, NAD+ replenishment for patients or use of reagents that promote mitochondrial function, all in combination with antibacterial drugs that are used to treat tuberculosis. These patient-targeted strategies could also apply to other bacterial and fungal pathogens that deplete NAD+. The role of RIPK3 as a cellular energy sensor may play a role in other diseases in which NAD+ deficiency is a common pathological factor, such as Type 2 diabetes and a variety of neurological and heart diseases. 

SOURCE: HealthDay News, July 2018

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 Peanut Allergies !

                               New test safely and accurately diagnoses peanut allergies

Researcher developed a new laboratory test to diagnose peanut allergy. The test has 98 per cent specificity and, unlike current options, it doesn't run the risk of false-positives or causing allergic reactions such as anaphylactic shock. The simple blood test is five times more cost-efficient compared to the oral food challenge (OFC) the standard food allergy test and could be adapted to test for other food allergies. Peanut allergies are among the most common food allergies in children. Currently, peanut allergy using a skin-prick test or IgE test but this may result in over-diagnosis or false-positives and it cannot differentiate between sensitivity and true food allergy. When skin-prick and IgE test results are unclear, allergists rely on an OFC, which consists of feeding peanut in incrementally larger doses to a patient in a highly-controlled setting in hospital to confirm allergy to the food. While the test is the gold-standard for diagnosing food allergies, there is risk of causing severe allergic reactions. Now, the researchers have developed a safer, accurate blood test in the lab. The new test, called the mast activation test (MAT), could act as a second line tool when skin-prick test results are inconclusive and before referring children and their families to specialists for an OFC. The lead researcher said that the current tests are not ideal. The new test is specific in confirming the diagnosis so when it's positive. It reduce by two-thirds the number of expensive, stressful oral food challenges conducted, as well as saving children from experiencing allergic reactions. Food allergy symptoms are triggered when allergens interact with an antibody called immunoglobulin E (or IgE). The food allergens activate IgE antibodies, triggering symptoms such as skin reactions, itching or constricting of the mouth, throat and airways, and digestive problems (such as stomach cramps, nausea or vomiting). The current skin-prick test and IgE test, which have been in use for decades, measure the presence of IgE antibodies. The new test focuses on mast cells, which play a crucial role in triggering allergic reactions. Mast cells activate by recognising the IgE in plasma and, in allergic patients, produce biomarkers associated with allergic reactions, which can be detected in the lab. The MAT test is five times cheaper to conduct than the OFC, which requires an allergist and specialist nurses on hand to monitor for adverse reactions and provide medical support if symptoms arise. The researchers believe the MAT test may have other uses, for example, in the food industry to detect the presence of allergens in products. Pharmaceutical companies could use it to monitor patients' allergic response to drugs being evaluated during clinical trials. The scientists plan to transition the biomarker test out of the laboratory and into a clinical setting. They will be testing blood samples from patients with suspected allergies to further validate its utility.

SOURCE: HealthDay News, July 2018

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 Breast Milk & Allergies !

Composition of complex sugars in breast milk may prevent future food allergies

The unique composition of a mother's breastmilk may help to reduce food sensitization in her infant. The findings, publishing in the June 15 issue of Allergy, further highlight the health role of human milk oligosaccharides (HMOs), which are not found in infant formula, and underscore their potential for therapeutic interventions. HMOs are structurally complicated sugar molecules unique to human breast milk. They are the third most abundant solid component in human milk after lactose (a different type of sugar) and fat. They are not actually digestible by infants, but act as a prebiotic, helping to guide development of the infant gut microbiota, which previous research suggests is a key influencer of allergic disease. Past research has shown that breastfed infants have a lower risk for a variety of medical conditions, such as wheezing, infections, asthma and obesity. Lead researcher analyzed milk samples and data from 421 infants and mothers participating in the CHILD Study, a longitudinal study tracking nearly 3,500 Canadian mothers and children from pregnancy to school age. Breast milk samples taken three-to-four months after birth were analyzed at the Larsson-Rosenquist Foundation Mother-Milk-Infant Center. At one year of age, infants were given skin prick tests to check for allergic sensitization to common allergens, including certain foods. A positive test is not necessarily proof of an allergy, but does indicate a heightened sensitivity. Sensitizations during infancy don't always persist into later childhood, but they are important clinical indicators and strong predictors of future allergic disease. The multidisciplinary team of scientists found that 59 of 421 infants (14 percent) displayed sensitization to one or more food allergens at age 1. No individual HMO was associated with food sensitization, but the overall HMO composition appeared to play a role. Composition of HMOs in breast milk is variable and determined by factors like lactation stage, gestational age, maternal health, ethnicity, geographic location and breastfeeding exclusivity. Researcher has identified a 'beneficial' HMO profile that was associated with a lower rate of food sensitization in children at one year," said Bode. "To our knowledge, this is the largest study to examine the association of HMOs and allergy development in infants, and the first to evaluate overall HMO profiles. This study establish long-term consequences of HMO composition on confirmed allergic disease in later childhood and begin to assess how HMO modification might be used therapeutically.

SOURCE: HealthDay News, July 2018

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 Red Meat & Heart Diseases !

Meat sensitivity spread by ticks linked to heart disease

Researchers have linked sensitivity to an allergen in red meat a sensitivity spread by tick bites with a buildup of fatty plaque in the arteries of the heart. This buildup may increase the risk of heart attacks and stroke. The bite of the lone star tick can cause people to develop an allergic reaction to red meat. However, many people who do not exhibit symptoms of the allergy are still sensitive to the allergen found in meat. UVA's new study linked sensitivity to the allergen with the increased plaque buildup, as measured by a blood test. This novel finding from a small group of subjects examined at the University of Virginia raises the intriguing possibility that asymptomatic allergy to red meat may be an under-recognized factor in heart disease. These preliminary findings underscore the need for further clinical studies in larger populations from diverse geographic regions. Looking at 118 patients, the researchers determined that those sensitive to the meat allergen had 30 percent more plaque accumulation inside their arteries than those without the sensitivity. Further, the plaques had a higher percentage with features characteristic of unstable plaques that are more likely to cause heart attacks. With the meat allergy, people become sensitized to alpha-gal, a type of sugar found in red meat. People with the symptomatic form of the allergy can develop hives, stomach upset, have trouble breathing or exhibit other symptoms three to eight hours after consuming meat from mammals. (Poultry and fish do not trigger a reaction.) Other people can be sensitive to alpha-gal and not develop symptoms. In fact, far more people are thought to be in this latter group. For example, up to 20 percent of people in central Virginia and other parts of the Southeast may be sensitized to alpha-gal but not show symptoms. There have been increasing numbers of cases of the meat allergy reported across the U.S., especially as the tick's territory grows. Previously found predominantly in the Southeast, the tick has now spread west and north, all the way into Canada. UVA's new study suggests that doctors could develop a blood test to benefit people sensitive to the allergen. This work raises the possibility that in the future a blood test could help predict individuals, even those without symptoms of red meat allergy, who might benefit from avoiding red meat. However, at the moment, red meat avoidance is only indicated for those with allergic symptoms.

SOURCE: HealthDay News, July 2018

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 Blood Diseases !

Relatively unknown gene linked to early emergence of blood diseases

Contribution of a specific gene in the proper development of blood cells that give rise to hematopoietic stem cells. Researcher also found that disruption of this gene resulted in various blood cancers and anemia in animal models. The findings identify a potential target for the development of treatments for some types of leukemia, anemia and other blood disorders. Many of the gene mutations associated with hematologic malignancies (cancers that affect the blood and lymph system) Frequently, the normal version of these genes are essential for making blood cells grow and mature, but researchers still lack a complete picture of disease-causing mutations. The study team used a genetic approach to investigate the earliest possible steps that occur in blood cells as they first bud from specific sites in the embryo called hemogenic endothelium. Using a genetic approach, the investigators traced back the mutations and found them in many of the previously known disease-causing genes, and also identified novel ones, like Pi4Ka, that resulted in disease. Working with several animal models and cell cultures, they learned that Pi4ka was associated with correct hematopoietic development. The gene was important for the maturation of certain blood cell types and when mutated, cells stopped maturing and further expanded leading to anemia and other blood anomalies. The contribution of Pi4Ka in normal hematopoiesis, particularly during the differentiation of red blood cells. It also showed that mutations in this gene at a hemogenic stage could result in erythroid and/or myeloid malignancies. The scientists further linked specific mutations of the Pi4ka gene in the emergence of cancer. The study identifies a new potential target for cancer and anemia therapies.

SOURCE: HealthDay News, July 2018

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New Products of SQUARE Pharmaceuticals Ltd.

  Product VolinacTM Gel
  Generic Name Diclofenac Sodium
  Strength 10 mg/gm
  Dosage form Gel
  Therapeutic Category NSAID
  Product Iventi-DTM   Eye Drops
Generic Name Moxifloxacin+Dexamethasone
Strength 0.50%+0.1%
Dosage form Eye Drops
Therapeutic Category Antiinfective and Intiinflammatory combination
  Product SuvotolTM
  Generic Name Suvorexant
  Strength 10 mg
  Dosage form Tablet
  Therapeutic Category Sedative Hypnotic

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