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Balakumar P.,AIMST University | Maung-U K.,U.S. Food and Drug Administration | Jagadeesh G.,U.S. Food and Drug Administration
Pharmacological Research | Year: 2016

Noncommunicable diseases (NCDs) have become important causes of mortality on a global scale. According to the report of World Health Organization (WHO), NCDs killed 38 million people (out of 56 million deaths that occurred worldwide) during 2012. Cardiovascular diseases accounted for most NCD deaths (17.5 million NCD deaths), followed by cancers (8.2 million NCD deaths), respiratory diseases (4.0 million NCD deaths) and diabetes mellitus (1.5 million NCD deaths). Globally, the leading cause of death is cardiovascular diseases; their prevalence is incessantly progressing in both developed and developing nations. Diabetic patients with insulin resistance are even at a greater risk of cardiovascular disease. Obesity, high cholesterol, hypertriglyceridemia and elevated blood pressure are mainly considered as major risk factors for diabetic patients afflicted with cardiovascular disease. The present review sheds light on the global incidence of cardiovascular disease and diabetes mellitus. Additionally, measures to be taken to reduce the global encumbrance of cardiovascular disease and diabetes mellitus are highlighted. © 2016

Balakumar P.,AIMST University | Jagadeesh G.,U.S. Food and Drug Administration
Journal of Molecular Endocrinology | Year: 2014

The renin-angiotensin system (RAS) plays an important role in the pathophysiology of cardiovascular disorders. Pharmacologic interventions targeting the RAS cascade have led to the discovery of renin inhibitors, angiotensin-converting enzyme inhibitors, and AT1receptor blockers (ARBs) to treat hypertension and some cardiovascular and renal disorders. Mutagenesis and modeling studies have revealed that differential functional outcomes are the results of multiple active states conformed by the AT1receptor upon interaction with angiotensin II (Ang II). The binding of agonist is dependent on both extracellular and intramembrane regions of the receptor molecule, and as a consequence occupies more extensive area of the receptor than a non-peptide antagonist. Both agonist and antagonist bind to the same intramembrane regions to interfere with each other’s binding to exhibit competitive, surmountable interaction. The nature of interactions with the amino acids in the receptor is different for each of the ARBs given the small differences in the molecular structure between drugs. AT1receptors attain different conformation states after binding various Ang II analogues, resulting in variable responses through activation of multiple signaling pathways. These include both classical and non-classical pathways mediated through growth factor receptor transactivations, and provide cross-communication between downstream signaling molecules. The structural requirements for AT1receptors to activate extracellular signal-regulated kinases 1 and 2 through G proteins, or G proteinindependently through β-arrestin, are different. We review the structural and functional characteristics of Ang II and its analogs and antagonists, and their interaction with amino acid residues in the AT1receptor. © 2014 Society for Endocrinology Printed in Great Britain.

Balakumar P.,AIMST University | Jagadeesh G.,U.S. Food and Drug Administration
Cellular Signalling | Year: 2014

Ang II, the primary effector pleiotropic hormone of the renin-angiotensin system (RAS) cascade, mediates physiological control of blood pressure and electrolyte balance through its action on vascular tone, aldosterone secretion, renal sodium absorption, water intake, sympathetic activity and vasopressin release. It affects the function of most of the organs far beyond blood pressure control including heart, blood vessels, kidney and brain, thus, causing both beneficial and deleterious effects. However, the protective axis of the RAS composed of ACE2, Ang (1-7), alamandine, and Mas and MargD receptors might oppose some harmful effects of Ang II and might promote beneficial cardiovascular effects. Newly identified RAS family peptides, Ang A and angioprotectin, further extend the complexities in understanding the cardiovascular physiopathology of RAS. Most of the diverse actions of Ang II are mediated by AT1 receptors, which couple to classical Gq/11 protein and activate multiple downstream signals, including PKC, ERK1/2, Raf, tyrosine kinases, receptor tyrosine kinases (EGFR, PDGF, insulin receptor), nuclear factor κB and reactive oxygen species (ROS). Receptor activation via G12/13 stimulates Rho-kinase, which causes vascular contraction and hypertrophy. The AT1 receptor activation also stimulates G protein-independent signaling pathways such as β-arrestin-mediated MAPK activation and Src-JAK/STAT. AT1 receptor-mediated activation of NADPH oxidase releases ROS, resulting in the activation of pro-inflammatory transcription factors and stimulation of small G proteins such as Ras, Rac and RhoA. The components of the RAS and the major Ang II-induced signaling cascades of AT1 receptors are reviewed. © 2014 Elsevier Inc.

Chidambaram R.,AIMST University
Recent Patents on Anti-Infective Drug Discovery | Year: 2015

Chronic kidney disease, (CKD) a gradual and inevitable deterioration in renal function, is the disease with the most associations in dentistry. Dosage adjustment is one amongst the vital elements to be familiar with during their oral care. CKD patients take extended duration to filter out medications, therefore dosage must always be tailored under the supervision of nephrologist. The relished benefits from antibiotic could transform as anti-microbial resistance on their abuse and nephrotoxic when contraindicated drugs are encouraged. New patented drug belonging to oxazoliodine group has driven the researchers to handle the emerging AMR. The present communication discusses the pharmacological factors influencing in prescribing the antibiotics for CKD patient from the dentist’s point of view. The formulas destined for calculating the optimal dosage of antibiotics have been documented to aid oral physicians. © 2015 Bentham Science Publishers.

Balakumar P.,AIMST University | Dhanaraj S.A.,AIMST University
Cellular Signalling | Year: 2013

Dipeptidyl peptidase 4 (DPP-4) is a serine protease enzyme expressed widely in many tissues, including the cardiovascular system. The incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released from the small intestine into the vasculature during a meal, and these incretins have a potential to release insulin from pancreatic beta cells of islets of Langerhans, affording a glucose-lowering action. However, both incretins are hurriedly degraded by the DPP-4. Inhibitors of DPP-4, therefore, enhance the bioavailability of GLP-1 and GIP, and thus have been approved for better glycemic management in patients afflicted with type 2 diabetes mellitus (T2DM). Five different DPP-4 inhibitors, often called as 'gliptins', namely sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin have been approved hitherto for clinical use. These drugs are used along with diet and exercise to lower blood sugar in diabetic subjects. T2DM is intricately related with an increased risk of cardiovascular disease. Growing body of evidence suggests that gliptins, in addition to their persuasive anti-diabetic action, have a beneficial pleiotropic action on the heart and vessels. In view of the fact of cardiovascular disease susceptibility of patients afflicted with T2DM, gliptins might offer additional therapeutic benefits in treating diabetic cardiovascular complications. Exploring further the cardiovascular pleiotropic potentials of gliptins might open a panorama in impeccably employing these agents for the dual management of T2DM and T2DM-associated perilous cardiovascular complications. This review will shed lights on the newly identified beneficial pleiotropic actions of gliptins on the cardiovascular system. © 2013 Elsevier Inc.

Chidambaram R.,AIMST University
Malaysian Journal of Medical Sciences | Year: 2015

Complexity in the health status of patients with kidney disease forces to seek the aid of medical devices such as the central venous catheter (CVC) that is essential in order to perform hemodialysis. Elementary information about the CVC, as required for the oral healthcare professionals, has been documented so as to serve as a medical manual. This communication is the first of its kind that conjointly delineates vital considerations, which precede dental maneuvers in patients implanted with a CVC. © Penerbit Universiti Sains Malaysia, 2015.

Ramasamy C.,AIMST University
Asian Journal of Pharmaceutical and Clinical Research | Year: 2014

Antibiotics are used in dentistry to treat an existing infection therapeutically or to prevent an infection prophylactically. They are cardinal in the management and prophylaxis of infection in patients at risk of experiencing microbial disease. Endodontics is the field of choice where antibiotics are used extensively. In addition, they are used to aid the host defences in the elimination of remaining bacteria. Most frequently, antibiotics are used and misused by dentists themselves. Dentists need to update the occurent knowledge of pharmacology, pertaining to antibiotics and its indications in dental office. The present communication highlights the relative contraindications of antibiotics for an endodontist in routine dental practice.

Sein K.K.,AIMST University
Midwifery | Year: 2013

Objective: to examine the postpartum beliefs and practices among young women (15-24 years). Design: both quantitative and qualitative approaches were used: a cross-sectional comparative study using a semi-structured questionnaire and focus group discussions (FGDs). Setting: Kyimyindaing Township in the western district of Yangon, Myanmar. Participants: young women (15-24 years) who had experience of at least one live birth were included. A total of 196 women for a quantitative survey and 31 women for FGDs were recruited. Measurement and findings: postpartum beliefs and practices at the last childbirth were explored by a pretested semi-structured questionnaire and four FGDs (two in urban and two in rural areas). The survey questionnaire covered socio-demographic data, food and behavioural restrictions and observances during the last postpartum period and underlying reasons for those practices. Majority of participants followed the traditional postpartum practices regardless of the area of residence and education level. Notion of 'dirty lochia' was identified. Key conclusions: traditional beliefs and practices surrounding post partum were highly prevalent among young women. Variation in degree and duration of adherence to postpartum taboos was noted. These beliefs and practices were imparted and perpetuated by women's close social network. Implications for practice: the findings point out the importance of awareness of postpartum beliefs and practices among health staff for providing culturally sensitive health care and gaining better co-operation and mutual understanding in giving health care. © 2012 Elsevier Ltd.

Adhikary A.K.,AIMST University | Banik U.,AIMST University
Journal of Clinical Virology | Year: 2014

Human adenovirus type 8 (HAdV-8) is the most common causative agent of a highly contagious eye disease known as epidemic keratoconjunctivitis (EKC). HAdV-8 strains have been classified into genome types HAdV-8A to 8K and HAdV/D1 to D12 according to restriction endonuclease analysis. This review focuses on the significance of HAdV-8 as an agent of EKC. Molecular analysis of HAdV-8 genome types HAdV-53 and HAdV-54 was performed to reveal potential genetic variation in the hexon and fiber, which might affect the antigenicity and tropism of the virus, respectively. On the basis of the published data, three patterns of HAdV-8 genome type distribution were observed worldwide: (1) genome types restricted to a microenvironment, (2) genome types distributed within a country, and (3) globally dispersed genome types. Simplot and zPicture showed that the HAdV-8 genome types were nearly identical to each other. HAdV-54 is very close to the HAdV-8P, B and E genomes, except in the hexon. In a restriction map, HAdV-8P, B, and E share a very high percentage of restriction sites with each other. Hypervariable regions (HVRs) of the hexon were conserved and were 100% identical among the genome types. The fiber knob of HAdV-8P, A, E, J and HAdV-53 were 100% identical. In phylogeny, HVRs of the hexon and fiber knob of the HAdV-8 genome types segregated into monophyletic clusters. Neutralizing antibodies against one genome type will provide protection against other genome types, and the selection of future vaccine strains would be simple due to the stable HVRs. Molecular analysis of whole genomes, particularly of the capsid proteins of the remaining genome types, would be useful to substantiate our observations. © 2014 Elsevier B.V.

Chidambaram R.,AIMST University
Asian Pacific Journal of Tropical Biomedicine | Year: 2014

Antibiotic treatment is a form of pharmacotherapy with the specialty of rendering both etiological and curative action. Dentists traditionally administer antibiotics, to restrain contagions and to handle the prevailing dental ailments. Penicillins have been the drug of choice to be opted by the dental practitioners in their routine dental practice. Prudent application of antibiotics in concoction with surgical therapy is the most pertinent mode to cure odontogenic contagions. Considerable prescriptions of antibiotics are ascribed especially in cases which induce bleeding in the oral cavity. Regardless of the obvious indications, perplexity prevails between the oral health care professional's pertaining to the administration of antibiotics in coalition with dental maneuvers. Dreadful ailments have been cured after the incipience of antibiotics in 1929. Besides it also leads to cumbersome consequences by virtue of its misuse. Irrational usage of antibiotic therapy leads to false positive effects on both health and financial grounds and poses a threat to the microbial resistance. The present communication aims to delineate the absolute indications, consequences of abuse and imperative factors to be considered while prescribing antibiotics in routine dental practice. © 2014 by the Asian Pacific Journal of Tropical Biomedicine.

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