Intron-specific Single Nucleotide Polymorphisms of Fat Mass and Obesity- Associated Gene in Obese and Overweight Individuals of the Indian Adult Population- A Pilot Study.

BACKGROUND: The Fat mass and obesity-associated gene (FTO) and its involvement in weight gain and obesity is well-known. However, no reports have been published on the Indian population regarding the relationship between single nucleotide polymorphisms (SNPs) in its intronic region and obesity. The aim of this pilot study was to evaluate the frequency and association of SNPs in intron-1 of the FTO gene in obese and overweight Indian adults. METHODS: This study group consisted of 80 adults, aged 23.5 ± 8.9 yr, with a mean BMI of 28.8 ± 6.2 kg/m2. Genomic DNA was isolated, exons1-3 & intron1 of FTO were amplified using polymerase chain reaction and sequenced by ABI sequencing detection system. The reported SNPs rs1420185, rs8050136, rs1121980 and rs55872725 were checked for their presence or absence in this group of the adult Indian population. RESULTS: No mutations were found in the exonic sequence of FTO, however, the association of rs1420185, rs8050136, rs1121980 and rs55872725 SNPs was identified in this population. The genotypic frequency at FTO rs8050136 was 32.2% for C>A, at rs55872725 it was 45.7% for C>T, at rs1420185 it was 27.1% for T>C and at rs1121980 it was 30.5% for G>A. All four SNPs in combination were observed in 6 participants (10.2%), all of whom were found to be either obese or overweight. CONCLUSION: These findings indicate that Indians with these SNPs are most likely to be at increased risk of obesity.

Antiplatelet and Anticoagulant Therapies for Prevention of Ischemic Stroke.

Ischemic stroke represents one of the leading causes of death and disability in both the United States and abroad, particularly for patients with prior ischemic stroke or transient ischemic attack (TIA). A quintessential aspect of secondary stroke prevention is the use of different pharmacological agents, mainly antiplatelets and anticoagulants. Antiplatelets and anticoagulants exhibit their effect by blocking the activation pathways of platelets and the coagulation cascade, respectively. Clinical trials have demonstrated the safety and efficacy of antiplatelets for noncardioembolic stroke prevention, while anticoagulants are more often used for cardioembolic stroke prevention. Commonly used antiplatelets include aspirin, clopidogrel, and aggrenox (aspirin plus extended-release dipyridamole). Furthermore, commonly used anticoagulants include warfarin, dabigatran, rivaroxaban, apixaban, and edoxaban. Each of these drugs has a unique mechanism of action, and they share some common adverse events such as gastrointestinal bleeding and intracranial hemorrhage in more serious cases. Consequently, physicians should carefully assess the benefits and risks of using different antiplatelet or anticoagulant therapies when managing patients with previous ischemic stroke or TIA. This review discuses the published literature on major clinical trials assessing the efficacy of different antiplatelet and anticoagulant drugs under varying circumstances and the subsequent guidelines that have been developed by the American Heart Association/American Stroke Association. Additionally, the role of imaging in stroke prevention is discussed.

Comparison of relative waist circumference between Asian Indian and US adults.

BACKGROUND: Relative to Europeans, Asian Indians have higher rates of type 2 diabetes and cardiovascular disease. Whether differences in body composition may underlie these population differences remains unclear. METHODS: We compared directly measured anthropometric data from the Chennai Urban Rural Epidemiology Study (CURES) survey of southern Indians (I) with those from three US ethnic groups (C: Caucasians, A: African Americans, and M: Mexican Americans) from NHANES III (Third National Health and Nutrition Examination Survey). A total of 15,733 subjects from CURES and 5,975 from NHANES III met inclusion criteria (age 20-39, no known diabetes). RESULTS: Asian Indian men and women had substantially lower body mass index, waist circumference, hip circumference, waist-to-hip ratio, and body surface area relative to US groups (P values <0.0001). In contrast, the mean (±se) waist-weight ratio was significantly higher (P < 0.001) in I (men 1.35 ± 0.002 and women 1.45 ± 0.002) than in all the US groups (1.09, 1.21, and 1.14 in A, M, and C men; 1.23, 1.33, and 1.26 in A, M, and C women (se ranged from 0.005 to 0.006)). CONCLUSIONS: Compared to the US, the waist-weight ratio is significantly higher in men and women from Chennai, India. These results support the hypothesis that Southeast Asian Indians are particularly predisposed toward central adiposity.

Intracerebral hemorrhage: a review of coagulation function.

Intracerebral hemorrhage (ICH) is associated with a higher mortality rate among stroke subtypes. The amount of hematoma at baseline and subsequent expansion are considered strong independent markers for determining poor clinical outcome. Even though reduction in blood pressure to prevent and control the amount of bleeding in ICH has received considerable amount of attention, the impact of coagulopathy and platelet dysfunction, on the bleeding diathesis has not been extensively investigated. With the increasing use of antiplatelets and/or anticoagulants, given the aging population, a deeper understanding of the interactions between ICH and hemostatic mechanisms is essential to help minimize the risk of a catastrophic coagulopathy-related ICH. In this review article, etiology and risk factors associated with coagulopathy-related ICH are discussed. An overview of coagulation abnormalities, hemostatic agents, and blood biomarkers pertaining to ICH is included.

Antiplatelet therapy: aspirin resistance and all that jazz!

Platelets play a crucial role in the pathogenesis of atherosclerosis, thrombosis, and stroke. Aspirin used alone or in combination with other antiplatelet drugs has been shown to offer significant benefit to patients at high risk of vascular events. Resistance to the action of aspirin may decrease this benefit. Aspirin resistance has been defined by clinical and/or laboratory criteria; however, detection by laboratory methods prior to experiencing a clinical event will likely provide the greatest opportunity for intervention. Numerous laboratory methods with different cutoff points have been used to evaluate the resistance. Noncompliance with aspirin treatment has also confounded studies. A single assay is currently insufficient to establish resistance. Combinations of results to confirm compliance and platelet inhibition may identify "at-risk" individuals who truly have aspirin resistance. The most effective strategy for managing patients with aspirin resistance is unknown; however, studies are currently underway to address this issue.

Bone regeneration in extraction sockets with autologous platelet rich fibrin gel.

AIM: To evaluate the effects of autologous platelet rich fibrin gel (PRF gel) on bone regeneration following extraction. MATERIALS AND METHODS: The study design was approved by the Institutional Ethical Committee. Study sample consisting of a total of 22 patients requiring bilateral transalveolar third molar extractions were included after written informed consent. One side was randomly chosen as case and the other side was the control. Autologous PRF gel was prepared from Fresh blood obtained from the patient. The PRF gel was placed in the extraction site and primary closure was obtained. The patient was called for a follow up on the first post op day, 1st week, one month, three month and six months post op. Regeneration of bone was measured using serial radiographs (RVG) at immediate post op, one, three and six months. This was then compared with the bone regeneration seen in the control group, with the radiographs taken at same intervals, to estimate the difference in bone regeneration if any. RVGs were assessed for amount of radiologic bone filling by the method described by Matteo Chiapasco et al. RESULTS AND CONCLUSION: Higher mean pixels was recorded in cases compared to controls at all the time intervals viz., immediate post op, 1 month post op, 3 months post op and 6 months post op. However, the difference in the mean pixels recorded between the two groups was not statistically significant (P > 0.05). For complete analysis, further follow up of the present patients and a larger sample size is required to obtain a conclusive result of the Bone Regeneration in extraction sockets with PRF gel.

Aspirin prophylaxis for the prevention of thrombosis: expectations and limitations.

Platelets play a very important role in the pathogenesis of acute vascular events leading to thrombosis of the coronary and cerebral arteries. Blockage of these arteries leading to regional ischemia of heart and brain tissues precipitate heart attacks and stroke. Acetyl salicylic acid (Aspirin) has been the drug of choice for over half a century for the primary and secondary prophylaxis of thrombotic events. In spite of its extensive use as an antiplatelet drug for the prevention of vascular thrombosis, there is considerable concern about the degree of protection it offers, to patients under aspirin therapy. In this paper, we explain the phenomenon of aspirin resistance, discuss the limitations of aspirin therapy, and suggest methods to monitor "at-risk" individuals. Ability to monitor and determine at risk patients will provide opportunities for the clinicians to customize antiplatelet therapies.

Oral versus vaginal combined hormonal contraceptives' effect on coagulation and inflammatory biomarkers among young adult women.

In order to compare the effect of combined oral contraceptive (COC) and combined vaginal contraceptive (CVC) methods on the inflammation and procoagulation, we recruited female participants in 3 groups: control participants, COC users, and CVC users. We measured different blood biomarkers. The users of both COC and CVC had higher levels of C-reactive protein (P < .0001) and factor VII (P < .0001). However, CD40 ligand was only higher for COC users (P < .0001) and not the CVC users. Even though the levels of thrombin/antithrombin III were not higher for COC and CVC users, as compared to the controls, CVC users had higher levels as compared to COC users (P = .0327). As compared to the control group, we observed higher levels von Willebrand factor among CVC users but not the COC users. Longitudinal studies with larger sample size are needed to better assess the inflammatory and procoagulation response due to CVC use.

Measurement of shear-activated platelet aggregate formation in non-anticoagulated blood: utility in detection of clopidogrel-aspirin-induced platelet dysfunction.

We studied the ability of a new instrument, the PlaCor PRT that measures shear-induced platelet aggregation in fingerstick, non-anticoagulated blood without added agonists, to detect platelet dysfunction ex vivo. Platelet reactivity time (PRT) and whole blood aggregation (WBA) were measured in 160 healthy volunteers, before and after aspirin and in 170 participants with established vascular disease or risk factors thereof treated with aspirin ± clopidogrel. Pretreatment PRT and WBA were significantly correlated (collagen r = -.63; arachidonate r = -.65; P < .0001). Following aspirin, the mean PRT increased from 82 to 142 seconds (P < .0001), and in participants treated with clopidogrel-aspirin, the mean PRT (286 seconds, n = 65) was significantly longer than with aspirin alone (166 seconds, n = 105; P < .001). Only 13% of PRTs of participants treated with clopidogrel and aspirin were within the normal range. We conclude that the PlaCor PRT is a simple, rapid, point-of-care instrument that compares favorably with published descriptions of other platelet function instruments.

Vascular disease: obesity and excess weight as modulators of risk.

Coronary artery diseases leading to heart attacks and cerebral artery disease leading to stroke rank number one and two respectively, in causing acute vascular events. Thrombosis of the veins and pulmonary embolism are major causes of hospital-associated acute vascular events. Increased bodyweight at all stages of life, from the very beginning of life (intrauterine growth), to adulthood, promote risks that are associated with vascular disease. An increase in bodyweight promotes risk factors for developing acute vascular events by a variety of mechanisms. In this article, we briefly describe some of the major risks associated with vascular diseases leading to vascular injury, and the modulatory role that increased bodyweight plays in promoting these risks.

Management of type-2 diabetes with anti-platelet therapies: special reference to aspirin.

Adult onset diabetes currently affects 380 million individuals worldwide and is expected to affect 380 million by 2025. Major defects contributing to this complex disease are insulin resistance and beta cell dysfunction. More than 80% of patients professing to type-2 diabetes are insulin resistant. Recent studies have shown that the Indian subcontinent ranks very high in the occurrence of Diabetes and Coronary artery disease (1, 2, 3). Patients with Type 2 diabetes carry an equivalent cardiovascular risk to that of a non-diabetic individual who has already experienced a coronary event. The risk of coronary artery disease in any given population seems to be 2-3 times higher in diabetics than non-diabetics. Inflammation, platelet activation, endothelial dysfunction and coagulation are the four processes, whose interplay determines the development of cardiovascular disease. In this article, we provide a brief overview on platelet physiology, vascular dysfunction, platelet hyper-function, and the role of platelet related clinical complications in diabetes mellitus and what is know about the management of this complex disease with anti-platelet drugs such as aspirin and Clopidogrel.

Effect of blood soluble clotting factors on coagulation profile.

OBJECTIVE: Recently, mechanical thrombolytic therapy has been introduced as an alternative or adjunct to pharmaceutical thrombolytic therapy in removing thrombus from vascular system. Recurrent thrombosis has been a challenge for thrombolytic therapies. We hypothesize that soluble clotting factors released during a mechanical thrombectomy procedure may be responsible for creating a localized hypercoagulable state and could be one of the underlying causes of recurrent thrombosis. METHOD: Blood samples were obtained from 20 participants with no history of hypertension, vascular disease, and antiplatelet/anticoagulation therapy. For each whole blood (WB) sample, we measured activated clotting time (ACT) and clotting rate (CR) at the baseline and then with added agitated and nonagitated clot serums. The same set of measurements was performed on platelet-rich plasma (PRP) samples of each participant. We tested for changes in coagulation profile between baseline samples and those with added supernatant serums obtained from autologous blood clot. RESULT: We observed a significant decrease in ACT for WB with agitated and nonagitated clot serums (49%, P < .0001 and 25%, P = .01, respectively) compared to the baseline WB. The same trend was observed for PRP samples with agitated and nonagitated clot serums (28%, P = .002 and 18%, P = .05, respectively). The CR was increased (a steeper slope) by 83% for samples with added agitated clot serum only (P = .007). CONCLUSION: We observed a significant change for ACT in WB samples with added clot serums as compared to the baseline WB samples. The results of this study suggest that the soluble substances released from clotting blood have profound procoagulant effects.

Past, present, and future of anti-platelet therapy.

INTRODUCTION: Anti-platelet drugs are useful in preventing unwanted clots, but the complexities of platelet activation and clot formation are challenging. BACKGROUND: Platelets can be activated by a variety of agents, including natural biomolecules, foreign materials, and drugs. Calcium mediates a number of the intracellular processs Once activated, platelets release factors that act on other circulating cells and vascular endothelial cells to promote formation of a clot. The original anti-platelet drug, aspirin, inhibits cyclooxegenase, interfering with a crucial step in the biochemical cascade. Aspirin is cost-effective but limited in its application. Newer drugs, ticlopidine and clopidogrel, act on the activation pathway at different points, so they can supplement aspirin. NEW DIRECTIONS: Abciximab represents a new generation of antiplatelet drug, being an antibody that binds to platelet surface receptors, thus inhibiting growth of thrombus. Other potential sites for antibody intervention are extracellular matrix and endothelial surface components. As new drugs are developed it becomes more imperative to find assays of platelet function that are sensitive and cost-effective. CONCLUSION: Although much progress has been made in anagement of clotting significant opportunities and challenges remain, both in treatment and in measurement of treatment effectiveness.

Aspirin resistance: does it exist?

Aspirin irreversibly inhibits platelet cyclooxygenase-1 (COX-1). Aspirin sensitivity can be measured easily by its inhibition of arachidonic acid (AA) -induced platelet aggregation. Aspirin resistance has to be defined by its inability to inhibit COX-1. By using this definition, aspirin resistance very likely does not exist. A specific rapid laboratory test using either AA-induced platelet aggregation or AA-induced malondialdehyde production in platelet-rich plasma is needed to test aspirin sensitivity. The reports on so-called aspirin resistance are usually due to noncompliance of aspirin intake or consumption of inadequate doses of aspirin. In addition, data generated from using nonspecific platelet function tests have added confusion to this observed phenomenon of aspirin resistance.