Anticoagulants for the treatment of acute coronary syndrome in the era of new oral agents

Acute coronary syndromes (ACS) cause cessation of myocardial blood flow leading to coronary ischemia. The standard medical treatment includes heparin or low molecular weight heparin in the hospital, antiplatelet agents in the hospital and long term, and occasionally warfarin long term. All of these therapies are associated with bleeding complications. Furthermore, warfarin, with its narrow therapeutic window and need for frequent laboratory monitoring, poses several disadvantages. The development of novel oral factor Xa inhibitors and oral direct thrombin inhibitors may provide an alternative to warfarin. In this review, we discuss the new agents, rivaroxaban, apixaban, and dabigatran, for the potential treatment of ACS. We also review the relevant clinical trials evaluating their effects in ACS. These novel anticoagulants allow convenience of use with no requirement for laboratory monitoring and limited drug interactions, which may provide multifaceted treatment options for ACS and anticoagulation in the future.     

A case of rhabdomyosarcoma masquerading as acute leukemia at presentation: a case report

Non-hematopoietic malignancies infiltrating bone marrow have always been a source of erroneous diagnosis. Among these, the small round cell tumors like neuroblastomas and rhabdomyosarcomas mimick the hematopoietic blasts. Several case reports of rhabdomyosarcoma mimicking acute leukemia, clinically and morphologically at presentation have been reported in the literature. To the best of our knowledge such an entity has not been reported in Indian literature. We report here one such case of alveolar rhabdomyosarcoma masquerading as acute leukemia. A thorough clinical examination with high degree of suspicion on bone marrow morphology and judicious use of appropriate immunohistochemistry markers will solve many of these cases.     

The HLA 8.1 ancestral haplotype is strongly linked to the C allele of -429T>C promoter polymorphism of receptor of the advanced glycation endproduct (RAGE) gene. Haplotype-independent association of the -429C allele with high hemoglobinA1C levels in diabetic patients

Previously we reported on strong linkage disequilibrium (LD) between the mono-S-C4B-RCCX module (mono-S) and the TNF2 allele (both known constituents of the 8.1 ancestral haplotype (8.1 AH)) in two Caucasian populations. The gene for the receptor of advanced glycation endproducts (RAGE) is encoded between the RCCX module and the HLA class II genes in the central MHC region. In order to assess the relationship between the promoter polymorphisms of the RAGE gene and the 8.1 AH, we performed a family study in eight informative families affected with type 1 diabetes mellitus; haplotypes of a RAGE promoter SNP (-429T>C) with the HLA-DQ2, -DR-3(17) and TNF2 alleles, as well as the mono-S genotype were determined. A similar analysis was performed in 82 unrelated patients with type 1 diabetes mellitus, and in unrelated healthy individuals of three different Caucasian populations (Hungarians, Ohioian females, Icelandics). In the diabetic patients clinical correlations were also investigated. Out of the 32 paternal and maternal chromosome 6 from the eight families, 15 different MHC haplotypes were found. Haplotypes containing at least three of the known constituents of the 8.1 AH (HLA-DQ2, -DR17, mono-S, TNF2) were always linked to the RAGE -429C allele. The RAGE -429C allele exhibited highly significant (p<0.0001) LD coefficients to known constituents of the 8.1 AH both in healthy persons and patients with type 1 diabetes. In the group of patients with diabetes we found significantly (p=0.013) higher maximal hemoglobinA1C concentration in the carriers of the RAGE -429C allele, this trait, however was not linked to the 8.1 AH. Our present findings indicate that the RAGE -429C allele can be considered as a candidate member of the 8.1 AH. The results also reveal a spectrum of recombinant MHC haplotypes in addition to the conserved ancestral haplotypes.     

Gossypol stimulates opening of a Ca2+‐ and Na+‐permeable but Ni2+‐ and Co2+‐impermeable pore in bEND.3 endothelial cells

Gossypol, a polyphenolic dialdehyde toxin isolated from cotton seed, has anti‐cancer properties and has recently shown some success in the treatment of glioma. Its effects on brain neurons and blood vessels are poorly understood. In this work we examined the effects of gossypol on cytosolic Ca²⁺ concentration ([Ca²⁺]_i) of mouse brain bEND.3 endothelial cells. Cell viability tests revealed that after 3 hour and 18 hour exposures, 10 µmol/L gossypol caused 23% and 65% cell death, respectively; 3 µmol/L gossypol caused no and 21% cell death, respectively. [Ca²⁺]_i was raised concentration‐dependently by 1‐10 µmol/L gossypol. We then explored the Ca²⁺ signalling triggered by 3 µmol/L gossypol, which inflicted minimal toxicity: the Ca²⁺ signal was composed largely of Ca²⁺ influx and to a small extent, intracellular Ca²⁺ release. Such Ca²⁺ influx was much larger than store‐operated Ca²⁺ influx triggered by maximal Ca²⁺ pool depletion. The Ca²⁺ influx triggered by 3 and 10 µmol/L gossypol caused NO release and cell death, respectively. Gossypol also triggered influx of Mn²⁺ and Na⁺, but not Ni²⁺ and Co²⁺. Gossypol‐triggered Ca²⁺ signal was inhibited only by 14% and 37% by 100 µmol/L La³⁺ and 10 µmol/L nimodipine, respectively; and not suppressed at all by 5 mmol/L Ni²⁺. Gossypol‐triggered Ca²⁺ signal was suppressed by 78% by 30 µmol/L ruthenium red, suggesting gossypol may act on TRPV channels. Our results suggest gossypol triggered opening of a non‐selective cation pore, possibly a member of the TRPV family.     

Personal Income and Substance Use among Emerging Adults in the United States

Background: Taxation and other policy measures have been implemented across the United States to curb the accessibility of substance use, especially among youth. While the inverse relationship between price and youth consumption is well known, available research on youth earned income and substance use is sparser, particularly among emerging adults. Objectives: We examined the association between emerging adult past-year personal income and 30-day substance use. Methods: We analyzed data from Wave 5 (n = 2,202) of the NEXT Generation Health Study, an annual survey study administered to a nationally representative sample of emerging adults in the U.S. Wave 5 (mean age = 20.28 years, SE = 0.02 years) was administered during the 2013–2014 academic year. After grouping participants into five levels of self-reported, pre-tax personal income, we used binomial logistic regression to examine the association between personal income and cigarette smoking, marijuana use, alcohol use, and heavy episodic drinking (HED). Results: In unadjusted models, those at certain levels of higher past-year income were more likely to smoke cigarettes, consume alcohol, or engage in HED at least once in the past 30 days. Several associations remained significant after controlling for covariates. Most associations were no longer significant after including perceived peer norms as additional covariates. Personal income was not associated with 30-day marijuana use in unadjusted or adjusted models. Conclusions/Importance: Higher earned income may provide emerging adults greater economic access to cigarettes and alcohol, but the association might be partly attenuated by social factors, particularly perceived peer norms.