Synthesis of 1,2,3-triazole tethered bifunctional hybrids by click chemistry and their cytotoxic studies

In view of the drug resistance with most of the currently used anticancer drugs, molecular hybrids of pyrazolyl chalcones and p-nitro benzyl functionalities tethered by triazole ring have been synthesised and evaluated for cytotoxic studies against three human cancer cell lines (THP, COLO-205, A-549). The results of the preliminary investigation exhibited marked dependence of the cytotoxic activity on the electronic factors. Placement of naphthyl (JGPT-11) and trimethoxy phenyl ring (JGPT-6) as ring A proved to be extremely beneficial in enhancing the cytotoxic potential. Thus we herein report the synthesis and cytotoxic studies of a new class of molecular hybrids. Detailed investigation on the biological mechanistic insights of JGPT-11 and 6 is under progress.     

Controversies in neuro-ophthalmology: Steroid therapy for traumatic optic neuropathy

Background:There is an increase in the incidence of traumatic optic neuropathy (TON) due to increasing urbanization and rapid spurt in the number of motor vehicles on the road. Despite early presentation and ease of diagnosis the visual outcomes in TON are still limited. There is also significant confusion about the timing, dose and efficacy of steroid treatment in its management.Purpose:To provide a clinical update of the pros and cons of steroid therapy for TON.Design:The paper is a retrospective review of the currently available literature in the English language indexed in PubMed.Methods:A PubMed search was conducted by the authors using the following terms: Traumatic optic neuropathy, megadose, steroids, methylprednisolone. Relevant original articles, review articles, and case reports related to the topic of discussion were evaluated and discussed in the paper.Results:There is no prospective randomized control trial evaluating the effect of steroids in TON. There are varying reports on the effect of steroid therapy from significant improvement to no difference compared to observation.Conclusion:The decision to give steroids to patients with TON has to be on an individual case to case basis and must involve informed consent from the patient. There are documented advantages and disadvantages of steroid therapy and a prospective, randomized, controlled trial is necessary comparing steroids, surgery and observation before definitive management can be evolved.     

Pseudolipoma of the Inferior Vena Cava

Pseudolipoma of inferior vena cava refers to a normal variant of adipose collection that is seen in typical pericaval or juxtacaval location; however, it mimics an intracaval mass lesion, especially fat-containing lesions such as lipoma. Awareness of this entity is very important to avoid misdiagnosis and unnecessary diagnostic procedures.     

Melatonin and serotonin: Mediators in the symphony of plant morphogenesis

Melatonin and serotonin are important signaling and stress mitigating molecules that play important roles across growth and development in plants. Despite many well‐documented responses, a systematic investigation of the entire metabolic pathway (tryptophan, tryptamine, and N‐acetylserotonin) does not exist, leaving many open questions. The objective of this study was to determine the responses of Hypericum perforatum (L.) to melatonin, serotonin, and their metabolic precursors. Two well‐characterized germplasm lines (#4 and 112) created by mutation and a haploid breeding program were compared to wild type to identify specific responses. Germplasm line 4 has lower regenerative and photosynthetic capacity than either wild type or line 112, and there are documented significant differences in the chemistry and physiology of lines 4 and 112. Supplementation of the culture media with tryptophan, tryptamine, N‐acetylserotonin, serotonin, or melatonin partially reversed the regenerative recalcitrance and growth impairment of the germplasm lines. Quantification of phytohormones revealed crosstalk between the indoleamines and related phytohormones including cytokinin, salicylic acid, and abscisic acid. We hypothesize that melatonin and serotonin function in coordination with their metabolites in a cascade of phytochemical responses including multiple pathways and phytohormone networks to direct morphogenesis and protect photosynthesis in H. perforatum.     

High order interactions of xenobiotic metabolizing genes and P53 codon 72 polymorphisms in acute leukemia

Polymorphisms in xenobiotic metabolizing genes are associated with altered metabolism of carcinogens in acute leukemia (AL). This study applied two data mining approaches to explore potential interactions among P53 and xenobiotic metabolizing genes in 230 AL patients [131 acute myeloid leukemia (AML) and 99 acute lymphoblastic leukemia (ALL)] and 199 controls. Individually, none of the genotypes showed significant associations with AML risk. However, in ALL the CYP1A12A TC genotype was associated with increased risk (OR = 2.02; 95% CI = 1.14–3.58; P = 0.01), whereas the GSTM1 null genotype imparted reduced risk (OR = 0.55; 95% CI = 0.31–0.96; P = 0.03). In classification and regression tree analysis, combinations of GSTM1 present, CYP1A12C AA or GG, EPHX1 exon3 TC, and EPHX1 exon4 AA or GG genotype strongly enhanced the risk of AML (OR = 5.89; 95% CI = 1.40–26.62; P = 0.01). In ALL, combinations of CYP1A12A TT, P53 GG or CC and GSTP1 AG genotypes conferred the highest risk (OR = 4.19; 95% CI = 1.45–12.25; P = 0.004). In multifactor dimensionality reduction analysis, a four locus model (GSTP1, P53, EPHX1 exon3, and CYP1A12A) was the best predictor model for ALL risk. The association between this model and ALL risk remained true even at low prior probabilities of 0.01% (false positive report probability = 0.05). Interaction entropy interpretations of the best model of ALL revealed that two‐way interactions were mostly synergistic. These results suggest that high order gene–gene interactions play an important role in AL risk. Environ. Mol. Mutagen., 2012. © 2012 Wiley Periodicals, Inc.     

Convergence model for effectual prevention and control of zoonotic diseases: a health system study on ‘One Health’ approach in Ahmedabad,India

The complexity and increasing burden of zoonotic diseases create challenges for the health systems of developing nations. Public health systems must therefore be prepared to face existing and future disease threats at the human–animal interface. The key for this is coordinated action between the human and the animal health systems. Although some studies deal with the question of how these two systems interact during unforeseen circumstances such as outbreaks, a dearth of literature exists on how these systems interact on early detection, prevention and control of zoonotic diseases; assessing this problem from the health system perspective in a developing nation adds further complexity. Systems thinking is one of the promising approaches in understanding the factors that influence the system’s complexity and dynamics of health maintenance. Therefore, this study aims to understand the generic structure and complexity of interaction between these actors within the domain of One Health for the effectual prevention and control of zoonotic diseases in India.The present study will be executed in Ahmedabad, located on the Western part of India, in Gujarat state, using a mixed methods approach. For the first step, zoonotic diseases will be prioritised for the local context through semi-quantitative tools. Secondly, utilising semi-structured interviews, stakeholders from the human and animal health systems will be identified and ranked. Thirdly, the identified stakeholders will be questioned regarding the current strength of interactions at various levels of the health system (i.e. managerial, provider and community level) through a quantitative network survey. Fourthly, utilising a vignette method, the ideal convergence strategies will be documented and validated through policy Delphi techniques. Finally, through a participatory workshop, the factors that influence convergence for the control and prevention of zoonotic diseases will be captured.This study will provide a comprehensive picture of the current strength of collaboration and network depth at various levels of the health system. Further, it will assist different actors in identifying the relevance of possible One Health entry points for participation, i.e. it will not only contribute but will also develop a system convergence model for the effectual prevention and control of zoonotic diseases.