Ascites in CML: a rare extramedullary manifestation

Ascites in chronic myeloid leukemia (CML) as an extramedullary manifestation is rarely reported in the literature. A young 23 year old female of chronic myeloid leukemia presenting with extramedullary disease as massive ascites. All stages of granulocytes and a few blasts similar to peripheral blood smear was present in ascitic fluid. Based on clinical symptoms and signs, bone marrow examination, ascitic fluid cytology and ultrasonography of abdomen she was diagnosed as a case of Chronic myeloid leukemia in chronic phase with extramedullary disease as massive ascites. After starting treatment with Imatinib mesylate favourable response was observed

Abamectin: an uncommon but potentially fatal cause of pesticide poisoning

Human intoxication with abamectin is not frequently reported. It is an uncommon but potentially fatal cause of pesticide poisoning. In contrast to common organophosphate poisoning the toxic effects of avermectin in humans are not clearly defined. Ingestion of a large dose of avermectin may be associated with life-threatening complications. The therapy for avermectin poisoning is mainly symptomatic and supportive. The prognosis of patients with avermectin poisoning is likely to be favorable unless they are complicated by severe hypotension or aspiration. We hereby report a case with abamectin poisoning with neurological toxicity and respiratory failure which responded to supportive line of therapy

PHARMACOPHORE MODELLING FOR THE DISCOVERY OF SYSTEM XC- ANTIPORTER INHIBITORS

Cancer is one of the major disorders with increasing rates of morbidity and mortality. Recent drug discovery of anti cancer drug has identified several molecular targets and tried to achieve a goal of therapeutic effecative and safe molecule. Amongst these, system xc- antiporter is a novel promising target to control cancer progression. This antiporter is found to be over expressed in majority of cancer cells and functions by transporting amino acids, cystine and glutamate, in opposite directions. System xc- antiporter uptakes one molecule of cystine with the release of one molecule of glutamate in extracellular space. As already known cystine is precursor for the synthesis of glutathione, an in vivo antioxidant which is utilized by cancer cells to combat oxidative stress. At the other side the released glutamate (an excitatory neurotransmitter), when released in higher concentration, may over excite neurones (specifically and brain tumour) causing cell death to metastasise cancer cells. Therefore, through inhibition of system xc- antiporter, it is possible to kill cancer cells by disturbing their redox status along with through prevention of excitotoxcity by glutamate. In context to this, several researches have reported diverse molecules having system xc- antiporter inhibition potential. Amongst these molecules, erastin and its analogues are most potent system xc- antiporter inhibitors but it lacks preclinical data. Moreover, sulfasalazine, a FDA approved drug also showed good inhibition potential against this antiporter and therefore in our study we have attempted to construct pharmacophore model using this series to aid in the discovery of potent inhibitors with desirable safety. Results of this study exhibited successful development of pharmacophore model with phase survival score. Additionally, fit scores of sulfasalazine analogues were also in acceptable range. Hence, the developed pharmacophore model may be used for design of potent System xc- antiporter inhibitors

Genetic diversity and relationship among three goat breed of Maharashtra state of India

Genetic diversity and relationship among in the three goat breed of Maharashtra, India namely Berari, Osmanabadi and Sangamneri were evaluated based on 25 microsatellite markers. A total of 567 alleles were observed among 129 assayed animals across the three breeds. The most diverse breed was Sangamneri followed by Berari and the least diverse breed was Osmanabadi in terms of number of allele. The overall mean of gene diversity across the studied loci for the Berari, Osmanabadi and Sangamneri breeds were 0.906±0.006, 0.870±0.017 and 0.901±0.010, respectively. The overall Fis value (0.161) was higher and significantly different from zero indicating departure from random mating and suggested that some of the studied loci were homozygous in the populations. The lower level of genetic differentiation (Fst) among the three breeds (3.9%) under study implied that 96.1% of the total genetic variation corresponded to differences among individuals within breed. The genetic distance tended to be the least (0.4032) between Berari and Sangamneri, moderate (0.4834) between Sangamneri and Osmanabadi and the widest (0.6319) between Berari and Osmanabadi. Lower level of genetic differentiation among the three breeds showed intermixing of the populations as breeding tract of three bred overlap hence, this may pose a danger to the purity of the breed in the long run

An outbreak of methicillin-resistant Staphylococcus aureus (MRSA) infection in dermatology indoor patients

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen. Indiscriminate and increased use of systemic antibiotics has led to the emergence of MRSA. Infected or colonized ward patients are the main reservoir of infection. Once colonized, the risk of subsequent local and systemic infections is high, especially in the elderly, and in debilitated and immunosuppressed patients. Methods: We report an outbreak of MRSA in the dermatology ward of a tertiary care hospital and describe measures taken to control it. Results: Ten patients were found to be MRSA positive over a span of three months while screening swabs from wet lesions in indoor patients. On the basis of risk assessment, they were treated with appropriate systemic and topical therapy. One patient died while the remaining nine patients showed a good response to therapy. All the MRSA isolates were found to be sensitive to vancomycin, teicoplanin and linezolid. Conclusion: This is the first case report of MRSA infection in dermatology indoor patients in India

Synthesis, molecular docking and biological evaluation of new quinoline analogues as potent anti-breast cancer and antibacterial agents

1215-1222A new class of quinoline analogues have been synthesized from isatin through two steps in good yields. They have been further evaluated for their anticancer activity against a breast cancer cell line (MDA-MB-231) and antibacterial activity against Gram-positive bacteria (Staphylococcus aureus 6538p and Bacillus subtilis) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). All synthesized compounds have been confirmed by spectral characterization viz. FT-IR, MS, HPLC, 1H and 13C NMR. Among them, compound 4h exhibits promising anti-breast cancer activity whereas compounds 4d, 4f, 4h and 4j exhibit moderate antibacterial activity against all the tested organisms. Molecular docking analysis demonstrates the interaction of compound 4h with the active site amino acid of Human Carbonic Anhydrase I, Protein Kinase A and Kinesin Spindle Protein (KSP)

Synthesis, molecular docking and biological evaluation of new quinoline analogues as potent anti-breast cancer and antibacterial agents

A new class of quinoline analogues have been synthesized from isatin through two steps in good yields. They have been further evaluated for their anticancer activity against a breast cancer cell line (MDA-MB-231) and antibacterial activity against Gram-positive bacteria (Staphylococcus aureus 6538p and Bacillus subtilis) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). All synthesized compounds have been confirmed by spectral characterization viz. FT-IR, MS, HPLC, 1H and 13C NMR. Among them, compound 4h exhibits promising anti-breast cancer activity whereas compounds 4d, 4f, 4h and 4j exhibit moderate antibacterial activity against all the tested organisms. Molecular docking analysis demonstrates the interaction of compound 4h with the active site amino acid of Human Carbonic Anhydrase I, Protein Kinase A and Kinesin Spindle Protein (KSP).

The developmental impacts of natural selection on human pelvic morphology

Evolutionary responses to selection for bipedalism and childbirth have shaped the human pelvis, a structure that differs substantially from that in apes. Morphology related to these factors is present by birth, yet the developmental-genetic mechanisms governing pelvic shape remain largely unknown. Here, we pinpoint and characterize a key gestational window when human-specific pelvic morphology becomes recognizable, as the ilium and the entire pelvis acquire traits essential for human walking and birth. We next use functional genomics to molecularly characterize chondrocytes from different pelvic subelements during this window to reveal their developmental-genetic architectures. We then find notable evidence of ancient selection and genetic constraint on regulatory sequences involved in ilium expansion and growth, findings complemented by our phenotypic analyses showing that variation in iliac traits is reduced in humans compared to African apes. Our datasets provide important resources for musculoskeletal biology and begin to elucidate developmental mechanisms that shape human-specific morphology