COMPARISON OF MAMMOGRAPHY AND ULTRASOUND COMBINED VERSUS ULTRASOUND ALONE IN EARLY EVALUATION OF SYMPTOMATIC BREAST CANCERS IN PAKISTAN

Purpose: The purpose of this study was to detect diagnostic accuracy of mammography and ultrasound combined versus ultrasound alone in early evaluation of symptomatic breast lesions.Materials and Methods: All new patients who presented to the breast clinic with symptomatic breast lesions, during the year 2012, were included in the study. A total of 695 patients were registered. Their clinical findings, mammogram, ultrasound and histopathology were reviewed.Results: Mammogram and ultrasound combined detected 693 (99.71%) lesions in total. Mammogram failed to detect lesions in 1.43% of patients, whereas the failure rate of ultrasound was 0.43%. The incidence of microcalcifications on mammogram was 19.13%.Conclusion: Ultrasound is a useful tool in the initial evaluation of symptomatic breasts. For places such as Pakistan where mammogram is not available at every centre, ultrasound can be used as an effective alternative for the assessment of symptomatic breast lesions.Key words: Breast cancer, mammography, ultrasoun

Breaking the spell: Combating Multidrug resistant ‘Superbugs’

Multidrug-resistant (MDR) bacteria have become a severe threat to community health. Conventional antibiotics are getting increasingly ineffective as a consequence of resistance, and so it is imperative to realize new antimicrobial strategies. In this review we emphasized the microorganisms primarily reported in the resistance process, the so called ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and enterobacteriaceae) accentuating their capacity to escape from common antibacterial regimes. The upcoming antimicrobial agents showing great potential and can serve as alternative therapeutic options are discussed. We also provided succinct overview of two evolving technologies; specifically network pharmacology and functional genomics profiling. Furthermore, In vivo imaging techniques can provide novel targets and a real time tool for potential lead molecule assessment. The employment of such approaches at early stages of the drug development enables more informed decisions on candidate drug selection and moreover to maximize or predict efficacy before clinical development

Enhanced Killing and Antibiofilm Activity of Encapsulated Cinnamaldehyde against Candida albicans

Candida sp. impelled opportunistic infection in immune-compromised patients ensuing from asymptomatic colonization to pathogenic forms. Moreover, slow spread of Candida species inducing refractory mucosal and invasive infections brings acute resistance to antifungal drugs. Hence, here we probed the effect of encapsulated preparation of cinnamaldehyde (CNMA) in multilamellar liposomes (ML) against Candida albicans. The efficacy of ML-CNMA against Candida biofilm was assessed by scanning electron microscopy, transmission electron microscopy, as well as light microscopy and its percent inhibition, was determined by XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] and crystal violet assay. ML-CNMA showed more fungicidal activity than free CNMA as well as multilamellar liposomal amphotericin B (ML-Amp B), which was further confirmed by spot test assay and Log-logistic dose–response analysis. Antifungal activity was driven by reactive oxygen species and cellular damage by sustained release of CNMA. Effect on hyphal formation during 48 h in presence/absence of ML-CNMA was observed under a microscope and further substantiated by RT-PCR by amplifying HWP1, the gene responsible for hyphal wall protein formation. Apoptotic programmed cell death was analyzed by FACS analysis which was further confirmed by cytochrome C release assay. This study elucidates the mechanistic insight of the enhanced antifungal activity of ML preparation of CNMA against Candida infections

Interaction of anesthetic supplement thiopental with human serum albumin

Thiopental (TPL) is a commonly used barbiturate anesthetic. Its binding with human serum albumin (HSA) was studied to explore the anesthetic-induced protein dysfunction. The basic binding interaction was studied by UV-absorption and fluorescence spectroscopy. An increase in the binding affinity (K) and in the number of binding sites (n) with the increasing albumin concentration was observed. The interaction was conformation-dependent and the highest for the F isomer of HSA, which implicates its slow elimination. The mode of binding was characterized using various thermodynamic parameters. Domain II of HSA was found to possess a high affinity binding site for TPL. The effect of micro-metal ions on the binding affinity was also investigated. The molecular distance, r, between donor (HSA) and acceptor (TPL) was estimated by fluorescence resonance energy transfer (FRET). Correlation between the stability of the TPL-N and TPL-F complexes and drug distribution is discussed. The structural changes in the protein investigated by circular dichroism (CD) and Fourier transform infrared (FT-IR) spectroscopy reflect perturbation of the albumin molecule and provide an explanation for the heterogeneity of action of this anesthetic

Inhibition of N-terminal lysines acetylation and transcription factor assembly by epirubicin induced deranged cell homeostasis.

Epirubicin (EPI), an anthracycline antitumour antibiotic, is a known intercalating and DNA damaging agent. Here, we study the molecular interaction of EPI with histones and other cellular targets. EPI binding with histone core protein was predicted with spectroscopic and computational techniques. The molecular distance r, between donor (histone H3) and acceptor (EPI) was estimated using Förster's theory of non-radiation energy transfer and the detailed binding phenomenon is expounded. Interestingly, the concentration dependent reduction in the acetylated states of histone H3 K9/K14 was observed suggesting more repressed chromatin state on EPI treatment. Its binding site near N-terminal lysines is further characterized by thermodynamic determinants and molecular docking studies. Specific DNA binding and inhibition of transcription factor (Tf)-DNA complex formation implicates EPI induced transcriptional inhibition. EPI also showed significant cell cycle arrest in drug treated cells. Chromatin fragmentation and loss of membrane integrity in EPI treated cells is suggestive of their commitment to cell death. This study provides an analysis of nucleosome dynamics during EPI treatment and provides a novel insight into its action

Optimization of DC-PCR for drug screening.

<p>Effect of cytoplasmic enzymes on DC-PCR (<b>A</b>). KMS-12-PE cells were diluted at 1∶25 in hypotonic PCR buffer with or without added protease inhibitors and incubated for 20 min before PCR was run to simulate the time required for pipetting during a small molecule screen. Inclusion of protease inhibitors in the PCR mastermix decreased the number of amplifiable sites in DAC treated and untreated KMS-12-PE cells suggesting that digestion of DNA binding proteins can occur in PCR buffer although epigenetic differences between samples are maintained in the studied example. Detection of DC-PCR product via UV transillumination of PCR plates and sensitivity compared to gel electrophoresis (<b>B</b>). Ethidium bromide was added to the PCR mastermix before serially diluted cells were submitted to DC-PCR: untreated, DAC treated or fibroblasts. After completion of thermal cycling samples were first analyzed under UV light (Left panel), then via agarose-gel electrophoresis (Right panel). Using gel-based detection, the level of detection for epigenetic differences of CDKN2A was lower, down to about 1 cell for site #6 compared to about 300 cells with direct UV transillumination. The primer numbers correspond to sequences on the map described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044690#pone-0044690-g001" target="_blank">Figure 1A</a>. Three independent experiments yielded the same detection levels. Correlation between direct UV transillumination and gel electrophoresis was seen in all experiments (hundreds).</p