Potential of Mobile Phones to Serve as a Reservoir in Spread of Nosocomial Pathogens

Objective: The use of cellular telephones by medical personnel and the associated nosocomial transmission of pathogens have not been thoroughly examined. The objective of this study was to determine the incidence of bacterial colonisation on mobile phones of Healthcare workers (HCWs) and its accompanying resistance to commonly used antimicrobials in a medical and dental hospital in India. Method: A total of 204 mobile phones of HCWs from medical and dental departments were screened. A sterile swab moistened with sterile saline was rotated over the external surface of the phone. Swabs were cultured on 5% sheep blood agar and MacConkey agar plates. Plates were incubated aerobically at 37°C for 24 hours. All isolates were tested for antimicrobial susceptibility. A questionnaire was used for data collection on mobile phone use in hospital. Result: 99% of the phones demonstrated evidence of bacterial contamination. 64.8% of medical samples showed growth of pathogenic micro-organisms and 37.9% showed growth of Multi drug resistant bacteria. 59.37% of dental samples showed growth of pathogenic micro-organisms and 43.75% showed growth of Multi drug resistant bacteria. Pathogens isolated included Methicillin-resistant Staphylococcus aureus, Methicillin-sensitive Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Acinetobacter, Enterococcus faecalis, and Pseudomonas aeruginosa. According to the questionnaire 40% admitted to using their phones between examination of patients. Only 6% used disinfectants to wipe their phones. Conclusion: This study reveals that mobile phones are commonly used by HCWs, even during patient contact and may serve as a potential vehicle for the spread of nosocomial pathogens

A Review of Vrushya Dravyas of Guduchyadi Varga of Bhavaprakasha Nighantu

Bhavaprakasha Nighantu, an important lexicon of Ayurveda consists of 23 Vargas where Guduchyadi Varga is one among them which consists of 190 drugs. Among them 28 drugs are attributed to Vrushya property. As Infertility has emerged as one of the most common health issues that many young couples are facing, there is a great demand for the treatment of infertility. While, the herbal therapies are better positioned to offer more holistic approaches to improve reproductive health. So here an attempt is made to screen the Vrushya Dravyas mentioned in Guduchyadi Varga of  Bhavaprakasha Nighantu with their Rasa, Guna, Veerya, Vipaka

Comparison of chewing ability, oral health related quality of life and nutritional status before and after insertion of complete denture amongst edentulous patients in a Dental College of Pune

BACKGROUND: The relationship between tooth loss and nutritional intake is important. As people age, their diminished physical capacity and  decreased income adversely affect their ability to maintain their teeth. The aim of the study was to assess and compare the chewing ability, oral health related quality of life and nutritional status before and after  fabrication and insertion of complete denture amongst edentulous participants in a dental college.MATERIAL AND METHODS: Non Randomized Intervention study. The study population consisted of 42 participants (16 females and 26 males), aged 50 years and above. Prior to commencement of the study, informed consent was obtained and validation and reliability test of the  questionnaire were done. The data for chewing ability, GOHAI and  nutritional status assessment was recorded at baseline, 3rd, 6th and12th month after denture fabrication and insertion. The statistical  comparisons were performed by repeated measure ANOVA and Chi-square test. P value<0.05 was considered as statistically significant.RESULTS: Chewing ability, GOHAI, BMI (Body Mass Index) and data from Food-intake questionnaire showed statistically significant improvement from baseline to 6th month but no statistically significant improvement was observed from 6th month to 12th month. Nutritive value of food (protein, energy and fat) showed no significant difference over a period of 12 months (p<0.05).Conclusion: Thus, it was concluded that the intervention (denture insertion) was effective in increasing the chewing ability, body weight, food-intake, and oral health related quality of life.KEYWORDS: nutrition, edentulousness, OHQoL, GOHAI, chewing abilit

Effect of pre-contraction on β-adrenoceptor-mediated relaxation of rat urinary bladder

Purpose The human physiological bladder contraction is largely mediated by acetylcholine acting on muscarinic receptors, but in pathophysiological settings the relative role of non-cholinergic stimuli gains importance. beta-Adrenoceptor agonists are currently in clinical development as treatments for the overactive bladder syndrome. Therefore, we have explored the ability of the beta-adrenoceptor agonist isoprenaline to induce rat isolated bladder strip relaxation on pre-contraction with the muscarinic agonist carbachol as compared to bladder tone induced by several non-cholinergic stimuli. Methods Bladder tone was induced by passive tension, receptor independently by KCl, carbachol, bradykinin or serotonin. Concentration-response curves were generated for relaxation by isoprenaline, and a single concentration of the receptor-independent relaxant forskolin was also tested. Results The various contractile stimuli induced different degrees of bladder tone, but the ability of isoprenaline or forskolin to relax rat bladder was not correlated with the degree of tone. Isoprenaline was significantly less potent and effective in causing relaxation against carbachol-induced tone than against any other stimulus, whereas no such relationship was observed for forskolin. Conclusions We conclude that beta-adrenoceptor agonists can induce rat bladder relaxation against a wide range of contractile stimuli and are more potent and/or effective against non-cholinergic stimuli than against muscarinic agonism. This profile appears desirable for agents intended for the treatment of overactive bladde

Muscarinic receptor subtypes and signalling involved in the attenuation of isoprenaline-induced rat urinary bladder relaxation

β-Adrenoceptors are important mediators of smooth muscle relaxation in the urinary bladder, but the concomitant presence of a muscarinic agonist, e.g., carbachol, can attenuate relaxation responses by reducing potency and/or efficacy of β-adrenoceptor agonists such as isoprenaline. Therefore, the present study was designed to explore the subtypes and signalling pathways of muscarinic receptors involved in the attenuation of isoprenaline-induced isolated rat detrusor preparations using novel subtype-selective receptor ligands. In radioligand binding studies, we characterized BZI to be a M3-sparing muscarinic agonist, providing selective M2 stimulation in rat bladder, and THRX-182087 as a highly M2-selective antagonist. The use of BZI and of THRX-182087 in the presence of carbachol enabled experimental conditions with a selective stimulation of only M2 or M3 receptors, respectively. Confirming previous findings, carbachol attenuated isoprenaline-induced detrusor relaxation. M2-selective stimulation partly mimicked this attenuation, indicating that both M2 and M3 receptors are involved. During M3-selective stimulation, the attenuation of isoprenaline responses was reduced by the phospholipase C inhibitor U 73,122 but not by the protein kinase C inhibitor chelerythrine. We conclude that both M2 and M3 receptors contribute to attenuation of β-adrenoceptor-mediated relaxation of rat urinary bladder; the signal transduction pathway involved in the M3 component of this attenuation differs from that mediating direct contractile effects of M3 receptors

Selective amplification of Brucella melitensis mRNA from a mixed host-pathogen total RNA

<p>Abstract</p> <p>Background</p> <p>Brucellosis is a worldwide anthropozoonotic disease caused by an in vivo intracellular pathogen belonging to genus <it>Brucella</it>. The characterization of brucelae transcriptome's during host-pathogen interaction has been limited due to the difficulty of obtaining an adequate quantity of good quality eukaryotic RNA-free pathogen RNA for downstream applications.</p> <p>Findings</p> <p>Here, we describe a combined protocol to prepare RNA from intracellular <it>B. melitensis </it>in a quantity and quality suitable for pathogen gene expression analysis. Initially, <it>B. melitensis </it>total RNA was enriched from a host:pathogen mixed RNA sample by reducing the eukaryotic RNA..Then, to increase the <it>Brucella </it>RNA concentration and simultaneously minimize the contaminated host RNA in the mixed sample, a specific primer set designed to anneal to all <it>B. melitensis </it>ORF allows the selective linear amplification of sense-strand prokaryotic transcripts in a previously enriched RNA sample.</p> <p>Conclusion</p> <p>The novelty of the method we present here allows analysis of the gene expression profile of <it>B. melitensis </it>when limited amounts of pathogen RNA are present, and is potentially applicable to both <it>in vivo </it>and <it>in vitro </it>models of infection, even at early infection time points.</p

hMYH and hMTH1 cooperate for survival in mismatch repair defective T-cell acute lymphoblastic leukemia

hMTH1 is an 8-oxodGTPase that prevents mis-incorporation of free oxidized nucleotides into genomic DNA. Base excision and mismatch repair pathways also restrict the accumulation of oxidized lesions in DNA by removing the mis-inserted 8-oxo-7,8-dihydro-2'-deoxyguanosines (8-oxodGs). In this study, we aimed to investigate the interplay between hMYH DNA glycosylase and hMTH1 for cancer cell survival by using mismatch repair defective T-cell acute lymphoblastic leukemia (T-ALL) cells. To this end, MYH and MTH1 were silenced individually or simultaneously using small hairpin RNAs. Increased sub-G1 population and apoptotic cells were observed upon concurrent depletion of both enzymes. Elevated cell death was consistent with cleaved caspase 3 accumulation in double knockdown cells. Importantly, overexpression of the nuclear isoform of hMYH could remove the G1 arrest and partially rescue the toxicity observed in hMTH1-depleted cells. In addition, expression profiles of human DNA glycosylases were generated using quantitative reverse transcriptase–PCR in MTH1 and/or MYH knockdown cells. NEIL1 DNA glycosylase, involved in repair of oxidized nucleosides, was found to be significantly downregulated as a cellular response to MTH1–MYH co-suppression. Overall, the results suggest that hMYH and hMTH1 functionally cooperate for effective repair and survival in mismatch repair defective T-ALL Jurkat A3 cells

New Human Papilloma Virus E2 Transcription Factor Mimics: A Tripyrrole-Peptide Conjugate with Tight and Specific DNA-Recognition

BACKGROUND: Human papillomavirus (HPV) is the main causative agent of cervical cancer, particularly high risk strains such us HPV-16, -18 and -31. The viral encoded E2 protein acts as a transcriptional modulator and exerts a key role in viral DNA replication. Thus, E2 constitutes an attractive target for developing antiviral agents. E2 is a homodimeric protein that interacts with the DNA target through an α-helix of each monomer. However, a peptide corresponding to the DNA recognition helix of HPV-16 E2 binds DNA with lower affinity than its full-length DNA binding domain. Therefore, in an attempt to promote the DNA binding of the isolated peptide, we have designed a conjugate compound of the E2 α-helix peptide and a derivative of the antibiotic distamycin, which involves simultaneous minor- and major-groove interactions. METHODOLOGY/PRINCIPAL FINDINGS: An E2 α-helix peptide-distamycin conjugate was designed and synthesized. It was characterized by NMR and CD spectroscopy, and its DNA binding properties were investigated by CD, DNA melting and gel shift experiments. The coupling of E2 peptide with distamycin does not affect its structural properties. The conjugate improves significantly the affinity of the peptide for specific DNA. In addition, stoichiometric amounts of specific DNA increase meaningfully the helical population of the peptide. The conjugate enhances the DNA binding constant 50-fold, maintaining its specificity. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that peptide-distamycin conjugates are a promising tool to obtain compounds that bind the E2 target DNA-sequences with remarkable affinity and suggest that a bipartite major/minor groove binding scaffold can be a useful approach for therapeutic treatment of HPV infection

Towards a three-dimensional microfluidic liver platform for predicting drug efficacy and toxicity in humans

Although the process of drug development requires efficacy and toxicity testing in animals prior to human testing, animal models have limited ability to accurately predict human responses to xenobiotics and other insults. Societal pressures are also focusing on reduction of and, ultimately, replacement of animal testing. However, a variety of in vitro models, explored over the last decade, have not been powerful enough to replace animal models. New initiatives sponsored by several US federal agencies seek to address this problem by funding the development of physiologically relevant human organ models on microscopic chips. The eventual goal is to simulate a human-on-a-chip, by interconnecting the organ models, thereby replacing animal testing in drug discovery and development. As part of this initiative, we aim to build a three-dimensional human liver chip that mimics the acinus, the smallest functional unit of the liver, including its oxygen gradient. Our liver-on-a-chip platform will deliver a microfluidic three-dimensional co-culture environment with stable synthetic and enzymatic function for at least 4 weeks. Sentinel cells that contain fluorescent biosensors will be integrated into the chip to provide multiplexed, real-time readouts of key liver functions and pathology. We are also developing a database to manage experimental data and harness external information to interpret the multimodal data and create a predictive platform. © 2013 BioMed Central Ltd

The muscarinic receptor antagonist propiverine exhibits α1-adrenoceptor antagonism in human prostate and porcine trigonum

Combination therapy of male lower urinary tract symptoms with α(1)-adrenoceptor and muscarinic receptor antagonists attracts increasing interest. Propiverine is a muscarinic receptor antagonist possessing additional properties, i.e., block of L-type Ca(2+) channels. Here, we have investigated whether propiverine and its metabolites can additionally antagonize α(1)-adrenoceptors. Human prostate and porcine trigone muscle strips were used to explore inhibition of α(1)-adrenoceptor-mediated contractile responses. Chinese hamster ovary (CHO) cells expressing cloned human α(1)-adrenoceptors were used to determine direct interactions with the receptor in radioligand binding and intracellular Ca(2+) elevation assays. Propiverine concentration-dependently reversed contraction of human prostate pre-contracted with 10 μM phenylephrine (-log IC(50) [M] 4.43 ± 0.08). Similar inhibition was observed in porcine trigone (-log IC(50) 5.01 ± 0.05), and in additional experiments consisted mainly of reduced maximum phenylephrine responses. At concentrations ≥1 μM, the propiverine metabolite M-14 also relaxed phenylephrine pre-contracted trigone strips, whereas metabolites M-5 and M-6 were ineffective. In radioligand binding experiments, propiverine and M-14 exhibited similar affinity for the three α(1)-adrenoceptor subtypes with -log K (i) [M] values ranging from 4.72 to 4.94, whereas the M-5 and M-6 did not affect [(3)H]-prazosin binding. In CHO cells, propiverine inhibited α(1)-adrenoceptor-mediated Ca(2+) elevations with similar potency as radioligand binding, again mainly by reducing maximum responses. In contrast to other muscarinic receptor antagonists, propiverine exerts additional L-type Ca(2+)-channel blocking and α(1)-adrenoceptor antagonist effects. It remains to be determined clinically, how these additional properties contribute to the clinical effects of propiverine, particularly in male voiding dysfunctio