Conservative management of vesicovaginal fistula: a rare case report

Vesicovaginal Fistula is a debilitating condition that has affected women for millinea. Spontaneous closures of VVF with continuous bladder drainage for varying periods have been reported by few authors. Here we present a case of post hysterectomy VVF managed conservatively. A 45 year old parous woman presented with continuous leakage of urine following hysterectomy. The clinical diagnosis of Vesicovaginal Fistula was proven by cystoscopy and CT cystography. VVF healed by continuous bladder drainage for 4 weeks. Non-surgical treatment with continuous bladder drainage can also result in complete healing of small VVFs

Investigation On Antidiarrhoeal Activity Of Aristolochia Indica Linn. Root Extracts In Mice

Background: The present study aimed at investigating the effect of ethanolic extract (EtAI), and aqueous extract (AqAI) of Aristolochia indica  Linn roots on castor oil-induced diarrhoea and study on small intestinal transit. Phytochemical analysis of extracts was performed as per standard procedure.Materials and Methods: The oral toxicity study using Swiss albino mice was performed in accordance with OECD guidelines. The EtAI and AqAI extracts of Aristolochia indica Linn were studied for antidiarrhoeal property using castor oil-induced diarrhoeal model and charcoalinduced gastrointestinal motility test in Swiss albino mice.Results: Among the tested doses of 200 and 400 mg/kg body weight, the extracts reduced the frequency and severity of diarrhoea in test animals throughout the study period. At the same doses, the extract delayed the intestinal transit of charcoal meal in test animals as compared to the control and the results were statistically significant.Conclusion: Experimental findings showed that ethanol extract of Aristolochia indica Linn root possess significant antidiarrheal activity and may be a potent source of anti-diarrhoeal drug in future.Key words: Antidiarrheal activity, Aristolochia indica Linn, ethanol extract, small intestinal transi

To hit or not to hit, that is the question -genome-wide structure-based druggability predictions for <i>pseudomonas aeruginosa </i>proteins

Pseudomonas aeruginosa is a Gram-negative bacterium known to cause opportunistic infections in immune-compromised or immunosuppressed individuals that often prove fatal. New drugs to combat this organism are therefore sought after. To this end, we subjected the gene products of predicted perturbative genes to structure-based druggability predictions using DrugPred. Making this approach suitable for large-scale predictions required the introduction of new methods for calculation of descriptors, development of a workflow to identify suitable pockets in homologous proteins and establishment of criteria to obtain valid druggability predictions based on homologs. We were able to identify 29 perturbative proteins of P. aeruginosa that may contain druggable pockets, including some of them with no or no drug-like inhibitors deposited in ChEMBL. These proteins form promising novel targets for drug discovery against P. aeruginosa

MYC functions are specific in biological subtypes of breast cancer and confers resistance to endocrine therapy in luminal tumours.

BACKGROUND: MYC is amplified in approximately 15% of breast cancers (BCs) and is associated with poor outcome. c-MYC protein is multi-faceted and participates in many aspects of cellular function and is linked with therapeutic response in BCs. We hypothesised that the functional role of c-MYC differs between molecular subtypes of BCs. METHODS: We therefore investigated the correlation between c-MYC protein expression and other proteins involved in different cellular functions together with clinicopathological parameters, patients' outcome and treatments in a large early-stage molecularly characterised series of primary invasive BCs (n=1106) using immunohistochemistry. The METABRIC BC cohort (n=1980) was evaluated for MYC mRNA expression and a systems biology approach utilised to identify genes associated with MYC in the different BC molecular subtypes. RESULTS: High MYC and c-MYC expression was significantly associated with poor prognostic factors, including grade and basal-like BCs. In luminal A tumours, c-MYC was associated with ATM (P=0.005), Cyclin B1 (P=0.002), PIK3CA (P=0.009) and Ki67 (P<0.001). In contrast, in basal-like tumours, c-MYC showed positive association with Cyclin E (P=0.003) and p16 (P=0.042) expression only. c-MYC was an independent predictor of a shorter distant metastases-free survival in luminal A LN+ tumours treated with endocrine therapy (ET; P=0.013). In luminal tumours treated with ET, MYC mRNA expression was associated with BC-specific survival (P=0.001). In ER-positive tumours, MYC was associated with expression of translational genes while in ER-negative tumours it was associated with upregulation of glucose metabolism genes. CONCLUSIONS: c-MYC function is associated with specific molecular subtypes of BCs and its overexpression confers resistance to ET. The diverse mechanisms of c-MYC function in the different molecular classes of BCs warrants further investigation particularly as potential therapeutic targets

Fiber-matrix interfaces in ceramic composites

The mechanical properties of ceramic matrix composites (CMCs) are governed by the relationships between the matrix, the interface material, and the fibers. In non-oxide matrix systems compliant pyrolytic carbon and BN have been demonstrated to be effective interface materials, allowing for absorption of mismatch stresses between fiber and matrix and offering a poorly bonded interface for crack deflection. The resulting materials have demonstrated remarkable strain/damage tolerance together with high strength. Carbon or BN, however, suffer from oxidative loss in many service environments, and thus there is a major search for oxidation resistant alternatives. This paper reviews the issues related to developing a stable and effective interface material for non-oxide matrix CMCs

Oxidation-resistant interfacial coatings for continuous fiber ceramic composites

Developing an oxidation-resistant interfacial coating for continuous fiber ceramic composites (CFCCs) continues to be a major challenge. CFCCs` mechanical behavior are influenced by the interfacial bonding characteristics between the fiber and the matrix. Finite element modeling studies suggest that a low-modulus interfacial coating material will be effective in reducing the residual thermal stresses that are generated upon cooling from processing temperatures. Nicalon/SiC composites with carbon, alumina and mullite interfacial coatings were fabricated with the SiC matrix deposited using a forced-flow chemical vapor infiltration process. Composites with mullite interfacial coatings exhibited considerable fiber pull-out even after oxidation and have potential as a composite system

The Hydrophobic Core of Twin-Arginine Signal Sequences Orchestrates Specific Binding to Tat-Pathway Related Chaperones

Redox enzyme maturation proteins (REMPs) bind pre-proteins destined for translocation across the bacterial cytoplasmic membrane via the twin-arginine translocation system and enable the enzymatic incorporation of complex cofactors. Most REMPs recognize one specific pre-protein. The recognition site usually resides in the N-terminal signal sequence. REMP binding protects signal peptides against degradation by proteases. REMPs are also believed to prevent binding of immature pre-proteins to the translocon. The main aim of this work was to better understand the interaction between REMPs and substrate signal sequences. Two REMPs were investigated: DmsD (specific for dimethylsulfoxide reductase, DmsA) and TorD (specific for trimethylamine N-oxide reductase, TorA). Green fluorescent protein (GFP) was genetically fused behind the signal sequences of TorA and DmsA. This ensures native behavior of the respective signal sequence and excludes any effects mediated by the mature domain of the pre-protein. Surface plasmon resonance analysis revealed that these chimeric pre-proteins specifically bind to the cognate REMP. Furthermore, the region of the signal sequence that is responsible for specific binding to the corresponding REMP was identified by creating region-swapped chimeric signal sequences, containing parts of both the TorA and DmsA signal sequences. Surprisingly, specificity is not encoded in the highly variable positively charged N-terminal region of the signal sequence, but in the more similar hydrophobic C-terminal parts. Interestingly, binding of DmsD to its model substrate reduced membrane binding of the pre-protein. This property could link REMP-signal peptide binding to its reported proofreading function