Renal pseudoaneurysm: a rare and potentially fatal complication following ureteroscopy and laser fragmentation of stones.

Ureteroscopy and laser fragmentation of stones is a commonly used method to treat ureteric and renal calculi. We report the exceedingly rare finding of a renal pseudoaneurysm in an interpolar renal artery following ureteroscopy and laser stone fragmentation, which was successfully managed with angioembolisation.

Dynamism of PGPR in bioremediation and plant growth promotion in heavy metal contaminated soil.

Heavy metal contamination, particularly of cultivable lands, is a matter of concern. Bioremediation helps in reversing such contamination to certain extent. Here, we report isolation, polyphasic identification and the role of siderophore producing rhizobacteria Alcaligenes feacalis RZS2 and Pseudomonas aeruginosa RZS3 in bioremediation of heavy metal contaminated soil and plant growth promotion activity in such contaminated soil. Siderophore produced by A. feacalis RZS2 and P. aeruginosa RZS3 strains chelated various heavy metal ions like MnCl2.4H2O, NiCl2.6H2O, ZnCl2, CuCl2 and CoCl2 other than FeCl3.6H2O at batch scale. Their bioremediation potential was superior over the chemical ion chelators like EDTA and citric acid. These isolates also promoted growth of wheat and peanut seeds sown in heavy metal contaminated soil. Effective root colonizing ability of these isolates was observed in wheat and peanut plants.

Pharmacological Characterization of ZYAN1, a Novel Prolyl Hydroxylase Inhibitor for the Treatment of Anemia.

Prolyl hydroxylase (PHD) inhibitors stabilize hypoxia inducible factor (HIF), and exert antianemic effect by potentiating erythropoietin (EPO) expression and down-regulation of hepcidin. ZYAN1 is a novel PHD inhibitor under clinical development for the treatment of anemia. The pharmacodynamic effects of acute and chronic dosing of ZYAN1 were assessed in normal and 5/6 nephrectomized Wistar rats. The effect of ZYAN1 was also investigated in cisplatin-induced anemia using C57 mice. Acute treatment with ZYAN1 increased circulating EPO levels (10.3 ± 3.7 and 40.0 ± 8.5 fold rise at 15 and 30 mg/kg, respectively), reticulocyte count (4.2 ± 0.5 and 6.0 ± 0.2 fold rise at 15 and 30 mg/kg, respectively) and stabilized HIF (28% increase at 45 mg/kg) in normal rats. Nephrectomized rats showed similar dose-related pharmacodynamic effects. In a 28-day study in nephrectomized rats, ZYAN1 administered every alternate day, caused increase in hemoglobin (1.9 ± 0.3 and 2.5 ± 0.4 g/dL) and RBC count (10.7 ± 4.0 and 14.0 ± 4.1%) at 15 and 30 mg/kg respectively. In cisplatin-treated mice also an increase in hemoglobin (3.4 ± 0.2 and 5.9 ± 0.2 g/dL) and RBC count (22.5 ± 2.2 and 37.3 ± 1.7%) at 15 and 30 mg/kg respectively was observed. ZYAN1's effects on hemoglobin and RBC count were distinct from darbepoietin. ZYAN1 demonstrated hematinic potential by combined effects on EPO release and efficient iron utilization. The efficacy of ZYAN1 in disease models of different etiologies suggests that it will be useful in treating wide spectrum of anemia patients.

Prognostic Performance of Current Stage III Oral Cancer Patients After Curative Intent Resection: Evidence to Support a Revision of the American Joint Committee on Cancer Staging System.

BACKGROUND: The American Joint Committee on Cancer (AJCC) stage III classification of oral cavity squamous cell carcinoma (OCSCC) represents a heterogeneous group of patients with early local disease with regional metastases (T1N1 and T2N1) and advanced local disease with or without regional metastasis (T3N0 and T3N1). OBJECTIVE: The aim of this study was to evaluate prognostic heterogeneity in the stage III category. METHODS AND PATIENTS: An international retrospective multicenter study of 1815 patients who were treated for OCSCC from 2003 to 2011. RESULTS: Kaplan-Meier survival analysis and multivariate models of stage III patients revealed better overall survival (OS; HR 2.12, 95 % CI 1.03-4.15; p = 0.01) and disease-specific survival (DSS; HR 1.7, 95 % CI 1.16-4.12; p = 0.04) rates for patients with T1-2N1/T3N0 disease than for patients with T3N1 disease. The outcomes of patients with T3N1 and stage IVa disease were similar (p = 0.89 and p = 0.78 for OS and DSS, respectively). Modifying stage classification by transferring the T3N1 category to the stage VIa group resulted in a better prognostic performance [Harrell's concordance index, C index 0.76; Akaike's Information Criterion (AIC) 4131.6] compared with the AJCC 7th edition staging system (C index 0.65; AIC 4144.9) for OS. When DSS was assessed, the suggested staging system remained the best performing model (C index 0.71; AIC 1061.3) compared with the current AJCC 7th edition staging (C index 0.64; AIC 1066.2). CONCLUSIONS: The prognosis of T3N1 and stage IVa disease are similar in OCSCC, suggesting that these categories could be combined in future revisions of the nodal staging system to enhance prognostic accuracy.

Plant growth promotion and root colonization by EPS producing Enterobacter sp. RZS5 under heavy metal contaminated soil.

The heavy metal resistant bacterium isolated from field soil and identified as Enterobacter sp. RZS5 tolerates a high concentration (100-2000 µM) of various heavy metal ions such as Mn2+, Ni2+, Zn2+, Cu2+, CO2+ and Fe2+ when grown in such environment and produces exopolysaccharides (EPS). Here, we have demonstrated EPS production by Enterobacter sp. RZS5 during 60 h of growth in yeast extract mannitol broth (YEMB). The yield increased by two fold after the addition of 60 µM of Ca2+; 50 µM of Fe2+ and 60 µM of Mg2+ ions in YEMB, and the optimization of physico-chemical parameters. EPS was extracted with 30% (v/v) of isopropanol as against the commonly used 50% (v/v) isopropanol method. EPS-rich broth promoted seed germination, shoot height, root length, number of leaves and chlorophyll content of wheat (Triticum aestivum) seed and peanut (Arachis hypogaea) seed. The higher colony-forming unit of Enterobacter sp. in soil inoculated with EPS rich broth of Enterobacter sp. indicated the root colonizing potential and rhizosphere competence of the isolate. The FTIR spectra of the EPS extract confirmed the presence of the functional group characteristics of EPS known to exhibit a high binding affinity towards certain metal ions. This overall growth and vigour in plants along with the effective root colonization, reflected the potential of the isolate as an efficient bio-inoculant in bioremediation.

Production of biocontrol traits by banana field fluorescent Pseudomonads and comparison with chemical fungicide.

Pseudomonas aeruginosa isolated from banana field rhizosphere produced different antifungal metabolites like bactriocin, hydrogen cyanide and siderophore. Bacteriocinogenic, siderophoregenic, and HCN rich broth of isolate inhibited the growth of phytopathogen like Aspergilus niger, Aspergilus flavus, Fusarium oxysporum and Alternaria alternata. The isolate exhibited more antifungal activity and comparatively low MIC vis-a-vis commonly used copper based systemic chemical fungicide;bil cop.

Lymph node density in oral cavity cancer: results of the International Consortium for Outcomes Research.

BACKGROUND: Lymph node density (LND) has previously been reported to reliably predict recurrence risk and survival in oral cavity squamous cell carcinoma (OSCC). This multicenter international study was designed to validate the concept of LND in OSCC. METHODS: The study included 4254 patients diagnosed as having OSCC. The median follow-up was 41 months. Five-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), locoregional control and distant metastasis rates were calculated using the Kaplan-Meier method. Lymph node density (number of positive lymph nodes/total number of excised lymph nodes) was subjected to multivariate analysis. RESULTS: The OS was 49% for patients with LND0.07 compared with 35% for patients with LND>0.07 (P<0.001). Similarly, the DSS was 60% for patients with LND0.07 compared with 41% for those with LND>0.07 (P<0.001). Lymph node density reliably stratified patients according to their risk of failure within the individual N subgroups (P=0.03). A modified TNM staging system based on LND ratio was consistently superior to the traditional system in estimating survival measures. CONCLUSION: This multi-institutional study validates the reliability and applicability of LND as a predictor of outcomes in OSCC. Lymph node density can potentially assist in identifying patients with poor outcomes and therefore for whom more aggressive adjuvant treatment is needed.

Clinical nodal stage is a significant predictor of outcome in patients with oral cavity squamous cell carcinoma and pathologically negative neck metastases: results of the international consortium for outcome research.

BACKGROUND: We aimed to study the importance of clinical N classification (cN) in a subgroup of patients with oral cavity squamous cell carcinoma (OSCC) and pathologically negative neck nodes (pN-). METHODS: A total of 2,258 patients from 11 cancer centers who underwent neck dissection for OSCC (1990-2011) had pN- disease. The median follow-up was 44 months. 5-year overall survival (OS), disease-specific survival (DSS), disease free survival, local control, locoregional control, and distant metastasis rates were calculated by the Kaplan-Meier method. cN classification and tumor, node, metastasis classification system staging variables were subjected to multivariate analysis. RESULTS: A total of 345 patients were preoperatively classified as cN+ and 1,913 were classified as cN-. The 5-year OS and DSS of cN- patients were 73.6 and 82.2 %, respectively. The 5-year OS and DSS of cN+ patients were 64.9 and 76.9 %, respectively (p < 0.0001 each). A cN+ classification was a significant predictor of worse OS (p = 0.03) and DSS (p = 0.016), regardless of treatment, depth of invasion, or extent of neck dissection. cN classification was associated with recurrence-free survival (p = 0.01) and locoregional (neck and primary tumor) control (p = 0.004), but not with local (p = 0.19) and distant (p = 0.06) recurrence rates. CONCLUSIONS: Clinical evidence of neck metastases is an independent predictor of outcome, even in patients with pN- nodes.

Development and Validation of RP-HPLC Method for the Simultaneous Estimation of Montelukast Sodium and Ebastine in Tablet Dosage Form.

A rapid and sensitive RP-HPLC method with UV detection (244 nm) for routine analysis of montelukast sodium and ebastine in a pharmaceutical formulation (Ebast-M) was developed. Chromatography was performed with mobile phase containing a mixture of methanol:acetonitrile:ammonium acetate (80:10:10, % v/v/v), pH of mobile phase was adjusted 5.5 using glacial acetic acid and flow rate was 1.2 ml/min. The method was validated for linearity, accuracy, robustness and intermediate precision. The linearity was established over the concentration range of 0.01-0.06 mg/ml for both drugs. The correlation coefficients (r (2)) for ebastine and montelukast were 0.9989 and 0.9955, respectively. Statistical analysis of the data showed that the method was precise, accurate, reproducible and selective for the analysis of ebastine and montelukast drugs. The method was successfully employed for the determination of ebastine and montelukast in commercially available tablet dosage form.

Menin liver-specific hemizygous mice challenged with high fat diet show increased weight gain and markers of metabolic impairment.

OBJECTIVE: The menin tumor suppressor protein is abundantly expressed in the liver, although no function has been identified because of lack of tumor development in multiple endocrine neoplasia type 1 (Men1) null livers. We examine the phenotype of mice lacking one functional allele of Men1 (consistent with the phenotype in humans with MEN1 syndrome) challenged with high fat diet (HFD) to elucidate a metabolic function for hepatic menin. METHODS: In this study, we challenged mice harboring a liver-specific hemizygous deletion of Men1 (HETs) alongside wild-type (WT) counterparts with HFD for 3 months and monitored the severity of metabolic changes. We demonstrate that the HET mice challenged with HFD for 3 months show an increased weight gain with decreased glucose tolerance compared with WT counterparts. Along with these changes, there was a more severe serum hormone profile involving increased serum insulin, glucose and glucagon, all hallmarks of the type 2 diabetic phenotype. In concert with increased serum hormones, we found that these mice have significantly increased liver triglycerides coupled with increased liver steatosis and inflammatory markers. Quantitative real-time PCR and western blotting studies show increases in enzymes involved with lipogenesis and hepatic glucose production. CONCLUSION: We conclude that hepatic menin is required for regulation of diet-induced metabolism, and our studies indicate a protective role for the Men1 gene in the liver when challenged with HFD.

Integrated genomic analyses identify WEE1 as a critical mediator of cell fate and a novel therapeutic target in acute myeloid leukemia.

Acute myeloid leukemia (AML) remains a therapeutic challenge despite increasing knowledge about the molecular origins of the disease, as the mechanisms of AML cell escape from chemotherapy remain poorly defined. We hypothesized that AML cells are addicted to molecular pathways in the context of chemotherapy and used complementary approaches to identify these addictions. Using novel molecular and computational approaches, we performed genome-wide short-hairpin RNA screens to identify proteins that mediate AML cell fate after cytarabine exposure; gene expression profiling of AML cells exposed to cytarabine to identify genes with induced expression in this context; and examination of existing gene expression data from primary patient samples. Integration of these independent analyses strongly implicates cell-cycle checkpoint proteins, particularly WEE1, as critical mediators of AML cell survival after cytarabine exposure. Knockdown of WEE1 in a secondary screen confirmed its role in AML cell survival. Pharmacologic inhibition of WEE1 in AML cell lines and primary cells is synergistic with cytarabine. Further experiments demonstrate that inhibition of WEE1 prevents S-phase arrest induced by cytarabine, broadening the functions of WEE1 that may be exploited therapeutically. These data highlight the power of integrating functional and descriptive genomics, and identify WEE1 as a potential therapeutic target in AML.

Epidemiological survey of equine influenza in horses in India.

A highly contagious virus infection in horses, influenza is the single most important equine respiratory disease in the world. This paper presents details of a one-year study (1 June 2008 to 31 May 2009) to determine the prevalence of equine influenza in the horses of Gujarat State in India. The prevalence of equine influenza A/equi-2 was 12.02%, but none of the samples were positive for equine influenza A/equi-1. The prevalence of equine influenza (A/equi-2) was 15.38%, 11.94%, 10.18%, and 9.09% in horses of the Kathiyawari breed, a non-descript breed, the Marwari breed and the Indian Thoroughbred breed, respectively. The highest prevalence of influenza was observed in yearlings (17.48%) and prevalence was at its highest in the month of April (28.89%). The prevalence rate in males, females and geldings was 11.95%, 10.38% and 8.47%, respectively. The mortality rate and case fatality rate were 1.28% and 10.64%, respectively.

Increased metabolic rate and insulin sensitivity in male mice lacking the carcino-embryonic antigen-related cell adhesion molecule 2.

AIMS/HYPOTHESIS: The carcino-embryonic antigen-related cell adhesion molecule (CEACAM)2 is produced in many feeding control centres in the brain, but not in peripheral insulin-targeted tissues. Global Ceacam2 null mutation causes insulin resistance and obesity resulting from hyperphagia and hypometabolism in female Ceacam2 homozygous null mutant mice (Cc2 [also known as Ceacam2](-/-)) mice. Because male mice are not obese, the current study examined their metabolic phenotype. METHODS: The phenotype of male Cc2(-/-) mice was characterised by body fat composition, indirect calorimetry, hyperinsulinaemic-euglycaemic clamp analysis and direct recording of sympathetic nerve activity. RESULTS: Despite hyperphagia, total fat mass was reduced, owing to the hypermetabolic state in male Cc2(-/-) mice. In contrast to females, male mice also exhibited insulin sensitivity with elevated ß-oxidation in skeletal muscle, which is likely to offset the effects of increased food intake. Males and females had increased brown adipogenesis. However, only males had increased activation of sympathetic tone regulation of adipose tissue and increased spontaneous activity. The mechanisms underlying sexual dimorphism in energy balance with the loss of Ceacam2 remain unknown. CONCLUSIONS/INTERPRETATION: These studies identified a novel role for CEACAM2 in the regulation of metabolic rate and insulin sensitivity via effects on brown adipogenesis, sympathetic nervous outflow to brown adipose tissue, spontaneous activity and energy expenditure in skeletal muscle.

Biocontrol Potential of Siderophore Producing Heavy Metal Resistant Alcaligenes sp. and Pseudomonas aeruginosa RZS3 vis-à-vis Organophosphorus Fungicide.

In present study in vitro phytopathogen suppression activity of siderophoregenic preparations of Ni and Mn resistant Alcaligenes sp. STC1 and Pseudomonas aeruginosa RZS3 SH-94B isolated from soil were found superior over the chemical pesticide. Siderophore rich culture broth and siderophore rich supernatant exerted antifungal activity against Aspergillus niger NCIM 1025, Aspergillus flavus NCIM 650, Fusarium oxysporum NCIM 1281, Alternaria alternata ARI 715, Cercospora arachichola, Metarhizium anisopliae NCIM 1311 and Pseudomonas solanacerum NCIM 5103. Siderophore rich broth and supernatant exhibited potent antifungal activity vis-à-vis oraganophosphorus chemical fungicide; kitazine. The minimum fungicidal concentration required was 25 µl for Aspergillus niger, Aspergillus flavus, Fusarium oxysporum, Cercospora arachichola, Metarhizium anisopliae, Pseudomonas solanacerum and 75 µl for A. alternata.

Production of Exo-polysaccharide by Rhizobium sp.

Two fold increase in the yield of glucose and maltose containing exo-polysaccharide (EPS) by Rhizobium sp. was observed during its growth in modified YEMB. EPS production, plant growth promotion activity and root colonization of Rhizobium sp. studies showed enhanced EPS synthesis, more seed germination and over all improvement in plant growth over control and R. meliloti treatment. Groundnut seeds bacterized with Rhizobium sp. resulted in 69.75% more root length, 49.51% more shoot height, 13.75% more number of branches and 13.60% more number of pods over the control and R. meliloti treatment. Bacterization of wheat seeds increased the dry matter yield of roots (1.7-fold), and roots adhering soil (RAS) (1.5) and shoot mass (1.9-fold). Rhizobium sp. inoculation also increased the population density of EPS-producing bacteria on the rhizoplane. Roots of plants inoculated with Rhizobium sp. maintained a higher K(+)/Na(+) ratio and K(+)-Na(+) selectivity.

In search of a rational approach to chronic kidney disease detection and management.

Rates of incident end-stage renal disease persist above established goals, driving efforts for early identification of chronic kidney disease (CKD) to reduce progression. The detection of CKD using existing electronic data sources has been proposed as an efficient identification method; however, this method is not without potential challenges and limitations.

[14C]bis(2-chloroethoxy)methane: comparative absorption, distribution, metabolism and excretion in rats and mice.

bis(2-Chloroethoxy)methane (BCM) is used primarily as a precursor in the synthesis of polysulfide elastomers. After administration of [(14)C]BCM, radioactivity is readily absorbed from the gastrointestinal tract and moderately absorbed through skin. Following absorption, BCM-derived radioactivity is rapidly distributed to all tissues, rapidly metabolized and excreted primarily in urine. Minimal effects of sex, species or dose in the range studied (0.1-10 mg kg(-1)) were observed on the fate of BCM in rats and mice after all routes of administration. The major metabolite (about 40% of the dose) of BCM in rat was isolated and identified as thiodiglycolic acid (TDGA) indicating that the ether linkage of BCM is cleaved to form 2-chloroethyl fragments that may be further metabolized to 2-chloracetaldehyde, conjugated with glutathione and the latter subsequently metabolized to TDGA. 2-chloroacetaldehyde has also been shown to be cardiotoxic, possibly accounting for BCM cardiotoxicity observed in repeated dose studies.

Trauma care systems in India.

Trauma-care systems in India are at a nascent stage of development. Industrialised cities, rural towns and villages coexist, with almost complete lack of organised trauma care. There is gross disparity between trauma services available in various parts of the country. Rural India has inefficient services for trauma care, due to the varied topography, financial constraints and lack of appropriate health infrastructure. There is no national lead agency to co-ordinate various components of a trauma system. No mechanism for accreditation of trauma centres and professionals exists. Education in trauma life-support (TLS) skills has only recently become available. A nation-wide survey encompassing various facilities has demonstrated significant deficiencies in current trauma systems.Although injury is a major public-health problem, the Government of India has failed to recognise it as a priority. Significant efforts to develop trauma-care systems across the country are seen mainly in the private sector. New initiatives under National Health Policy 2002 are expected to result in improvement in the systems, but the allocation of funds remains grossly inadequate for any significant impact on the outcome.