PubMed Health⌕ Search

Biomedical subjects

S Murthy

Publications and source records attributed to S Murthy.

At least 19 recordsLinked to original sources
PubMed2006

Pre-endoscopic proton pump inhibitor therapy reduces recurrent adverse gastrointestinal outcomes in patients with acute non-variceal upper gastrointestinal bleeding.

BACKGROUND: Proton pump inhibitors (PPIs) following endoscopic haemostasis reduce rebleeding rates in patients with high-risk acute non-variceal upper gastrointestinal bleeding. Many advocate the use of PPIs prior to endoscopy, although its incremental benefit is unproven. AIM: To determine if providing PPIs before endoscopy reduces adverse gastrointestinal outcomes in acute non-variceal upper gastrointestinal bleeding patients. METHODS: We performed a retrospective review to identify patients presenting to two tertiary care centres with acute non-variceal upper gastrointestinal bleeding between 1999 and 2004. Subjects receiving PPI therapy before endoscopy were compared with those not receiving pre-endoscopic PPI therapy. The primary outcome measure was the development of any adverse bleeding outcome (rebleeding, surgery for control of bleeding, in-hospital mortality, readmission within 30 days for acute non-variceal upper gastrointestinal bleeding). RESULTS: 385 patients were included in our study [132 (12 intravenous/120 po) pre-endoscopic PPI vs. 253 no pre-endoscopic PPI]. Patients receiving pre-endoscopic PPI therapy were significantly less likely to develop adverse outcomes compared with those not given pre-endoscopic PPIs (25% vs. 13%, P = 0.005). Rebleeding, upper gastrointestinal surgery, mortality and length of hospital stay were also significantly lower in patients receiving pre-endoscopic PPI. CONCLUSIONS: The use of PPIs before endoscopy significantly reduces the risk of developing adverse gastrointestinal outcomes in patients with acute non-variceal upper gastrointestinal bleeding. Future studies are required to better characterize this relationship.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2006

Neurofibromatosis type 1 gene haploinsufficiency reduces AP-1 gene expression without abrogating the anabolic effect of parathyroid hormone.

Approximately 50% of neurofibromatosis type 1 (NF1) patients exhibit skeletal pathology, such as premature osteoporosis or pseudoarthroses. Loss of neurofibromin deregulates Ras signal transduction to affect generation of mitogen-activated protein kinase and Akt, both of which have been implicated in parathyroid hormone (PTH) anabolic mechanisms. Our aim was to determine if loss of neurofibromin impaired the anabolic effect of PTH on bone mass. Nf1 heterozygote (Nf1(+/-)) and wild type (Nf1(+/+)) mice were treated with recombinant human PTH(1-34) or vehicle once daily for 3-28 days. PTH enhanced mRNA expression of c-fos, junB, and fra2 in the distal femur metaphyses of both genotypes; expression of these transcripts was consistently lower in PTH-treated Nf1(+/-) mice. Despite lowered c-fos expression in Nf1(+/-) mice, PTH increased bone mass equivalently in both genotypes by 28 days. Ex vivo, Nf1 heterozygosity was associated with increased inducible osteoclasts in PTH-treated bone marrow cells and impairment of the actin stress fiber and cyclic adenosine monophosphate response to PTH in osteoprogenitors. Lower c-fos expression was previously thought to abrogate PTH responsiveness. Our results suggest crosstalk might occur between Ras signal transduction and the protein kinase A pathway in Nf1(+/-) mice. Ras signal transduction does not appear to be essential for the anabolic actions of PTH on bone. Because PTH was effective in the absence of Nf1, it may offer a useful approach to treat osteoporosis in NF1 patients.

Acid Phosphatase↗
PubMed2006

High-solids centrifuge is a boon and a curse for managing anaerobically digested biosolids.

High-solids centrifugation can reduce the cost of managing or disposing of anaerobically digested biosolids. High-solids centrifuges can increase relative cake solids by as much as 5% DS compared with other dewatering devices, such as belt filter presses, with a resulting 15-20% reduction in overall mass of hauled biosolids. Cost reductions can be similar (15-20%) or more, depending on the type of disposal or management involved. For example, the additional removal of water from the cake increases the energy content in the biosolids, thereby facilitating incineration or heat drying processes. For land application, the benefits are more mixed. As explained in this paper, increases in biosolids odours associated with high-solids centrifuges may increase digestion requirements and may compel producers to transport biosolids to more remote, distant sites, potentially increasing transportation costs. High-solids centrifuges shear anaerobically digested biosolids. The shear results in a net increase in labile protein, an odour precursor. Additionally, high-solids centrifugation also results in the inhibition of methanogenesis, a major mechanism for degradation of organosulphur odours. Therefore, the risks and benefits should both be weighed when considering high-solids centrifuges for land application of anaerobically digested biosolids.

Centrifugation↗
PubMed2006

Chemical phosphorus removal to extremely low levels: experience of two plants in the Washington, DC area.

Chemical phosphorus removal using metal (iron and aluminium) salts is frequently used to control effluent soluble phosphorus levels in wastewater treatment plants. In the Washington DC area effluent phosphorus requirements are extremely stringent to protect the Chesapeake Bay. Full-scale data from two plants in the area were analysed to establish phosphate behaviour in the presence of iron. Titration experiments and mathematical modelling were performed to determine the role of ferric phosphate and hydroxide precipitation and other mechanisms that may potentially be involved in phosphorus removal. Iron addition is described in the model using a chemical equilibrium approach extended with surface charges and adsorption. The model verifies key observations from full-scale data: (a) extremely low orthophosphate levels can be achieved over a wide range of pH values, (b) a mixture of ferric phosphate and ferric hydroxide precipitate is forming with the hydroxide acting as sorbent, (c) molar ratios of Fe/P (iron dosed to phosphate removed) vary widely (1.0-3.9) based on the technology used and residual phosphate levels. The model will be a useful tool for engineers to optimise preliminary, simultaneous and tertiary P removal, both for design and plant operation.

District of Columbia↗
PubMed2006

Examining the influence of substrates and temperature on maximum specific growth rate of denitrifiers.

Facilities across North America are designing plants to meet stringent limits of technology (LOT) treatment for nitrogen removal (3-5 mg/L total effluent nitrogen). The anoxic capacity requirements for meeting LOT treatment are dependent on the growth rates of the denitrifying organisms. The Blue Plains Advanced Wastewater Treatment Plant (AWTP) is one of many facilities in the Chesapeake Bay region that is evaluating its ability to meet LOT treatment capability. The plant uses methanol as an external carbon source in a post-denitrification process. The process is very sensitive to denitrification in the winter. One approach to improve anoxic capacity utilization is to use an alternative substrate for denitrification in the winter to promote the growth of organisms that denitrify at higher rates. The aim of this study was to evaluate denitrification maximum specific growth rates for three substrates, acetate, corn syrup and methanol, at two temperatures (13 degrees C and 19 degrees C). These temperatures approximately reflect the minimum monthly and average annual wastewater temperature at the Blue Plains AWTP. The results suggest that the maximum specific growth rate (mu(max)) for corn syrup (1.3 d(-1)) and acetate (1.2 d(-1)) are higher than that for methanol (0.5d(-1)) at low temperature of 13 degrees C. A similar trend was observed at 19 degrees C.

Biomass↗
PubMed2005

Chemical phosphorus removal model based on equilibrium chemistry.

Regulations in many regions of the world require total phosphorus (TP) levels lower than 0.10 mgP/L (100 microgP/L) in effluents, resulting in the need to achieve very low ortho-phosphate (OP) concentrations. Chemical precipitation is a widely used technology for controlling effluent OP discharge, either on its own or supplementing biological methods. The various chemical and physico-chemical mechanisms that result in extremely low residual OP levels are complex and depend on pH. In practice, engineering calculations frequently use an empirical precipitation model. This model requires pH as input and predicts the lowest achievable OP residual of 35 microgP/L at a narrow optimum pH of 6.9-7.0, when an excess of ferric is added. The model has been combined with a biokinetic and weak acid/base chemistry based pH model, to allow accurate prediction of pH, OP residuals and chemical sludge production. Analysis of effluent data from the Blue Plains plant shows that residuals as low as 10 microgP/L OP can be achieved regularly, over a wider pH range. The precipitation model was recalibrated to match the newly available data. Subsequently it was compared with a new, mechanistic precipitation model based on solubility and dissociation constants for actual chemical compounds. The need for more accurate measurement of extremely low OP concentrations and considering the role of organics, adsorption and coagulation in chemical phosphorus removal is demonstrated.

Acid-Base Equilibrium↗
PubMed2004

Water Environment Research Foundation (WERF) anaerobic digestion and related processes, odour and health effects study.

Biosolids odour emissions can affect the ability of wastewater utilities to implement beneficial biosolids processing and reuse programs. Communities often become more sensitised and vocal about biosolids issues, once they experience odours emanating from a nearby site. Odour impacts from biosolids, including potential human health effects, have been targeted recently by many national and local newspapers, citizens' groups, and regulatory agencies, who have raised significant concerns, ranging from viable disposal methods/sites to outright bans. Many national and local regulatory agencies in the United States are considering biosolids disposal bans in their communities because of misinformation, poor science, and citizen pressure, but primarily because of odour impact concerns. The wastewater industry has a relatively poor understanding of the operations and treatment parameters that influence biosolids odour emissions. Thus, wastewater treatment plants are often unable to control the odour quality of the biosolids that are delivered into communities. A research study to demonstrate the influence of anaerobic digestion, mechanical dewatering, and storage design and operating parameters on the odour quality of the final product was performed and is the subject of this paper. Established and new sampling and analytical methods were used to measure biosolids odour emissions from 11 test sites in North America. By determining the impacts of these control variables on biosolids odour quality, design and operations of anaerobic digestion systems might be enhanced. This paper also summarises a corollary study performed as part of the WERF research study that addresses the health effects of biosolids odours.

Community Participation↗
PubMed2003

AMP-activated protein kinase, super metabolic regulator.

The AMP-activated protein kinase (AMPK) is a metabolic-stress-sensing protein kinase that regulates metabolism in response to energy demand and supply by directly phosphorylating rate-limiting enzymes in metabolic pathways as well as controlling gene expression.

AMP-Activated Protein Kinases↗
PubMed2002

RDP58, a locally active TNF inhibitor, is effective in the dextran sulphate mouse model of chronic colitis.

OBJECTIVE AND DESIGN: RDP58 is a novel anti-inflammatory peptide that inhibits TNF synthesis and upregulates heme oxygenase-1. RDP58 therapy was evaluated in the dextran sodium sulphate (DSS) model of chronic colitis. MATERIAL: Colitis was induced by giving DSS to mice (n = 8 animals/group). Toxicity studies were done in Rhesus monkeys (n = 5), dogs (n = 3) and mice (n = 10). TREATMENT: In colitis, mice were treated with p.o. vehicle (saline), RDP58 (5 and 10 mg/kg/day) or 5-ASA (50 mg/kg/day). METHODS: Disease activity index (DAI) was used as the endpoint of efficacy. RESULTS: RDP58 therapy significantly reduced DAI and histological scores in all animals. DAI scores in RDP58 treated animals declined faster than 5-ASA. RDP58 at 5 or 10 mg/ kg/day significantly reduced DAI compared to 5-ASA. RDP58 significantly reduced acute, chronic and total inflammation scores. It enhanced re-epithelialization by reducing crypt scores. RDP58 was not bioavailable and was well tolerated. CONCLUSIONS: Therapeutic efficacy of RDP58 combined with a lack of bioavailibility and toxicity suggest that RDP58 may be a promising new therapeutic for IBD.

Animals↗
PubMed2002

Squamous cell carcinoma and adenocarcinoma of the lower third of the esophagus and gastric cardia: similarities and differences.

Squamous cell carcinoma (SCC) and adenocarcinoma (ADC) of the lower esophagus and gastric cardia were compared in their clinical features and long-term prognosis. Two hundred and ninety-five patients with SCC and 263 with ADC were reviewed. Resectability rates for SCC and ADC were 74.2% and 73.2% respectively (P=0.8). Among those who underwent resection, ADC was more advanced, with 22.3% at stage IV compared with 7.4% for SCC (P=0.001). Postoperative cardiac events occurred in 24.2% of SCC patients and 14.7% of ADC patients (P=0.015), and major respiratory complications in 20.1% and 8.6% respectively (P=0.001). Thirty-day mortality rates were 2.7% and 4% (P=0.46), and hospital mortality rates were 11.4% and 7.6% (P=0.19). Median survival rates were 12.5 months for SCC and 11.6 months for ADC (P=0.99) and 5-year survival rates were 19.9% and 17.6% (P=0.55) respectively. Squamous cell carcinoma of the lower esophagus and ADC of the cardia differed in patient demographics and clinical features but long-term prognoses were similar.

Adenocarcinoma↗
PubMed2002

Characterization of wastewater and solids odors using solid phase microextraction at a large wastewater treatment plant.

A simple and reliable technique has been developed and used to detect odorous gases, i.e. propionic and butyric acids, carbon disulfide, dimethyl sulfide, dimethyl disulfide, and trimethylamine, emitted from various materials generated by the wastewater treatment process. The method detection limits are in the low ppb range and comparable to the odor threshold for human detection. In this study solid phase microextraction (SPME) was employed to characterize and quantify odorous compounds in the headspace over samples collected from various unit processes at the District of Columbia Wastewater Treatment Plant, Washington DC, USA. The patterns of odorous chemicals released from wastewater influent, thickened sludge, dewatered sludge and biosolids were evaluated. Volatile reduced sulfurs were more prevalent in samples collected from downstream processes and corresponded with decreased oxidation-reduction potential (ORP) conditions. Volatile fatty acids were consistently identified in the primary gravity thickeners, while trimethylamine could only be detected from biosolids after the post-liming process.

Chemical Phenomena↗
PubMed2001

Novel nonsecosteroidal vitamin D receptor modulator inhibits the growth of LNCaP xenograft tumors in athymic mice without increased serum calcium.

BACKGROUND: We recently reported on novel vitamin D receptor (VDR) modulators that are structurally distinct from the secosteroid 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), the endogenous activator of VDR. One of these compounds, LG190119, was tested for the ability to inhibit the growth of LNCaP human prostate cancer cell-derived tumors in athymic mice. METHODS: In one study, athymic mice with established LNCaP xenograft tumors were dosed orally every day with LG190119 (3 or 10 mg/kg) or with a synthetic analog of 1,25(OH)(2)D(3), EB1089 (1 microg/kg), for 15 days. In another study ("prevention mode"), oral administration (every other day) of 10 mg/kg LG190119 or a non-hypercalcemic dose of 1,25(OH)(2)D(3) (0.5 microg/kg) was initiated prior to tumor development and continued for 84 days. In both studies, tumor volumes, mouse weights, and serum calcium levels were measured. RESULTS: In the established tumor study, LG190119 at each dose resulted in significant tumor growth inhibition without hypercalcemia at both 10 and 15 days. EB1089 treatment resulted in significant tumor growth inhibition only at Day 10 and resulted in hypercalcemia at Day 15. In the prevention-mode study, LG190119 markedly slowed tumor growth without increased serum calcium in comparison with either vehicle or 1,25(OH)(2)D(3) treatment (P < 0.001). CONCLUSIONS: LG190119 effectively inhibited LNCaP xenograft tumor growth without increased serum calcium levels or any other apparent side effects. Compounds of this class may represent promising new therapeutics for treatment of prostate cancer and other cancers with fewer undesirable side effects than currently used drugs.

Animals↗
PubMed2001

Regulation of sterol regulatory element-binding proteins in hamster intestine by changes in cholesterol flux.

A control chow diet or diets containing 1% cholesterol (cholesterol-enriched) or 4% cholestyramine and 0.15% lovastatin (cholesterol-depletion) were fed to hamsters for 2 weeks. Sterol regulatory element-binding protein (SREBP)-1a, SREBP-1c, SREBP-2, 3-hydroxy-3-methylglutaryl-coenzyme A reductase, 3-hydroxy-3-methylglutaryl-coenzyme A synthase, and LDL receptor mRNA levels and SREBP-1 and -2 protein expression were estimated in villus cell populations from duodenum, jejunum, and ileum. SREBP-1a was a minor transcript in hamster intestine, and its gene expression was not altered by changes in dietary cholesterol flux. In contrast, SREBP-1c gene expression was increased by dietary cholesterol and decreased by cholesterol depletion. mRNA levels for SREBP-2 and the other sterol-responsive genes were increased in intestines of animals on the cholesterol depletion diet but minimally suppressed if at all, by the diet enriched in cholesterol. In general, the amount of the precursor form of SREBP-1 was higher in cells of the upper villus and lower in cells of the lower villus. SREBP-2 precursor was higher in cells of the lower villus and lower in cells of the upper villus. Protein expression of precursor correlated with the location of gene expression for SREBPs. The amount of precursor mass of SREBP-2 was not altered by cholesterol feeding but was increased by cholesterol depletion. The mature form of SREBP-2 was in very low abundance and difficult to detect in intestines of animals fed control chow or cholesterol. It was readily detectable and increased in intestines of animals on the cholesterol-depletion diet. The diets did not significantly alter the amount of precursor or mature forms of SREBP-1. Cholesterol feeding had no effect on cholesterol or fatty acid synthesis, whereas synthesis of these lipids was increased in intestines of hamsters on the cholesterol-depleted diet. These results suggest that SREBP-1a has little or no role in regulating intestinal cholesterol synthesis. It is postulated that under basal conditions, SREBP-1c regulates intestinal fatty acid synthesis and SREBP-2 regulates cholesterol synthesis. Following marked changes in cholesterol flux across the intestine, SREBP-2 assumes the role of SREBP-1 and regulates both cholesterol and fatty acid synthesis in intestine.

Animals↗