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Staphylococcus aureus is resistant to β-lactam antibiotics and causes several skin diseases to life-threatening diseases. FmtA is found to be one of the main factors involved in methicillin resistance in S. aureus. FmtA exhibits an esterase activity that removes the D-Ala from teichoic acid. Teichoic acids played a significant role in cell wall synthesis, cell division, colonization, biofilm formation, virulence, antibiotic resistance, and pathogenesis. The virtual screening of drug molecules against the crystal structure of FmtA was performed and the binding affinities of top three molecules (ofloxacin, roflumilast, and furazolidone) were predicted using molecular docking. The presence of positive potential and electron affinity regions in screened drug molecules by DFT analysis illustrated that these molecules are reactive in nature. The protein-ligand complexes were subjected to molecular dynamics simulation. Molecular dynamics analysis such as RMSD, RMSF, Rg, SASA, PCA, and FEL results suggested that FmtA-drug(s) complexes are stable. MM-GBSA binding affinity and QM/MM results (ΔG, ΔH, and ΔS) revealed that active site residues (Ser127, Lys130, Tyr211, Asp213, and Asn343) of FmtA played an essential for the binding of the drug(s) to form a lower energy stable protein-ligand complexes. FmtAΔ42 was purified using cation exchange and gel filtration chromatography. Fluorescence spectroscopy and circular dichroism results showed that interactions of drugs with FmtAΔ42 affect the tertiary structure and increase the thermostability of the protein. The screened molecules need to be tested and could be further modified to develop the antimicrobial compounds against S. aureus.

The Coronavirus Disease 2019 (COVID-19), caused by the SARS-CoV-2 virus has raised severe health problems in china and across the world as well. CoVs encode the nucleocapsid protein (N-protein), an essential RNA-binding protein that performs different roles throughout the virus replication cycle and forms the ribonucleoprotein complex with viral RNA using the N-terminal domain (NTD) of N-protein. Recent studies have shown that NTD-N-protein is a legitimate target for the development of antiviral drugs against human CoVs. Owing to the importance of NTD, the present study focuses on targeting the NTD-N-protein from SARS-CoV-2 to identify the potential compounds. The pharmacophore model has been developed based on the guanosine monophosphate (GMP), a RNA substrate and further pharmacophore-based virtual screening was performed against ZINC database. The screened compounds were filtered by analysing the in silico ADMET properties and drug-like properties. The pharmacokinetically screened compounds (ZINC000257324845, ZINC000005169973, and ZINC000009913056) were further scrutinized through computational approaches including molecular docking and molecular dynamics simulations and revealed that these compounds exhibited good binding affinity as compared to GMP and provide stability to their respective complex with the NTD. Our findings could disrupt the binding of viral RNA to NTD, which may inhibit the essential functions of NTD. These findings may further provide an impetus to develop the novel and potential inhibitor against SARS-CoV-2.

With the ever-growing volume of waste around the world, the tackling methods have also expanded. Among these, currently the most prevailing technology is the municipal solid waste (MSW) incineration. If used right, the advantages of the said technology are incredible. In this paper, we will discuss some key points and best practices for a successful MSW incineration and will look into the noteworthy case of Japan in this area.

Gene therapy is the product of man's quest to eliminate diseases. Gene therapy has three facets namely, gene silencing using siRNA, shRNA and miRNA, gene replacement where the desired gene in the form of plasmids and viral vectors, are directly administered and finally gene editing based therapy where mutations are modified using specific nucleases such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regulatory interspaced short tandem repeats (CRISPR)/CRISPR-associated protein (Cas)-associated nucleases. Transfer of gene is either through transformation where under specific conditions the gene is directly taken up by the bacterial cells, transduction where a bacteriophage is used to transfer the genetic material and lastly transfection that involves forceful delivery of gene using either viral or non-viral vectors. The non-viral transfection methods are subdivided into physical, chemical and biological. The physical methods include electroporation, biolistic, microinjection, laser, elevated temperature, ultrasound and hydrodynamic gene transfer. The chemical methods utilize calcium- phosphate, DAE-dextran, liposomes and nanoparticles for transfection. The biological methods are increasingly using viruses for gene transfer, these viruses could either integrate within the genome of the host cell conferring a stable gene expression, whereas few other non-integrating viruses are episomal and their expression is diluted proportional to the cell division. So far, gene therapy has been wielded in a plethora of diseases. However, coherent and innocuous delivery of genes is among the major hurdles in the use of this promising therapy. Hence this review aims to highlight the current options available for gene transfer along with the advantages and limitations of every method.

Background: Coronary artery disease (CAD) is one of the leading causes of mortality and morbidity worldwide. We thereby sought to investigate whether the biomarkers, angiopoietin-like 4 (ANGPTL-4) and galectin-3, reflect the severity of CAD. Methods: Patients were screened based on inclusion/exclusion criteria and written informed consent was obtained from the patients. Serum ANGPTL-4 and galectin-3 was quantified using enzyme-linked immunosorbent assay (ELISA) and correlated with the Global Registry of Acute Coronary Events (GRACE) and GENSINI score using Spearman’s rank correlation coefficient and multivariate analysis. Results: A total of 226 patients consisting of ST-segment elevation myocardial infarction (STEMI), non-STEMI/unstable angina (USA), chronic stable angina (CSA) and normal controls (NCs) participated in the study. ANGPTL-4 and galectin-3 were significantly higher in CAD than the NC group. ANGPTL-4 showed significant negative correlation with GRACE score in acute coronary syndrome (ACS) ( r = −0.211, p = 0.03) patients. ANGPTL-4 showed significant positive correlation with serum creatinine ( r = 0.304, p = 0.056) and body mass index (BMI) ( r = 0.424, p = 0.009) in CSA patients. A modest positive correlation was observed between the serum galectin-3 levels and GRACE score ( r = 0.187, p = 0.055) in ACS patients. However, on multivariate analysis the positive correlation relationship between ANGPTL-4 and galectin-3 with the severity of CAD was not sustained. Conclusion: In conclusion, ANGPTL-4 and galectin-3 do not appear to have a promising role for assessing the severity of CAD. Nevertheless these biomarkers do warrant further exploration in improving the management of CAD.

All the computational operations in digital processor are performed by its ALU. Multiplier is a combinational logic circuit which is used for multiplication of two binary bits that is basically a shift add operation. For achieving the desired output, most of the digital systems require high speed multiplication but if we go for the conventional multiplication of two 8-bit numbers, procedure will be lengthy and time taking. This paper aims at designing high speed 8-bit multipliers on the basis of Wallace tree multiplier. Tree multiplier is updated to Wallace tree multiplier that uses carry save algorithm. In this work, 8-bit multiplier is simulated in Xilinx Vivado software and implemented on BASYS3 Artix-7 FPGA Board. The total negative Slack and total hold slack is 0.00 ns and power consumption is 37.564 W.

Coronavirus pandemic has emerged as an extraordinary healthcare crisis in modern times. The SARS-CoV-2 novel coronavirus has high transmission rate, is more aggressive and virulent in comparison to previously known coronaviruses. It primarily attacks the respiratory system by inducing cytokine storm that causes systemic inflammation and pulmonary fibrosis. Decorin is a pluripotent molecule belonging to a leucine rich proteoglycan group that exerts critical role in extracellular matrix (ECM) assembly and regulates cell growth, adhesion, proliferation, inflammation, and fibrogenesis. Interestingly, decorin has potent anti-inflammatory, cytokine inhibitory, and anti-fibrillogenesis effects which make it a potential drug candidate against the COVID-19 related complications especially in the context of lung fibrosis. Herein, we postulate that owing to its distinctive pharmacological actions and immunomodulatory effect, decorin can be a promising preclinical therapeutic agent for the therapy of COVID-19.

Introduction: This study evaluated and compared techniques of postspace preparation for induction of dentinal microcracks utilizing microcomputed tomography (CT). Materials and Methods: A total of 45 extracted micro-CT scanned mandibular premolars were prepared and obturated. After the second micro-CT, samples were divided into three groups (n = 15). In Group 1, postspace preparation was done using hand K files up to the size of #110. In Group 2, postspace preparation was done using Peeso reamer up to the number of #3. In Group 3, postspace preparation was done using ParaPost XT Drills with the tip diameter of 1.1 mm. Thereafter, the third micro-CT scan was performed for microcracks evaluation, and statistical analysis was performed. Results: Few unprepared samples showed the presence of microcracks (1.54%). There was statistically significant (P < 0.05) percentage increase in the number of microcracks after root canal preparation and obturation (5.44%) and after postspace preparation (8.35%). The percentage increase in microcracks observed for Group 1, 2, and 3 from obturation to postspace preparation was 0.19%, 4.21%, and 6.86%. There was a significant difference among the three techniques of postspace preparation (P < 0.05). Conclusion: Microcracks may exist preoperatively. Postspace preparation increased the number of microcracks irrespective of the technique utilized. ParaPost XT Drills produces maximum microcracks in the root dentin followed by Peeso reamers and K files.

We live in an era doomed by various environmental issues. These issues have escalated the use of more effective renewal energy systems. There are a number of DC-DC converters used in Solar PV system for matching the impedance between the source and the load. This paper explains various different types of converters used in a Solar PV System giving an overview of their application along with their advantages and disadvantages. The PV System is controlled for maximum power point tracking.

Rajasthan is a home to various tribes who have very interesting history of origin, customs and social practices. About 39 per cent of Rajasthan tribal consists of Bhils. The present study was planned with the objective to assess the food habits and cutoms of Bhil tribe of Jhadol and Girwa panchayat samiti in Udaipur district. Five villages were randomly selected from each panchayat samiti. Ten families from each village were interviewed, thus making a total sample size of hundred families for the study. Food habits of Bhils are greatly influenced by beliefs, traditions, customs and taboos of the society. All the respondents were non-vegetarian. They consider the importance of special foods during various physiological conditions i.e. pregnancy, lactation, illness and fasting. Due to their low socio-economic condition they cannot afford the foods that are important during such conditions. Meal and alcohol plays a very important role in every occasion. Specific type of meal is prepared in different occasions that to depend upon the customs, food habits, and availability of the food in the particular area. Food habits of the tribes need to be assessed because it differs from one tribe to another and from one region to another and it has a major effect on the nutritional status of the population. There is a rich habitat of natural foods in Indian tribal environments that need to be used to promote food security, nutrition and health.

Deferoxamine has shown cutaneous wound healing potential by increased neovascularization. We hypothesized that topically applied deferoxamine facilitates wound healing in diabetic rats by modulating important cytokines and growth factors that take part in healing processes in a time-dependent manner. Diabetes was induced in male Wistar rats by streptozotocin and wound was created under pentobarbitone anesthesia. The diabetic rats were divided into two groups, of which one (control) was treated with ointment base and other with deferoxamine ointment (0.1%). Wound closure measurement and tissue collection were done on days 3, 7, 14 and 19 post-wounding. The relative expressions of hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), stromal cell-derived factor 1-alpha (SDF-1α), transforming growth factor beta 1 (TGF-β1), tumor necrosis factor-alpha (TNF-α), matrix metalloproteinase-9 (MMP-9), interleukin-1 beta (IL-1β) and interleukin-10 (IL-10) mRNA and proteins were determined in the wound tissues. CD-31 staining and collagen content were evaluated by immunohistochemistry and picrosirius red staining, respectively. Histological changes were assessed by H&E staining. The per cent wound closure was significantly higher from day 7 onwards in deferoxamine-treated rats. HIF-1α, VEGF, SDF-1α, TGF-β1, IL-10 mRNA and their protein levels were significantly higher on days 3, 7 and 14 in deferoxamine-treated rats. The mRNA expression and protein levels of TNF-α, MMP-9 and IL-1β were progressively and markedly reduced in deferoxamine-treated rats. The collagen deposition and formation of blood vessels were greater in deferoxamine-treated rats. It is suggested that topical application of deferoxamine ointment might be useful in cutaneous wound healing in diabetic patients.

Background The aim of the present study was to assess the effect of seven days daidzein pretreatment in cecal ligation and puncture (CLP) model of sepsis. Methods We assessed the survival benefit of daidzein and its effect on lung injury in CLP-induced sepsis in mice and determined the bacterial load in peritoneal fluid, blood, and lung homogenates. Tumor necrosis factor α (TNF-α) and corticosterone levels were measured by enzyme-linked immunosorbent assay; relative mRNA expression was estimated by real-time polymerase chain reaction, and standard biochemical techniques were used to measure nitrite level, myeloperoxidase activity, and vascular permeability. Results Daidzein pretreatment for seven days at a dose of 1 mg/kg body weight subcutaneously increased the survival time of septic mice. Daidzein decreased the bacterial load in peritoneal fluid, blood, and lungs, reduced the tumor necrosis factor α and nitrite level in plasma, and partially suppressed lung injury by reducing vascular permeability and myeloperoxidase activity in septic mice. Further, it restored the relative mRNA expressions of inducible nitric oxide synthase, glucocorticoid receptor α, and glucocorticoid receptor β genes in septic lungs were restored by daidzein pretreatment. Conclusions Daidzein pretreatment for 7 d in sepsis increased the survival time in mice, which may be relate to decrease in bacterial load, anti-inflammatory effect, and protection from lung injury.

We have recently reported that pre-treatment, but not the post-treatment with atorvastatin showed survival benefit and improved hemodynamic functions in cecal ligation and puncture (CLP) model of sepsis in mice. Here we examined whether combined treatment with atorvastatin and imipenem after onset of sepsis can prolong survival and improve vascular functions. At 6 and 18 h after sepsis induction, treatment with atorvastatin plus imipenem, atorvastatin or imipenem alone or placebo was initiated. Ex vivo experiments were done on mouse aorta to examine the vascular reactivity to nor-adrenaline and acetylcholine and mRNA expressions of α 1D AR, GRK2 and eNOS. Atorvastatin plus imipenem extended the survival time to 56.00 ± 4.62 h from 20.00 ± 1.66 h observed in CLP mice. The survival time with atorvastatin or imipenem alone was 20.50 ± 1.89 h and 27.00 ± 4.09 h, respectively. The combined treatment reversed the hyporeactivity to nor-adrenaline through preservation of α 1D AR mRNA/protein expression and reversal of α 1D AR desensitization mediated by GRK2/G βγ pathway. The treatment also restored endothelium-dependent relaxation to ACh through restoration of aortic eNOS mRNA expression and NO availability. In conclusion, combined treatment with atorvastatin and imipenem exhibited survival benefit and improved vascular functions in septic mice.

Unhealthy eating patterns and lack of physical activity develop obesity in school going children. If childhood obesity persists, it may bring the child at risk stage in his adolescent and adulthood. A study was undertaken on children from different schools in Bhubaneswar, Orissa to identify nutritional status based on anthropometric measurements and dietary intakes. Approximately 8.3 per cent boys (4-6 years age) in GEMS; 25 per cent boys in PNS and GEMS and 66.66 per cent girls of 7-9 years age in GEMS were stunted. About 50-75 per cent children in 7-9 years age group recorded normal to +1 (Z-score) BMI in PNS and GEMS whereas, 66.4 per cent boys and 91.63 per cent girls in SXHS (high parental income group) recorded BMI normal to +2 (Z-score). The data also indicated that around 8.33per cent girls and 25per cent boys of SXHS were obese with BMI of +3 . The income of the parents had profound influence on their calorie consumption and weight of school going children.

Science & Technology Asia, 23, 4, 7-17

The present study was undertaken to evaluate the effect of alcoholic extract of Dalbergia sissoo leaf extract (DSE) on isoproterenol (ISP)-induced myocardial injury in rats. Evaluation of three doses (30, 100 and 300 mg/kg of body weight) of DSE was done in ISP-treated rats. ISP was used at 85 mg/kg body weight by subcutaneous route for two subsequent days to induce myocardial injury in rats. Assessment of myocardial injury was done by estimation of different cardiac injury markers like LDH, CK-MB. Serum cholesterol, LDL, HDL, triglycerides in serum, myocardial infarcted area, oxidative stress and histopathology in heart tissue were also assessed in rats. Mean arterial pressure and heart rate were recorded in all the groups. Rats pretreated with DSE (30, 100 and 300 mg/kg of body weight) showed significant (p < 0.05-0.001) improvement in the heart weight/body weight ratio, myocardial infarcted areas, heart rate and mean arterial pressure in ISP-induced myocardial injury. DSE showed significant (p < 0.05-0.001) improvement in serum LDH, CK-MB, cholesterol, LDL and triglyceride levels at all the dose levels. However, DSE pretreatment had no significant effect on serum HDL level. Pretreatment with DSE (30, 100 and 300 mg/kg body weight) showed significant (p < 0.001) reduction in MDA level in comparison with myocardial injured rats. Further, antioxidant potential was also improved in terms of improved activities of reduced glutathione, superoxide dismutase and catalase with the DSE pretreatment. Histopathology also showed significant improvement in heart tissue. The study suggests that DSE showed beneficial effect in ISP-induced myocardial injury in rats.

Oxidative injury is markedly responsible for wound complications in diabetes mellitus. The biological actions of bilirubin may be relevant to prevent oxidant-mediated cell death, as bilirubin application at a low concentration scavenges reactive oxygen species. Hence, we hypothesized that topical bilirubin application might improve wound healing in diabetic rats. Diabetes was induced in adult male Wistar rats, which were divided into two groups, i.e., diabetic control and diabetic treated. Non-diabetic healthy rats were also taken as healthy control group. Wound area was measured on days 3, 7, 14, and 19 post-wounding. The levels of malondialdehyde (MDA) and reduced glutathione (GSH) and the activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) were estimated in the granulation tissue. There was a significant increase in percent wound closure in healthy control and diabetic treated rats on days 7, 14, and 19, as compared to diabetic control rats on days 7, 14, and 19. There was significant decrease in MDA levels on days 7, 14, and 19 in diabetic treated rats, as compared to diabetic control rats. Levels of GSH were significantly increased on days 3, 7, 14, and 19 in diabetic treated rats, as compared to diabetic control rats. GPx, SOD, and CAT activities were significantly higher on days 3, 7, and 14 in diabetic treated rats, as compared to diabetic control rats. The findings indicate that bilirubin is effective in reducing the oxidant status in wounds of diabetic rats which might have accelerated wound healing in these rats.

Post translational modifications (PTMs) are involved in variety of cellular activities and phosphorylation is one of the most extensively studied PTM, which regulates a number of cellular functions like cell growth, differentiation, apoptosis and cell signaling in healthy condition. However, alterations in phosphorylation pathways result in serious outcomes in the form of diseases, especially cancer. Many signalling pathways including Tyrosine kinase, MAP kinase, Cadherin–catenin complex, Cyclin-dependent kinase etc. are major players of the cell cycle and deregulation in their phosphorylation-dephosphorylation cascade has been shown to be manifested in the form of various types of cancers. Tyrosine kinase family encompasses the greatest number of oncoproteins. MAPK cascade has an importance role in cancer growth and progression. Bcl-2 family proteins serve either proapoptotic or antiapoptotic function. Cadherin–catenin complex regulates cell adhesion properties and cyclins are the key regulators of cell cycle. Altered phosphorylations in any of the above pathways are strongly associated with cancer, at the same time they serve as the potential tergets for drug development against cancer. Drugs targeting tyrosine kinase are potent anticancer drugs. Inhibitors of MEK, PI3K and ERK signalling pathways are undergoing clinical trials. Thus, drugs targeting phosphorylation pathways represent a promising area for cancer therapy.

The present study was conducted with the objective to assess impact of Nutrition Education Programme (NEP) on nutritional status of adolescent girls. Fifty girls enrolled in Kasturba Gandhi Balika Vidhayalaya were selected. Study was conducted in Mangrop village of Suwana block of Bhilwara district. Different aspects of nutrition were selected i.e., food, food groups, functions of food, nutritional deficiency disorders. Food intake was calculated using 24 h recall method. Anthropometric measurements viz. height and weight were measured and Body Mass Index (BMI) was also calculated of each girl. Thinness has been assessed using the indicator BMI-for-age. Result of the study related to anthropometric measurement revealed that maximum percentage of subjects belonged to underweight, followed by ideal BMI. According to the z-score moderate malnutrition was found in 30% respondents at base line and after NEP it was found in 28% of respondent. At base line 68% of the respondents were lying in normal category, after NEP this percent was increased up to 72%. Food intake data showed that the mean nutrient intake of all the nutrients except calcium were lower than the recommended dietary allowances. Their diet was found grossly inadequate at base line in cereals, pulses, milk and milk products, green leafy vegetables, fruits, other vegetables and fats and oils, whereas adequacy for sugar was found more than Recommended Dietary Intake. The results of the study thus conclude that NEP made a significant impact in nutritional status of adolescent girls.

Results of phytochemical tests showed presence of different kinds of phyto-constituents in aqueous, ether and methanol extract of Stevia rebaudiana leaves. Daily single dose (2.0 g/kg) administration of aqueous extract (A.E.), ether extract (E.E.) and methanol extract (M.E.) for 28 days of S. rebaudiana could not show any significant change in ALT and AST levels in rats. Blood sugar level was found to be decreased on day 28 in groups of rats treated with A.E., E.E. and M.E. of S. rebaudiana .

This experiment was designed to assess the effect of chronic fenvalerate toxicity on tissue Cu concentration in goats and to explore the pathways responsible for it. A significant decrease in tissue Cu concentration of kidney, heart, and brain while an increase in the liver were recorded in fenvalerate intoxicated goats at 15 mg/kg b.w. orally daily for 270 days. Concentration of total Cu, protein-free Cu, and protein-bound Cu in the wet intestine of fenvalerate-treated goats revealed a significant decrease in Cu concentration of the intestine due to the decrease in trichloroacetic acid (TCA)-insoluble Cu, while TCA-soluble Cu remained almost unaffected. Rabbit duodenal loop technique was used to assess the relative absorption of nonisotopic copper in a living animal. This technique enabled to compare Cu absorption from the lumen of three closely associated loops, each receiving 100 µg of copper along with different doses (0, 15, and 30 µg) of fenvalerate. A significant dose-dependent decrease in Cu absorption from the lumen due to fenvalerate treatment was recorded. A decrease in total copper (TCA-insoluble fraction) suggested an interference in active transport of copper due to the inhibition of absorption of protein-bound copper. It was concluded that fenvalerate interfered in copper absorption mostly by inhibiting its active or mediated transport.

Bilirubin has shown cutaneous wound healing potential in some preliminary studies. Here we hypothesize that bilirubin facilitates wound healing in diabetic rats by modulating important healing factors/candidates and antioxidant parameters in a time-dependent manner. Diabetes was induced in male Wistar rats by streptozotocin. In all diabetic rats wounds were created under pentobarbitone anesthesia. All the rats were divided into two groups, of which one (control) was treated with ointment base and other with bilirubin ointment (0.3%). Wound closer measurement and tissue collection were done on days 3, 7, 14 and 19 post-wounding. The relative expressions of hypoxia inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 alpha (SDF-1α), transforming growth factor- beta1 (TGF-β1()), tumor necrosis factor-α (TNF-α) and interlukin-10 (IL-10) mRNA and proteins and the mRNA of interlukin-1 beta (IL-1β) and matrix metalloprteinase-9 (MMP-9) were determined in the wound tissues. CD-31 staining and collagen content were evaluated by immunohistochemistry and picrosirius red staining, respectively. Histopathological changes were assessed by H&E staining. The per cent wound closer was significantly higher from day 7 onwards in bilirubin-treated rats. HIF-1α, VEGF, SDF-1α, TGF-β1, IL-10 mRNA and protein levels were significantly higher on days 3, 7 and 14 in bilirubin-treated rats. The mRNA expression and protein level of TNF-α and the mRNA of IL-1β and MMP-9 were progressively and markedly reduced in bilirubin-treated rats. The collagen deposition and formation of blood vessels were greater in bilirubin-treated rats. Bilirubin markedly facilitated cutaneous wound healing in diabetic rats by modulating growth factors, cytokines, neovasculogenesis and collagen contents to the wound site. Topical application of bilirubin ointment might be of great use in cutaneous wound healing in diabetic patients.

Sepsis is a common cause of acute kidney injury (AKI) and is associated with substantial morbidity and mortality. Objective of the study was to evaluate the effect of betulinic acid, a triterpenoid in sepsis-induced AKI using cecal ligation puncture (CLP) mouse model. Mice subjected to CLP developed histologic AKI at 18h after CLP. There was an increase in renal proinflammatory response (nuclear factor-kappa B expression, tumor necrosis factor-alpha, interleukin (IL)-6 and IL-10), matrix metalloproteinase-9, plasma creatinine, renal neutrophil gelatinase-associated lipocalin and oxidant stress response (malondialdehyde, inducible nitric oxide synthase, total nitrite and superoxide); decrease in anti-oxidant levels (superoxide dismutase and catalase) at 18h of CLP. However, BA pretreatment at the doses of 10 and 30mg/kg prevented the CLP-induced kidney damage by restoring the aforementioned inflammatory mediators, oxidant and anti-oxidant imbalance. These evidences suggest that, the protective effects of BA on kidney are associated with defending action against inflammatory and oxidative stress response in CLP mice and BA could be potential therapeutic agent in sepsis-induced AKI.

Aims The aim of the present study was to characterize TRPV4 channels in pregnant and nonpregnant mouse uterus and examine their functional role in spontaneous and agonist-induced contractions. Main methods We used RT-PCR, Western blot and immunohistochemistry experiments to demonstrate the presence of TRPV4 mRNA and protein, respectively in both pregnant and nonpregnant mouse uterus. Tension experiments were conducted for functional characterization of the TRPV4 channels. Key findings TRPV4 mRNA and protein were detected in both pregnant and nonpregnant mouse uterus with distribution in both endometrium and myometrium. The TRPV4 channel agonist GSK1016790A (GSK) increased myometrial contraction in pregnant (E max 336.8 ± 21.35%; pD 2 7.79 ± 0.29) and nonpregnant (E max 238 ± 28.13%; pD 2 7.61 ± 0.57) animals. HC067047 (1 μM), a selective blocker of the TRPV4 channel, antagonized the contractions to GSK in pregnant (E max 171 ± 18.26%; pD 2 6.58 ± 0.37) and nonpregnant (E max 78.12 ± 9.32%; pD 2 7.54 ± 0.9) uteri. Further, HC067047 (1 μM) inhibited contractions induced by PGF2α in the pregnant (E max 183.2 ± 13.94%; pD 2 7.01 ± 0.30 versus control E max 495.7 ± 42.49%; pD 2 7.12 ± 0.24) and nonpregnant (E max 105.3 ± 7.10%; pD 2 7.24 ± 0.34 versus control E max 232.5 ± 12.27%; pD 2 7.83 ± 0.29) uteri. Significance TRPV4 channels are present in the pregnant and nonpregnant mouse uteri, and their activation by endogenous ligands like prostaglandin increases myometrial contractility. Thus, the TRPV4 channel can be an important target in reducing myometrial contractility in preterm labor.

Sepsis commonly progresses to acute lung injury (ALI), an inflammatory lung disease with high morbidity and mortality. Septic ALI is characterized by excessive production of proinflammatory mediators. It remained refractory to present therapies and new therapies need to be developed to improve further clinical outcomes. Betulinic acid (BA), a pentacyclic lupane group triterpenoid has been shown to have anti-inflammatory activities in many studies. However, its therapeutic efficacy in polymicrobial septic ALI is yet unknown. Therefore, we investigated the effects of BA on septic ALI using cecal ligation and puncture (CLP) model in mice. Vehicle or BA (3, 10, and 30mg/kg) was administered intraperitoneally, 3 times (0, 24 and 48h) before CLP and CLP was done on 49(th)h of the study. Survival rate was observed till 120h post CLP. Lung tissues were collected for analysis by sacrificing mice 18h post CLP. BA at 10 and 30mg/kg dose significantly reduced sepsis-induced mortality and lung injury as implied by attenuated lung histopathological changes, decreased protein and neutrophils infiltration. BA also decreased lung NF-κB expression, cytokine, intercellular adhesion molecule-1, monocyte chemoattractant protein-1 and matrix metalloproteinase-9 levels. These evidences suggest that, the protective effects of BA on lungs are associated with defending action against inflammatory response and BA could be a potential modulatory agent of inflammation in sepsis-induced ALI.

Impaired cardiac β-adrenoceptor signaling is an important cause of sepsis-induced myocardial depression in man and experimental animals. We examined the effect of atorvastatin (ATR) pretreatment on myocardial β1-adrenoceptor (β1-AR) expressions and post-receptor signaling in a mouse model of sepsis (cecal ligation and puncture [CLP]). After 20 ± 2 h of surgery, hearts were isolated for the measurement of left ventricular functions (left ventricular developed pressure, dp/dt(max) and dp/dt(min)) using Langendorff setup. Western blot was used to determine β1-AR and G protein-coupled receptor kinase 2 protein expressions. Real-time polymerase chain reaction was done to determine β1-AR mRNA expression. Atorvastatin prevented sepsis-induced decrease in left ventricular functions, such as left ventricular developed pressure (CLP 75.90 ± 0.53 vs. ATR 100.24 ± 1.64 mmHg), dp/dtmax (CLP 3,742 ± 71 vs. ATR 4,291 ± 88 mmHg/s), and dp/dt(min) (CLP -1,010 ± 24 vs. ATR -1,346 ± 84 mmHg/s). Associated with functional impairments, sepsis decreased both myocardial β1-AR protein and mRNA expressions by 52% ± 9% and 62% ± 7%, respectively. However, ATR treatment of CLP mice (ATR) preserved β1-AR protein (96% ± 11%) and mRNA (88% ± 14%) expressions comparable to sham-operated level. Furthermore, it not only attenuated sepsis-induced decrease in basal cardiac adenosine 3',5'-cyclic monophosphate content (CLP 1.30 ± 0.27 vs. ATR 6.30 ± 0.67 pmol/mg protein), but also prevented its refractoriness to dobutamine stimulation (CLP 1.72 ± 0.27 vs. ATR 10.83 ± 1.37 pmol/mg protein). Atorvastatin also inhibited sepsis-induced increase in cardiac G protein-coupled receptor kinase 2 protein expression (CLP 1.73 ± 0.18-fold vs. ATR 1.10 ± 0.18-fold), protein kinase A activity (CLP 1.12 ± 0.14 vs. ATR 0.66 ± 0.08 U/mg protein) and plasma catecholamines (CLP 138 ± 22 vs. ATR 59 ± 2 pg/mL). In conclusion, ATR seems to improve left ventricular functions in vitro through the preservation of β(1)-AR signaling in sepsis.

Dedicated servers are deployed by companies to meet the ever growing computing demand. More storage and more security are sought after by companies. The inefficient scaling of hardware, higher deployment time, installation of old operating systems on new hardware are just some of the areas where dedicated servers suffer. Cloud severs can be used in lieu of dedicated servers. This will not only decrease the overall IT budget of companies but will be more flexible. This paper is a survey done on three start-up companies to inquire about the dedicated servers. Amazon Web Services have been used to rent a cloud server which hosts a website. Comparisons are done graphically and some observations drawn by the companies' executives about cloud and dedicated servers are mentioned in the latter stage of the paper.

The purpose of the present study was to characterize TRPV4 channels in the rat pulmonary artery and examine their role in endothelium-dependent relaxation. Tension, Real-Time polymerase chain reaction (Real-Time PCR) and Western blot experiments were conducted on left and right branches of the main pulmonary artery from male Wistar rats. TRPV4 channel agonist GSK1016790A (GSK) caused concentration-related robust relaxation (Emax 88.6±5.5%; pD2 8.7±0.2) of the endothelium-intact pulmonary artery. Endothelium-denudation nearly abolished the relaxation (Emax 5.6±1.3%) to GSK. TRPV4 channel selective antagonist HC067047 significantly attenuated GSK-induced relaxation (Emax 56.2±6.6% vs. control Emax 87.9±3.3%) in endothelium-intact vessels, but had no effect on either ACh-induced endothelium-dependent or SNP-induced endothelium-independent relaxations. GSK-induced relaxations were markedly inhibited either in the presence of NO synthase inhibitor L-NAME (Emax 8.5±2.7%) or sGC inhibitor ODQ (Emax 28.1±5.9%). A significant portion (Emax 30.2±4.4%) of endothelium-dependent relaxation still persisted in the combined presence of L-NAME and cyclooxygenase inhibitor indomethacin. This EDHF-mediated relaxation was sensitive to inhibition by 60mM K(+) depolarizing solution or K(+) channel blockers apamin (SKCa; KCa2.3) and TRAM-34 (IKCa; KCa3.1). GSK (10(-10)-10(-7)M) caused either modest decrease or increase in the basal tone of endothelium-intact or denuded rings, respectively. We found a greater abundance (>1.5 fold) of TRPV4 mRNA and protein expressions in endothelium-intact vs. denuded vessels, suggesting the presence of this channel in pulmonary endothelial and smooth muscle cells as well. The present study demonstrated that NO and EDHF significantly contributed to TRPV4 channel-mediated endothelium-dependent relaxation of the rat pulmonary artery.

While the Competition Law is still evolving in India, we often come across Cartelisation across all market sectors - oil, gas, potash, cement and so on. Cartelisation refers to the process of forming Cartels which is a group of independent companies engaged in similar business that join together to fix prices, limit production or share consumers. The Competition Act, 2002, a part of which came into effect in 2009 prohibits “Cartels”. However, this prohibition is not sufficed to put deal with the problems that such cartels pose for the economy and ultimately, the consumers. The paper studies the reasons why the present competition law in India is not adequately competent in dealing with prohibition of cartels and penalising the corporations involved in such unfair trade practices. It further discusses plausible amendments that can be made to the current legislation so as to ensure effective application of the same by way of comparing the competition laws across different nations.

Disposition kinetics of levofloxacin was investigated after single dose intravenous administration at the dose of 10 mg/kg in six healthy and six mastitic Black Bengal lactating goats. Mastitis was induced in goats by coagulase positive Staphylococcus aureus . The maximum milk concentration was higher in mastitic goats (17.01 ± 0.67 μg/ ml) as compared to healthy (14.75 ± 0.95 μg/ml). The therapeutic milk concentration in mastitic goats (0.10 ± 0.00 to 16.61 ± 0.70 μg/ml) was maintained for 48 h, which was significantly longer than healthy goats (36 h). The t ½ β in plasma (5.08 ± 0.18 h) and milk (7.28 ± 0.09 h) of mastitic goats were significantly longer than healthy goats (4.04 ± 0.24 and 4.16 ± 0.76 h). The total body clearence in plasma of healthy goats (5.64 ± 0.78 ml/kg/min) was almost similar to mastitic goats (5.82 ± 0.44 ml/kg/min). The AUC milk /AUC plasma ratio (3.36) in mastitic goats indicated extensive penetration of levofloxacin from plasma to milk. The t 1/2 milk /t 1/2 plasma ratio was 1.43. The AUC/MIC ratio in plasma and milk of mastitic goats were 296 and 1014 respectively. Based on the plasma kinetic parameters, it was concluded that levofloxacin may be used for treatment of mastitis in goats.

Disposition kinetic studies of gati fl oxacin (GAT) was conducted after single i.v. dose (10 mg/kg) in six healthy and six mastitic Black Bengal lactating goats. Mastitis was induced by coagulase positive S. aureus . The concentration of the drug was estimated by HPLC. The maximum milk concentration was found to be signi fi cantly (p< 0.05) higher in mastitic goats (12.78 ± 3.11 μ g/ml) than healthy (9.17 ± 1.41 μ g/ml). The therapeutic milk concentration in mastitic goats (0.13 ± 0.05 to 12.41 ± 2.99 μ g/ml) was maintained for 48 h which was signi fi cantly (p

Background : Stevia rebaudiana regulates blood sugar, prevents hypertension and tooth decay. Other studies have shown that it has antibacterial as well as antiviral property. Methods : Preliminary phytochemical screening of aqueous, ether and methanolic extracts of S. rebaudiana was done. Acute and sub-acute toxicity were conducted on twenty four Albino rats, divided into one control (Group I) and three treatment groups viz. aqueous extract (Group II), ether extract (Group III) and methanolic extract (Group IV). For the study of antidiabetic effect of S. rebaudiana rats were divided into seven groups (n=6). Diabetes was induced by a single dose of 5% alloxan monohydrate (125 mg/kg, i.p.) after 24 hour fasting.Blood samples were analysed on day 0, 1, 5, 7, 14 and 28. Results : Phytochemical tests showed presence of different kinds of phyto-constituents in aqueous, ether and methanol extract of Stevia rebaudiana leaves. Daily single dose (2.0 g/kg) administration of aqueous extract (A.E.) , ether extract (E.E.) and methanol extract (M.E.) for 28 days of S. rebaudiana could not show any significant change in ALT and AST levels in rats. Blood sugar level was found to be decreased on day 28 in groups of rats treated with A.E., E.E. and M.E. of S. rebaudiana. Conclusion : The extracts of Stevioside rebaudiana could decrease the blood glucose level in diabetic rats in time dependent manner.