DEVELOPMENT OF A PROLONGD RELEASE GASTRORETENTIVE TABLET FORMULATION OF LEVOFLOXACIN

Objective: The present investigation concerns the design and evaluation of floating tablets of Levofloxacin, which after oral administration prolong the gastric residence time and increased drug bioavailability. Methods: Levofloxacin is a synthetic chemotherapeutic agent used to treat severe or life-threatening bacterial infections. The present work was designed to formulate floating tablet of Levofloxacin with various swelling agents. Formulations were prepared using various concentrations of Guar gum, Carbopol, hydroxy propyl methyl cellulose and Ethyl Cellulose by direct compression technique. The selected batches were evaluated for various parameters like weight variation, thickness, diameter, friability, floating lag time, duration of floating, swelling index, content uniformity and in-vitro drug release. The data obtained from the in-vitro dissolution studies of optimized batch F7 were fitted in different models. Results: The optimized formulation F7 showed 99.25% drug content, floating lag time of 10 min and swelling index of 40%. Drug release mechanism was found to be zero order along with higuchi release kinetics exhibiting diffusion along with dissolution of the drug from the tablet by non fickian mechanism. Conclusion: Levofloxacin floating tablets exhibited increased gastric residence time, there by improved bioavailability and therapeutic effect of the drug. Keywords: Levofloxacin, Gastro retentive, Guar gum, Hydroxy propyl methyl cellulose, Ethyl Cellulose, Carbopol

Future changes in the Western North Pacific tropical cyclone activity projected by a multidecadal simulation with a 16-km global atmospheric GCM

How tropical cyclone (TC) activity in the northwestern Pacific might change in a future climate is assessed using multidecadal Atmospheric Model Intercomparison Project (AMIP)-style and time-slice simulations with the ECMWF Integrated Forecast System (IFS) at 16-km and 125-km global resolution. Both models reproduce many aspects of the present-day TC climatology and variability well, although the 16-km IFS is far more skillful in simulating the full intensity distribution and genesis locations, including their changes in response to El Niño–Southern Oscillation. Both IFS models project a small change in TC frequency at the end of the twenty-first century related to distinct shifts in genesis locations. In the 16-km IFS, this shift is southward and is likely driven by the southeastward penetration of the monsoon trough/subtropical high circulation system and the southward shift in activity of the synoptic-scale tropical disturbances in response to the strengthening of deep convective activity over the central equatorial Pacific in a future climate. The 16-km IFS also projects about a 50% increase in the power dissipation index, mainly due to significant increases in the frequency of the more intense storms, which is comparable to the natural variability in the model. Based on composite analysis of large samples of supertyphoons, both the development rate and the peak intensities of these storms increase in a future climate, which is consistent with their tendency to develop more to the south, within an environment that is thermodynamically more favorable for faster development and higher intensities. Coherent changes in the vertical structure of supertyphoon composites show system-scale amplification of the primary and secondary circulations with signs of contraction, a deeper warm core, and an upward shift in the outflow layer and the frequency of the most intense updrafts. Considering the large differences in the projections of TC intensity change between the 16-km and 125-km IFS, this study further emphasizes the need for high-resolution modeling in assessing potential changes in TC activity

MINING WEB GRAPHS FOR RECOMMENDATIONS

Recommender frameworks which under goes web content mining have turned out to be critical as client produced data is all the more free-form and unstructured, that makes troubles in mining imperative data from information sources. Thus, with a specific end goal to fulfill the data necessities of Web clients and to grow the client involvement in many Web applications, proposal framework has been considered in the scholarly community and broadly conveyed in industry. This paper displays the framework, in which information sources can be demonstrated as different sorts of web charts utilizing DRec calculation. These web diagrams can be utilized for different proposal frameworks. This system is based upon warmth dissemination which will make a web chart dispersion show. The work is stretched out with customized question proposal and relative examination of calculation and demonstrates the outcomes in the terms of exactness. Also, this framework can be utilized to the vast majority of the web diagrams for question proposals, picture suggestion, and social and additionally customized suggestion

Dimerisation induced formation of the active site and the identification of three metal sites in EAL-phosphodiesterases

The bacterial second messenger cyclic di-3′,5′-guanosine monophosphate (c-di-GMP) is a key regulator of bacterial motility and virulence. As high levels of c-di-GMP are associated with the biofilm lifestyle, c-di-GMP hydrolysing phosphodiesterases (PDEs) have been identified as key targets to aid development of novel strategies to treat chronic infection by exploiting biofilm dispersal. We have studied the EAL signature motif-containing phosphodiesterase domains from the Pseudomonas aeruginosa proteins PA3825 (PA3825EAL) and PA1727 (MucREAL). Different dimerisation interfaces allow us to identify interface independent principles of enzyme regulation. Unlike previously characterised two-metal binding EAL-phosphodiesterases, PA3825EAL in complex with pGpG provides a model for a third metal site. The third metal is positioned to stabilise the negative charge of the 5′-phosphate, and thus three metals could be required for catalysis in analogy to other nucleases. This newly uncovered variation in metal coordination may provide a further level of bacterial PDE regulation

Processing of spatial-frequency altered faces in schizophrenia: Effects of illness phase and duration

Low spatial frequency (SF) processing has been shown to be impaired in people with schizophrenia, but it is not clear how this varies with clinical state or illness chronicity. We compared schizophrenia patients (SCZ, n534), first episode psychosis patients (FEP, n522), and healthy controls (CON, n535) on a gender/facial discrimination task. Images were either unaltered (broadband spatial frequency, BSF), or had high or low SF information removed (LSF and HSF conditions, respectively). The task was performed at hospital admission and discharge for patients, and at corresponding time points for controls. Groups were matched on visual acuity. At admission, compared to their BSF performance, each group was significantly worse with low SF stimuli, and most impaired with high SF stimuli. The level of impairment at each SF did not depend on group. At discharge, the SCZ group performed more poorly in the LSF condition than the other groups, and showed the greatest degree of performance decline collapsed over HSF and LSF conditions, although the latter finding was not significant when controlling for visual acuity. Performance did not change significantly over time for any group. HSF processing was strongly related to visual acuity at both time points for all groups. We conclude the following: 1) SF processing abilities in schizophrenia are relatively stable across clinical state; 2) face processing abnormalities in SCZ are not secondary to problems processing specific SFs, but are due to other known difficulties constructing visual representations from degraded information; and 3) the relationship between HSF processing and visual acuity, along with known SCZ- and medication-related acuity reductions, and the elimination of a SCZ-related impairment after controlling for visual acuity in this study, all raise the possibility that some prior findings of impaired perception in SCZ may be secondary to acuity reductions

Apoptosis-like cell death in Leishmania donovani treated with KalsomeTM10, a new liposomal amphotericin B

The present study aimed to elucidate the cell death mechanism in Leishmania donovani upon treatment with KalsomeTM10, a new liposomal amphotericin B. Methodology/Principal findings We studied morphological alterations in promastigotes through phase contrast and scanning electron microscopy. Phosphatidylserine (PS) exposure, loss of mitochondrial membrane potential and disruption of mitochondrial integrity was determined by flow cytometry using annexinV-FITC, JC-1 and mitotraker, respectively. For analysing oxidative stress, generation of H2O2 (bioluminescence kit) and mitochondrial superoxide O2 − (mitosox) were measured. DNA fragmentation was evaluated using terminal deoxyribonucleotidyl transferase mediated dUTP nick-end labelling (TUNEL) and DNA laddering assay. We found that KalsomeTM10 is more effective then Ambisome against the promastigote as well as intracellular amastigote forms. The mechanistic study showed that KalsomeTM10 induced several morphological alterations in promastigotes typical of apoptosis. KalsomeTM10 treatment showed a dose- and time-dependent exposure of PS in promastigotes. Further,study on mitochondrial pathway revealed loss of mitochondrial membrane potential as well as disruption in mitochondrial integrity with depletion of intracellular pool of ATP. KalsomeTM10 treated promastigotes showed increased ROS production, diminished GSH levels and increased caspase-like activity. DNA fragmentation and cell cycle arrest was observed in KalsomeTM10 treated promastigotes. Apoptotic DNA fragmentation was also observed in KalsomeTM10 treated intracellular amastigotes. KalsomeTM10 induced generation of ROS and nitric oxide leads to the killing of the intracellular parasites. Moreover, endocytosis is indispensable for KalsomeTM10 mediated anti-leishmanial effect in host macrophag

Apolipoprotein E Polymorphism And It’s Lifestyle Impact

The Apolipoprotein E Polymorphism, with its three main allelic variants (APOE2, APOE3, and APOE4), has gained prominence in genetic research due to its critical implications for human health. This review article offers a concise introduction to the APOE protein polymorphism and its influence on individual’s way of life. The APOE gene encodes apolipoprotein E, a critical component of lipid metabolism that is essential for both cholesterol transport and neuron repair in the central nervous system. APOE ℇ4 raises Alzheimer's risk, ℇ2 protects, and ℇ3 is neutral. Lifestyle choices, such as diet, exercise, and cognitive engagement, predict susceptibility to chronic illnesses like Alzheimer's and cardiovascular disease (CVD). For APOE ℇ4 carriers, a heart-healthy lifestyle can reduce elevated risk, while ℇ2 carriers, being less vulnerable, may need less intervention

Neutrino mixing matrices with relatively large θ13\theta_{13} and with texture one-zero

The recent T2K, MINOS and Double Chooz oscillation data hint a relatively large $\theta_{13}$, which can be accommodated by some general modification of the Tribimaximal/Bimaximal/Democratic mixing matrices. Using such matrices we analyze several Majorana mass matrices with texture one-zero and show whether they satisfy normal or inverted mass hierarchy and phenomenologically viable or not.Comment: 16 pages, 3 figures, minor modification in the text, version to appear in EPJ