FORMULATION DEVELOPMENT AND CHARACTERIZATION OF LYOPHILIZED FEBUXOSTAT NANOSUSPENSION

Objective: The study aims to prepare and evaluate febuxostat nanosuspension to improve oral bioavailability. Methods: Febuxostat nanosuspension was prepared by the solvent-antisolvent method, followed by a lyophilization technique using PVP K-30 as a stabilizer and sodium lauryl sulfate as a surfactant. Drug content, differential scanning calorimetry, powder x-ray diffraction, Fourier transform infrared spectroscopy, and in vitro dissolution studies were used to characterize the nanosuspension. Results: The results of the characterization studies indicated the formation of nanosuspension. The lyophilized FXT NS particle size is 2170.2 nm, the PDI value is 0.63, the negative zeta potential is 1.6 mV, and the drug content is 19.02%. Functional characterization studies demonstrated that the particle size reduced due to the interaction between the stabilizer and surfactant. Conclusion: It can be concluded that the prepared febuxostat nanosuspension enhances the aqueous solubility of FXT and improves its oral bioavailability

Efficacy, safety and cost effectiveness of levocetrizine and ebastine in allergic rhinitis: a comparative study

Background: Allergic rhinitis is a ubiquitous aliment affecting a large population of individuals. The mainstay of treatment includes antihistamines and topical steroids. With a large assortment available, the choice of the drugs needs to be non-random and evidenced based. Hence this study was undertaken to compare Levocetrezine and Ebastine in terms of efficacy, safety and cost effectiveness in treatment of allergic rhinitis.Methods: Newly diagnosed patients with allergic rhinitis were categorized into two groups and treated with Levocetrizine 5mg and Ebastine 20mg per day respectively. Severity of the symptoms at the commencement and at the end of second and the fourth weeks of therapy were assessed using a four-point Likert scale and assigning a Total Nasal Symptoms Score (TNSS). The primary efficacy measure was mean change from baseline TNSS at each follow up visit. Change in TNSS was compared using Independent sample test. Adverse effects in both the groups were compared using Chi square test. Cost effectiveness was inferred by calculation of the Average Cost Effectiveness Ratio.Results: A total of 159 patients 84 from Levocetrizine group (L group) and 75 from the Ebastine group (E group) were available for study. At the end of second week, the E group showed a better reduction in TNSS(p-0.04). However, both the groups showed similar reduction in TNSS at the concluding visit (p-value of 0.09). The incidence of adverse effects was significantly higher in the L than in E. Levocetrezine was found to be more cost effective than Ebastine.Conclusions: Levocterezine and Ebastine are equally efficacious in treatment of allergic rhinitis. Hence treatment will have to be personalized to the individual patients based on other factors such as adverse drug effects and cost effectiveness

Divergence of chikungunya virus in India: Tale of two cities

n/

Immune Activation, Cd4+ T Cell Counts, and Viremia Exhibit Oscillatory Patterns over Time in Patients with Highly Resistant HIV Infection

The rates of immunologic and clinical progression are lower in patients with drug-resistant HIV compared to wild-type HIV. This difference is not fully explained by viral load. It has been argued that reductions in T cell activation and/or viral fitness might result in preserved target cells and an altered relationship between the level of viremia and the rate of CD4+ T cell loss. We tested this hypothesis over time in a cohort of patients with highly resistant HIV. Fifty-four antiretroviral-treated patients with multi-drug resistant HIV and detectable plasma HIV RNA were followed longitudinally. CD4+ T cell counts and HIV RNA levels were measured every 4 weeks and T cell activation (CD38/HLA-DR) was measured every 16 weeks. We found that the levels of CD4+ T cell activation over time were a strong independent predictor of CD4+ T cell counts while CD8+ T cell activation was more strongly associated with viremia. Using spectral analysis, we found strong evidence for oscillatory (or cyclic) behavior in CD4+ T cell counts, HIV RNA levels, and T cell activation. Each of the cell populations exhibited an oscillatory behavior with similar frequencies. Collectively, these data suggest that there may be a mechanistic link between T cell activation, CD4+ T cell counts, and viremia and lends support for the hypothesis of altered predator-prey dynamics as a possible explanation of the stability of CD4+ T cell counts in the presence of sustained multi-drug resistant viremia

Chitohexaose Activates Macrophages by Alternate Pathway through TLR4 and Blocks Endotoxemia

Sepsis is a consequence of systemic bacterial infections leading to hyper activation of immune cells by bacterial products resulting in enhanced release of mediators of inflammation. Endotoxin (LPS) is a major component of the outer membrane of Gram negative bacteria and a critical factor in pathogenesis of sepsis. Development of antagonists that inhibit the storm of inflammatory molecules by blocking Toll like receptors (TLR) has been the main stay of research efforts. We report here that a filarial glycoprotein binds to murine macrophages and human monocytes through TLR4 and activates them through alternate pathway and in the process inhibits LPS mediated classical activation which leads to inflammation associated with endotoxemia. The active component of the nematode glycoprotein mediating alternate activation of macrophages was found to be a carbohydrate residue, Chitohexaose. Murine macrophages and human monocytes up regulated Arginase-1 and released high levels of IL-10 when incubated with chitohexaose. Macrophages of C3H/HeJ mice (non-responsive to LPS) failed to get activated by chitohexaose suggesting that a functional TLR4 is critical for alternate activation of macrophages also. Chitohexaose inhibited LPS induced production of inflammatory molecules TNF-α, IL-1β and IL-6 by macropahges in vitro and in vivo in mice. Intraperitoneal injection of chitohexaose completely protected mice against endotoxemia when challenged with a lethal dose of LPS. Furthermore, Chitohexaose was found to reverse LPS induced endotoxemia in mice even 6/24/48 hrs after its onset. Monocytes of subjects with active filarial infection displayed characteristic alternate activation markers and were refractory to LPS mediated inflammatory activation suggesting an interesting possibility of subjects with filarial infections being less prone to develop of endotoxemia. These observations that innate activation of alternate pathway of macrophages by chtx through TLR4 has offered novel opportunities to cell biologists to study two mutually exclusive activation pathways of macrophages being mediated through a single receptor

Cardio-renal syndromes: report from the consensus conference of the Acute Dialysis Quality Initiative

A consensus conference on cardio-renal syndromes (CRS) was held in Venice Italy, in September 2008 under the auspices of the Acute Dialysis Quality Initiative (ADQI). The following topics were matter of discussion after a systematic literature review and the appraisal of the best available evidence: definition/classification system; epidemiology; diagnostic criteria and biomarkers; prevention/protection strategies; management and therapy. The umbrella term CRS was used to identify a disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other organ. Different syndromes were identified and classified into five subtypes. Acute CRS (type 1): acute worsening of heart function (AHF–ACS) leading to kidney injury and/or dysfunction. Chronic cardio-renal syndrome (type 2): chronic abnormalities in heart function (CHF-CHD) leading to kidney injury and/or dysfunction. Acute reno-cardiac syndrome (type 3): acute worsening of kidney function (AKI) leading to heart injury and/or dysfunction. Chronic reno-cardiac syndrome (type 4): chronic kidney disease leading to heart injury, disease, and/or dysfunction. Secondary CRS (type 5): systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. Consensus statements concerning epidemiology, diagnosis, prevention, and management strategies are discussed in the paper for each of the syndromes

Search for Eccentric Black Hole Coalescences during the Third Observing Run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass $M>70$ $M_\odot$) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities $0 < e \leq 0.3$ at $0.33$ Gpc$^{-3}$ yr$^{-1}$ at 90\% confidence level.Comment: 24 pages, 5 figure

Open data from the third observing run of LIGO, Virgo, KAGRA and GEO

The global network of gravitational-wave observatories now includes five detectors, namely LIGO Hanford, LIGO Livingston, Virgo, KAGRA, and GEO 600. These detectors collected data during their third observing run, O3, composed of three phases: O3a starting in April of 2019 and lasting six months, O3b starting in November of 2019 and lasting five months, and O3GK starting in April of 2020 and lasting 2 weeks. In this paper we describe these data and various other science products that can be freely accessed through the Gravitational Wave Open Science Center at https://gwosc.org. The main dataset, consisting of the gravitational-wave strain time series that contains the astrophysical signals, is released together with supporting data useful for their analysis and documentation, tutorials, as well as analysis software packages.Comment: 27 pages, 3 figure