298 research outputs found
Optimized threshold for serum HCV RNA to predict treatment outcomes in hepatitis C patients receiving peginterferon alfa-2a/ribavirin
Get PDFAdefovir-resistant hepatitis B can be associated with viral rebound and hepatic decompensation.
No full textBACKGROUND/AIMS: The susceptibility of adefovir-resistant hepatitis B virus (HBV) mutants is only reduced by 3-10-fold in in vitro studies, suggesting that virologic breakthrough and clinical deterioration are unlikely. The aim of this study was to describe the clinical course of patients with adefovir-resistant HBV infection. METHODS: Testing for adefovir-resistant mutations was performed on patients who had a suboptimal response or virologic breakthrough on adefovir. Adefovir-resistant mutations were detected using a line probe assay and direct sequencing of the HBV P-gene. RESULTS: Eight male patients with pre-existing lamivudine resistance or breakthrough (mean age 47+/-13 years) were found to have adefovir-resistant mutations rtA181V/T or rtN236T. Baseline median ALT was 66IU/L (range, 27-1161) and median HBV DNA 7.9log(10) copies/ml (range, 6-8.3). At the time of adefovir resistance (mean of 20+/-9 months), HBV DNA increased to >/=5log(10) copies/ml in 7 patients. After detection of adefovir resistance, hepatic decompensation occurred in 2 patients, 1 of whom died. Salvage therapy with lamivudine, entecavir or tenofovir was given to 7 patients and a reduction in HBV DNA by >/=3log(10) was seen in 3 patients. CONCLUSIONS: In conclusion, adefovir resistance can be associated with significant viral rebound and hepatic decompensation which may be fatal
Predicting Early and Sustained Virological Responses in Prior Nonresponders to Pegylated Interferon alpha-2b Plus Ribavirin Retreated With Peginterferon alpha-2a Plus Ribavirin and The Benefit-Risk Ratio of Retreatment t
No full textGOALS:
To evaluate the predictive value of complete early virological response (cEVR) on sustained virological response (SVR) following retreatment with peginterferon alpha-2a (40 kDa) plus ribavirin in previous nonresponders to peginterferon alpha-2b (12 kDa).
BACKGROUND:
In the randomized multinational retreatment with Pegasys in patients not responding to PegIntron therapy study, a 72-week regimen of peginterferon alpha-2a (40 kDa) plus ribavirin improved SVR rates over a standard 48-week regimen in previous nonresponders to peginterferon alpha-2b (12 kDa). cEVR, defined as hepatitis C virus RNA <50 IU/mL at treatment week 12, was an important predictor of SVR.
STUDY:
We conducted an exploratory analysis of the retreatment with Pegasys in patients not responding to PegIntron therapy study data to better define the predictive value of cEVR for SVR in this patient population.
RESULTS:
In total, 157 of the 942 patients achieved a cEVR (16.7%). SVR rates were higher with 72 versus 48 weeks of retreatment in patients with a cEVR (57% vs. 35%), whereas SVR rates were <5% in patients without cEVR in both groups. The relative adverse event (AE) burden was lower with 72 weeks of treatment (8.1 vs. 10.1 AEs/y of treatment) as was the estimated number of AEs per SVR achieved (55 vs. 100). Cumulative treatment duration required to achieve 1 SVR was lower with 72 weeks of treatment (6.7 vs. 10.0 y/SVR) and lower still assuming that treatment was stopped at week 12 for non-cEVR patients (3.6 vs. 7.1 y/SVR).
CONCLUSIONS:
cEVR is a reliable predictor of SVR in patients retreated with peginterferon alpha-2a (40 kDa) plus ribavirin. Seventy-two-week retreatment has a more favorable benefit-risk ratio than 48 weeks, especially when cEVR is used to identify patients most likely to be cured
A study of the effect of electron donating and electron withdrawing groups on the catalytic performance of V-MIL-47
Get PDFMetal Organic Frameworks (MOFs) are crystalline porous solids composed of a three-dimensional network of metal ions held in place by multidentate organic molecules. In recent years, MOFs have received considerable attention as potentially valuable materials for gas storage and catalysis. Until now, most of the studies on the catalytic activity of MOFs are focused on structures that contain coordinative unsaturated metal sites, as it is often believed that the coordinative saturated MOFs will not be catalytically active.
In this contribution we discuss the catalytic performance of a completely saturated Metal Organic Framework, V-MIL-47 [1], in the oxidation of cyclohexene [2]. This MOF was compared with several vanadium containing reference catalysts: VO(acac)2, VAPO-5 and VOx/SiO2, showing that MIL-47 exhibits a high catalytic performance and an interesting product distribution as can be seen in the figure below.
Figure: The catalytic performance of MIL-47
Subsequently, we have synthesized the amine and nitro functionalised MIL-47. The latter was synthesized by an oxidation of the amine group [3]. The catalytic performance of these MIL-47 analogues with extra electron donating or withdrawing groups will be discussed in comparison to the conventional MIL-47 in the oxidation of cyclohexene. All systems have also been modelled on the B3LYP/6-311+g(3df,2p) level of theory to calculate the reaction kinetics.
[1] Barthelet K, Marrot J., Riou D., Férey G., Angew. Chem. Int. Ed 41 (2002) 281.
[2] Leus K., Muylaert I., Vandichel M., Marin G. B., Waroquier M.,Van Speybroeck V., Van Der Voort P., Chem.Commun 46 (2010) 5085.
[3] Rajender Reddy K., Uma Maheswari C., Venkateshwar M., Lakshmi Kantam M., Advanced Synthesis and Catalysis 351 (2009) 93
Let's Make a Deal: Shortening the Solid Organ Transplant Waiting Time in Exchange for Transmitting and Treating Hepatitis C Infection in the Era of Safe and Effective Directly Acting Antivirals
No full textSolar PV and Biogas Hybrid Electrical Power Generation for a Remote Place
No full text<p>This paper discuss about how to increase the system efficiency and to limit the use of conventional energy resources. To meet the load demands, different renewable energy sources require to be integrated, .It includes the study of solar photo voltaic with battery back-up and go-bar gas hybrid system, which can be easily implemented in villages where solar energy is available at free of cost, animals waste can be easily provided from cattle’s either at free of cost or at very low cost. This hybrid system is a perfect fit for electrification of rural remote hilly place where erection of transmission lines is costly and difficult. The proposed grid-assisted system is one of the solutions for meeting the energy demand of the remote places. </p>
ChemInform Abstract: Metal Free Oxidative Coupling of Aryl Formamides with Alcohols for the Synthesis of Carbamates.
No full textNon-alcoholic fatty liver disease: Not time for an obituary just yet!
Get PDFThere has been a concerted effort to change the nomenclature of non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD), and one wonders if it is appropriate and timely to bid adieu to the good old term. Numerous reasons have been put forth to justify this, as outlined in a recently published statement proposing the change.
However, there are considerable flaws in the proposal, and changing NAFLD to MAFLD is unlikely to move the field forward.We have serious misgivings on this matter.o begin with, the statement by the MAFLD consensus group that the term NAFLD was coined by Ludwig and colleagues is factually incorrect. Although the histological features of NAFLD were first described decades ago, Klatskin and his colleagues, in 1979, were the first to use the term ‘non-alcoholic liver disease’.Later, while reporting similar findings, Ludwig and colleagues coined the term “non-alcoholic steatohepatitis (NASH)”.Although an association between metabolic syndrome (MS) and NAFLD has been established and NAFLD termed the hepatic manifestation of MS, this generalisation has since been questioned, since the complex heterogeneity of this entity precludes any single postulation to explain its pathogenesis. Besides, individuals with normal BMI also develop NAFLD, and studies in non-Caucasian populations have shown that a significant proportion of patients with NAFLD do not have insulin resistance (IR).Further, even with elevated hepatic triacylglycerol and diacylglycerol content, hepatic IR has not been observed in murine models,and dissociation of hepatic steatosis from IR has also been noted in a subset of individuals.
Importantly, in subjects with PNPLA3 polymorphisms,steatosis occurs independently of IR and serum lipid concentration. Further, increased serum bile acid levels also seem to be independently associated with NASH in non-diabetics.NAFLD is also associated with gut dysbiosis independent of BMI and IR. Finally, “soft” drink consumption has also been linked to the development of fatty liver independent of obesity, diabetes and hyperlipidemia.and last but not least, cigarette smoking too has been found to be an independent risk factor in NAFLD progression. Thus it is clear that pathogenesis of NAFLD is multifactorial and complex, involving multiple and divergent pathways.In Medicine, a change of name of any disease has significant implications for both medical professionals and patients.The term ‘NAFLD’ aptly describes individuals who have fatty liver but neither consume significant amounts of alcohol nor had any other reason for fatty liver. Research in NAFLD to date has failed to pinpoint any factor as the sole cause for hepatic steatosis and NAFLD still encompasses a spectrum of disorders, metabolic syndrome being a part – maybe a major part – of that spectrum with a relatively barren treatment armamentarium. Will changing nomenclature address these concerns? We fear it might paradoxically misdirect therapeutics in the direction of MS alone which may ultimately turn out to be a red herring. The consensus group found multiple faults with the term NAFLD; these include: i) NAFLD is a disease of exclusion instead of being defined by inclusion, ii) NAFLD is a vastly heterogeneous entity and cannot be managed as one single condition and iii) patients with NAFLD do consume alcohol and the impact of alcohol, albeit in non-significant amounts, is under scrutiny. In Medicine, naming a disease through exclusion has been acceptable since time immemorial. Non-Hodgkin lymphoma encompasses vastly diverse malignancies and yet the terminology very effectively delineates those disorders from Hodgkin lymphoma. Regarding heterogeneity, it is not clear how a mere change of name would make the entity more homogeneous. If the word “metabolic” in MAFLD is meant as a reference to MS, it would be a rejection of much of the scientific evidence gathered on NAFLD pathogenesis. In contrast to the assertion of the proponents of MAFLD, who after splitting “nonalcoholic” into - ‘non’ and ‘alcoholic’, suggest that the word “non” trivializes the problem while the word “alcoholic” demeans the patient, we believe that the word ‘nonalcoholic’ does go a long way in destigmatizing the patient. The European Liver Patients Association (ELPA) is believed to have expressed displeasure with the term NAFLD to the European Commission in 2018, and suggested that a change in nomenclature was required.
The degree of assertion and the rationale for such a suggestion are unclear; it is also unclear whether the diverse pathogenesis of NAFLD – especially in non-Caucasians – was considered in the decision. Further, an opinion on the impact of non-significant alcohol intake on hepatic steatosis is also unclear as acknowledged in the consensus statement. Notably, metabolic abnormalities and BMI are well described risk factors for alcoholic liver disease too,but it is unclear why both conditions more or less related to alcohol should be brought under the umbrella of MAFLD. The change of nomenclature has also been argued against since NAFLD is treated by cardiologists, diabetologists and primary care providers in addition to hepatologists; a name change could create unnecessary clinical confusion and coding issues.
The heterogeneity of NAFLD and presence of multiple pathophysiological pathways inherent to its progression implies that the time is ripe to classify NAFLD in a novel way that takes into account the various pathophysiological processes. We wish to propose the ‘MEGA-D’ classification emphasising the ‘mega diversity’ or heterogeneity in NAFLD where NAFLD remains the umbrella entity with different subgroups under it (NAFLD-M: Metabolic syndrome associated NAFLD, NAFLD-E: Environmental Stressor Related NAFLD, NAFLD-G: Genetic Factor Associated NAFLD, NAFLD-A: Bile Acid Dysregulation Related NAFLD, NAFLD-D: Gut Dysbiosis Related NAFLD) representing separate pathways culminating in hepatic steatosis. We feel, instead of semantic juggling, collaborative efforts should be launched worldwide to better understand the vast heterogeneity in NAFLD across populations and ethnicities and explore its different pathophysiologic mechanisms, with the sole purpose of modifying disease progression, bolstering the treatment arsenal and curbing this epidemic
Synthesis of novel β<sup>2,2</sup>-amino acid from D-mannose and attempted synthesis of peptides from the amino acid
No full textChemInform Abstract: Pyrrolidine-Catalyzed Condensation of Ethyl Diazoacetate to Aldehydes in Water.
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