Percentage distribution of Rotavirus-positivity among hospitalalized infants <2 yrs age suffering from severe diarrhea in Patna.

<p>(A-B) Temporal distribution of Rotavirus positivity: data of 2 consecutive years (A) and age wise stratified data among all patients (B). (C) Breast-feeding wise distribution of Rotavirus positivity among all patients.</p

Relation of breast feeding status with Rotavirus infection and related outcome.

<p>(A) Breast-feeding wise distribution of Rotavirus positivity among all patients. (B, D-E) Age stratified data among breastfed and non-breastfed infants for Rotavirus positivity (B), Rotavirus antigenemia (D), and Rotavirus RNAemia (E). (C) Percentage positivity for Rotavirus antigenemia and Rotavirus RNAemia among breastfed and non-breastfed infants of the study.</p

Correlation of Rotavirus antigenemia and RNAemia with stool viral load.

<p>(A-D) Correlation of stool viral load with Rotavirus antigenemia (A,B) and Rotavirus RNAemia (C,D) in acute-phase (A,C) and convalescent phase (B,D) serum of infants suffering from acute gastroenteritis and diarrhea. Paired acute-phase and convalescent phase sera were tested for (i) Rotavirus antigenemia levels, that is denoted by levels of Rotavirus antigen (optical density/O.D.) measured by RV-EIA at 450 nm X 1000 units and (ii) Rotavirus RNAemia levels, denoted by levels of Rotavirus RNA in form of VP7 gene in reverse-transcriptase PCR calculated by band scanning software, as mentioned in the text. Stool viral load is represented by C(t) values in real-time RT-PCR.</p

Rotavirus antigenemia levels among the study groups.

<p>(A-C) Data demonstrates level of Rotavirus antigenemia in acute-phase (A) and convalescent phase (B) sera in infants suffering from severe diarrhea in comparison with the healthy control group. Paired acute-phase and convalescent phase sera were tested for Rotavirus antigenemia levels, that is denoted by levels of Rotavirus antigen (optical density/O.D.) measured by RV-EIA at 450 nm X 1000 units, as mentioned in the text. Broken lines denote the cut-off value.</p

3‑Substituted 1,5-Diaryl‑1<i>H</i>‑1,2,4-triazoles as Prospective PET Radioligands for Imaging Brain COX‑1 in Monkey. Part 1: Synthesis and Pharmacology

Cyclooxygenase-1 (COX-1) is a key enzyme in the biosynthesis of proinflammatory thromboxanes and prostaglandins and is found in glial and neuronal cells within brain. COX-1 expression is implicated in numerous neuroinflammatory states. We aim to find a direct-acting positron emission tomography (PET) radioligand for imaging COX-1 in human brain as a potential biomarker of neuroinflammation and for serving as a tool in drug development. Seventeen 3-substituted 1,5-diaryl-1<i>H</i>-1,2,4-triazoles were prepared as prospective COX-1 PET radioligands. From this set, three 1,5-(4-methoxyphenyl)-1<i>H</i>-1,2,4-triazoles, carrying a 3-methoxy (<b>5</b>), 3-(1,1,1-trifluoroethoxy) (<b>20</b>), or 3-fluoromethoxy substituent (<b>6</b>), were selected for radioligand development, based mainly on their high affinities and selectivities for inhibiting human COX-1, absence of carboxyl group, moderate computed lipophilicities, and scope for radiolabeling with carbon-11 (<i>t</i>_1/2 = 20.4 min) or fluorine-18 (<i>t</i>_1/2 = 109.8 min). Methods were developed for producing <b>[¹¹C]­5</b>, <b>[¹¹C]­20</b>, and [<i>d</i>₂-¹⁸F]<b>6</b> from hydroxy precursors in a form ready for intravenous injection for prospective evaluation in monkey with PET

Design and Synthesis of Ligand Efficient Dual Inhibitors of Janus Kinase (JAK) and Histone Deacetylase (HDAC) Based on Ruxolitinib and Vorinostat

Concomitant inhibition of multiple oncogenic pathways is a desirable goal in cancer therapy. To achieve such an outcome with a single molecule would simplify treatment regimes. Herein the core features of ruxolitinib (<b>1</b>), a marketed JAK1/2 inhibitor, have been merged with the HDAC inhibitor vorinostat (<b>2</b>), leading to new molecules that are bispecific targeted JAK/HDAC inhibitors. A preferred pyrazole substituted pyrrolopyrimidine, <b>24</b>, inhibits JAK1 and HDACs 1, 2, 3, 6, and 10 with IC₅₀ values of less than 20 nM, is <100 nM potent against JAK2 and HDAC11, and is selective for the JAK family against a panel of 97 kinases. Broad cellular antiproliferative potency of <b>24</b> is supported by demonstration of JAK-STAT and HDAC pathway blockade in hematological cell lines. Methyl analogue <b>45</b> has an even more selective profile. This study provides new leads for assessment of JAK and HDAC pathway dual inhibiton achieved with a single molecule