The effects of TRH and its metabolically stable analog NS-3 [(3R,6R)-6-methyl-5-oxo-3-thiomorpholinylcarbonyl-L-histidyl-L-pro linamide tetrahydrate] on thermoregulation and circulatory control have been investigated. Both NS-3 (1-100 ng/kg ICV) and TRH (0.1-10 micrograms/kg ICV) increased rectal temperature and metabolic rate with a transient cutaneous vasoconstriction in conscious rabbits. They also increased arterial blood pressure, heart rate, respiratory rate, and renal sympathetic nerve activity (RSNA) in urethane-anesthetized rabbits. Ten ng/kg of NS-3 and 10 micrograms/kg of TRH had comparable hyperthermic, pressor, and tachycardic activities, while the relative potency of NS-3 to increase RSNA was greater and that to increase metabolic rate was smaller than the other effects. In conclusion, NS-3 was more potent than TRH in all of the effects measured, but there was a dissociation in the relative potency of NS-3 in the different autonomic effects.
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Sensors (Basel)
September 2024
Department of Electronic and Biomedical Engineering, Faculty of Physics, University of Barcelona, 08028 Barcelona, Spain.
Digital histogram generation for time-resolved measurements with single-photon avalanche diode (SPAD) sensors requires the storage of many timestamp signals. This work presents a mixed-signal time-to-digital converter (TDC) that uses analog storage to achieve an area-efficient design that can be integrated in large SPAD arrays. Fabricated using a 150 nm CMOS process, the prototype occupies an area of only 18.
View Article and Find Full Text PDFIntern Med
May 2022
Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Japan.
A 66-year-old man, who had undergone plasma exchange 30 years previously in Egypt for the treatment of falciparum malaria, was referred to our hospital for treatment of chronic hepatitis C (HCV). An analysis of the 655-nucleotide 5'-untranslated region-core region sequence revealed infection with HCV subtype 1g. A phylogenetic analysis of the full-length HCV genome confirmed that the patient's HCV was subtype 1g, which was the first case identified in Japan.
View Article and Find Full Text PDFPLoS Pathog
March 2021
Center for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States of America.
There is an urgent need for a vaccine to prevent chronic infection by hepatitis C virus (HCV) and its many genetic variants. The first human vaccine trial, using recombinant viral vectors that stimulate pan-genotypic T cell responses against HCV non-structural proteins, failed to demonstrate efficacy despite significant preclinical promise. Understanding the factors that govern HCV T cell vaccine success is necessary for design of improved immunization strategies.
View Article and Find Full Text PDFACS Omega
August 2017
IFM-Department of Chemistry, Linköping University, Linköping 581 83, Sweden.
It was previously reported that two naphthyl-based -stilbene probes, ()-4-(2-(naphthalen-1-yl)vinyl)benzene-1,2-diol () and ()-4-(2-(naphthalen-2-yl)vinyl)benzene-1,2-diol (), can bind to both native transthyretin (TTR) and misfolded protofibrillar TTR at physiological concentrations, displaying distinct emission maxima bound to the different conformational states (>100 nm difference). To further explore this amyloid probe scaffold to obtain extended fluorescence lifetimes, two new analogues with expanded aromatic ring systems (anthracene and pyrene), ()-4-(2-(anthracen-2-yl)vinyl)benzene-1,2-diol () and ()-4-(2-(pyren-2-yl)vinyl)benzene-1,2-diol (), were synthesized employing the palladium-catalyzed Mizoroki-Heck reaction. ()-4-Styrylbenzene-1,2-diol (), , , and were investigated with respect to their photophysical properties in methanol and when bound to insulin, lysozyme, and Aβ1-42 fibrils, including time-resolved fluorescence measurements.
View Article and Find Full Text PDFInt J Mol Sci
May 2017
Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan.
We evaluated the transition of dominant resistance-associated substitutions (RASs) in hepatitis C virus during long-term follow-up after the failure of DAAs (direct acting antivirals)-based therapy. RASs in non-structure (NS)3/4A, NS5A, NS5B, and deletions in NS5A from 20 patients who failed simeprevir/pegylated-interferon/ribavirin (SMV/PEG-IFN/RBV) and 25 patients who failed daclatasvir/asunaprevir (DCV/ASV) treatment were examined by direct sequencing. With respect to SMV/PEG-IFN/RBV treatment, RAS was detected at D168 in NS3/4A but not detected in NS5A and NS5B at treatment failure in 16 of 20 patients.
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