The effects of ATP on the contractions of rat and mouse fast skeletal muscle.

INTRODUCTION: The aim of this study was to compare the effects of adenosine-5'-triphosphate (ATP) and adenosine on the contractility of rodent extensor digitorum longus (EDL) muscle at normal and low temperatures. METHODS: Contractions of rat and mouse isolated EDL were induced by either electrical stimulation (ES) or exogenous carbachol and recorded in the presence of ATP or adenosine (both at 100 µM). RESULTS: ATP at all temperatures caused a decrease of the contractions induced by carbachol in rat and mouse EDL and ES-induced contractions in rat EDL, while it potentiated the ES-induced contractions of mouse EDL. Adenosine reduced the contractility of rat and mouse EDL evoked by ES and did not affect the carbachol-induced contractions of rat and mouse EDL at any temperature. DISCUSSION: Under various temperature conditions, ATP inhibits pre- but potentiates postsynaptic processes in the mouse EDL; in the rat EDL ATP causes only inhibition of neuromuscular conduction. Muscle Nerve 59:509-516, 2019.

Effects of ATP and adenosine on contraction amplitude of rat soleus muscle at different temperatures.

INTRODUCTION: The aim of this study was to evaluate the effects of adenosine 5'-triphosphate (ATP) and adenosine on the contractility of mammalian skeletal muscle under hypothermic conditions. METHODS: Contractions of isolated rat soleus muscle were induced by either electrical stimulation (ES) or carbachol at physiological temperatures (37°C) and hypothermic conditions (30-14°C) and recorded in the presence of ATP, adenosine, suramin, and 8-(p-sulfophenyl)-theophylline (8-SPT). RESULTS: At 37°C, incubation of the muscles with ATP inhibited ES-induced contractions; the inhibitory effect of ATP disappeared at 14°C. Adenosine inhibited ES-induced contractions at all temperature levels; 8-SPT fully prevented the action of adenosine. ATP and adenosine did not significantly affect carbachol-induced contractions at 37°C, while at lower temperatures ATP potentiated them. Suramin fully prevented effects of ATP. CONCLUSIONS: ATP is involved in both pre- and postsynaptic regulation of rat soleus muscle contractility, and these processes are significantly more pronounced at low temperatures. Muscle Nerve 55: 417-423, 2017.

Design, Synthesis, and Cancer Cell Growth Inhibitory Activity of Triphenylphosphonium Derivatives of the Triterpenoid Betulin.

A series of new triphenylphosphonium (TPP) derivatives of the triterpenoid betulin (1, 3-lup-20(29)-ene-3ß,28-diol) have been synthesized and evaluated for cytotoxic effects against human breast cancer (MCF-7), prostate adenocarcinoma (PC-3), vinblastine-resistant human breast cancer (MCF-7/Vinb), and human skin fibroblast (HSF) cells. The TPP moiety was applied as a carrier group through the acyl linker at the 28- or 3- and 28-positions of betulin to promote cellular and mitochondrial accumulation of the resultant compounds. A structure-activity relationship study has revealed the essential role of the TPP group in the biological properties of the betulin derivatives produced. The present results showed that a conjugate of betulin with TPP (3) enhanced antiproliferative activity toward vinblastine-resistant MCF-7 cells, with an IC50 value as low as 0.045 µM.

Pharmacoepidemiological Analysis of Antibacterial Agents Used in a Provisional Hospital in Aktobe, Kazakhstan, in the Context of COVID-19: A Comparison with the Pre-Pandemic Period.

In the context of the global spread of Coronavirus Disease 2019 (COVID-19), the issue of evaluating and optimizing the use of antibacterial drugs becomes especially relevant. The coronavirus pandemic has provided a unique opportunity to study the dynamics of the consumption of antibacterial agents and their impact on public health. The rational use of antibiotics is a key aspect of the fight against antimicrobial resistance, which makes this study particularly important. The aim of this study was to assess changes in the consumption of antibacterial drugs among patients hospitalized with COVID-19 during the peak of the 2020 pandemic and compare them with data from 2019 prior to the pandemic. This study collated data on antibacterial drug consumption in a regional hospital in Aktobe, which served a large population of patients during the pandemic. A pharmacoepidemiological study was conducted using the Anatomical Therapeutic Chemical (ATC)/Defined Daily Dose (DDD) methodology. The pharmacoepidemiological study using the international ATC/DDD methodology revealed a concerning pattern of irrational consumption of antibacterial drugs, including cephalosporins, azalides, second-generation fluoroquinolones, and systemic aminoglycosides in Aktobe. Among antibacterial drugs during the pandemic, the most significant increase in consumption was from the group of cephalosporins (19,043 DDD/100 bed-days). The share of their consumption was 35.4% of the total consumption of antibacterial drugs. Pharmacoepidemiological studies using the international methodology ATC/DDD showed an alarming picture of irrational consumption of antibacterial drugs of the group of cephalosporins, azalides, fluoroquinolones, and aminoglycosides in Aktobe, and, in this case, excessive use of the identified antibiotics raises concerns about the possibility of increasing the problem of resistance to microbes.

Palivizumab and respiratory syncytial virus disease: selling sickness for future?

Over the past two decades Russia has gone through dramatic "democratic" changes resulting in unprecedented deterioration of health, loss of lives and extinction of population. The health system turned into a ridiculous monster of poorly organized business exploiting reminiscent social values of the past to build profits on selling sickness-for-all in consumer culture. We present facts and conclude that introduction of palivizumab into clinical practice for the most vulnerable patient category was done without confirmation of efficacy, without pharmacoeconomics evaluations, without any precautionary measures in a country with undeveloped pharmacovigilance system. The situation calls for immediate action of responsible authorities and the society as a whole.

Efforts to secure universal access to HIV/AIDS treatment: a comparison of BRICS countries.

This article illustrates how the BRICS countries have been building their focused leadership, making important high level commitment and national policy changes, and improving their health systems, in addressing the HIV/AIDS epidemics in respective settings. Specific aspects are focused on efforts of creating public provisions to secure universal access to ARVs from the aspects of active responsive system and national program, health system strengthening, fostering local production of ARVs, supply chain management, and information system strengthening. Challenges in each BRICS country are analyzed respectively. The most important contributors to the success of response to HIV/AIDS include: creating legal basis for healthcare as a fundamental human right; political commitment to necessary funding for universal access and concrete actions to secure equal quality care; comprehensive system to secure demands that all people in need are capable of accessing prevention, treatment and care; active community involvement; decentralization of the management system considering the local settings; integration of treatment and prevention; taking horizontal approach to strengthen health systems; fully use of the TRIPS flexibility; and regular monitoring and evaluation to serve evidence based decision making.