ABSTRACT
BACKGROUND: The implementation of modified, all-oral shorter regimens for treatment of rifampicin-resistant tuberculosis has started in Armenia since August 2020 under the conditions of operational research. OBJECTIVE: This study aims to evaluate the safety and effectiveness of shorter regimens. METHODS: We evaluated cumulative incidence rates of serious adverse events, adverse events of grade 3 and greater and events resulting in treatment modifications or suspension for 52 study participants. RESULTS: A new, different pattern of adverse events emerged compared with the previous evaluations of drug safety of treatment for rifampicin-resistant tuberculosis. Arthralgia (23.1%) and peripheral neuropathy (21.2%) took leading positions among the adverse events resulting in modifications of treatment. Some adverse events of interest (prolonged QT interval, elevated liver enzymes and anemia) remained relevant for the patients receiving new combinations of anti-TB drugs. The other adverse events (impaired hearing, acute kidney injury and hypokalemia) lost their significance for safety surveillance of rifampicin-resistant tuberculosis treatment. One unexpected serious adverse event (lymphoproliferative skin lesion) brought to a "failed treatment" outcome. The other serious adverse event was anemia. CONCLUSION: The shorter regimens proved to be safe and effective for treatment of rifampicin-resistant tuberculosis, but proper follow-up of adverse events is necessary.
ABSTRACT
OBJECTIVES: The influence of 5-hydroxyadamantane-2-on was studied on the rats' brain blood flow and on morphological state of brain tissue under the condition of brain ischemia. The interaction of the substance with NMDA receptors was also studied. METHODS: Study has been implemented using the methods of local blood flow registration by laser flowmeter, [(3)H]-MK-801binding, and morphological examination of the brain tissue. We used the models of global transient ischemia of the brain, occlusion of middle cerebral artery, and hypergravity ischemia of the brain. RESULTS: Unlike memantine, antagonist of glutamatergic receptors, the 5-hydroxyadamantane-2-on does not block NMDA receptors but enhances the cerebral blood flow of rats with brain ischemia. This effect is eliminated by bicuculline. Under conditions of permanent occlusion of middle cerebral artery, 5-hydroxyadamantane-2-on has recovered compensatory regeneration in neural cells, axons, and glial cells, and the number of microcirculatory vessels was increased. 5-Hydroxyadamantane-2-on was increasing the survival rate of animals with hypergravity ischemia. CONCLUSIONS: 5-Hydroxyadamantane-2-on, an adamantane derivative, which is not NMDA receptors antagonist, demonstrates significant cerebrovascular and neuroprotective activity in conditions of brain ischemia. Presumably, the GABA-ergic system of brain vessels is involved in mechanisms of cerebrovascular and neuroprotective activity of 5-hydroxyadamantane-2-on.
