Hypotension caused by intravenous infusion of rifampicin and its relation to the administration schedule

It was shown in studies on animals that bolus administration of rifampicin induced hypotension whose severity depended on the rate of the antibiotic administration. When the antibiotic was administered in the 5-, 10- or 15-minute regimen in a dose of 10 mg/kg the maximum decrease in blood pressure was 44, 34 or 21% of the initial level and the maximum antibiotic concentration attained in the blood was 34.4, 27.2 or 22.6 micrograms/ml, respectively. With the infusion for 30 minutes, the maximum antibiotic concentration in the blood was 17.6 micrograms/ml and the blood pressure did not undergo any significant changes. When the rate of the antibiotic infusion was high there was pharmacokinetic heterogeneity of the blood serum and biophase which could lead to unpredictable results. After repeated administrations of rifampicin to the same animals pronounced tachyphylaxis to the antibiotic was noted, which manifested itself in decreasing of hypotension, though the serum antibiotic level was 1.5 to 2 times higher that the initial one. It was concluded that administration of rifampicin in the therapeutic dose equal to 10 mg/kg for 30 minutes was the most sparing regimen for the antibiotic bolus intravenous infusion. Gradual increase in the antibiotic dose and administration rate in patients is possible under careful control of blood pressure and pharmacokinetic studies.     

Tolerance of gentacycol--a local dosage form of gentamicin based on collagen--animal experiments

Gentacycol is a local dosage form of gentamicin based on collagen for implantation to wounds in treatment of patients with infections of soft tissues and prevention of contamination of open injuries of the bones and soft tissues. General toxic and organotropic properties of gentacycol were studied on animals with subcutaneous implantation of the dosage form in doses equivalent to the therapeutic dose for man and exceeding it 2-fold. The study showed that the dosage form had no unfavourable side effects on the animal general state, hearing, the functional state of the liver and kidneys and the peripheral blood. In the doses tested gentacycol did not influence the indices of the cardiovascular system and neuromuscular conduction. Morphological examination of the skin and hypodermic tissues in the implantation site revealed no damaging action of the dosage form on the surrounding tissues.     

Changes in the lymph nodes of rabbits following application of the breakdown products of fluoroplast]

Tracheobronchial, mesenterial and inguinal lymph nodes of 15 mature rabbits which were subjected to inhalation of valatile products of fluoroplast destruction were studied. The action of this drug for 1-40 days activated the reactive centers of follicles. The amount of blasts, plasmic cells, eosinophils, macrophages, lymphocytes increased in regional tracheobronchial and distant mesenterial lymph nodes. The prolonged action during 120 days resulted in decreased blasto- and lymphopoesis in the regional tracheobroncheal lymph nodes, depression of the reticular epithelium, suppression of the phagocytic and plasm cell reactions, decreased nucleic metabolism in the cells. Mesenterial lymph nodes retained their functions. The lymphopoesis in them and nucleic metabolism in the cells were intensified. The blastic, plasmic cell, eosinophilic and mast cell reactions were well pronounced.     

A protein whose binding to Na,K-ATPase is regulated by ouabain

Immunoprecipitation of Na,K-ATPase from kidney homogenate by antibodies against alpha1-subunit results in the precipitation of several proteins together with the Na,K-ATPase. A protein with molecular mass of about 67 kD interacting with antibodies against melittin (melittin-like protein, MLP) was found in the precipitate when immunoprecipitation was done in the presence of ouabain. If immunoprecipitation was done using antibodies against melittin, MLP and Na,K-ATPase alpha1-subunit were detected in the precipitate, and the amount of alpha1-subunit in the precipitate was increased after the addition of ouabain to the immunoprecipitation medium. MLP was purified from mouse kidney homogenate using immunoaffinity chromatography with antibodies against melittin. The addition of MLP to purified FITC-labeled Na,K-ATPase decreases fluorescence in medium with K+ and increases it in medium with Na+. The enhancement of fluorescence depends upon the MLP concentration. The N-terminal sequence of MLP determined by the Edman method is the following: HPPKRVRSRLNG. No proteins with such N-terminal sequence were found in the protein sequence databases. However, we revealed five amino acid sequences that contain this peptide in the middle part of the chain at distance 553 amino acids from the C-terminus (that corresponds to protein with molecular mass of about 67 kD). Analysis of amino acid sequence located between C-terminus and HPPKRVRSRLNG in all found sequences has shown that they were highly conservative and include WD40 repeats. It is suggested that the 67-kD MLP either belongs to the found protein family or was a product of proteolysis of one of them.     

Delivery and processing of exogenous double-stranded DNA in mouse CD34 + hematopoietic progenitor cells and their cell cycle changes upon combined treatment with cyclophosphamide and double-stranded DNA

We previously reported that fragments of exogenous double-stranded DNA can be internalized by mouse bone marrow cells without any transfection. Our present analysis shows that only 2% of bone marrow cells take up the fragments of extracellular exogenous DNA. Of these, ~ 45% of the cells correspond to CD34 + hematopoietic stem cells. Taking into account that CD34 + stem cells constituted 2.5% of the total cell population in the bone marrow samples analyzed, these data indicate that as much as 40% of CD34 + cells readily internalize fragments of extracellular exogenous DNA. This suggests that internalization of fragmented dsDNA is a general feature of poorly differentiated cells, in particular CD34 + bone marrow cells.     

An overview of malaria transmission from the perspective of Amazon Anopheles vectors

In the Americas, areas with a high risk of malaria transmission are mainly located in the Amazon Forest, which extends across nine countries. One keystone step to understanding the Plasmodium life cycle in Anopheles species from the Amazon Region is to obtain experimentally infected mosquito vectors. Several attempts to colonise Ano- pheles species have been conducted, but with only short-lived success or no success at all. In this review, we review the literature on malaria transmission from the perspective of its Amazon vectors. Currently, it is possible to develop experimental Plasmodium vivax infection of the colonised and field-captured vectors in laboratories located close to Amazonian endemic areas. We are also reviewing studies related to the immune response to P. vivax infection of Anopheles aquasalis, a coastal mosquito species. Finally, we discuss the importance of the modulation of Plasmodium infection by the vector microbiota and also consider the anopheline genomes. The establishment of experimental mosquito infections with Plasmodium falciparum, Plasmodium yoelii and Plasmodium berghei parasites that could provide interesting models for studying malaria in the Amazonian scenario is important. Understanding the molecular mechanisms involved in the development of the parasites in New World vectors is crucial in order to better determine the interaction process and vectorial competence.     

Mechanism of charge separation and their stabilization in bacterial reaction centers

The nuclear wavepacket formed by 20-fs excitation on the P* potential energy surface in native and mutant (YM210W and YM210L) reaction centers of Rhodobacter (Rb.) sphaeroides and Chloroflexus (C.) aurantiacus RCs was found to be reversibly transferred to the P+BA- surface at 120, 380, and 640-fs delays (monitored by measurements of BA- absorption at 1020-1028 nm). The reaction centers of YM210W(L) mutant show the most simple pattern of fs oscillations with a period of 230 fs in stimulated emission from P* and in the product P+BA-. The mechanisms of the electron transfer pathway between P* and BA and of the stabilization of the state P+BA- in bacterial reaction centers are discussed.     

Hsp70 protein levels and thermotolerance in Drosophila subobscura: a reassessment of the thermal co-adaptation hypothesis

Theory predicts that geographic variation in traits and genes associated with climatic adaptation may be initially driven by the correlated evolution of thermal preference and thermal sensitivity. This assumes that an organism's preferred body temperature corresponds with the thermal optimum in which performance is maximized; hence, shifts in thermal preferences affect the subsequent evolution of thermal-related traits. Drosophila subobscura evolved worldwide latitudinal clines in several traits including chromosome inversion frequencies, with some polymorphic inversions being apparently associated with thermal preference and thermal tolerance. Here we show that flies carrying the warm-climate chromosome arrangement O(3+4) have higher basal protein levels of Hsp70 than their cold-climate O(st) counterparts, but this difference disappears after heat hardening. O(3+4) carriers are also more heat tolerant, although it is difficult to conclude from our results that this is causally linked to their higher basal levels of Hsp70. The observed patterns are consistent with the thermal co-adaptation hypothesis and suggest that the interplay between behaviour and physiology underlies latitudinal and seasonal shifts in inversion frequencies.