Effect of T-activin on the formation of conditioned reflex and manifestations of unconditioned reflex of avoidance in August strain rats]

It has been revealed that intraperitoneal injection of T-activin (humoral factor of the thymus) to August rats leads to more rapid and stable conditioned reflex formation to a sound and to a decrease of avoidance time when electric current is given to a shuttle chamber. Furthermore, less amount of uneffective series in testing unconditioned avoidance is registered in the test animals. A positive T-activin effect on conditioned reflex formation and unconditioned reflex manifestation is probably connected with its ability to alter hippocampus functional parameters and (or) with anti-stressor properties of the preparation.     

Oogenesis (Prophase 1 of Meiosis) and Mitotic Chromosomes of Parthenogenetic Species Darevskia armeniaca (Family Lacertidae)

Biology Bulletin - In parthenogenetic hybrid Darevskia armeniaca species, the development of early oogenesis and early meiosis were analyzed. It has been shown for the first time that the number of...     

Meiotic drive in mice carrying t-complex in their genome

The deviation of alleles and chromosomes from Mendelian inheritance is characteristic of the meiotic drive. This review describes the mechanism in question using the best-studied example of transmitted ratio distortion in the heterozygous male mice carrying t-haplotypes. The t-complex is best model for studying the meiotic drive under laboratory conditions. Putative mechanisms of meiotic drive that influence the frequency of t-haplotypes in natural populations are considered, of which prezygotic selection is the most important. The role of meiotic drive in male hybrid sterility is emphasized. The factors and models that determine the phenomenon of meiotic drive are discussed in detail.

     

Severe Painful Vaso-Occlusive Crises and Mortality in a Contemporary Adult Sickle Cell Anemia Cohort Study

Background

Frequent painful vaso-occlusive crises (VOCs) were associated with mortality in the Cooperative Study of Sickle Cell Disease (CSSCD) over twenty years ago. Modern therapies for sickle cell anemia (SCA) like hydroxyurea are believed to have improved overall patient survival. The current study sought to determine the relevance of the association between more frequent VOCs and death and its relative impact upon overall mortality compared to other known risk factors in a contemporary adult SCA cohort.

Methods

Two hundred sixty four SCA adults were assigned into two groups based on patient reported outcomes for emergency department (ED) visits or hospitalizations for painful VOC treatment during the 12 months prior to evaluation.

Results

Higher baseline hematocrit (p = 0.0008), ferritin (p = 0.005), and HDL cholesterol (p = 0.01) were independently associated with 1 or more painful VOCs requiring an ED visit or hospitalization for acute pain. During a median follow-up of 5 years, mortality was higher in the ED visit/hospitalization group (relative risk [RR] 2.68, 95% CI 1.1-6.5, p = 0.03). Higher tricuspid regurgitatant jet velocity (TRV) (RR 2.41, 95% CI 1.5-3.9, p < 0.0001), elevated ferritin (RR 4.00, 95% CI 1.8-9.0, p = 0.001) and lower glomerular filtration rate (RR=2.73, 95% CI 1.6-4.6, p < 0.0001) were also independent risk factors for mortality.

Conclusions

Severe painful VOCs remain a marker for SCA disease severity and premature mortality in a modern cohort along with other known risk factors for death including high TRV, high ferritin and lower renal function. The number of patient reported pain crises requiring healthcare utilization is an easily obtained outcome that could help to identify high risk patients for disease modifying therapies.

Trial Registration

ClinicalTrials.gov NCT00011648 http://clinicaltrials.gov/     

Role of additive stochastic modulation of the heart activity in the formation of 0.1-Hz blood flow oscillations in the human cardiovascular system

In the framework of our previous hypothesis about the participation of structural and hydrodynamic properties of the vascular bed in the formation of the 0.1-Hz component of blood flow oscillations in the human cardiovascular system and on the basis of the reduced hydrodynamic model, the role of additive stochastic perturbations of the operation of the single-chamber pump that simulates the heart was investigated. It was shown that aperiodic noise modulation of the rigidity of the walls of the pump or its valves generates low-frequency oscillations of pressure and blood flow velocity of arterial vascular bed with the maximum amplitude at a frequency close to 0.1 Hz.     

Respiratory burst activated by Escherichia coli in human neutrophils primed with different lipopolysaccharides

Endotoxic shock is a dangerous complication of infection caused by gram-negative bacteria. Searching for agents capable to block the effects of endotoxins is a fundamental scientific and medical problem. Here we studied the effects of neutrophil priming with non-toxic lipopolysaccharide from Rhodobacter capsulatus (LPS _{Rb. caps.} ) and toxic LPS from Escherichia coli (LPS _{E. coli} ) on the respiratory burst evoked in neutrophils by opsonized E. coli. We found that preincubation of neutrophils with each of the LPS increased ROS production by neutrophils as compared to non-primed neutrophils. Subsequent incubation of neutrophils with LPS _{Rb. caps.} and then with LPS _{E. coli} practically abolished the effects of both endotoxins.     

Variations of the effect of insulin on neutrophil respiratory burst. The role of tyrosine kinases and phosphatases

The priming effect of insulin on the fMLP-induced respiratory burst of mouse neutrophils as well as the involvement of tyrosine protein kinases and phosphatases in this process have been studied. Peritoneal evoked neutrophils of NMRI strain mice were incubated with 0.01-100 nM insulin for 1-60 min at 22, 30, or 37°C and activated by 0.1-50 M N-formyl-methionyl-leucyl-phenylalanine (fMLP). The production of reactive oxygen species (ROS) by neutrophils was monitored by luminol-dependent chemiluminescence. We found that ¹²⁵I-labeled insulin binding by mouse neutrophils occurred with saturation and high affinity. Insulin itself did not change the basal level of the ROS production but could modulate fMLP-induced respiratory burst. The effect of insulin depended on temperature and duration of pretreatment of the neutrophils with insulin and the concentration combination of the insulin and fMLP. The tyrosine kinase inhibitor tyrphostin 51 decreased the fMLP-induced respiratory burst significantly. Insulin did not change the fMLP response of neutrophils pretreated with tyrphostin. However, the effect of tyrphostin on the response to 50 M fMLP was considerably decreased in neutrophils treated with insulin. There was no such effect during activation by 5 M fMLP, for which the priming effect of insulin was not observed. Insulin did not increase the fMLP-induced respiratory burst in neutrophils treated with the protein phosphatase inhibitors orthovanadate and pyrophosphate. If the inhibitors were added after insulin, the combined effect was nearly additive. It is possible that priming by insulin of the fMLP-induced respiratory burst is triggered by tyrosine phosphorylation, realized with its participation, and involves the signaling pathways initiated by tyrosine phosphorylation but subsequently is not dependent on the latter. The role of protein phosphatases in priming by insulin is of little importance. The data indirectly confirm the idea that priming of the neutrophil respiratory burst is a result of crosstalk of signaling pathways of the insulin and fMLP receptors with the participation of tyrosine phosphorylation.