BDNF Overexpression Enhances the Preconditioning Effect of Brief Episodes of Hypoxia, Promoting Survival of GABAergic Neurons.

Hypoxia causes depression of synaptic plasticity, hyperexcitation of neuronal networks, and the death of specific populations of neurons. However, brief episodes of hypoxia can promote the adaptation of cells. Hypoxic preconditioning is well manifested in glutamatergic neurons, while this adaptive mechanism is virtually suppressed in GABAergic neurons. Here, we show that brain-derived neurotrophic factor (BDNF) overexpression in neurons enhances the preconditioning effect of brief episodes of hypoxia. The amplitudes of the NMDAR- and AMPAR-mediated Ca2+ responses of glutamatergic and GABAergic neurons gradually decreased after repetitive brief hypoxia/reoxygenation cycles in cell cultures transduced with the (AAV)-Syn-BDNF-EGFP virus construct. In contrast, the amplitudes of the responses of GABAergic neurons increased in non-transduced cultures after preconditioning. The decrease of the amplitudes in GABAergic neurons indicated the activation of mechanisms of hypoxic preconditioning. Preconditioning suppressed apoptotic or necrotic cell death. This effect was most pronounced in cultures with BDNF overexpression. Knockdown of BDNF abolished the effect of preconditioning and promoted the death of GABAergic neurons. Moreover, the expression of the anti-apoptotic genes Stat3, Socs3, and Bcl-xl substantially increased 24 h after hypoxic episodes in the transduced cultures compared to controls. The expression of genes encoding the pro-inflammatory cytokines IL-10 and IL-6 also increased. In turn, the expression of pro-apoptotic (Bax, Casp-3, and Fas) and pro-inflammatory (IL-1ß and TNFα) genes decreased after hypoxic episodes in cultures with BDNF overexpression. Inhibition of vesicular BDNF release abolished its protective action targeting inhibition of the oxygen-glucose deprivation (OGD)-induced [Ca2+]i increase in GABAergic and glutamatergic neurons, thus promoting their death. Bafilomycin A1, Brefeldin A, and tetanus toxin suppressed vesicular release (including BDNF) and shifted the gene expression profile towards excitotoxicity, inflammation, and apoptosis. These inhibitors of vesicular release abolished the protective effects of hypoxic preconditioning in glutamatergic neurons 24 h after hypoxia/reoxygenation cycles. This finding indicates a significant contribution of vesicular BDNF release to the development of the mechanisms of hypoxic preconditioning. Thus, our results demonstrate that BDNF plays a pivotal role in the activation and enhancement of the preconditioning effect of brief episodes of hypoxia and promotes tolerance of the most vulnerable populations of GABAergic neurons to hypoxia/ischemia.

The selective BDNF overexpression in neurons protects neuroglial networks against OGD and glutamate-induced excitotoxicity.

Objective: Cerebral ischemia is accompanied by damage and death of a significant number of neurons due to glutamate excitotoxicity with subsequent a global increase of cytosolic Ca2+ concentration ([Ca2+]i). This study aimed to investigate the neuroprotective action of BDNF overexpression in hippocampal neurons against injury under ischemia-like conditions (oxygen and glucose deprivation) and glutamate-induced excitotoxicity (GluTox).Methods: The overexpression of BDNF was reached by the transduction of cell cultures with the adeno-associated (AAV)-Syn-BDNF-EGFP virus construct. Neuroprotective effects were mediated by Ca2+-dependent BDNF release followed by activation of the neuroprotective signaling cascades and changes of the gene expression. Thus, BDNF overexpression modulates Ca2+ homeostasis in cells, preventing Ca2+ overload and initiation of apoptotic and necrotic processes.Results:Antiapoptotic effect of BDNF overexpression is mediated via activation of phosphoinositide-3-kinase (PI3K) pathway and changing the expression of PI3K, HIF-1, Src and an anti-inflammatory cytokine IL-10. On the contrary, the decrease of expression of proapoptotic proteins such as Jun, Mapk8, caspase-3 and an inflammatory cytokine IL-1ß was observed. These changes of expression were accompanied by the decrease of quantity of IL-1ß receptors and the level of TNFα in cells in control, as well as 24 h after OGD. Besides, BDNF overexpression changes the expression of GABA(B) receptors. Also, the expression of NMDA and AMPA receptor subunits was altered towards a change in the conductivity of the receptors for Ca2+.Conclusion: Thus, our results demonstrate that neuronal BDNF overexpression reveals complex neuroprotective effects on the neurons and astrocytes under OGD and GluTox via inhibition of Ca2+ responses and regulation of gene expression.

Use of plasma "reconstitution" during cardio pulmonary bypass for a heart transplant after previous left ventricular assist device implant surgery.

The case report describes a novel technique of pre-emptive plasma "reconstitution" prior to disengagement from cardiopulmonary bypass (CPB) to minimize RV volume overload. The concomitant use of hemoconcentration facilitates volume and blood product management in cardiac transplant after previous left ventricular assist device implant surgery.

Effect of intravenous low-intensity laser irradiation of the blood on clinical and laboratory parameters of hepatocellular insufficiency.

Patients with hepatocellular insufficiency received a course of intravenous laser irradiation of the blood. After the treatment, a positive dynamics of clinical and biochemical indices of the major hepatic syndromes was observed: alleviation of the major clinical symptoms and significant positive changes in biochemical parameters (AST, ALT, bilirubin, alkaline phosphatase, lactate dehydrogenase, and total cholesterol).

[Noninvasive estimation of the oxygen state of experimental tumor by diffuse optical spectroscopy].

The potentialities of diffuse optical spectroscopy for the noninvasive estimation of the oxygen state of experimental tumors have been demonstrated. The distribution of total, oxygenated and deoxygenated hemoglobin, as well as the level oxygen saturation of blood have been shown using two tumor models differing in the histological structure and functional characteristics. The results obtained by the optical method have been verified by immunohistochemical examination of tissue specimens with the exogenous hypoxia marker pimonidazole.

Influence of an oscillating circuit on the radiation of transient acoustic waves by an electroelastic cylinder.

The problem of nonstationary wave radiation in an infinitely long thick-wall piezoelectric cylinder in fluid medium is considered. The influence of an oscillating circuit with lumped parameters on characteristics of transient process is taken into consideration. Problem formulation is executed within the forced electrostatic theory, acoustic approximations, and quasistatic theory for electric circuit. The solution method is based on the integral Laplace transform in time. This allows analytically reducing the problem to solving a system of Volterra integral equations with retarded arguments. The numerical results of calculations are presented and analyzed.

A multicenter randomized controlled trial to assess the feasibility of testing modified ultrafiltration as a blood conservation technology in cardiac surgery.

OBJECTIVES: Modified ultrafiltration is a technique after cardiopulmonary bypass whereby blood withdrawn from the aortic cannula is passed across a semipermeable membrane to hemoconcentrate. Unblinded trials have suggested that modified ultrafiltration is efficacious for blood conservation. The objective of this trial was to assess the feasibility of a model testing modified ultrafiltration in which all members of the surgical team were blinded to the intervention. METHODS: Patients (<65kg) undergoing procedures involving cardiopulmonary bypass were randomized to undergo either modified ultrafiltration (n=29) or sham (circulation without an interposed filter, n=36) for 15minutes. The circuit was shielded from all members of the team except the perfusionist. A questionnaire was administered to determine the blinding success. RESULTS: Modified ultrafiltration resulted in a removal of 1000+/-251mL of fluid and a reduction in the pump balance (1025+/-807 vs 1804+/-838; P < .001) with an increase in hemoglobin immediately after intervention (increase of 7.7+/-8.8g/L in modified ultrafiltration vs 3.8+/-5.1g/L in sham; P=.04). Introduction or increase in dose of vasopressors was more frequent in the modified ultrafiltration group (52% vs 28%; P=.048). Differences in red cell transfusion rates between groups did not reach statistical significance (P=.59). Blinding was successful for the anesthetist (blinding index 0.13 [95% confidence interval, 0.11-0.38] and the intensivist (blinding index, 0.09 [95% confidence interval, 0.14-0.31]) but not for the surgeon (blinding index, 0.24 [95% confidence interval, 0.05-0.42]). The compliance rate for the transfusion protocol was greater than 90%. CONCLUSIONS: Modified ultrafiltration was effective for hemoconcentration after cardiopulmonary bypass in patients of low body weight, but it is associated with an increased need for vasopressor support. The anesthetist and intensivist were successfully blinded to the intervention.

[Prevention and correction of cognitive disorders in arterial hypertension].

In this review we systematized literature data illuminating problems of prevention and correction of cognitive disorders in patients with arterial hypertension (AH). On the basis of results of multicenter randomized studies we have demonstrated close interrelationship between cardiac and cerebral pathology and value of treatment of concomitant neurologic and cardiovascular disorders for prevention of cognitive disturbances in patients with AH. We have shown rational approach to planning antihypertensive therapy and to degree of arterial pressure (AP) lowering in patients with AH, including those with cerebrovascular pathology having high risk of development of stroke and dementia. It has been also shown that in patients with AH calcium antagonists, angiotensin II receptor blockers, and inhibitors of angiotensin converting enzyme posses definite advantages over antihypertensive drugs from other classes in prevention of dementia and less severe cognitive disturbances.

Delayed thrombin generation is not associated with fibrinopeptide formation during prolonged cardiopulmonary bypass with hirudin anticoagulation.

Patients with heparin-induced thrombocytopenia urgently requiring surgery with cardiopulmonary bypass (CPB) present a unique management challenge that must be addressed by the use of alternative anticoagulants. Although clinical success with the direct thrombin inhibitor hirudin has been reported, there is sparse information in the literature supporting the efficacy of this drug as an anti-thrombotic to prevent fibrin formation during CPB. In this report, we describe the efficacy of this drug to prevent thrombin-mediated fibrin formation during CPB.

Influence of age on atrial activation as measured by the P-wave signal-averaged electrocardiogram.

We used the P-wave signal-averaged electrocardiogram (SAECG) prospectively in 93 healthy volunteers of different ages and observed: (1) a positive correlation between P-wave duration on the SAECG and age (r = 0.39, p < 0.0001); and (2) the proportion of subjects with prolonged P-wave duration was increased with older age. These findings confirm the hypothesis that age-related atrial conduction delay in healthy subjects is present, and detectable by the P-wave SAECG.

[New technological means in medical diagnosis]. / Novye tekhnologicheskie sredstva v meditsinskoi diagnostike.

Diagnostic methods using a Pulsar radar measuring computer unit have been developed. The methods are based on the contactless recording of respiratory parameters and pulse and they evaluate human body's functions in real time from the measurements of the duration of cardiac rhythms and calculate the differential function of their distribution and the spectrum of a cardiac rhythmogram.

[Ultrasonic diagnosis in selecting the treatment method for varicocele]. / Ul'trazvukovaia diagnostika v vybore metoda lecheniia varikotsele.

The paper deals with ultrasound diagnosis as a modality able to recognize indications either to surgical or endovascular treatment of varicocele. Forty-two patients aged 12-28 with varicocele degree I-III were examined using sector ultrasonic transducers (3.5,5 MHz) which visualized renal and internal testicular veins. Relevant ultrasonic and phlebographic findings were compared. The impossibility to predict outcomes of the endovascular treatment is attributed to the absence of primary information on the structure of the renotesticular portion of varicocele patients' venous bed. Ultrasonography can provide such information. The detection rate of multiple internal testicular veins and other renotesticular anomalies appears rather high.

[Multiple relaparotomies]. / O mnogokratnykh relaporotomiiakh.

Under analysis was the material of the department of urgent and consultation medical aid (sanitary aviation) for the last 20 years. It was found that under conditions of surgical departments of central regional hospitals multiple relaparotomies made up 12.5% of all reoperations. It was shown that results of the multiple relaparotomies were dependent on urgent coming of a consultant and active surgical treatment on the spot. Reconstructive operations for intestinal fistulas must be performed under conditions of a specialized proctological department.

[Anatomic correction of transposition of the great arteries in infants:experience of the first 10 operations]. / Anatomicheskaia korrektsiia transpozitsii magistral'nykh arterii u grudnykh detei: opyt pervykh 10 operatsii.

In the period March 1992 to January 1993, ten patients with transposition of great arteries (TGV) whose age ranged from 9 days to 8 months and body weight 3.2 to 7.2 kg were operated on using the arterial switch. A single-stage anatomic correction was made in 2 patients with patent arterial duct, 4 with ventricular septal defect (VSD), one with multiple VSD. Three patients with common TGA underwent correction in 2 stages: arterial switch followed prior constriction of the pulmonary artery switch followed prior constriction of the pulmonary artery and subclavian-pulmonary anastomosis. In all cases of single VSD, it was closed with a flap made from the Gore-Tex material. In the whole series of operations, 2 patients died: one being on the operating table due to anesthesiological errors, the other due to coronary blood flow disorder 3 hours after surgery. Six of the 8 discharged patients were followed 3-8 months after surgery. Two patients needed digitalis. No sign of myocardial ischemia was detected in antibody. All the patients were found to have normal left ventricular pump function. These surgeries are the first in our country and so our little experience may be of interest for national specialists.

[Current problems in occupational hygiene of the construction industry in hot climate conditions]. / Sovremennye problemy okhrany truda rabochikh promyshlennosti stroitelnykh materialov v usloviiakh zharkogo klimata.

The article covers results of long-standing hygienic investigations analyzing the occupational factors development in technologic process of nonmetalliferous building materials production, ferroconcrete large-panel constructions production and their assembling during various seasons and shift times. The study pointed out the main hazards influencing the quality of workplace in the stated enterprises. The hazards are hygienically evaluated in connection with the functional parameters of cardiovascular, central nervous and muscular systems, thermoregulation, work hardiness and strain.

[The baroreceptor reflex as a predictor of crises in arterial hypertension]. / Sostoianie baroretseptornogo refleksa kak prediktor krizovogo techeniia arterial'noi gipertonii.

The sensitivity of baroreceptor reflex was determined by the "neck chamber" method at a pressure of 40 mm Hg in patients with mild, moderate and malignant arterial hypertension (AH). A 24-hour blood monitoring was performed in patients with mild and moderate AH. There was a negative correlation between the lowering values in blood pressure on baroreceptor stimulation and the incidence of hypertensive crises in all the groups. There was also a negative correlation between the baroreceptor sensitivity and the daily blood pressure variations in patients with moderate AH. The findings suggest that a decrease in baroreceptor sensitivity might be a predictor of the critical course of AH.

[ Combined therapy with isosorbide dinitrate, propranolol and nifedipine in patients with chronic ischemic heart disease]. / Primenenie kombinirovannoi terapii izosorbida dinitratom, propranololom i nifedipinom u bolnykh khronicheskoi ishemicheskoi bolezníu serdtsa.

Forty six patients with stable effort angina were treated with a combination of propranolol, nifedipine, and isosorbide dinitrate which produced a more profound anti-antianginal effect than each of them given alone. The combination also exerted more marked antihypertensive and antiarrhythmic effects. The combined therapy with the three drugs caused a moderate reduction in heart rate and peripheral resistance, but failed to result in clear-cut disturbances in the orthostatic regulation of the circulatory system. There was a more infrequent and less pronounced ST-segment depression, less marked pressor responses and higher heart rate with the combined therapy during exercise; the cardiac index also increased as before therapy. Physical fitness increased to a greater extent than with monotherapy. The combined therapy with three drugs is indicated when monotherapy fails and that with two agents is indicated when patients have concurrent essential hypertension and cardiac arrhythmias.