Identification of neurite extension inducing peptides by means of soluble combinatorial peptide libraries

To identify hexapeptides capable of inducing neurite outgrowth, we used three groups of soluble combinatorial peptide libraries each consisting of 100 mixtures of hexapeptides (each mixture consisting of 10,000 individual peptides) with partially predetermined sequences (in two out of six amino acid positions). Using this approach a number of neuritogenic peptides were identified. Three selected peptides, QSGKKF, QSGPLA and QSGKQG, were found to induce neurite outgrowth from primary hippocampal neurons with potency comparable to that of growth factors. None of the peptides protected cerebellar granule neurons from cell death induced by withdrawal of potassium chloride. The approach described here suggests the feasibility to use combinatorial peptide libraries in order to identify compounds capable of modulating a specific functional response in the nervous system, without prior knowledge of a molecular target.     

Effect of long-term treatment with enalapril, losartan and their combination on the quality of life of patients with congestive heart failure

AIM: To study the effect a combination of enalapril and losartan on life quality in patients with congestive heart failure (HF). MATERIAL AND METHODS: One hundred and eighty six patients with NYHA functional classes II to IV HF were examined. The study inclusion criteria were as follows: a left ventricular (LV) end-diastolic volume of > 160 ml, a LV ejection fraction of < 35%, sinus rhythm, a cardiothoracic index of > 0.55, no history data on prior treatment with an angiotensin-converting enzyme inhibitor (ACEI) and/or an AT1-antagonist, a patient's written free-will consent to participate in the study. The exclusion criteria were as follows: pacemaker migration, an artificial pacemaker, high-degree block, atrial fibrillation, cerebral circulatory disorders. All the patients were divided into 4 groups and received basic therapy with cardicet, 60-120 mg/day, aspirin, 250 mg/day, furosemide, 80-440 mg/week, and digoxin, 0.25-0.5 mg/day. Group 1 comprised 60 patients who refused therapy with ACEI and/or AT1-antagonist despite that they had indications for their use and they had been convinced many times. In Group 2 (n = 82) enalapril, an ACEI, was added to the basic therapy. Its initial dose of 2.5 mg/day was given once and slowly incremented to the therapeutical one (10-20 mg/day). Group 3 patients (n = 56) on the basic therapy were additionally treated with the AT1-antagonist losartan in a daily dose of 25-50 mg. They were started on 12.5 mg a day. In group 4 the basic therapy was added by a combination of enalapril and losartan in the same doses. The follow-up was 48 weeks. The efficiency of the treatments was controlled by the personal questionnaires SF-36, Life with Heart Failure, by evaluating the magnitude of clinical HF manifestations and by estimating the total life quality inxed. The data were analyzed by assuming that all the patients received the treatments. RESULTS: As compared with the conventional therapy and the use of each drug alone, a combination of the ACEI enalapril and the AT1-antagonist losartan promotes a more significant increase in the satisfaction of the patients with their vital activity, in the critical rate of their self-assessment of the "internal picture" of disease, and leads to a greater improvement of the quality of their life as a whole. CONCLUSION: The ICAE-AT1-antagonist combination exerts a positive impact on life quality in patients with heart failure.     

Differences in motility pattern between human buccal fibroblasts and periodontal and skin fibroblasts

Migration of fibroblasts from surrounding normal tissue into the wound bed is an important requirement for successful wound healing. This study investigated the motility pattern of buccal, periodontal and skin fibroblasts to determine whether differences in the wound healing efficiency at these sites can be explained by differences in the motile behavior of their respective fibroblast populations. The migratory characteristics were studied in a two-dimensional culture system. The migration of single cells was time-lapse video recorded at intervals of 15 min for a period of 6 h using a computer-assisted microscope work-station. For evaluation of cell morphology, cell contours were recognized semiautomatically and used for determination of cell area, cell spreading and number and length of processes. We found that the cellular displacement of the buccal fibroblasts was only approximately 50% of the cellular displacement of periodontal and skin fibroblasts. The decreased cellular displacement of the buccal fibroblasts was found to be due to both lower cellular speed and less persistence in direction. The buccal fibroblasts also displayed smaller areas and longer processes. The differences in cellular morphology and motility pattern amongst the three fibroblast types could not be explained by differences in secretion of extracellular matrix components and are therefore believed to reflect phenotypic differences amongst fibroblast subpopulations.     

Dimephosphon in complex therapy of acute edematous pancreatitis

Clinical investigations of 120 patients have shown that Dimephosphon included in complex treatment of acute edematous pancreatitis facilitates more rapid arrest of the symptoms. An important effect of the drug is its ability to decrease the level of endogenous intoxication by both the hydrophilic and hydrophobic components. It was established that one of the mechanisms of favorable action of the drug is its ability to inhibit LPO, to decrease activity of phospholipase A2. The drug possessing the cytoprotecting effect promotes rapid restoration of the functional state of the liver, in particular its detoxicating, albumin synthesizing ability that is not least of the factors of optimization of the complex therapy.     

Relationship between myocardial remodeling and neurohumoral activation in patients with cardiac failure

50 healthy subjects and 685 patients with heart failure (NYHA functional class I-IV) due to coronary heart disease (CHD) aged 34-74 years (mean age 48.1 +/- 8.22 years) were examined. Cardio-hemodynamics was assessed by M- and B-echocardiography from parasternal, subcostal and apical view on a short and long axis with transmitral Doppler. Plasma levels of epinephrine, norepinephrine, serotonin, aldosterone, STH, hydrocortisone were measured in the patients. Progression of cardiac failure is characterized by evolution of the left ventricular ellipse form into a ball shape primarily due to an increase in cross sectional cavity size. The changes of the left ventricular geometry in heart failure patients are combined with progressive reduction of the relative wall thickness index, intensification of the myocardial stress and impairment of diastolic function. The clearest intercoupling between myocardial remodeling and neurohumoral activation was registered in patients with asymptomatic heart failure. With growing severity of left ventricular dysfunction, plasm activity of serotonin, hydrocortisone and aldosterone increase more than levels of norepinephrine, epinephrine and STH.     

Impact of a practice guideline for patients with atrial fibrillation on medical resource utilization and costs

Health care resource utilization is high for patients presenting with acute atrial fibrillation (AF). The potential for treatment algorithms to safely reduce resource consumption in this setting has not been prospectively evaluated. We designed and implemented a practice guideline for the management of patients presenting to the emergency department (ED) with the primary diagnosis of AF, with emphasis on appropriate cardioversion, use of oral rate-controlling medications, and expedited referral to an outpatient AF clinic. We prospectively collected clinical and resource utilization data on all such patients for 14 months before and after institution of the guideline. Institution of the guideline was associated with a decreased rate of hospital admission (from 74% to 38%), with no differences in ED return visits or hospital readmission within 30 days. No strokes or deaths were observed. This large decrease in resource utilization during the intervention phase of the study translated to an average decrease in 30-day total direct health care costs of approximately $1,400 US dollars per patient. Our clinical and cost outcomes were minimally affected after statistical adjustment for baseline differences between study groups. We conclude that the implementation of our practice guideline was feasible, safe, and effective. Widespread adoption of such practices may have large financial implications for the health care system.     

Chromatographic behavior of the hepatitis B virus surface antigen in donor plasma

Behavior of HBsAg in adsorption chromatography of the antigen-containing plasma in a column with unmodified macropore silica was studied. Under the employed conditions of overlaying and elution, five maximum yields of plasma proper proteins from the column (peaks 1-5) were observed. HBsAg was determined mainly in the material of peaks 4 and 5 in which the dominating host protein was lipoprotein HDL. No HBsAg was detected in albumin-enriched fraction. Similarities of chromatographic behavior of all the three classes of particles whose surface is presented by HBsAg, 20 nm particles, filamentous forms, and Dane particles, were observed.