We have created a structure-selectivity database (AMPad) of frog-derived, helical antimicrobial peptides (AMPs), in which the selectivity was determined as a therapeutic index (TI), and then used the novel concept of sequence moments to study the lengthwise asymmetry of physicochemical peptide properties. We found that the cosine of the angle between two sequence moments obtained with different hydrophobicity scales, defined as the D-descriptor, identifies highly selective peptide antibiotics. We could then use this descriptor to predict TI changes after point mutations in known AMPs, and to aid the prediction of TI for de novo designed AMPs. In combination with an amino acid selectivity index, a motif regularity index and other statistical rules extracted from AMPad, the D-descriptor enabled construction of the AMP-Designer algorithm. A 23 residue, glycine-rich, peptide suggested by the algorithm was synthesized and the activity and selectivity tested. This peptide, adepantin 1, is less than 50% identical to any other AMP, has a potent antibacterial activity against the reference organism, E. coli, and has a significantly greater selectivity (TI > 200) than the best AMP present in the AMPad database (TI = 125).
Number of hemodialysis patients each day is increasing. The quality of their lives is largely determined by the quality of hemodialysis treatment. One of the most important factors is the type of applied blood approach. The type of blood approach in the most case is artery venous fistula, permanent, temporary catheters, grafts. Any complications of blood strand approach inevitably leads to lower quality of hemodialysis treatment which is connected with not adequate dialysis and poorer general state of patients. Our research was carried out as a prospective study, for the period of 36 months. In the study were included 31 patients, which are on chronic haemodialysis treatment. During this study, we are followed all complications, which occurred at temporary, and permanent tunneled haemodialysis catheters. Complications have occurred in terms of thrombotic problems, low blood flow, occurrence of infection. All patients are divided in two groups, 16 patients with permanent and 15 patients with temporary catheters. In the course of the study was analyzed blood flow and dialysis adequacy (Kt/Vdp) as well as complications and results was compared with randomly selected 16 patients who haemodialysis treatment performed by artery venous fistula (AVF). Two patients were lost to further follow-up to the end of the study. 26 patients at the end of the study had functional catheters, while in the case of 3 patients the catheter was removed. Infection was found in 10 patients while thrombotic complications were observed in 27 cases regardless of catheter type. Mean blood flow in patients with permanent catheter was significantly higher (296,9+/-28,45 cm3/min) compared to patients with temporary catheter (226,3+/-39,8 cm3/min) (p<0,001). Kt/Vdp delivered was 1,22+/-0,15 on patients with permanent catheter and 1,30+/-0,18 for artery venous fistula (AVF) access respectively. The loss of dialysis efficacy using catheters was estimated at 6%. However, in all cases Kt/Vdp values remained above the recommended values (Kt/Vdp > or = 1,2).
Due to heightened risk for thromboembolic complications, nonvalvular atrial fibrillation (NVAF) presents an absolute indication for long-term oral anticoagulation therapy. This was an observational, analytical, randomised, one-year clinical study, conducted in the Blood Transfusion Institute Sarajevo, Bosnia & Herzegovina. The aim of this study was to present the oral anticoagulation treatment in terms of International normalised ratio (INR) monitoring and warfarin/acenocoumarol dose titration in 117 patients with NVAF. INR values, the doses of warfarin and acenocoumarol, as well as the tendency and adequacy of their changes were monitored. Percentages of the therapeutic INR values were 51,77% and 53,62%, subtherapeutic 42,84% and 35,86%, and supratherapeutic 5,39% and 10,53% for the warfarin and acenocoumarol treatment, respectively. The average total weekly doses (TWD) which most frequently achieved the therapeutic INR values were 27,89+/-12,34 mg and 20,44+/-9,94 mg, for warfarin and acenocoumarol, respectively. The dose changes with the INR values 1,7 or lower/3,3 or higher were omitted in 13,46% and 15,63%, and with the INR values 1,8-3,2 were noted in 8,62% and 13,48% of all the check-up visits in the warfarin and acenocoumarol group, respectively. The annual dose changes were noted in 24,65% and 31,41%, and the daily dose changes in 74,43% and 73,36% of all the check-up visits of warfarin and acenocoumarol group, respectively. We can conclude that the management of the oral anticoagulation treatment in our country is in accordance with the relevant recommendations, but with the present tendency toward underdosing and unnecessary frequent dose changing.
UNLABELLED Delayed kidney graft function and acute rejection in the early post-transplant period affect both short and long-term allograft survival. Allograft rejection, as an inflammatory state, results in increased erythropoietin resistance, which leads to decreased haemoglobin (Hb) level. We conducted this study to evaluate whether inflammation in the early post-transplant period could predict later anemia.This is a retrospective cohort study based on the analysis of 64 existing clinical records. PREDICTOR White blood cells (WBC) count obtained by the end of the first week post-transplant (W1). Covariates: Donor's age, recipient's age and sex. OUTCOME Anemia identified at 12 months (M12) post engraftment. Median WBC count at W1 was 9,5 x103/microL (5th - 95th percentile 5,2 x103/microL -17,8 x103/microL). Mean Hb values at M12 were 129,9 +/- 20,3 g/L, in males 136,2 +/- 20,1 g/L and in females 119,4 +/- 16,2 g/L. The significant correlation was found between WBC at W1 and Hb at M12. Pearson coefficient of correlation r was -0,26, and 95% confidence interval (CI) for r was -0,47 to -0,015 (p=0,03). Univariate logistic regression showed significant association between WBC at W1 and Hb at M12 (OR 1,20; 95% CI 1,04 to 1,39, p=0,01). After the adjustment for donor's and recipient's age by transplantation and recipient's sex, multiple regression showed that WBC count remained predictive of anemia at M12 (OR 1,17; 95% CI 1,01 to 1,36, p=0,03). Early post-transplant inflammatory response predicts later anemia in kidney transplant recipients. An increase in WBC count in the first week post-transplant by 109/L increases the risk for anemia after twelve months by 17%.
The aim of this study was to analyze (i) ratios between pro-inflammatory cytokines interleukin 6 (IL-6), interleukin 1 (IL-1), tumour necrosis factor alpha (TNF-alpha) and anti-inflammatory cytokine interleukin 10 (IL-10) in patients with acute myocardial infarction (AMI) and stable angina pectoris (ii) as well as correlation between IL-6 and IL-10 in AMI and (iii) correlation between IL-6 and lipoproteins in AMI.The total of 71 patients were enrolled in this study, 41 of them with AMI (study group) and 30 with stable angina pectoris (control group). The concentrations of cytokines and lipoproteins were measured from blood samples. Pro-inflammatory to anti-inflammatory cytokine ratios were calculated by dividing concentrations of pro-inflammatory cytokines with IL-10. In statistical analyses we used descriptive statistics, normality tests and analysis of correlation.IL-6: IL-10 ratio is significantly higher in AMI than in stable angina (P < 0,001), TNF-alpha: IL-10 is also higher in study group but the difference is not significant. We found positive linear correlation between IL-6 and IL-10 (r =0,43; p = 0,015) and negative linear correlation between IL-6 and high density lipoprotein HDL (r = -0,47; p= 0,008) in AMI.IL-6: IL-10 ratio is higher in AMI than in stable angina. There is linear correlation between IL-6 and IL-10 and IL-6 and HDL in AMI.
The role of meconium in the respiratory system was studied in newborns, who died from various causes (250 up to 3000 g of weight). We monitored tracheal rings response to dopamine, serotonin and ethanol in different concentrations (dopamine: 0,05 mg/ml, 0,5 mg/ml, 5 mg/ml; serotonin (5-HT): 10-4, 10-3, 10-2, 10-1 mol/dm3; ethanol: 0,02 ml, 0,5 ml, 1,0 ml; 96%). Tracheal smooth musculature tonus (TSM) was examined in 48 tracheal preparations taken after the newborn exitus due to different reasons. Based on functional researche of isolated preparations of tracheas, it may be concluded that: aspiration of meconium has not changed the response of TSM to dopamine, serotonin and ethanol (p>0,1) in comparison with the control group, which have died due to different lung inflammatory processes (e.g. pneumonia, bronchopneumonia, atelectasis, cerebral hemorrhage). The results suggest that meconium does not potentiate the constricting action of dopamine, serotonin and ethanol in tracheobronchial system. Meconium causes mild relaxation of the TSM through a mechanism that is not intermediated by the products of cyclooxygenases (prostaglandins, prostacyclins) from the tracheal epithelium or proteins. Also, as it seems, the direct activity of many tested acids in the smooth musculature has no significant impact on increase of the airways tonus in MAS syndrome.
The aim of this study was to examine the effects of hypoglycaemic drug-agonists of PPAR-gama receptors-rosiglitazone (Avandia,4 mg - Glaxo Smith Kline) on values of wide-spread risk - markers-fibrinogen, C-reactive protein and uric acid and glicolysated haemoglobin HbA1C as parameter of metabolic control .We included fourty patients with criteria for metabolic syndrome and evaluated results into groups of diabetic and prediabetic patients according to criteria of IDF (International Diabetic Federation)These risk markers and glicolysated haemoglobin HbA1C were observed at the start of therapy, then after four, eight and twelve weeks and results were compared and statistically calculated. Three months initial therapy with rosiglitazone significantly reduced values of HbA1C, fibrinogen and CRP but not uric acid in prediabetic patients.Rosiglitazone initial three months therapy significantly reduced HbA1C, fibrinogen and uric acid, but not CRP in diabetic patients.
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