Laboratory and sonographic findings in dialyzed patients with bilateral chronic knee pain versus dialyzed asymptomatic patients

The aim of this study is to evaluate connection of plasma level of beta2-microglobulin, C-reactive protein and uric acid as well as sonographic parameters like thickness of synovial membrane, thickness of femoral condylar cartilage and presence of joint effusion and Baker's cysts with bilateral knee pain in dialyzed patients, comparing them with parameters in asymptomatic dialyzed patients. Plasma levels of beta2-microglobulin and C-reactive protein were significantly higher in symptomatic patients while uric acid level showed no difference among the groups. In symptomatic patients synovial membrane was thicker and in those patients there were more knee effusions and Baker's cysts. Thickness of femoral condylar cartilage showed no difference between groups. That suggests that inflammatory mechanisms developing from beta2-microglobulin accumulation could be important factor in bilateral knee pain in dialyzed patients even in shorter duration dialysis.     

Synthesis and characterization of pyrrolidine derivatives as potent agonists of the human melanocortin-4 receptor

A series of trans-4-phenylpyrrolidine-3-carboxamides were synthesized and characterized as potent ligands of the human melanocortin-4 receptor. Interestingly, a pair of diastereoisomers 20f-1 and 20f-2 displayed potent functional agonist and antagonist activity, respectively. Thus, the 3S,4R-compound 20f-1 possessed a K(i) of 11nM and an EC(50) of 24nM, while its 3R,4S-isomer 20f-2 exhibited a K(i) of 8.6 and an IC(50) of 65nM. Both compounds were highly selective over other melanocortin receptor subtypes. The MC4R agonist 20f-1 also demonstrated efficacy in diet-induced obese rats.     

Effects of sprint and plyometric training on muscle function and athletic performance

The purpose of this study was to evaluate the effects of sprint training on muscle function and dynamic athletic performance and to compare them with the training effects induced by standard plyometric training. Male physical education students were assigned randomly to 1 of 3 groups: sprint group (SG; n = 30), plyometric group (PG; n = 30), or control group (CG; n = 33). Maximal isometric squat strength, squat- and countermovement jump (SJ and CMJ) height and power, drop jump performance from 30-cm height, and 3 athletic performance tests (standing long jump, 20-m sprint, and 20-yard shuttle run) were measured prior to and after 10 weeks of training. Both experimental groups trained 3 days a week; SG performed maximal sprints over distances of 10-50 m, whereas PG performed bounce-type hurdle jumps and drop jumps. Participants in the CG group maintained their daily physical activities for the duration of the study. Both SG and PG significantly improved drop jump performance (15.6 and 14.2%), SJ and CMJ height ( approximately 10 and 6%), and standing long jump distance (3.2 and 2.8%), whereas the respective effect sizes (ES) were moderate to high and ranged between 0.4 and 1.1. In addition, SG also improved isometric squat strength (10%; ES = 0.4) and SJ and CMJ power (4%; ES = 0.4, and 7%; ES = 0.4), as well as sprint (3.1%; ES = 0.9) and agility (4.3%; ES = 1.1) performance. We conclude that short-term sprint training produces similar or even greater training effects in muscle function and athletic performance than does conventional plyometric training. This study provides support for the use of sprint training as an applicable training method of improving explosive performance of athletes in general.     

Silver‐induced conformational changes of polypeptides: a CD study

The role of silver ions in various pathologies, as well as their effect on peptide conformation and properties are less understood. Consequently, we synthesized several peptides with various residues in their sequence to investigate silver‐induced conformational changes at various pH values by Circular Dichroism spectroscopy. Uniquely, the glycine‐based, histidine‐containing peptide showed a severe change from a random coil and β‐turn conformation to large α‐helices during silver binding. When comparing the effect of silver ions on the conformation of bradykinin a similar tendency was found. Besides, silver ions reduced the amyloid‐β peptide tendency to aggregation. Our results suggest a specific and protective role for silver ions in brain pathologies, which is related to their high affinity toward physiologically and pharmacologically active peptides. Fourier transform infrared spectroscopy studies as well as the mass spectrometric ones support our conclusions. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.     

Prediction of Associations between microRNAs and Gene Expression in Glioma Biology

Despite progress in the determination of miR interactions, their regulatory role in cancer is only beginning to be unraveled. Utilizing gene expression data from 27 glioblastoma samples we found that the mere knowledge of physical interactions between specific mRNAs and miRs can be used to determine associated regulatory interactions, allowing us to identify 626 associated interactions, involving 128 miRs that putatively modulate the expression of 246 mRNAs. Experimentally determining the expression of miRs, we found an over-representation of over(under)-expressed miRs with various predicted mRNA target sequences. Such significantly associated miRs that putatively bind over-expressed genes strongly tend to have binding sites nearby the 3'UTR of the corresponding mRNAs, suggesting that the presence of the miRs near the translation stop site may be a factor in their regulatory ability. Our analysis predicted a significant association between miR-128 and the protein kinase WEE1, which we subsequently validated experimentally by showing that the over-expression of the naturally under-expressed miR-128 in glioma cells resulted in the inhibition of WEE1 in glioblastoma cells.     

Plasma N-glycome composition associates with chronic low back pain

Background

Low back pain (LBP) is the symptom of a group of syndromes with heterogeneous underlying mechanisms and molecular pathologies, making treatment selection and patient prognosis very challenging. Moreover, symptoms and prognosis of LBP are influenced by age, gender, occupation, habits, and psychological factors. LBP may be characterized by an underlying inflammatory process. Previous studies indicated a connection between inflammatory response and total plasma N-glycosylation. We wanted to identify potential changes in total plasma N-glycosylation pattern connected with chronic low back pain (CLBP), which could give an insight into the pathogenic mechanisms of the disease.

Medical sequencing of candidate genes for nonsyndromic cleft lip and palate

Nonsyndromic or isolated cleft lip with or without cleft palate (CL/P) occurs in wide geographic distribution with an average birth prevalence of 1/700. We used direct sequencing as an approach to study candidate genes for CL/P. We report here the results of sequencing on 20 candidate genes for clefts in 184 cases with CL/P selected with an emphasis on severity and positive family history. Genes were selected based on expression patterns, animal models, and/or role in known human clefting syndromes. For seven genes with identified coding mutations that are potentially etiologic, we performed linkage disequilibrium studies as well in 501 family triads (affected child/mother/father). The recently reported MSX1 P147Q mutation was also studied in an additional 1,098 cleft cases. Selected missense mutations were screened in 1,064 controls from unrelated individuals on the Centre d'Étude du Polymorphisme Humain (CEPH) diversity cell line panel. Our aggregate data suggest that point mutations in these candidate genes are likely to contribute to 6% of isolated clefts, particularly those with more severe phenotypes (bilateral cleft of the lip with cleft palate). Additional cases, possibly due to microdeletions or isodisomy, were also detected and may contribute to clefts as well. Sequence analysis alone suggests that point mutations in FOXE1, GLI2, JAG2, LHX8, MSX1, MSX2, SATB2, SKI, SPRY2, and TBX10 may be rare causes of isolated cleft lip with or without cleft palate, and the linkage disequilibrium data support a larger, as yet unspecified, role for variants in or near MSX2, JAG2, and SKI. This study also illustrates the need to test large numbers of controls to distinguish rare polymorphic variants and prioritize functional studies for rare point mutations.     

Present state and possibilities for improvement of cancer prevention and early detection in the Osijek-Baranya county

Cancer morbidity and mortality are on a steady increase in Croatia. Technologic possibilities for appropriate management are available for four cancer sites, i.e. cancer of the breast, cervix uteri, colorectum and prostate, and include cancer prevention and early detection in individuals yet free from manifest signs of the disease. The magnitude of the problem, the experience acquired to date, health care personnel available, and additional resources required to launch a systematic program of early detection of the disease are presented. The program should be initially launched in a county with greatest experience in early detection of cancer, where health care service is ready to immediately start its implementation. The role of family physician, gynecologic service at primary health care level, and polyclinic-consultation hospital service in program implementation is described. The following three possible options for early detection of cancer are analyzed and proposed: minimal program (early detection every 3 years), medium program (the same individuals examined every 2 years), and optimal program proposed by the American Cancer Society and other national and international organizations.     

Structure-activity relationship studies on a series of cyclohexylpiperazines bearing a phanylacetamide as ligands of the human melanocortin-4 receptor

Synthesis and structure-activity relationship studies of a series of cyclohexylpiperazines bearing an amide side chain as ligands of the MC4 receptor are discussed. Compounds such as 11i from this series are potent agonists (EC(50)=33nM, IA=96%).