Good clinical practice: International quality standard for clinical trials

A clinical trial is one of the most important examples of experimental studies. Clinical trials represent an indispensable tool for testing, in a rigorous scientific manner, the efficacy of new therapies. Good Clinical Practice is an international ethical and scientific quality standard for clinical trials, concerning the design, conduct, performance, monitoring auditing, recording, analysis and reporting. This is an assurance to the public that the rights, safety and well-being of trial subjects are protected, and that clinical trial data is credible. The above definitions are consistent with the principles that have their origin in the declaration of Helsinki. The objectives of Good Clinical Practice are to protect the rights of trial subjects, to enhance credibility of data and to improve the quality of science

Preclinical pharmacology of bombesin antagonists

Ispitivana je serija analoga bombesina na antikancersku aktivnost prema različitim humanim tumorima u in vitro i in vivo uslovimaPreclinial pharmacology of different bombesin anatgonists has been investigated in vitro and in vivo against various human cancer

RESULTADOS CLÍNICOS DA REDUÇÃO DO DÉFICIT DE TORQUE EM EXTENSORES E FLEXORES DO JOELHO APÓS A RECONSTRUÇÃO DO LIGAMENTO CRUZADO ANTERIOR

In this prospective study, we presented the effect of isokinetic training on the clinical outcome of rehabilitation in relation to the reduction of the torque deficit in thigh muscles (DEF) after anterior cruciate ligament (LCA) reconstruction. The prospective study followed 144 subjects, 72 women and 72 men, with a mean age of 28.20 ± 4.52, four months after anterior cruciate ligament reconstruction with a hamstring graft. Subjects were divided into two groups according to the type of rehabilitation treatment they underwent. Subjects of the isokinetic group (72 subjects, 36 males and 36 females), underwent kinesitherapy according to the isokinetic exercise protocol which consisted of a one-day isokinetic training lasting for thirty minutes, five times a week for six weeks. Subjects of the classical group (72 subjects, 36 males and 36 females) underwent kinesitherapy based on standard isotonic exercises to increase muscle strength, i.e. exercises with weights and in the gym. The difference in the outcome of rehabilitation was objectified by a concentric-concentric isokinetic test at an angular velocity of 60 °/s before the start, after three weeks and after six weeks of rehabilitation. The monitoring parameters were: torque deficit of the injured leg knee extensor in relation to the uninjured leg (EXDEF) -% and torque deficit of the knee flexor of the injured leg in relation to the uninjured leg (FLDEF) -%. Neste estudo prospectivo, apresentamos o efeito do treinamento isocinético no resultado clínico da reabilitação em relação à redução do déficit de torque nos músculos da coxa (DEF) após a reconstrução do ligamento cruzado anterior (LCA). O estudo prospectivo acompanhou 144 indivíduos, 72 mulheres e 72 homens, com média de idade de 28,20 ± 4,52, quatro meses após a reconstrução do ligamento cruzado anterior com enxerto de isquiotibiais. Os indivíduos foram divididos em dois grupos de acordo com o tipo de tratamento de reabilitação que realizaram. Os sujeitos do grupo isocinético (72 sujeitos, 36 homens e 36 mulheres), foram submetidos à cinesioterapia de acordo com o protocolo de exercícios isocinéticos que consistia em um dia de treinamento isocinético com duração de trinta minutos, cinco vezes por semana, durante seis semanas. Os sujeitos do grupo clássico (72 sujeitos, 36 homens e 36 mulheres) foram submetidos à cinesioterapia baseada em exercícios isotônicos padrão para aumentar a força muscular, ou seja, exercícios com pesos e na academia. A diferença no resultado da reabilitação foi objetivada por um teste isocinético concêntrico-concêntrico com velocidade angular de 60 ° / s antes do início, após três semanas e após seis semanas de reabilitação. Os parâmetros de monitoramento foram: déficit de torque do extensor do joelho da perna lesada em relação à perna não lesada (EXDEF) -% e déficit de torque do flexor do joelho da perna lesada em relação à perna não lesada (FLDEF) -%

DIAGNOSTIC OF SPINAL COLUMN MOBILITY USING SCHOBER’S TEST FOR LUMBAL SYNDROME BY APPLICATION OF PHYSICAL THERAPY AND SPORT RECREATION

The research was conducted on the sample of 90 male and female subjects with chronic lumbar syndrome, aged between 20 and 50, of which 45 men and 45 women who were divided in three groups, 30 subjects per each group, formed on the basis of exercises done by the subjects during and upon the rehabilitation (III groups). The longitudinal and time bound research was executed (8 months). The research was conducted in the Department V “Banja Slatina”, in the Institute for Physical Medicine and Rehabilitation “Dr Miroslav Zotović” in Banja Luka, including three Fitness centres in Banja Luka. The goal of the research was to compare results of testing of subjects who continued to engage in sport recreation after termination of a rehabilitation process in the Institution for Physical Medicine and Rehabilitation - IPMR “Dr Miroslav Zotović” in Banja Luka (by means of usual physical procedures) and the results of those subjects who did not continue kinesitherapy, nor sport-recreational activities. For the statistical analysis in the SPSS program ANOVA was used, especially Post Hoc Test – Tukey HSD. The results showed that during the eight-month research there was a statistically significant improvement of the observed parameters (Schober index), but with the application of programmed physiotherapy with recreation (gr. II) the best results were achieved, as well as more stable remission, which could be explained by biological effects of the programmed physiotherapy together with sport recreation.  Article visualizations

Telmisartan induces melanoma cell apoptosis and synergizes with vemurafenib in vitro by altering cell bioenergetics

Objective: Despite recent advancements in targeted therapy and immunotherapies, prognosis for metastatic melanoma patients remains extremely poor. Development of resistance to previously effective treatments presents a serious challenge and new approaches for melanoma treatment are urgently needed. The objective of this study was to examine the effects of telmisartan, an AGTR1 inhibitor and a partial agonist of PPAR gamma, on melanoma cells as a potential agent for repurposing in melanoma treatment. Methods: Expression of AGTR1 and PPAR gamma mRNA in melanoma patient tumor samples was examined in publicly available datasets and confirmed in melanoma cell lines by qRT-PCR. A panel of melanoma cell lines was tested in viability, apoptosis and metabolic assays in presence of telmisartan by flow cytometry and immunocytochemistry. A cytotoxic effect of combinations of telmisartan and targeted therapy vemurafenib was examined using the Chou-Talalay combination index method. Results: Both AGTR1 and PPAR gamma mRNA were expressed in melanoma patient tumor samples and decreased compared to the expression in the healthy skin. In vitro, we found that telmisartan decreased melanoma cell viability by inducing cell apoptosis. Increased glucose uptake, but not utilization, in the presence of telmisartan caused the fission of mitochondria and release of reactive oxygen species. Telmisartan altered the cell bioenergetics, thereby synergizing with vemurafenib in vitro, and even sensitized vemurafenib-resistant cells to the treatment. Conclusions: Given that the effective doses of telmisartan examined in our study can be administered to patients and that telmisartan is a widely used and safe antihypertensive drug, our findings provide the scientific rationale for testing its efficacy in treatment of melanoma progression

Identifying and testing for hereditary susceptibility to breast/ovarian cancer in Serbia: Where are we now?

About 90% of all breast cancers can be considered as sporadic, without inherited gene alteration. The rest of breast cancers (about 5 to 10%) are considered hereditary, most commonly caused by alterations of BRCA1/2 tumor suppressor genes. Lifetime risks for breast and ovarian cancers are increased among BRCA1/2 mutation carriers - 4 to 8 and 10 to 20 fold higher respectively. Due to the small proportion of hereditary form of disease, as well as to the high cost, BRCA testing is not screening test for general population. It is addressed to selected part of population that fit to recommended criteria. Full coding region sequencing of both genes is "gold standard" for detection of BRCA mutation. Concerning BRCA testing in Serbia, complete or partial sequencing of BRCA1/2 coding region was performed in 60 samples. The presence of 4 BRCA1 known mutations, previously detected elsewhere, has been shown: 185delAG, C61G, 3447del4 and 5382insC (detected twice). In BRCA1 gene, exon 16, an unclassified variant M1652I was found. Polymorphic variants in BRCA1 (8 polymorphisms) and BRCA2 (5 polymorphisms) genes were also detected. The majority of found BRCA1 and BRCA2 polymorphic variants are the missense ones and their influence on breast/ovarian cancer risk in our population has to be proved. Identification of BRCA mutations carriers and establishment of spectra and frequency of BRCA mutations should enable introduction of BRCA1/2 testing into the clinical practice of Serbia.

Chemical composition, antiproliferative and antioxidant activity of differently processed Ganoderma lucidum ethanol extracts

The content of phenolic compounds (TPC) and glucans, as well as the effectiveness of antiproliferative and antioxidant activity of differently processed Ganoderma lucidum ethanol extracts were determined and compared. The content of glucans (total, alpha- and beta-) strongly depended on the extraction time and particle size, but only interaction of these parameters influenced the TPC. Gallic acid, quercetin, trans-cinnamic acid, kaempferol, hesperetin and naringenin were detected in extracts by HPLC-DAD. The most abundant phenols were hesperetin (1.875-3.222 mu g/g) and naringenin (1.235-2.856 mu g/g). The ethanol extracts exhibited noteworthy antioxidant activity, but the significant amount of phenolic compounds was strongly linked to polysaccharides, and hence reduced their antioxidant capacity. The results of the antiproliferative activity in vitro showed that the analyzed extracts were the most effective against HeLa cells. Significant correlations were observed between the antiproliferative effect and the TPC/glucan content of extracts