The impact of PLA2G4A and PTGS2 gene polymorphisms,and red blood cell PUFAs deficit on niacin skin flush response in schizophrenia patients

We investigated the etiology of the attenuated niacin skin flush response in schizophrenia patients. Skin response to topical niacin of 0.1 M, 0.01 M, 0.001 M, and 0.0001 M concentrations was rated using method of volumetric niacin response (VNR) and correlated to two functional A/G polymorphisms in genes: phospholipase A2 group IVA (BanI of the PLA2G4A), and rs689466 of the prostaglandin synthase-2 (PTGS2). We further tested the possible correlation between niacin response and fatty acid (FA) content of red blood cells (RBCs). We detected statistically significant but weak impact of both polymorphisms on niacin flush response in schizophrenia patients. The dosage of the G alleles of both polymorphisms was associated with higher VNR values, although each polymorphic variant accounted for only 1% of the overall flush response variability. Regarding FA content, both n?3 and n?6 polyunsaturated FAs (PUFAs) were significantly reduced in the patient group, but an association with niacin sensitivity was not detected.     

Nail position has an influence on anterior knee pain after tibial intramedullary nailing

Our aim was to determine the possible relationship between anterior knee pain (AKP) and nail position marked as a distance from tip of nail to tibial plateau (NP) and to the tuberositas tibiae (NT). Nail position has an influence on anterior knee pain after tibial intramedullary nailing. We evaluated postoperative outcome results of 50 patients in the last 3 years with healed fractures initially treated with intramedullary (IM) reamed nails with 2 or 3 interlocking screws on both parts of the nail and with the use of medial paratendinous incision for nail entry portal. Patients marked a point on the visual analog scale (VAS) that corresponded to the level of postoperative AKP felt. Two groups of patients were formed on the basis of AKP (pain level was neglected): groups A and B, with and without pain, respectively. The difference between the two groups concerning NP measurements was statistically significant (p < 0.05), but not concerning NT measurements at the p < 0.05 level. Patients were classified by pain with high accuracy (98%) according to a classification tree. Symptoms of AKP did not appear if the tip of the nail position was more than 6.0 mm from the NP and more than 2.6 mm from the NT. However, for better evaluation of these results it will be necessary to examine a larger number of postoperative patients with AKP.     

Hepatic and pancreatic glycosphingolipid phenotypes of the neurological different rat strains

Among three commonly used strains of laboratory rats, Wistar rats perform more neurological tasks better then Lewis and Sprague-Dawley (SD) rats. Liver is the main site of insulin-like growth factor (IGF) production and pancreas is the exclusive site of insulin production. Insulin stimulates neuronal development and appropriate IGF-I input is critical in brain growth. Glycosphingolipids (GSLs) are important mediators of insulin secretion and action. Therefore, this study investigated GSL phenotypes of liver and pancreas with hypothesis that they are different in three rat strains. Total GSL fractions (neutral and gangliosides) were analysed by high performance thin-layer chromatography (HPTLC). Complex gangliosides were detected by HPTLC immunostaining using cholera toxin B subunit after neuraminidase pretreatment. Wistar rats had the highest liver weight/body weight ratio and SD rats had the highest pancreas weight/body weight ratio. Ganglioside GM3 was more expressed in the liver of Wistar compared to Lewis and SD rats. SD rats contained scarce quantities of GD1a and b-series gangliosides in the liver compared to Wistar and Lewis rats. Pancreatic b-series ganglioside content was also the lowest in SD rats. This study represents differences in the hepatic and pancreatic ganglioside phenotypes of three rat strains that could influence IGF and insulin secretion and action.     

Alternative coreceptor requirements for efficient CCR5- and CXCR4-mediated HIV-1 entry into macrophages

Macrophage tropism of human immunodeficiency virus type 1 (HIV-1) is distinct from coreceptor specificity of the viral envelope glycoproteins (Env), but the virus-cell interactions that contribute to efficient HIV-1 entry into macrophages, particularly via CXCR4, are not well understood. Here, we characterized a panel of HIV-1 Envs that use CCR5 (n = 14) or CXCR4 (n = 6) to enter monocyte-derived macrophages (MDM) with various degrees of efficiency. Our results show that efficient CCR5-mediated MDM entry by Env-pseudotyped reporter viruses is associated with increased tolerance of several mutations within the CCR5 N terminus. In contrast, efficient CXCR4-mediated MDM entry was associated with reduced tolerance of a large deletion within the CXCR4 N terminus. Env sequence analysis and structural modeling identified amino acid variants at positions 261 and 263 within the gp41-interactive region of gp120 and a variant at position 326 within the gp120 V3 loop that were associated with efficient CXCR4-mediated MDM entry. Mutagenesis studies showed that the gp41 interaction domain variants exert a significant but strain-specific influence on CXCR4-mediated MDM entry, suggesting that the structural integrity of the gp120-gp41 interface is important for efficient CXCR4-mediated MDM entry of certain HIV-1 strains. However, the presence of Ile326 in the gp120 V3 loop stem, which we show by molecular modeling is located at the gp120-coreceptor interface and predicted to interact with the CXCR4 N terminus, was found to be critical for efficient CXCR4-mediated MDM entry of divergent CXCR4-using Envs. Together, the results of our study provide novel insights into alternative mechanisms of Env-coreceptor engagement that are associated with efficient CCR5- and CXCR4-mediated HIV-1 entry into macrophages.     

Analysis of cystic fibrosis gene mutations and associated haplotypes in the Croatian population

The aim of this study was to reveal the CFTR gene mutation status in the Croatian population as well as to establish the haplotypes associated with cystic fibrosis (CF) and those associated with specific gene mutations. A total of 48 unrelated CF patients from Croatia were examined. Among 96 tested alleles, we found nine different mutations: DeltaF508, 58.33%; G542X, 3.12%; N1303K, 2.08%; R1162X; 621 + 1G --> T; G85E; Y569C; E585X; and S466X, 1.04%. Analysis of three polymorphic loci revealed 15 different haplotypes. Two of them (21-23-13 and 21-17-13) occurred with a higher frequency (40% and 24%). Both of these haplotypes also carried a CFTR gene mutation (DeltaF508 or G542X) on 27 out of 32 chromosomes. Among 12 (of all together 29) CF alleles on which no mutations were found, we detected 10 different haplotypes. Because there are still no published data on the distribution of polymorphic loci in Croatia, nor haplotypes associated with mutations in the CFTR gene, our results greatly contribute to knowledge regarding the genetic background of CF in this region.     

Self-Medication Practices and Risk Factors for Self-Medication among Medical Students in Belgrade,Serbia

Introduction

Self-medication among future health care professionals can represent a serious threat to professionalism in medicine and it has potential to put at risk public trust into this profession. The aim of this research was to investigate prevalence and risk factors for self-medication among population of medical students, because it was previously shown that their attitudes towards pharmacotherapy could affect the way they could prescribe medication in the future.

Material and Methods

Research was performed as a cross-sectional study and it included 1296 (84.1%) 1st, 3rd and 6th year students of School of Medicine, University of Belgrade. Students filled out a demographic and self-medication questionnaire created for the purpose of this research and the Physical Health Questionnaire – 9 (PHQ-9). Questions about self-medication were related to the period of the previous year.

Results

Self-medication was reported by 79.9% students. The most frequently self-prescribed medications were analgesics (55.4%). Independent risk factors for self-medication were possession of home-pharmacies (OR = 5.3, CI 95% 3.89–7.23), lower level of father''s education (OR = 1.6, CI 95% 1.18–2.25), consumption of alcoholic beverages (OR = 1.5, CI 95% 1.13–2.08), less than 1 hour spent in physical activity per week (OR = 1.4, CI 95% 1.00–2.02), female gender (OR = 1.4, CI 95% 1.02–1.89), older age (OR = 1.1, CI 95% 1.07–1.21) and higher PHQ-9 score (OR = 1.09, CI 95% 1.05–1.12).

Conclusions

Self-medication is an important issue among population of medical students. Prevalence of self-medication could be controlled through regulatory authorities and further education.     

Fatty-Acid Profile of Total and Polar Lipids in Cultured Rainbow Trout (Oncorhynchus mykiss) Raised in Freshwater and Seawater (Croatia) Determined by Transmethylation Method

Fatty acids from total lipids and polar lipids in cultured rainbow trout (Oncorhynchus mykiss) raised in seawater (SW) and freshwater (FW) were identified and quantified from the muscle samples in January, April, and July. The highest total lipid and polar lipid amounts were found in April. July contents of total lipids were low, but percent of the polyunsaturated fatty acids (PUFAs) was high in SW and FW environment (particularly n-3 PUFAs). Variety of 17 fatty acids was identified by GC-FID after transmethylation. The predominant fatty acids in rainbow trout from SW and FW were: docosahexaenoic acid among n-3 PUFAs, palmitic acid among saturated fatty acids (SFAs), and oleic acid among monounsaturated fatty acids (MUFAs). Appreciably higher n-3/n-6 ratio was found in total lipids in April (6.40, FW fish) and in polar lipids in July (18.76; SW fish). High n-3/n-6 ratio in total lipids and polar lipids of rainbow trout from SW and FW, besides beneficial n-3/n-6 ratio in the commercial fish food, could be characteristic for the local environmental conditions (Croatia).     

Neurodevelopmental outcome in children with periventricular leukomalacia

The purpose of this study was to question the correlation of different grades of periventricular leukomalacia (PVL) and subsequent neurodevelopmental outcome. In a prospective study we followed 52 preterm infants. Infants were divided into three groups according to their cranial ultrasound findings of PVL (De Vries classification). Seventeen children had PVL 1, 20 children had PVL 2, and 15 children had PVL 3. All 15 (100%) children with PVL 3 developed cerebral palsy with additional visual perceptual dysfunctions and epilepsy. Children with PVL 1 had high frequency of mild neuromotoric delay and visual impairment. PVL 2 and 3 have great predictive value for subsequent severe neurodevelopmental disorder which refers to cerebral palsy, different cognitive deficits, vision impairment and epilepsy. We have determined that due to high frequency of visual impairment and epilepsy we need to include neurophysiologic examinations very early in children with PVL lesions.     

West syndrome with periventricular leukomalacia: ten-year clinical study

The aim of the study was to evaluate magnetic resonance imaging (MRI) findings in infants with periventricular leukomalacia (PVL) and West syndrome (WS) and determine the neurodevelopmental outcome in children with West syndrome and PVL. Ultrasound and brain MRI were performed in 37 infants with recognized PVL. PVL was categorized according to De Vries, whereas West syndrome was categorized according to International League Against Epilepsy 1989. West syndrome in our patients developed during the first 2 years of life. The most common interictal abnormality was hypsarrhythmia. All, except two patients had delayed development and various degrees of mental retardation. The most characteristic neuroimaging findings were major reduction in cerebral cortical gray matter volume, reduction in the volume of brain myelin, and delayed myelination. These findings may explain the anatomical association between the West syndrome onset and PVL and intellectual and cognitive deficit in premature infants with PVL.     

Phenylcyclobutyl triazoles as selective inhibitors of 11beta-hydroxysteroid dehydrogenase type I

3-(Phenylcyclobutyl)-1,2,4-triazoles were identified as selective inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). These were active both in vitro and in an in vivo mouse pharmacodynamic (PD) model. Fluorine substitution of the cyclobutane ring improved the pharmacokinetic profile significantly. The synthesis and structure-activity relationships are presented.