Inhibition of human glutathione transferases by pesticides: Development of a simple analytical assay for the quantification of pesticides in water

Glutathione transferases (GSTs; EC 2.5.1.18) form a group of multifunctional enzymes that are involved in phase II cellular detoxification mechanism. Here, screening of the inhibition potency of a wide range of pesticides toward selected human GST isoenzymes (hGSTA1-1, hGSTP1-1, hGSTT2-2 and hGSTO1-1) was carried out. hGSTA1-1 was found more susceptible to inhibition by pesticides than other isoenzymes. The insecticides dieldrin and spiromesifen were identified as potent reversible inhibitors toward hGSTA1- 1 with IC50 values equal to 17.9 ± 1.7 M and 12.1 ± 3.4 M, respectively. Based on in silico docking analysis and kinetic inhibition studies it was concluded that dieldrin and spiromesifen bind specifically to the enzyme presumably at a distinct position that partially overlaps with both the G- and H-site. The ability of dieldrin and spiromesifen to inhibit hGSTA1-1 activity was exploited for the development of analytical quantification assays for these two pesticides. Linear calibration curves were obtained for dieldrin and spiromesifen, with useful concentration in the range of 0–10 M. The reproducibility of the assay response, expressed by relative standard deviation, was in the order of 4.1% (N = 28). The method was successfully applied to the determination of these pesticides in real water samples without sample preparation steps

Survivors of war in the Northern Kosovo (II): baseline clinical and functional assessment and lasting effects on the health of a vulnerable population

<p>Abstract</p> <p>Background</p> <p>This study documents torture and injury experience and investigates emotional well-being of victims of massive violence identified during a household survey in Mitrovicë district in Kosovo. Their physical health indicators such as body mass index (BMI), handgrip strength and standing balance were also measured. A further aim is to suggest approaches for developing and monitoring rehabilitation programmes.</p> <p>Methods</p> <p>A detailed assessment was carried out on 63 male and 62 female victims. Interviews and physical examination provided information about traumatic exposure, injuries, and intensity and frequency of pain. Emotional well-being was assessed using the "WHO-5 Well-Being" score. Height, weight, handgrip strength and standing balance performance were measured.</p> <p>Results</p> <p>Around 50% of victims had experienced at least two types of torture methods and reported at least two injury locations; 70% had moderate or severe pain and 92% reported constant or periodic pain within the previous two weeks. Only 10% of the victims were in paid employment. Nearly 90% of victims had experienced at least four types of emotional disturbances within the previous two weeks, and many had low scores for emotional well-being. This was found to be associated with severe pain, higher exposure to violence and human rights violations and with a low educational level, unemployment and the absence of political or social involvement.</p> <p>Over two thirds of victims were overweight or obese. They showed marked decline in handgrip strength and only 19 victims managed to maintain standing balance. Those who were employed or had a higher education level, who did not take anti-depressant or anxiety drugs and had better emotional well-being or no pain complaints showed better handgrip strength and standing balance.</p> <p>Conclusions</p> <p>The victims reported a high prevalence of severe pain and emotional disturbance. They showed high BMI and a reduced level of physical fitness. Education, employment, political and social participation were associated with emotional well-being. Interventions to promote physical activity and social participation are recommended. The results indicate that the rapid assessment procedure used here offers an adequate tool for collecting data for the monitoring of health interventions among the most vulnerable groups of a population exposed to violence.</p

Impact of capsule endoscopy in obscure small-bowel bleeding: defining strict diagnostic criteria for a favorable outcome

Background: The most frequent indication For capsule endoscopy is to diagnose the cause of obscure GI bleeding. The objective of the study was to determine the impact of capsule endoscopy on the outcome of patients with GI bleeding of obscure origin. Methods: Ninety-six patients (53 men, 43 women; mean [standard deviation] age, 60.84 years [16.55 years]) were enrolled in the study. All patients have been Subjected to gastroscopy colonoscopy, small-bowel barium follow-through or enteroclysis, and push enteroscopy; no bleeding site had been identified. Capsule endoscopy was performed with the Given M2A video capsule system. By using strict criteria, studies were classified as having positive findings, findings of uncertain significance, and no findings. Outcome was defined as continued or complete resolution of bleeding. Results: Positive findings, findings of uncertain significance, and no findings were identified in 41.7%, 20.8%, and 37.5% of our Study population, respectively The most common lesions seen were angiodysplasias of the small intestine. Therapeutic intervention was possible in 82.5% of patients with positive findings and in 35.0% of patients with findings of uncertain significance. Complete resolution of bleeding, after a median (interquartile range) follow-up period of 14 months (9-17 months), occurred significantly more often in patients with positive findings (68.4%) compared with patients with findings of uncertain significance and no findings (40.8%, P = 0.009). Conclusions: Capsule endoscopy increases the diagnostic yield in the workup of patients with obscure small-bowel bleeding. Strictly defined positive findings are associated with a favorable outcome

HLA-DPB1*03 as risk allele and hla-dpb1*04 as protective allele for both early-and adult-onset multiple sclerosis in a hellenic cohort

Background: Human Leucocyte Antigens (HLA) represent the genetic loci most strongly linked to Multiple Sclerosis (MS). Apart from HLA-DR and HLA–DQ, HLA-DP alleles have been previously studied regarding their role in MS pathogenesis, but to a much lesser extent. Our objective was to investigate the risk/resistance influence of HLA-DPB1 alleles in Hellenic patients with early-and adult-onset MS (EOMS/AOMS), and possible associations with the HLA-DRB1*15:01 risk allele. Methods: One hundred MS-patients (28 EOMS, 72 AOMS) fulfilling the McDonald-2010 criteria were enrolled. HLA genotyping was performed with standard low-resolution Sequence-Specific Oligonucleotide techniques. Demographics, clinical and laboratory data were statistically processed using well-defined parametric and nonparametric methods and the SPSSv22.0 software. Results: No significant HLA-DPB1 differences were found between EOMS and AOMS patients for 23 distinct HLA-DPB1 and 12 HLA-DRB1 alleles. The HLA-DPB1*03 allele frequency was found to be significantly increased, and the HLA-DPB1*02 allele frequency significantly decreased, in AOMS patients compared to controls. The HLA-DPB1*04 allele was to be found significantly decreased in AOMS and EOMS patients compared to controls. Conclusions: Our study supports the previously reported risk susceptibility role of the HLA-DPB1*03 allele in AOMS among Caucasians. Additionally, we report for the first time a protective role of the HLA-DPB1*04 allele among Hellenic patients with both EOMS and AOMS. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

HLA-DRB1 differences in allelic distribution between familial and sporadic multiple sclerosis in a Hellenic cohort

Objective: Familial Multiple Sclerosis (fMS) is reported to have distinct clinical and imaging characteristics in comparison to the sporadic disease (sMS). Nevertheless, the genetic/immunogenetic profile of fMS has never been investigated in depth, so far. In this study, we examined differences of HLA-DRB1 allelic frequencies between 57 fMS and 141 sMS Hellenic patients, with reference to 246 previously genotyped healthy controls (HCs). Patients and Methods: All patients underwent medical interview and DRB1 genotyping, using a low-resolution SSOP technique. Statistical analyses were performed using SPSS v.21.0 software, with significance set at 0.05, and p value corrected according to the Benjamini–Yekutieli method. Results: 29 fMS cases had at least one 1st degree relative affected (fMS 1st), while the rest had at least one 2nd or 3rd degree relative affected (fMS 2nd/3rd). Parent-of-origin effects were observed, with the prevalence of maternal inheritance. Frequency of DRB1*15 was significantly increased in fMS and sMS, in comparison to HCs (p = 0.002 and &amp;lt;0.001, respectively). After fMS stratification, this result was mainly attributed to the fMS 2nd/3rd subgroup. DRB1*11 frequency was significantly decreased only in sMS (p &amp;lt; 0.001) with fMS approximating HCs’ frequency, especially for the fMS 1st subgroup. Heterozygosity was favored over homozygosity in all groups. Conclusion: We propose possible HLA-DRB1 allelic distribution differences between fMS and sMS, which become more apparent as proximity of affected relative/-es in fMS increases, supporting a rather degraded role of DRB1 alleles in fMS HLA/immunogenetics and indicating the concomitant implication of other HLA and non-HLA polymorphisms. © 2019, © 2019 Informa UK Limited, trading as Taylor &amp; Francis Group

Electrocardiographic Changes in Elderly Patients During Endoscopic Retrograde Cholangiopancreatography

BACKGROUND: Cardiorespiratory complications may occur during gastrointestinal endoscopy, and elderly people seem to be more vulnerable to these complications during endoscopic procedures involving the manipulation of abdominal viscera. OBJECTIVES: To determine the incidence of cardiac arrhythmias, changes in oxygen saturation, heart rate and blood pressure during endoscopic retrograde cholangiopancreatography (ERCP) via Holter monitoring in elderly patients older than 70 years of age