The role of DENND1A and CYP19A1 gene variants in individual susceptibility to obesity in Turkish population-a preliminary study.

Single nucleotide polymorphisms (SNPs), the most common genetic variations in human genome, can manage the predisposition of certain complex diseases or situations such as obesity. Genetic polymorphisms also play an important role as they can impact a population's susceptibility to being overweight or obese and developing related chronic complications such as hypertension, coronary heart disease, diabetes and cancer. The present study comprised of 193 unrelated healthy volunteers (120 females and 73 males) with Turkish origin. Only female adolescents (n = 110) were divided into 2 categories according to their BMI values as overweight (BMI ≥ 25) and normal (18.5 < BMI < 25) according to WHO classification. Genomic DNA was isolated from venous blood samples and genotyping of DENND1A rs10818854 and CYP19A1 rs2414096 variants was performed on Roche Light Cycler 2.0 Real-Time PCR platform. Serum hormone levels were analyzed by Electrochemiluminescent Immunoassay (ECLIA; Roche diagnostics). The genotype distributions were consistent with the Hardy-Weinberg equilibrium for both SNPs in the studied population (p > 0.05). The genotype distribution of DENND1A rs10818854 was determined for the first time in Turkish population and the variant allele frequency was found as 0.095. According to reduced sex hormone-binding globulin levels and increased free androgen index in the present study, obesity was linked with hyperandrogenism in female subjects. Both polymorphisms were investigated as potential genetic susceptibility markers for obesity and neither DENND1A nor CYP19A1 showed any associations.

Evaluation of low-to-moderate arsenic exposure, metabolism and skin lesions in a Turkish rural population exposed through drinking water.

BACKGROUND: There is no human data regarding the exposure, metabolism and potential health effects of arsenic (As) contamination in drinking water in the Central Anatolian region of Turkey. METHODS: Residents in ten villages with drinking water of total As (T-As) level >50 µg L-1 and 10-50 µg L-1 were selected as an exposed group (n = 420) and <10 µg L-1 as an unexposed group (n = 185). Time-weighted average-As (TWA-As) intake was calculated from T-As analysis of drinking water samples. Concentrations of T-As in urine and hair samples, urinary As species [i.e., As(III), As(V), MMA(V) and DMA(V], and some micronutrients in serum samples of residents of the study area were determined. Primary and secondary methylation indices (PMI and SMI, respectively) were assessed from urinary As species concentrations and the presence of skin lesion was examined. RESULTS: TWA-As intake was found as 75 µg L-1 in the exposed group. Urinary and hair T-As and urinary As species concentrations were significantly higher in the exposed group (P < 0.05). The PMI and SMI values revealed that methylation capacities of the residents were efficient and that there was no saturation in As metabolism. No significant increase was observed in the frequency of skin lesions (hyperpigmentation, hypopigmentation, keratosis) of the exposed group (P > 0.05). Only frequency of keratosis either at the hand or foot was higher in individuals with hair As concentration >1 µg g-1 (P < 0.05). CONCLUSIONS: Individuals living in the study area were chronically exposed to low-to-moderate As due to geological contamination in drinking water. No significant increase was observed in the frequency of skin lesions. Because of the controversy surrounding the health risks of low-to-moderate As exposure, it is critical to initiate long-term follow-up studies on health effects in this region.

New Therapeutic Approaches in Cystic Fibrosis.

Cystic fibrosis (CF) is a hereditary, multisystemic disease caused by different mutations in the CFTR gene encoding CF transmembrane conductance regulator. CF is mainly characterized by pulmonary dysfunction as a result of deterioration in the mucociliary clearance and anion transport of airways. Mortality is mostly caused by bronchiectasis, bronchiole obstruction, and progressive respiratory dysfunction in the early years of life. Over the last decade, new therapeutic strategies rather than symptomatic treatment have been proposed, such as the small molecule approach, ion channel therapy, and pulmonary gene therapy. Due to considerable progress in the treatment options, CF has become an adult disease rather than a pediatric disease in recent years. Pulmonary gene therapy has gained special attention due to its mutation type independent aspect, therefore being applicable to all CF patients. On the other hand, the major obstacle for CF treatment is to predict the drug response of patients due to genetic complexity and heterogeneity. The advancement of 3D culture systems has made it possible to extrapolate the disease modeling and individual drug response in vitro by producing mini adult organs called "organoids" obtained from rectal cell biopsies. In this review, we summarize the advances in the novel therapeutic approaches, clinical interventions, and precision medicine concept for CF.

Psychoactive Bath Salts and Neurotoxicity Risk.

Synthetic cathinones are new designer drugs that possess hallucinogenic and psychostimulant properties, and are designed to mimic the effects of illegal substances such as cocaine, amphetamines, and 3.4-methylenedioxymethamphetamine (ecstasy) and to produce rewarding effects, circumventing existing laws and penalties. Synthetic cathinones, also referred to as 'bath salts', have become popular particularly among young people since the mid-2000s. Similar to other psychomotor stimulants, synthetic cathinones have the potential to increase monoamine concentration in the synaptic cleft by targeting the plasma membrane transporters of dopamine, norepinephrine, and serotonin. Because of their structural similarities to amphetamines, it has been suggested that synthetic cathinones may have a neurotoxicity profile similar to that of their amphetamine congeners. Therefore, it has been hypothesized that synthetic cathinones may induce neurotoxicity on monoamine nerve endings in the striatum, hippocampus, and cortex. To date, with regard to synthetic cathinone neurotoxicity, parameters such as monoamine depletion, biosynthetic enzyme inhibition, cytotoxicity, generation of reactive oxygen species, pro-oxidation status, and the ability to induce neuroinflammation were investigated in both in vitro and in vivo experimental studies. Compared with amphetamines, synthetic cathinones appear to have more moderate effects than their amphetamine congeners in terms of neurotoxic effects. However, many synthetic cathinone users take these substances simultaneously with other substances such as benzodiazepines, amphetamines, ecstasy, tetrahydrocannabinol, and ethanol and this abuse can modify their neurotoxic effects. Hence, it is important to understand the underlying mechanism of early neurotoxic effects in case of polysubstance use. In this review, we aimed to present up-to-date information on the abuse potential of synthetic cathinones, their legal status, mechanism of action, and particularly their neurotoxic effects.