Biomonitoring of Trace Metals in the Keban Dam Reservoir (Turkey) Using Mussels (Unio elongatulus eucirrus) and Crayfish (Astacus leptodactylus)

Biological Trace Element Research - Freshwater mussels and crayfish are commonly used as biomonitors of trace metals. In the present study, the concentrations of ten metals were determined in...     

Carbonic anhydrase inhibitors: Synthesis and inhibition of the human carbonic anhydrase isoforms I,II, VII,IX and XII with benzene sulfonamides incorporating 4,5,6,7-tetrabromophthalimide moiety

A series of 4,5,6,7-tetrabromo-1,3-dioxoisoindolin-2-yl benzenesulfonamide derivatives (compounds 1–8) was synthesized by reaction of benzene sulfonamide derivatives with 4,5,6,7-tetrabromophthalic anhydride moiety. These new sulfonamides were investigated as inhibitors of the zinc metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) and more specifically against the human (h) cytosolic isoforms hCA I, II and VII and the transmembrane tumor-associated isoform hCA IX and XII. The new compounds were good hCA I inhibitors (Kis in the range of 143 to >10,000 nM), but were moderately effective, as hCA II inhibitors (Kis of 47–190 nM) and poor hCA VII inhibitors (Kis in the range of 54–175 nM) compared to acetazolamide. The tumor-associated hCA IX was effectively inhibited with Kis ranging between 8.5 and 234 nM and hCA XII with inhibition constants in the range of 6.1–197 nM with high selectivity ratio. The structure–activity relationship (SAR) with this series of sulfonamides is straightforward, with the main features leading to good activity for each isoforms being established. The high sequence hCA alignment homology and molecular docking study of compounds was performed to rationalize the SAR reported over here.     

Occupational health and safety risk assessment in hospitals: A case study using two-stage fuzzy multi-criteria approach

Occupational Health and Safety (OHS) is a basis to reduce occupational accidents in an acceptable level, and it covers employee health, safety, and welfare in the workplaces. Hospitals as the largest employer group in healthcare industry in Turkey face major hazards categorized as chemical, biological, physical, ergonomic, and psychosocial risks. Although Turkey demonstrates rapid economic growth, OHS practices have not been fully put into practice, and necessary attention has not been paid to the health industry. For this reason, this paper aims to assess risks for health staff, contribute for planning of health services, and enhance regulations. A case study was carried out in a leading hospital in Turkey using a two-stage fuzzy multi-criteria approach, which provides more consistency in decision-making process and gives an appropriate final rank of hazard types. Fuzzy Analytic Hierarchy Process (FAHP) is used in weighing five risk parameters, which are severity, occurrence, undetectability, sensitivity to maintenance non-execution, and sensitivity to personal protective equipment (PPE) non-utilization. The fuzzy VIKOR (FVIKOR) approach is then applied for prioritization of hazard types in each department of the hospital. On conclusion of the hazard control hierarchy, measures are overtaken for the hazards, and areas open for improvement are presented.     

Virtual screening of small molecules databases for discovery of novel PARP-1 inhibitors: combination of in silico and in vitro studies

Poly(ADP-ribose) polymerase-1 (PARP-1) enzyme has critical roles in DNA replication repair and recombination. Thus, PARP-1 inhibitors play an important role in the cancer therapy. In the current study, we have performed combination of in silico and in vitro studies in order to discover novel inhibitors against PARP-1 target. Structure-based virtual screening was carried out for an available small molecules database. A total of 257,951 ligands from Otava database were screened at the binding pocket of PARP-1 using high-throughput virtual screening techniques. Filtered structures based on predicted binding energy results were then used in more sophisticated molecular docking simulations (i.e. Glide/standard precision, Glide/XP, induced fit docking – IFD, and quantum mechanics polarized ligand docking – QPLD). Potential high binding affinity compounds that are predicted by molecular simulations were then tested by in vitro methods. Computationally proposed compounds as PARP-1 inhibitors (Otava Compound Codes: 7111620047 and 7119980926) were confirmed by in vitro studies. In vitro results showed that compounds 7111620047 and 7119980926 have IC₅₀ values of 0.56 and 63 μM against PARP-1 target, respectively. The molecular mechanism analysis, free energy perturbation calculations using long multiple molecular dynamics simulations for the discovered compounds which showed high binding affinity against PARP-1 enzyme, as well as structure-based pharmacophore development (E-pharmacophore) studies were also studied.     

Effects of different methods and times of 17β-estradiol treatment on the feminization success in the narrow-clawed crayfish Astacus leptodactylus (Eschscholtz, 1823)

Sex differentiation is a profitable technique in crayfish aquaculture. Most of the studies have focused on sex differentiation in crayfish by ablation or implantation of androgenic glands. There is no research on sex differentiation using hormones in crayfish. In the present study, the effects of 17β-estradiol (E2) injections (10^?7 mol/crayfish) to females and baths (50 μg 17β-estradiol/L) to pleopodal eggs and stage1, 2, and 3 juveniles on the feminization of freshwater crayfish, Astacus leptodactylus were investigated. Results showed that E2 injection to females, bath to pleopodal eggs and bath to stage 1, 2, and 3 juveniles increased feminization rate significantly (p < 0.05) in comparison to the control in A. leptodactylus. Best feminization rate (male to female, 0.25:1) was observed after hormonal injection to the females combined with application of both for their both pleopodal eggs and stage 1, 2, and 3 juveniles. In conclusion, it is possible to obtain 75% females A. leptodactylus by E2 injection to females and bath to pleopodal eggs and stage 1, 2, and 3 juveniles. However, future studies are needed to investigate the mechanism of E2 in crayfish feminization and the sexual development of juveniles obtained from feminization.     

Arterial Stiffness,Carotid Intima-Media Thickness,Endocan, and A Disintegrin and Metalloproteinase With Thrombospondin Type I Motif 9 Levels and Their Relationship With Disease Activity in Patients With Acromegaly With and Without Cardiovascular Risk Factors

ObjectiveCardiovascular complications such as cardiomyopathy and endothelial dysfunction, which are frequently seen in patients with acromegaly, are among the most important causes of morbidity and mortality. In this study, we aimed to investigate arterial stiffness, carotid intima-media thickness, endocan level, and A disintegrin and metalloproteinase with thrombospondin type I motif 9 level and their relationship with disease activity in patients with acromegaly with and without cardiovascular risk factors.MethodsA total of 60 patients with acromegaly—25 with active disease, 26 with well-controlled disease, and 9 with newly diagnosed disease—and 60 age-, sex-, and body mass index (BMI)-matched healthy control subjects were enrolled in this study. All the subjects’ height, weight, BMI, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG) level, insulin, hemoglobin A1C (HbA1C), C-reactive protein , lipid, endocan, A disintegrin and metalloproteinase with thrombospondin type I motif 9 levels, pulse wave velocity (PWV), and carotid intima-media thickness were measured.ResultsThe SBP, DBP, FPG level, HbA1C level, and PWV of the acromegaly group were higher than those of the control group. In patients with acromegaly with cardiovascular disease (CVD) risk factors, the PWV was higher than that in the control group, and in patients with acromegaly without CVD risk factors, the PWV was similar to that in the control group. In a correlation analysis, a positive correlation was found between PWV and age, BMI, SBP, DBP, FPG level, and HbA1C level in the acromegaly group.ConclusionIn our study, we found that arterial stiffness increased in patients with acromegaly with CVD risk factors and that increased arterial stiffness was associated with hemodynamic (SBP and DBP) and metabolic (BMI, FPG level, and HbA1C level) parameters.     

Primary mono- and bis-sulfonamides obtained via regiospecific sulfochlorination of N-arylpyrazoles: inhibition profile against a panel of human carbonic anhydrases

A diverse set of mono- and bis-sulfonamide was obtained via a direct, chemoselective sulfochlorination of readily available yet hitherto unexplored N-arylpyrazole template. Biochemical profiling of compounds thus obtained against a panel of human carbonic anhydrases (hCA I, hCA II, hCA IV and hCA VII) revealed a number of leads that are promising from the isoform selectivity prospective and exhibit potent inhibition profile (from nanomolar to micromolar range). The observed SAR trends have been rationalized by in silico docking of selected compounds into the active site of all four isoforms. The results reported in this paper clearly attest to the power of direct sulfochlorination as the means to create carbonic anhydrase focused sets in order to identify isoform selective inhibitors of closely related enzymes.     

A review of occupational health and safety risk assessment approaches based on multi-criteria decision-making methods and their fuzzy versions

Occupational health and safety (OHS) is a multidisciplinary activity working under the tasks of protection of workers and worksites. Risk assessment, as a compulsory process in implementation of OHS, stands out as evaluating the risks arising from the hazards, taking into account the required control measures, and deciding whether or not the risks can be reduced to an acceptable level. The diversity in risk assessment approaches is such that there are many methods for any industry. Multicriteria decision-making (MCDM)-based approaches contribute to risk assessment knowledge with their ability on solving real-world problems with multiple, conflicting, and incommensurate criteria. This article conducts a critical state-of-the-art review of OHS risk assessment studies using MCDM-based approaches. Additionally, it includes fuzzy versions of MCDM approaches applied to OHS risk assessment. A total of 80 papers are classified in eight different application areas. The papers are reviewed by the points of publication trend, published journal, risk parameters/factors, and tools used. This critical review provides an insight for researchers and practitioners on MCDM-based OHS risk assessment approaches in terms of showing current state and potential areas for attempts to be focused in the future.     

Effect of salt stress on in vitro organogenesis from nodal explant of Limnophila aromatica (Lamk.) Merr. and Bacopa monnieri (L.) Wettst. and their physio-morphological and biochemical responses

Physiology and Molecular Biology of Plants - Salinity is one of the most severe abiotic stress factors that limit crop productivity by affecting the growth of plants. Therefore, it is significant...