Genotoxic potential of cyclosporin A in patients with renal transplantation

We analyzed the induction of sister chromatid exchange (SCE) by cyclosporin A (CsA) as a marker of genotoxic potential. In 30 patients undergoing renal transplantation, SCE induction was tested before the introduction of CsA and 3 months later. We found that SCE frequency increased significantly at the end of 3 months. To our knowledge, this is the first study demonstrating in vivo induction of SCE by CsA in humans. We conclude that CsA has a genotoxic potential on human lymphocytes.     

In silico design of novel hERG-neutral sildenafil-like PDE5 inhibitors

Cyclic nucleotide phosphodiesterase enzymes (PDEs) have functions in regulating the levels of intracellular second messengers, 3′, 5′-cyclic adenosine monophosphate (cAMP) and 3′, 5′-cyclic guanosine monophosphate (cGMP), via hydrolysis and decomposing mechanisms in cells. They take essential roles in modulating various cellular activities such as memory and smooth muscle functions. PDE type 5 (PDE5) inhibitors enhance the vasodilatory effects of cGMP in the corpus cavernosum and they are used to treat erectile dysfunction. Patch clamp experiments showed that the IC₅₀ values of the human ether-à-go-go-related gene (hERG1) potassium (K) ion channel blocking affinity of PDE5 inhibitors sildenafil, vardenafil, and tadalafil as 33, 12, and 100 μM, respectively. hERG1 channel is responsible for the regulation of the action potential of human ventricular myocyte by contributing the rapid component of delayed rectifier K⁺ current (I_Kr) component of the cardiac action potential. In this work, interaction patterns and binding affinity predictions of selected PDE5 inhibitors against the hERG1 channel are studied. It is attempted to develop PDE5 inhibitor analogs with lower binding affinity to hERG1 ion channel while keeping their pharmacological activity against their principal target PDE5 using in silico methods. Based on detailed analyses of docking poses and predicted interaction energies, novel analogs of PDE5 inhibitors with lower predicted binding affinity to hERG1 channels without loosing their principal target activity were proposed. Moreover, molecular dynamics (MD) simulations and post-processing MD analyses (i.e. Molecular Mechanics/Generalized Born Surface Area calculations) were performed. Detailed analysis of molecular simulations helped us to better understand the PDE5 inhibitor–target binding interactions in the atomic level. Results of this study can be useful for designing of novel and safe PDE5 inhibitors with enhanced activity and other tailored properties.     

Lichens of Barla Mountain in Isparta,Turkey: Diversity study and ecological assessment of the area

This study reports on 230 infrageneric lichenized and lichenicolous taxa from Barla Mountain, Isparta, Turkey and assesses the ecological features of the area using the distribution of the lichens in the region and their poleophoby and solar irradiation ecological indicator values. One lichenized fungus, Protoblastenia terricola, and one lichenicolous fungus, Zwackhiomyces dispersus, are recorded as new in Turkey and 194 taxa are reported for the first time from Barla Mountain. After this research, number of the lichenized and lichenicolous fungi taxa of Barla Mountain rose to 241. Based on assessments using the ecological indicator values, the area is dominated by natural or semi-natural and well-preserved habitats.     

Investigation of PDE5/PDE6 and PDE5/PDE11 selective potent tadalafil-like PDE5 inhibitors using combination of molecular modeling approaches,molecular fingerprint-based virtual screening protocols and structure-based pharmacophore development

The essential biological function of phosphodiesterase (PDE) type enzymes is to regulate the cytoplasmic levels of intracellular second messengers, 3′,5′-cyclic guanosine monophosphate (cGMP) and/or 3′,5′-cyclic adenosine monophosphate (cAMP). PDE targets have 11 isoenzymes. Of these enzymes, PDE5 has attracted a special attention over the years after its recognition as being the target enzyme in treating erectile dysfunction. Due to the amino acid sequence and the secondary structural similarity of PDE6 and PDE11 with the catalytic domain of PDE5, first-generation PDE5 inhibitors (i.e. sildenafil and vardenafil) are also competitive inhibitors of PDE6 and PDE11. Since the major challenge of designing novel PDE5 inhibitors is to decrease their cross-reactivity with PDE6 and PDE11, in this study, we attempt to identify potent tadalafil-like PDE5 inhibitors that have PDE5/PDE6 and PDE5/PDE11 selectivity. For this aim, the similarity-based virtual screening protocol is applied for the “clean drug-like subset of ZINC database” that contains more than 20 million small compounds. Moreover, molecular dynamics (MD) simulations of selected hits complexed with PDE5 and off-targets were performed in order to get insights for structural and dynamical behaviors of the selected molecules as selective PDE5 inhibitors. Since tadalafil blocks hERG1 K channels in concentration dependent manner, the cardiotoxicity prediction of the hit molecules was also tested. Results of this study can be useful for designing of novel, safe and selective PDE5 inhibitors.     

EXTRACELLULAR LIPOLYTIC ENZYME ACTIVITY OF A NEWLY ISOLATED DEBARYOMYCES HANSENII

A strain isolated from waste of a milk products plant and exhibited extracellular lipolytic activity was identified as Debaryomyces hansenii by 5.8S rRNA and 28S rRNA gene sequence analyses. Lipolytic activity was assayed spectrophotometrically by using p-nitrophenylpalmitate. Higher specific lipolytic activities were obtained in the presence of tristearin (0.68 U/mg prot), oleic acid (0.56 U/mg prot), and soybean oil (0.36 U/mg prot) than other triglycerides, fatty acids, and vegetable oils considered as carbon sources. Cheese whey appeared to be a good alternative to lipidic substances for lipolytic activity. Among various organic and inorganic nitrogen sources, soy flour was found to attain the lipolytic activity similar to that provided by universal yeast medium components. This work is the first report on the discussion of lipolytic activity enhancement by D. hansenii through modulating the cultivation medium. It also proposes low cost medium nutrients that could be of industrial value and could serve as basal nutrients for further optimization studies on the lipase production by D. hansenii.     

Growth and reproduction of a stream population of Cobitis turcica in central Anatolia (Turkey)

Cobitis turcica is endemic to Anatolia, and being of a bottom‐dwelling nature is highly influenced by habitat degradation. Due to drought and water pollution, in 2006 this species was included in the IUCN Red List as endangered. Therefore in order to develop conservation strategies, knowledge of its life history traits is important. The study presents first time data on the basic life history traits of C. turcica captured in a small stream flowing from P?narba?? Springs to Kozanl? Gök Lake in central Anatolia. In total, 1356 specimens were caught between March 2003 and August 2004. The overall sex ratio (M : F) was 1 : 0.62. Longevity in females, which reaches a maximum age of 6+, is 1 year longer than for males. Females are longer and heavier than males of the same age group. Maximum observed total lengths were 103.6 mm in a 5+ year‐old male and 126.75 mm in a 6+ year‐old female. Length–weight relationships were calculated for males, females, and juveniles, with the b exponent of the relationships as 2.9068, 2.8326, and 3.6859, respectively. Spawning was fractional, beginning in April and continuing until the end of July. Mean total fecundity was 2238 at age 5+.     

The influence of a longer photoperiod on growth parameters of European sea bass Dicentrarchus labrax (Linnaeus, 1758) reared in sea cages

The aim of this study was to investigate the effects of a long‐term photoperiod (15L : 9D) on both the somatic growth and husbandry parameters of sea bass Dicentrarchus labrax. Experiments were conducted in triplicate in high density polyethylene (HDPE) floating cages with net depths of 14 m and diameters of 20 m. Experiments were performed with approximately 170 000 sea bass with initial average weights of 110.63 ± 3.12 g and 110.26 ± 29.70 g for the experimental and control groups, respectively. Beginning in April 2008, extended artificial lighting was used in the experimental cages for 13 months; the control group received no additional illumination. At the end of the experiments, the average weights of the experimental and control groups were 362.13 ± 7.72 and 310.34 ± 18.15 g, respectively. Specific growth rate (SGR) was relatively high in the experimental group compared to the control fish. Feed conversion ratio (FCR) was 2.02 and 2.21 for the experimental and control groups, respectively, with significant differences also found between these groups (P < 0.05). Moreover, gonadal fish weight in the control group was significantly higher than in the experimental group, with the gonadosomatic index fluctuating within a 1.71‐fold increase.     

Multi-substrate growth kinetics of Pseudomonas putida for phenol removal

The biodegradation of phenol by a pure culture of Pseudomonas putida was investigated in a continuously fed stirred-tank reactor, under aerobic conditions. The dilution rate was varied between 0.0174 h⁻¹ and 0.278 h⁻¹, covering a wide range of dissolved oxygen and the inhibition region of phenol. Through non-linear analysis of the data, a dual-substrate growth kinetics, Haldane kinetics for phenol and Monod kinetics for oxygen, was derived with high correlation coefficients. Respective biokinetic parameters were evaluated as μ_m = 0.569 h⁻¹, K _p = 18.539 mg/l, K _i = 99.374 mg/l, K _o = 0.048 mg/l, Y _x/p = 0.521 g microorganism/g phenol and Y _x/o = 0.338 g microorganism/g oxygen, being in good agreement with other studies in the literature. Maintenance factors for both phenol and oxygen were calculated for the first time for P. putida while the saturation coefficient for oxygen, K _o, was genuinely evaluated from the constructed model, not imported or adapted from other studies as reported in the literature. All pertinent biokinetic parameters for P. putida have been calculated from continuous system data, which are most appropriate for use in continuous bioprocess applications. Received: 29 July 1996 / Received revision: 18 November 1996 / Accepted: 23 November 1996     

Increased Arterial PET/CT 18F-Fluorodeoxyglucose Uptake in Obese and Overweight Patients

ObjectivesWe aimed to investigate the association between BMI and early atherosclerotic activity in cancer patients. We also compared the inflammatory and macroscopic calcification processes of atherosclerosis in the aortic segments and large arteries by ¹⁸F-FDG PET/CT of between normal and high BMI patients.MethodsWe conducted a retrospective review of cancer patients presented to our institution within the period between February and May 2018. Patients were classified according to their BMI into two groups: normal BMI group and high BMI group. Data of average SUVmax and SUVmean for four segments of the aorta, common iliac arteries, and femoral arteries were estimated and compared between both groups. Moreover, the macroscopic calcification on CT images for each vascular section was also reported.ResultsNinety-eight patients were classified into two groups: normal BMI group (n = 52; 53.1%), and high BMI group (n = 46; 46.9%). Average SUVmax was significantly higher in obese participants in all arterial segments (P < 0.05). However, the SUVmean was significantly higher in obese patients in only three arterial segments aortic arch, left femoral artery and descending thoracic aorta (P < 0.05).Moreover, the differences between the two study groups in terms of the frequency of macroscopic calcifications were not statistically significant for all vascular segments. BMI positively correlated with SUVmax and SUVmean of the vascular segments (r value from 0,219 to 0,575/p value between 0,023 and 0,0001).ConclusionsFluorine-18-FDG PET/CT imaging revealed that patients with high BMI have more accelerated atherosclerotic inflammatory process in their major vessels compared to their age-matched controls with normal BMI. Future studies should assess the associated between these findings and the cardiovascular events in the long term.