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Tadalafil attenuates ischemic damage as well as reperfusion injury in the rat ovary
Objective: Tadalafil is a selective phosphodiesterase type-5 inhibitor with a long half-life. It has a dual function in ischaemic and re-perfused tissues, i.e. vasodilatation and anti-oxidant effects. These features of tadalafil distinguish it from other anti-oxidants. We investigated the dual effect of tadalafil on ischaemia and reperfusion injury in the rat ovary. Material and Methods: We established five study groups. Group 1 (n=6): sham-operated; group 2 (n=6): torsion; group 3 (n=6): torsion and Tadalafil; group 4 (n=6): torsion/de-torsion; and group 5 (n=6): torsion/de-torsion and tadalafil. Ovarian samples were harvested from animals and evaluated in terms of histopathologic changes, tissue malondialdehyde (MDA) concentrations, lactate production, and plasma cyclic guanosine monophosphate (cGMP). Results: Follicular degeneration, oedema, haemorrhage, and inflammatory cells were significantly decreased in group 5 in comparison with group 4. Group 2 and group 3 were compared in terms of vascular congestion and haemorrhage; these parameters were significantly decreased in group 3. In addition, significantly decreased MDA and lactate concentrations were observed in group 5 in comparison with group 4. Increased cGMP concentrations were detected in group 3 and group 5. Conclusion: We conclude that tadalafil might be useful in protecting the ovary against ischaemia and reperfusion injury. In the evet of ovarian torsion, it will provide a greater therapeutic effect than only performing de-torsion of the ovary or using other anti-oxidant agents. (J Turk Ger Gynecol Assoc 2020; 21: 35-40
Therapeutic effects of vitamin D on acetic acid-induced colitis in rats
Erdogan, Mumin/0000-0003-0048-444XWOS: 000540300900001PubMed: 32555936Purpose: To analyze the effect of calcitriol treatment on acute colitis in an experimental rat model. Methods: A total of 24 adult Sprague Dawley albino rats were randomly separated into 3 equal groups: control group (n:8), colitis group (n:8), calcitriol administered group (n:8). A single dose of acetic acid (1 ml of 4% solution) was administered intrarectally to induce colitis. Group 1 was given 1 ml/kg 0.9% NaCl intraperitoneally; rats belonging to Group 2 were administered calcitriol 1 mu g/kg for 5 days. Results: Plasma tumor necrosis factor alpha, Pentraxin 3, and malondialdehyde levels were significantly lower in the calcitriol administered colitis group than in the standard colitis group (p<0.01). in the Calcitriol group, there was a significant histological improvement in hyperemia, hemorrhage and necrotic areas in the epithelium compared to the placebo group (p<0.000). Conclusion: the findings suggest that calcitriol may be an agent that could be used in acute colitis treatment
Warfarin pharmacogenetics in patients with heart valve replacement
Karaalp, Atila/0000-0003-3382-9483; Bezci, Kivanc/0000-0002-5741-6395WOS: 000560607800005Background: Warfarin treatment is crucial to prevent thrombolytic complications after the heart valve replacement (HVR) operation. Our purpose was to investigate the prevalence of CYP2C9 *2 and *3 gene polymorphisms, which are essential in warfarin metabolism in patients with and without HVR surgery prescribed with warfarin. Material and method: 47 patients with and without HVR were genotyped for the CYP2C9*2 (rs1799853, 430 C> T), CYP2C9*3 (rs1057910, 1075 A> C) polymorphisms by PCR-RFLP assay. Results: Homozygous wild (CC), heterozygous and homozygous polymorphic (CT+TT) genotype frequencies of CYP2C9 *2 were determined respectively as 69.6% and 30.4% for patients with HVR; 79.2% and 20.8% for patients without HVR. Homozygous wild (AA) and heterozygous (AC) genotype frequencies of CYP2C9 *3 polymorphism were determined respectively as 73.9% and 26.1%f for patients with HVR; 79.2% and 20.8% for patients without HVR. CYP2C9 *2 and *3 genotype frequencies did not show any statistically significant difference between with and without HVR groups. Conclusion: in the present study, no significant difference was observed between patients with and without HVR with respect to CYP 2C9 *2 and *3 gene polymorphisms in Turkish subjects. Further studies with higher number of patients are needed to evaluate the importance of CYP 2C9 *2 and *3 pharmacogenetic testing in patients with HVR using warfarin
Erythropoietin shows gender dependent positive effects on social deficits, learning/memory impairments, neuronal loss and neuroinflammation in the lipopolysaccharide induced rat model of autism
Alnak, Alper/0000-0002-3515-8217; Erdogan, Mumin/0000-0003-0048-444XWOS: 000571919100007PubMed: 32736811We aimed to evaluate the effects of EPO in the lipopolysaccharide (LPS) induced rat model of autism in terms of social deficits, learning and memory impairments, as well as their neurochemical correlates. Sixteen female Sprague Dawley rats randomly distributed into two equel groups, then were caged with fertile males for mating. At the 10th day of pregnancy, 0.5 ml %0,9 NaCl saline was given to first group, 100 mu g/kg LPS was given to second group to induce autism. on postnatal 21th day, forty-eight littermates were divided into four groups as; 8 male, 8 female controls, 16 male and 16 female LPS-exposed. Then, LPS groups were also divided in to two groups as saline (1 mg/kg/day) and EPO 600 U/kg/day groups, and animals were treated 45 days. At 50th day, after behavioral evaluations, brain levels of TNF-alpha, nerve growth factor (NGF) were measured. Histologically, hippocampal neuronal density and GFAP expression were assessed. Three-chamber sociability and social novelty test, passive avoidance learning test were revealed significant differences among the EPO and control groups. Histologically, hippocampal CAl & CA3 regions displayed significant alterations regarding gliosis (GFAP-positive cells) and regarding frontal cortical thickness in EPO groups compare to controls. Biochemical measurements of the brain levels of TNF-alpha and NGF levels showed significant differences between controls and EPO groups. According to our findings EPO treatment has beneficial effects on ASD-like symptoms, learning and memory processes, neuronal loss and neuroinflammation in the LPS induced rat model of autism, with some gender differences through inflammatory and neurotrophic pathways
Intravoxel Incoherent Motion of Colon Cancer Liver Metastases for the Assessment of Response to Antiangiogenic Treatment: Results from a Pilot Study
WOS: 000567965000004PubMed: 31914438Objective:This study was aimed at evaluating the intravoxel incoherent motion (IVIM) parameter alterations of liver metastases of colorectal carcinoma (CRC) during antiangiogenic bevacizumab combination therapy.Methods:Twenty-five patients with CRC liver metastases treated with bevacizumab in combination with FOLFOX-or-FOLFIRI protocols were enrolled in the study. MRI was performed using a 1.5-tesla scanner pre-treatment (PT) and at 3, 6, and 9 months of therapy. Routine abdominal MRI sequences and an IVIM-DWI (diffusion-weighted imaging) sequence were obtained. the IVIM-DWI sequence was executed with 16 b-values varying from 0 to 1,400 s/mm(2). the mean values of apparent diffusion coefficient (ADC), true diffusion (D), pseudodiffusion (D*), and perfusion fraction (f) of each metastasis were obtained for all b-values, and the time-related changes were recorded to analyze the chronologic responses to antiangiogenic therapy. the RECIST 1.1 criteria were used for the evaluation of treatment response.Results:The diameters of the metastases diminished significantly at 9 months when compared with PT (p= 0.03). the D (p= 0.10) and ADC (p= 0.21) values of the metastases increased at 9 months of therapy. D* was the highest at 3 months (p =0.24); it decreased at 6 (p =0.97) and 9 months (p =0.87) of therapy. the f value had peaked at 3 months (p =0.51) and started to decrease thereafter. At 6 months, f decreased to the lowest values (p =0.12).Conclusion:IVIM parameters, particularly the perfusion fraction, may quantitatively reflect the response to antiangiogenic treatment. the antiangiogenic response manifests after 3 months of therapy before the RECIST-related response
Unexpectedly High Prevalence of Low Alpha-Galactosidase A Enzyme Activity in Patients with Focal Segmental Glomerulosclerosis
Hasbal, Nuri Baris/0000-0002-2229-5140WOS: 000576771000001PubMed: 32997080OBJECTIVES: Fabry disease (FD) is a rare disease associated with sphingolipid accumulation. Sphingolipids are components of plasma membranes that are important in podocyte function and accumulate in various glomerular diseases such as focal segmental glomerulosclerosis (FSGS). Both FD and FSGS can cause podocyte damage and are classified as podocytopathies. in this respect, FD and FSGS share the same pathophysiologic pathways. Previous screening studies have shown that a significant proportion of end-stage renal disease (ESRD) patients receiving hemodialysis (HD) have unsuspected FD, and the prevalence of low alpha-galactosidase A (aGLA) enzyme activity in these patients is higher than that in the normal population. We aimed to compare aGLA enzyme activity in patients with biopsy-proven FSGS and ESRD receiving HD. METHODS: the records of 232 patients [62 FSGS (F/M: 33/29); 170 HD (M/F: 93/79)] were evaluated retrospectively. the screening was performed based on the aGLA enzyme activity on a dried blood spot, with the confirmation of plasma LysoGb3 levels, and the known GLA mutations were tested in patients with low enzyme activities. the two groups were compared using these parameters. RESULTS: the mean level of aGLA enzyme activity was found to be lower in FSGS patients than in the HD group (2.88 +/- 1.2 mmol/L/h versus 3.79 +/- 1.9 mmol/L/h, po0.001). There was no significant relationship between the two groups with regard to the plasma LysoGb3 levels (2.2 +/- 1.22 ng/ml versus 1.7 +/- 0.66 ng/ml, p: 0.4). in the analysis of GLA mutations, a D313Y mutation [C(937G4T) in exon p] was found in one patient from the FSGS group. CONCLUSIONS: We found that aGAL activity in patients with FSGS is lower than that in patients undergoing HD. the low enzyme activity in patients with FSGS may be explained by considering the similar pathogenesis of FSGS and FD, which may also lead to sphingolipid deposition and podocyte injury
Cerebral Venous Sinus Thrombosis in Women: Subgroup Analysis of the VENOST Study
Sahin, Sevki/0000-0003-2016-9965; Uzuner, Nevzat/0000-0002-4961-4332; UZUNER, NEVZAT/0000-0002-4961-4332; Yayla, Vildan/0000-0002-4188-0898WOS: 000570429300001PubMed: 32953038Background. Early diagnosis of cerebral venous sinus thrombosis (CVST) associated with reproductive health-related risk factors (RHRF) including pregnancy, puerperium, and oral contraceptive (OC) use can prevent severe neurological sequelae; thus, the symptoms must be documented in detail for each group.Methods. Out of 1144 patients with CVST, a total of 777 women were enrolled from a multicenter for the study of cerebral venous sinus thrombosis (VENOST). Demographic, biochemical, clinical, and radiological aspects were compared for 324 cases with RHRF and 453 cases without RHRF.Results. the mean age of the RHRF (-) group (43.2 +/- 13 years) was significantly higher than of the RHRF (+) group (34 +/- 9years). A previous history of deep venous thrombosis (3%), isolated cavernous sinus involvement (1%), cranial neuropathy (13%), comorbid malignancy (7%), and its disability scores after 12 months (9%) were significantly higher in the RHRF (-) group. the RHRF (+) group consisted of 44% cases of puerperium, 33% cases of OC users and 23% of pregnant women. the mean age was found to be higher in OC users (38 +/- 9years). A previous history of deep venous thrombosis was slightly higher in the pregnancy subgroup (4%). Epileptic seizures were more common in the puerperium group (44%).Conclusion. the results of our study indicate that the risk of CSVT increases parallel to age, OC use, and puerperium period. in addition, when considering the frequency of findings and symptoms, epileptic seizures in the puerperium subgroup of the RHRF (+) group and malignancies in the RHRF (-) group may accompany the CSVT. in daily practice, predicting these risks for the CSVT and early recognition of the symptoms will provide significant benefits to patients.NIA NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [U54 AG044170] Funding Source: Medlin
Autonomic dysfunction in restless legs syndrome
WOS: 000559837000024PubMed: 31520300Objective Autonomic dysfunction in patients with RLS has been described in some domains; however, detailed studies on this subject are limited and report conflicting results. in this study, we aimed to evaluate autonomic functions electrophysiologically and clinically in patients with restless legs syndrome (RLS). Methods Fifty-two adult patients with RLS and 40 healthy controls were enrolled in this prospective study. Electrophysiological tests of sympathetic skin response (SSR) and RR interval variability (RRIV) analysis were performed, and the SCOPA-AUT questionnaire was applied to evaluate autonomic functions. Results There was no significant difference in terms of SSR results between patients and controls (p > 0.05). However, there were significant differences between the patient and control groups in terms of RRIV analyses at rest, deep breathing, and valsalva, and also valsalva ratio (p = 0.037,p = 0.049,p = 0.017,p = 0.020). the mean SCOPA-AUT total score was higher in the RLS group compared with the control group (20.7 +/- 10 vs 14.2 +/- 8;p = 0.003). Significant differences were found regarding gastrointestinal, urinary, and cardiovascular domains (p = 0.01,p = 0.007,p = 0.049); on the other hand, pupillomotor, thermoregulatory, and sexual function did not significantly differ (p > 0.05). Conclusion Autonomic functions should be questioned in detail as well as motor and sensory symptoms of RLS, and care should be taken especially on cardiac dysfunction
Investigation of the protective effects of boric acid on ethanol induced kidney injury
WOS: 000513481900001PubMed: 32041435Boric acid (BA) is used as an antioxidant and anti-inflammatory agent, and for regulating mitochondrial membrane potential in many disorders. We investigated the protective effects of BA against chronic ethanol toxicity in rat kidney. We used 32 male rats in four groups of eight: control (C), BA, ethanol (E), and ethanol + BA (E + BA). Kidney samples were taken for histology and biochemistry. Kidney injury was assessed using hematoxylin and eosin (H & E) and periodic acid-Schiff (PAS) staining. TUNEL and caspase-3 immunohistochemistry were used as indicators of apoptosis. We measured biochemical markers of ethanol induced oxidative stress in the kidneys including malondialdehyde (MDA), total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI). the E + BA group TOS, OSI and MDA levels decreased, whereas the TAS level increased compared to group E. Caspase-3 and TUNEL activity in the E + BA group were decreased compared to group E. BA acted as an antioxidant against renal tubule injury caused by chronic use of ethanol. BA protects against apoptosis in renal tubules by decreasing oxidative damage.TUBITAK (The Scientific and Technological Research Council of Turkey)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [113S546]This study was supported by TUBITAK (The Scientific and Technological Research Council of Turkey) project number 113S546
Whole exome sequencing reveals novel candidate gene variants for MODY
WOS: 000582504300017PubMed: 32645390Maturity-onset diabetes of the young (MODY) is a monogenic subtype of diabetes mellitus. Although 14 genes were associated to different subtypes of MODY, 30-40% of MODY patients have unidentified genetic mutations. in this study, we conducted whole exome sequencing (WES) in four Turkish MODY suspected patients in two families who do not carry any pathological variants in four frequent MODY genes (HNF1A, GCK, HNF1B and HNF4A). Initially, the variants were scanned for the known 14 MODY genes and a gene set related to glucose metabolism. Secondly, the destructive (frameshift, inframe insertion/deletion, initiator codon variant, splice acceptor/ donor variant, stop gained/lost) and missense variants in novel candidate genes shared by two patients of the same family were assessed by different bioinformatic tools. As a result, a total of three rare and novel probably pathogenic heterozygous missense variants (p.His307Gln in c-Myc, p.Asp129Asn in CDK4 and p.Gly107Ser in ARHGDIA) in candidate genes were identified in two families. This study revealed the presence of nonsynonymous alterations in novel candidate genes which were implicated in the insulin secretion. This is the first WES study which reveals novel candidate genes in Turkish MODY patients although functional analyses are required to confirm the pathogenicity of these variants.Scientific and Technological Research Council of Turkey (TUBITAK), TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [113S218]Research project was funded by Scientific and Technological Research Council of Turkey (TUBITAK), Turkey (Grant number: 113S218)