The role of the progesterone receptor PROGINS variant in the development of fibromyalgia syndrome and its psychological findings.

Fibromyalgia syndrome (FMS), a chronic pain disorder of unknown etiology, is more common in women. This suggests that biological sex is important. Therefore, we performed an analysis to determine whether the progesterone receptor (P GR) gene Alu insertion (named P ROGINS) variant is associated with an increased risk of FMS in the Turkish population. A total of 288 subjects, including 138 patients diagnosed with FMS according to the 2016 American College of Rheumatology criteria and 150 healthy subjects, were evaluated. Genotyping of the P GR P ROGINS variant was determined by polymerase chain reaction (P CR) analysis. The results of the analyses were evaluated for statistical significance. There were no subjects in the control group carrying the T2 allele. The P GR P ROGINS T1/T2 genotype was more prevalent in both all patients and female patients compared to all controls and female controls (p = 0.001, p = 0.003, respectively). A statistically significant relationship was observed in both all patients and female patients when compared to the control group according to T1/T1 vs. T1/T2+T2/T2 (p < 0.000, p < 0.001, respectively). The current study suggests that the P GR Alu insertion variant T2 allele might influence FMS susceptibility in the Turkish population. Large-sample sizes and studies of different ethnicities are required to further evaluate the association between this variant and FMS.

Association of MIF-173G/C, IL-4 VNTR, and IL-1RA VNTR variants with FMF-related amyloidosis in a Turkish cohort.

The most important complication of familial Mediterranean fever (FMF) is secondary amyloidosis. The aim of this study is to investigate the risk of developing FMF-related amyloidosis with macrophage migration inhibitory factor (MIF), interleukin 4 (IL-4), and IL-1 receptor antagonist (IL-1RA) variants. This study included 62 FMF patients with amyloidosis, 110 FMF patients without amyloidosis, and 120 controls. The clinical information of the patient groups was compared. MIF-173G/C, IL-4 variant number tandem repeat (VNTR), and IL-1RA VNTR variants were analyzed for all participants. The use of colchicine, pleurisy, and appendectomy was more common in FMF patients with amyloidosis than in FMF patients without amyloidosis. MIF-173G/C C/C genotype and C allele were higher in both patient groups compared to controls. IL-1RA VNTR A1/A2 and A1/A4 genotypes and A1-A4 alleles were more common in both patient groups than controls. The IL-4 VNTR P1 allele was more common in FMF patients with amyloidosis compared to controls. The MIF-173G/C allele and the IL-1RA VNTR A1-A4 allele are associated with FMF in the Turkish population but not with amyloidosis risk in FMF patients. The IL-4 VNTR P1 allele is more common in FMF patients with amyloidosis than in healthy individuals.

The effect of a 18 bp deletion/insertion variant of VEGF gene on the FMF development.

Objective: Familial Mediterranean fever (FMF) is one of the most common inherited autoinflammatory diseases. Angiogenesis is a feature of inflammatory activation and part of pathogenic processes in autoimmune diseases. Therefore, this study aimed to investigate the role of the Vascular endothelial growth factor (VEGF) gene insertion/deletion (I/D) functional variant in FMF Turkish patients. Methods: MEFV gene mutations were detected in all patients. The FMF patients (N:105) and the healthy controls (N:100) were genotyped for the VEGF I/D variant using PCR followed by agarose gel electrophoresis. The results were statistically analyzed by calculating the odds ratios (OR) and their 95% confidence intervals (95% CI) using the χ2-tests. Results: The mean age of patients was 25.46 ± 10.09. Fifty-nine patients (56.2%) had two or more MEFV gene mutations. The most common MEFV mutation was M694V/M694V. The VEGF I/D variant genotype distribution exhibited a statistically significant difference between the patients and the controls. VEGF I/D genotype was higher in controls compared to patients, while D/D genotype was higher in patients compared to the controls (p = 0.003, p = 0.013, respectively). When we examined the clinical findings, joint pain was more common in patients with VEGF D/D and I/D genotypes compared to I/I genotype (p = 0.043). Although not statistically significant, the most common genotype in patients with two or more MEFV mutations was VEGF D/D (28.6%). Conclusion: The results provided evidence supporting that the D/D genotype of the VEGF I/D variant is associated with an increased risk of FMF in a group of Turkish populations.

Uterine Serosal Inclusion Cysts with Greater Omentum Involvement in a Cat.

A 7-year-old nulliparous Chinchilla queen was admitted to a veterinary clinic for routine ovariohysterectomy. Examination of the uterus, greater omentum and varicose ovarian veins revealed multiple thin-walled cysts filled with a transparent fluid over the serosal surfaces of these organs. Histologically, the cysts were of variable size, filled with a small amount of mucinous fluid, and had thin walls that contained hypocellular collagen and a few small calibre vessels. The inner and outer epithelium of the cyst walls and the cells that lined the uterine serosa were immunopositive for cytokeratin and vimentin, suggesting a mesothelial origin. Alpha-smooth muscle actin immunolabelling was patchy or continuous in smooth muscle in the wall of many of the cysts.

A circadian rhythm gene (PER3) VNTR variant as possible risk factor in cohort of Turkish females with primary dysmenorrhea.

Primary dysmenorrhea (PDM), which is the most prevalent problem related to the menstrual cycle in women of reproductive age, is due to sleep disorders and negative moods. Circadian rhythms, which are the immediate 24-h processes, enable an organism to adapt the suitable physiological responses to the environmental light-dark changes. Disturbed circadian rhythms are closely associated with several diseases, including sleep disorders. It has been reported that variable number tandem repeat (VNTR) variant in the coding region of circadian rhythm gene PERIOD 3 (PER3) affects sleep. Therefore, in the present study, we investigated the association between PDM and PER3 VNTR variant in Turkish females. A sample of 122 females with PDM and 150 healthy females were included in the study. Genoytyping of PER3 VNTR variant was performed on DNA by polymerase chain reaction (PCR) analysis using specific primers. We evaluated the relation between PER3 VNTR variant and PDM by calculating the odds ratios (ORs) and 95% confidence intervals (CIs). In our analyses of genotype data collected from total 272 subjects, we found that the PER3 VNTR variant was associated with development of PDM [codominant model (5/5 vs. 4/4 + 4/5): OR = 0.664; 95% CI, 0.39-1.10; p = 0.05). The three genotypes of the VNTR variant (4/4, 4/5, and 5/5) and their allelic frequencies showed nonsignificant differences between patients and control group (p > 0.05). In summary, PER3 VNTR variant may be associated with PDM in a Turkish female. However, further studies in different ethnic populations are needed to address the full role of this variant in PDM.

Topical Administration of Carvacrol Improves Healing in Nasal Septal Perforation: An Experimental Animal Study.

BACKGROUND: Clinicians are exploring alternative treatments for nasal septum perforation since surgical treatment is challenging. OBJECTIVE: The effects of topical carvacrol on the healing of nasal septal perforation were investigated in an animal model. METHOD: Twenty-one male New Zealand rabbits were randomly divided into three equal groups. A 5-mm circular biopsy punch was used to perforate the nasal septum behind the columella. For 14 days, bilateral gelatin sponges impregnated with carvacrol in olive oil in group 1, and only olive oil in group 2 were placed. Perforation only was performed in the control group. Animals were then sacrificed, and their nasal septums were removed. The closure of the perforation was measured, and samples were examined histopathologically. MMP-9 reactivity was evaluated using the immunoperoxidase technique. Histopathologic parameters were scored as 0 = none, 1 = mild, 2 = moderate, and 3 = strong. RESULTS: The septum perforation closure in the carvacrol group was statistically significant compared with the other groups (p < 0.001). Cartilage regeneration, connective tissue density, and MMP-9 immunoreactivity were significantly higher in the carvacrol group (p = 0.020, p = 0.009, and p = 0.008, respectively). CONCLUSION: Topically administered carvacrol enhances wound healing in rabbit nasal septum perforation. It accelerated perforation closure by increasing cartilage regeneration, connective tissue, and MMP-9 expression.

Synthetic pyrethroids common metabolite 3-phenoxybenzoic acid induces caspase-3 and Bcl-2 mediated apoptosis in human hepatocyte cells.

Synthetic pyrethroids are a group of insecticides frequently used in public health and agriculture, and 3-PBA is a common metabolite of them. Although the liver is the primary organ responsible for metabolizing many compounds including pesticides, to the authors' knowledge there have been no studies on the direct hepatotoxic effects of 3-PBA. Therefore, this study aimed to investigate the possible hepatotoxic effects of 3-PBA on a Human Hepatoma Cell Line (HepG2) and the underlying apoptotic mechanisms. Firstly, an LC50 of 1041.242 µM was calculated for 3-PBA by using the WST-1 test with concentrations ranging between 1 µM and 10 mM. Following that, the HepG2 cells in the experimental group were exposed to 3 different concentrations of 3-PBA (1/5 LC50, 1/10 LC50 and 1/20 LC50) for 24 hours. The apoptotic mechanism was evaluated by using flow cytometry, and immunofluorescence assays for Caspase 3 and Bcl-2. In the flow cytometry assay, the total number of apoptotic cells increased in a dose dependent manner (p < 0.05). In the immunofluorescence assay, the Caspase 3 protein showed strong immunoreactivity in the experimental groups, while the reaction to the Bcl-2 protein was minimal. These results demonstrated that 3-PBA has a significant hepatotoxic effect on HepG2 cells and induces apoptosis via the regulation of Caspase-3 and Bcl-2. Furthermore, our results could further the understanding of the fundamental molecular mechanisms of 3-PBA hepatotoxicity. More studies are needed to determine the effects of long-term exposure to 3-PBA and also the molecular mechanisms underlying hepatotoxicity.

Neuroprotective effects of sinapic acid involve the iron regulatory role on the rotenone-induced Parkinson's disease model

Abstract In the last decades, ferroptosis and its relationship with Parkinson's disease have gained significant attention. Compounds that affect ferroptosis and iron-dependent pathways in particular, have possible candidates for study in this context.Sinapic acid is an iron-chelator and high antioxidant bioactive phenolic acid. Its neuroprotective action, due to the antioxidant capacity, has been shown in several experimental models.However, the relationship between iron and antioxidant actions is still misunderstood and therefore, in the current study, we tried to investigate the effects of sinapic acid in rotenone-induced Parkinson's disease with the aspect of ferroptosis and iron-dependent alterations.The Parkinson's disease model was induced by a single dose intrastriatal and intrategmental rotenone (5µg/µl) injection.Sinapic acid (30mg/ kg) was orally administered during a 28-day period after the Parkinson's disease model was validated.Our results demonstrated that sinapic acid treatment attenuated rotenone-induced increase of serum transferrin and iron levels.Furthermore, sinapic acid inhibited rotenone-induced heme oxygenase-1(HO-1) increase and decrease of glutathione peroxidase-4 (GPx-4) levels in brain tissue. Also, sinapic acid treatment decreased motor impairment, likely as a result of the ameliorative effects on the tyrosine hydroxylase immunoreactivity loss after the rotenone insult.Our study suggests that the iron regulatory role of sinapic acid possibly plays a role in the protective effect on rotenone-induced neuronal damage.

Marek's disease virus in vaccinated poultry flocks in Turkey: its first isolation with molecular characterization.

Marek's disease (MD) is an important disease of avian species and a potential threat to the poultry industry worldwide. In this study, 16 dead commercial chickens from flocks with suspected MD were necropsied immediately after death. Pathological findings were compatible with MD, and gallid alphaherpesvirus 2 was identified in PCR of spleen samples. Virus isolation was performed in primary cell culture, and partial sequencing of the meq gene of the isolate revealed >99% nucleotide sequence identity to virulent and very virulent plus strains from a number of European countries, placing it in the same subclade of clade III as two virulent Italian strains and a very virulent plus Polish strain as well as virulent strains of geese and ducks. The data reported here indicate that a virulent strain of Marek's disease virus is circulating in Turkey and has not been stopped by the current national vaccination programme.

Idebenone Ameliorates Rotenone-Induced Parkinson's Disease in Rats Through Decreasing Lipid Peroxidation.

Oxidative stress is considered one of the mechanisms responsible for neurodegenerative diseases, especially for Parkinson's disease. Since oxidative stress causes pathological changes in neuronal structures antioxidant compounds gained significant attention the last decades. Although several antioxidant compounds showed neuroprotective actions in Parkinson's disease models, only a few of them demonstrated protective effects against loss of striatal dopaminergic neurons. Idebenone is an analog of the well-known antioxidant compound coenzyme Q10 (CoQ10). Clinical safety of idebenone is well described, and due to its high antioxidant capacity currently used to treat Freidrich's ataxia and Alzheimer's disease. Like Parkinson's disease, these diseases are characterized by oxidative stress and impaired mitochondrial balance in neurons. However, knowledge about the effects of idebenone on Parkinson's disease is limited. Therefore, in this study we aimed to investigate and delineate the possible effects of idebenone in rotenone-induced Parkinson's disease models. Idebenone (200 mg/kg, p.o.) inhibited the decrease of striatal expression of NAD(P)H dehydrogenase[quinone]-1, which is an essential element for mitochondrial respiration. Idebenone decreased the striatal levels of the lipid peroxidation products and increased the expression of glutathione peroxidase-4 (GPx-4), which is primarily known for lipid peroxidation and ferroptosis. Furthermore, idebenone mitigated motor impairment and increased tyrosine hydroxylase-positive neuron survival. Together our results thus indicate that that idebenone has protective effects against a rotenone insult with pleiotropic actions on the cellular oxidative enzymes and lipid peroxidation.

Analysis of Interleukin-1 Receptor Antagonist Variable Number Tandem Repeat Variant in Recurrent Aphthous Stomatitis.

BACKGROUND/AIMS: Recurrent aphthous stomatitis (RAS) is one of the common oral inflammatory diseases. As immunological and genetic factors have been held responsible for the pathogenesis of RAS, the objective of this study was to determine whether the interleukin-1 receptor antagonist (IL-1Ra) gene variable number tandem repeat (VNTR) variant is a risk factor for the development of RAS in Turkish patients and to define its contribution to the increased risk. METHODS: The IL-1Ra VNTR variant was evaluated in 169 RAS patients and 171 healthy controls by the polymerase chain reaction (PCR) method. RESULTS: No statistically significant difference was found in the genotype distributions and allele frequencies of IL-1Ra VNTR variant between RAS patients and healthy controls. CONCLUSION: Lack of association between IL-1Ra VNTR variant and RAS could indicate that IL-1Ra has no significant role in the pathophysiology of RAS. However, it still appears to be very worthwhile to continue to search for cytokine gene variants in order to predict the development of such disease.

Impact of Endothelial NOS VNTR Variant on Susceptibility to Diabetic Neuropathy and Type 2 Diabetes Mellitus.

PURPOSE: The aim of this study was to evaluate whether the VNTR intron 4b/4a variant in the eNOS gene is associated with type 2 diabetes mellitus (T2DM) and DPN. METHODS: A total of 598 subjects were enrolled in the study. eNOS VNTR 4b/4a variant was genotyped by polymerase chain reaction (PCR) method. RESULTS: eNOS VNTR intron 4b/4b genotype and b allele increased in patients with both DPN and T2DM compared healthy controls (p=0.0005, OR:1.94, p= 0.000002, OR:4.10, respectively). 4a/4b genotype was more prevalent in controls than in DPN and T2DM patients (p=0.00008, OR:0.46; p=0.000004, OR:0.24, respectively). eNOS VNTR b allele was more common in DPN patients and T2DM patients compared with controls (p=0.007, p=0.00002, respectively). CONCLUSION: The eNOS VNTR "4b/4b" homozygous genotype and hence "4b"allele as a genetic risk factor for T2DM and DPN, which may serve as a useful marker of increased susceptibility to the risk of these disorders.