Assessment of Pathogenic Variants in the PAH Gene and Genotype-Phenotype Correlation in Phenylketonuria Patients from Turkey.

This study aims to determine the allele and genotype frequency, evaluate genotype-phenotype correlation and contribute to the spectrum of pathogenic variants in the PAH gene. Ninety-three individuals diagnosed with PKU were included in the study. Next-generation sequencing was utilized for detecting variants in the PAH gene. Copy Number Variations in patients without biallelic pathogenic variant were investigated by Multiplex Ligation-dependent Probe Amplification method. Genotype-phenotype correlations and genotype-based phenotype predictions were examined by comparing molecular test results with BIOPKUdb database. The clinical distributions of the patients were as follows: classic PKU 21% (n = 19), mild PKU 3% (n = 3), and mild hyperphenylalaninemia 76% (n = 71), respectively. Thirty-nine distinct variants and 70 distinct genotypes were found in patients. The most frequently observed variant was p.(Ala300Ser) (13.9%) and the most frequently observed genotype was p.[Ala300Ser];[Ala300Ser] (5.6%). Compound heterozygous genotypes (%69) were more prevalent than homozygous genotypes. A novel variant, c.441+4A>C, was observed. Predicted metabolic phenotypes in the database showed consistency with patient phenotypes (n = 33/41). BH4 responsiveness showed partial consistency with database predictions (n = 13/25). Establishing genotype-phenotype correlations can facilitate personalized management approaches. Overall, this study contributes to understanding the genetic basis and clinical course of PKU.

Evaluation of the effect of obesity, dietary glycemic index and metabolic profiles on the cardiovascular risk in children with classical phenylketonuria.

OBJECTIVES: To compare the glycemic index(GI),obesity,echocardiographic,and arterial stiffness measurements with the healthy control group to evaluate the cardiovascular risk of pediatric classical phenylketonuria(PKU). METHODS: The study was a prospective observational,involving 104 pediatric volunteers between 2019 and 2020.Two groups were formed:the PKU patient group and the healthy control group.These two groups were further divided into three subgroups:obese,overweight,and normal weight.The patients' anthropometric measurements,body fat analysis,biochemical analysis, GI and glycemic load(GL),arterial stiffness measurements,and echocardiographic findings were recorded. RESULTS: The PKU patient group's glucose,total cholesterol,LDL,and HDL values were significantly lower than the healthy control group(p = 0.010 for glucose and p = 0.001 for total cholesterol,LDL and HDL).Triglyceride levels were higher in the PKU patient group than in the healthy controls(109.6 vs. 76.7 mg/dl,p = 0.001). GI and GL were significantly lower in the PKU patient group than in the healthy control group(GI 453 vs. 392.9,p = 0.017 and GL 101.1 vs. 85.5,p = 0.036).Left ventricular mass(LVM)-z-score and LVM index were significantly higher in the PKU group than in the healthy control group(LVM z-score 0.9 vs. 0.5,p = 0.014 and LVM index 38.9 vs. 32.7 g/m2.7,p = 0.001). A moderately statistically significant positive correlation was found between the mean phenylalanine(phe) value and pulse wave velocity(PWV) among the PKU patient groups(R: 0.477,p < 0.001).A moderately statistically significant positive correlation was also found between waist circumference and PWV in the PKU patient group(R:0.541, p < 0.001). CONCLUSIONS: Our study found that close follow-up of phe levels and PWV is more critical than obesity, GI, and GL in the cardiovascular evaluation of classical PKU patients.A large number of multicenter pediatric studies are needed in this area.

Furan promotes cytotoxic effects through DNA damage and cell apoptosis in Leydig cells.

Furan is an organic chemical that can cause adverse effects on human health and is formed as a result of the thermal decomposition of many food components during cooking, storage, and processing techniques. Studies have shown that exposure to furan causes nephrotoxicity, hepatotoxicity, immunotoxicity, and reproductive toxicity. According to our current knowledge of the literature, the genotoxic mode of action of furan is highly controversial. The genotoxic effects of furan on the male reproductive system, however, have not been studied. In this study, the TM3 Leydig cell line was treated with 750, 1500, and 3000 µM concentrations of furan for 24 h. Following the completion of the exposure period, the cytotoxicity of furan in TM3 Leydig cells was assessed using a cell viability assay and a spectrophotometric measurement of lactate dehydrogenase (LDH) enzyme levels. The double fluorescence staining method was used to demonstrate furan-induced apoptosis, and DNA damage was shown using the micronucleus, comet, and chromosomal aberration assays. The result indicated that furan administration of Leydig cells resulted in an increase in structural chromosomal aberration, comet, and micronucleus formation, reduced cell viability, increased LDH activity, and a higher incidence of apoptotic cells. These findings revealed that furan induces DNA damage in TM3 Leydig cells, causing genotoxicity and DNA damage-induced cytotoxicity.

The Effect of the Meditation Based Mandala Programme on Distress, Anxiety and Depression in the Caregivers of Cancer Patients in Palliative Care Unit.

Mental health problems were found to be more common than physical health problems in cancer caregivers in palliative care units. This is a quasi-experimental study planned to determine the effect of the meditation based mandala programme on distress, anxiety and depression in caregivers of cancer patients in a palliative care unit. Planned as a single-group pre-test/post-test design, with a total of 11 caregivers. Data were collected with the Caregiver Diagnosis Form, Distress Thermometer, Beck Depression Inventory, and Beck Anxiety Inventory. Caregivers participated in the Meditation Based Mandala Programme once a week, which lasted 2 hours for 5 weeks. The distress, depression and anxiety levels of the patients were measured before the programme started and at the end of the programme. Meditation based mandala programme is effective in reducing the distress, depression and anxiety levels of caregivers of cancer patients in the palliative care unit.

Identifying Clinical Characteristics of Hypoparathyroidism in Turkey: HIPOPARATURK-NET Study.

Hypoparathyroidism is an orphan disease with ill-defined epidemiology that is subject to geographic variability. We conducted this study to assess the demographics, etiologic distribution, treatment patterns and complication frequency of patients with chronic hypoparathyroidism in Turkey. This is a retrospective, cross-sectional database study, with collaboration of 30 endocrinology centers located in 20 cities across seven geographical regions of Turkey. A total of 830 adults (mean age 49.6 ± 13.5 years; female 81.2%) with hypoparathyroidism (mean duration 9.7 ± 9.0 years) were included in the final analysis. Hypoparathyroidism was predominantly surgery-induced (n = 686, 82.6%). The insulting surgeries was carried out mostly due to benign causes in postsurgical group (SG) (n = 504, 73.5%) while patients in nonsurgical group (NSG) was most frequently classified as idiopathic (n = 103, 71.5%). The treatment was highly dependent on calcium salts (n = 771, 92.9%), calcitriol (n = 786, 94.7%) and to a lower extent cholecalciferol use (n = 635, 76.5%) while the rate of parathyroid hormone (n = 2, 0.2%) use was low. Serum calcium levels were most frequently kept in the normal range (sCa 8.5-10.5 mg/dL, n = 383, 46.1%) which might be higher than desired for this patient group. NSG had a lower mean plasma PTH concentration (6.42 ± 5.53 vs. 9.09 ± 7.08 ng/l, p < 0.0001), higher daily intake of elementary calcium (2038 ± 1214 vs. 1846 ± 1355 mg/day, p = 0.0193) and calcitriol (0.78 ± 0.39 vs. 0.69 ± 0.38 mcg/day, p = 0.0057), a higher rate of chronic renal disease (9.7% vs. 3.6%, p = 0.0017), epilepsy (6.3% vs. 1.6%, p = 0.0009), intracranial calcifications (11.8% vs. 7.3%, p < 0.0001) and cataracts (22.2% vs. 13.7%, p = 0.0096) compared to SG. In conclusion, postsurgical hypoparathyroidism is the dominant etiology of hypoparathyroidism in Turkey while the nonsurgical patients have a higher disease burden with greater need for medications and increased risk of complications than the postsurgical patients.

False recognitions in the DRM paradigm: the role of stress and warning.

For the last decades, the factors increasing or decreasing the frequency of false memories have been of great interest. Some research also examined the effect of stress and warning on the true and false recognitions; however, so far most of the studies have yielded contradictory results or seems inadequate to understand the effect of these factors on false memory phenomenon. The purpose of this study is to examine the joint effects of stress and warning on the frequency of false and true memories elicited by the list-learning paradigm. The word lists derived from the Deese-Roediger-McDermott (DRM) paradigm were used in order to measure false and true recognition rates. Participants (N = 126) were exposed to either the Trier Social Stress Test (a stress condition) or a filler task at the beginning of the experiment (no-stress condition). Then, they were either subjected to a warning about false memories before DRM (pre-warning condition), subjected to a warning about false memories after DRM (post-warning condition), or given no warning at all (no-warning condition). Results showed that stress had a statistically significant effect on true recognition but not on false recognition. Furthermore, warning given after the DRM lists had a decreasing effect on the frequency of false memories. No significant interaction effect between stress and warning was found. Although our hypotheses were not confirmed, this study can contribute to the existing body of research by providing evidence that stress and warning have differential effects on both true and false memories derived from the DRM paradigm.

Evaluation of citrinin-induced toxic effects on mouse Sertoli cells.

Penicillium citrinum-derived mycotoxin citrinin (CTN) is known to be a toxic agent for humans and animals. Previous studies have shown that CTN leads to toxicity in many biological systems; however, a limited number of studies have been performed to demonstrate the harmful effects of CTN on the male reproductive system. In the present study, the effects of CTN on cytotoxicity and apoptosis were examined in Sertoli cells as a model. Sertoli cells were treated with eight different CTN concentrations (from 0 up to 200 µM, for 6-72 h). Toxic potential of CTN was estimated by measuring metabolic activity (MTT test), DNA synthesis (BrdU test), and cell membrane damage (LDH test) as well as apoptosis and necrosis (via staining with propidium iodide and Hoechst 33342). The results showed that CTN significantly decreased the cell viability and cell proliferation, increased cytotoxicity, apoptosis, and necrosis in a concentration-dependent manner. Furthermore, CTN showed cytotoxicity in Sertoli cells with an IC50 value of 116.5 µM for 24 h. In conclusion, these findings clearly showed that, CTN affects Sertoli cells even at low concentrations. Thus, as a result of the damage of CTN shown in Sertoli cells, it can be deduced that CTN may also have detrimental effects on the testes.

The effect of 4.5 G (LTE Advanced-Pro network) mobile phone radiation on the optic nerve.

PURPOSE: Rapid development in mobile phone technologies increase the average mobile phone usage duration. This increase also triggers exposure to radiofrequency radiation (RF), which is a risk factor for the health. In this study, it was aimed to investigate the effect of mobile phone working with LTE-Advanced Pro (4.5 G) mobile network on the optic nerve, which is responsible for the transmission of visual information. MATERIAL AND METHODS: Thirty-two rats divided into two groups as control (no RF, sham exposure) and experimental (RF exposure using a mobile phone with LTE-Advanced Pro network; 2 hours/day, 6 weeks). The visual evoked potential (VEP) was recorded and determined amplitudes and latencies of VEP waves. Optic nerve malondialdehyde level, catalase and superoxide dismutase activities were determined. Furthermore, ultrastructural and morphometric changes of optic nerve were evaluated. RESULTS: In VEP recordings, the mean VEP amplitudes of experimental group were significantly lower than control group. In ultrastructural evaluation, myelinated nerve fibres and glial cells were observed in normal histologic appearance both in sham and experimental group. However, by performing morphometric analysis, in the experimental group, axonal diameter and myelin thickness were shown to be lower and the G-ratio was higher than in the sham group. In the experimental group, malondialdehyde level was significantly higher and superoxide dismutase and catalase activities were significantly lower than sham group. There was a high correlation between VEP wave amplitudes and oxidative stress markers. CONCLUSION: Findings obtained in this study support optic nerve damage. These results point out an important risk that may decrease the quality of life.

Vitamin C inhibits glycidamide-induced genotoxicity and apoptosis in Sertoli cells.

Exposure to the food contaminant acrylamide and its reactive epoxide metabolite glycidamide (GA) induces reactive oxygen species (ROS)-mediated oxidative stress and subsequent cellular death. Recent studies have revealed that the toxic effects of acrylamide may be due to GA, especially on male reproductive system cells. In this regard, it is important to determine the effects of GA on Sertoli cells, which are essential cells for the male reproductive system. Antioxidants should be consumed in sufficient quantities to minimise the effects of environmental pollutants. This study aimed to determine the direct toxic effects of GA and protective effects of vitamin C (VitC) against GA-induced damage in Sertoli cells by measuring cell viability, cytotoxicity, lipid peroxidation, ROS, antioxidant enzyme levels, apoptosis and DNA damage. Sertoli cells were exposed to GA for 24 hours at four different concentrations (ranging between 1 and 1000 µM) and in addition to these GA concentrations to VitC (50 µM). The results of cytotoxicity markers, such as cell viability and lactate dehydrogenase (LDH) showed that GA significantly reduced cell viability and increased LDH levels. We also found that GA induced overproduction of intracellular ROS, increased lipid peroxidation in cellular membrane and triggered cell apoptosis and genotoxicity. In addition, VitC supplementation ameliorated the adverse effects of GA on Sertoli cells. Consequently, these findings suggest that GA may damage the cell function in Sertoli cells, depending on the concentration. Additionally, it was evidenced that VitC has an ameliorative effect on toxicity caused by GA.

Prevalence and risk factors for sexual dysfunction in reproductive-aged married women: A cross-sectional epidemiological study.

AIM: We aimed (i) to evaluate the point prevalence for sexual dysfunction in a population of reproductive-aged married women living in an urban area in Isparta, Turkey, (ii) to examine demographic and psychosocial risk factors for sexual dysfunction. METHODS: In a cross-sectional design, following single-stage cluster sampling all married women living in three representative areas (n = 1323) were approached at their place of residence. Female sexual dysfunction, poor mental health and marital adjustment were assessed with the 9-item Index of Female Sexual Function, the 12-item General Health Questionnaire, and Locke-Wallace Short Marital-Adjustment Test, respectively. Descriptive data were presented as frequencies, percentages and mean ± standard deviations. Chi-square and independent samples t-test were used for univariate analysis. Logistic regression model was constructed to define independent risk factors for sexual dysfunction. P < 0.05 was considered statistically significant. RESULTS: Of the 1216 women included in analyses (response rate 91.9%), 45.0% experience sexual dysfunction. Poor marital adjustment and poor mental health are associated with sexual dysfunction (odds ratio = 4.06; 95% confidence interval = 2.97-5.54; odds ratio = 2.74; 95% confidence interval = 2.00-3.72, respectively). Lack of social insurance, chronic disease of the spouse, perception of deficient knowledge on sexuality-related topics, perceived sexual problems, and increasing duration of marriage were also associated with sexual dysfunction (P < 0.05 for all). CONCLUSION: Screening of married women for sexual dysfunction and the risk factors revealed in the present study may permit appropriate preventive interventions.

Sodium arsenite-induced detriment of cell function in Leydig and Sertoli cells: the potential relation of oxidative damage and antioxidant defense system.

Arsenic is commonly found in the natural environment and is toxic agent for living organism in many countries in the world. Studies on animal models suggest that exposure to arsenic may cause reproductive toxicity; however, effect of arsenic on reproductive toxicity has still not been clearly described. This study was focused on cytotoxicity, oxidative stress, and the antioxidant defense system induced with exposure to sodium arsenite in Mus musculus Leydig and Sertoli cells. The cells were exposed to two different concentrations of sodium arsenite of 50 ppb (0.4 µM) and 1000 ppb (7.7 µM) for 24, 48, and 72 h. Following the exposure time, cell viability, cell proliferation, and lactate dehydrogenase (LDH) activity were determining using colorimetric method. Also, we evaluated oxidative stress markers such as glutathione (GSH), lipid peroxidation, hydroxyl radical, hydrogen peroxide levels, and cellular enzymatic antioxidants such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione-s-transferase, and γ-glutamyl transpeptidase (γ-GT). As a result, sodium arsenite exposure in Leydig and Sertoli cells caused cellular cytotoxicity and downregulated the antioxidant defense system by inducing oxidative stress depending on concentration and time. Furthermore, this study demonstrated that when compared with Sertoli cells, Leydig cells were more affected by arsenite toxicity.

Potential protective effects of naringenin against vancomycin-induced nephrotoxicity via reduction on apoptotic and oxidative stress markers in rats.

Vancomycin (VCM), a glycopeptide antibiotic, is a drug widely used in severe infections. However, VCM induce notable nephrotoxic side effects. Naringenin (NAR) is a natural of flavonoid and are known as strongly antioxidant, nefroprotective, antiapoptotic, and anti-inflammatory. The purpose of this study was to determine the potential protective effects of NAR against VCM-induced nephrotoxicity by measuring apoptotic and oxidative stress markers and evaluating histopathological alterations in rats. For this purpose, we used male Wistar albino rats that divided into seven groups: (i) Control [saline, intraperitoneally (i.p.)], (ii) carboxymethyl cellulose (0.5% CMC, orally), (iii) VCM (400 mg/kg, i.p.), (iv) NAR100 (100 mg/kg, orally), (v) VCM + NAR25 (25 mg/kg, orally), (vi) VCM + NAR50 (50 mg/kg, orally), and (vii) VCM + NAR100 (100 mg/kg, orally) groups. VCM administration was started one day after the first treatment of NAR and continued across 7-day. Caspase-3, -8, and-9 activities and malondialdehyde (MDA) and nitric oxide (NO) levels were measured by colorimetric methods in the kidney tissues, creatinine, and blood urea nitrogen (BUN) levels were analyzed based on ELISA in serum. Caspase-3 and -8 activities, NO levels, serum creatinine and BUN levels were significantly higher in VCM group in comparison with VCM + NAR (25, 50, and 100) groups (p < 0.05). Caspase-9 activity and MDA were significantly higher in VCM group compared to VCM + NAR (25 and 50) groups (p < 0.05). Histopathological alterations in VCM group were significantly diminished by administration of NAR, especially NAR 25. In conclusion, NAR 25 and 50 mg have more potent protective effects on VCM-induced nephrotoxicity compared to NAR 100 mg.

Potential renoprotective effects of silymarin against vancomycin-induced nephrotoxicity in rats.

Silymarin (SLY), a flavonoid complex isolated from the seeds of Silybum marianum (Asteraceae), has antioxidant, anti-apoptotic, anti-inflammatory, and anti-lipid peroxidative effects. Vancomycin (VA), used for treating serious infections, has been associated with nephrotoxicity, which limits its use. Therefore, this study aimed to investigate the potential renoprotective effects of SLY on VA-induced nephrotoxicity using renal, apoptotic (caspase-3, caspase-8, and caspase-9 enzyme activities), and oxidative stress [nitric oxide (NO) and malondialdehyde (MDA)] markers; serum blood urea nitrogen (BUN) and creatinine levels; and histopathological examination. A total of 49 male Wistar albino rats were used (n = 7): control [saline, intraperitoneally (i.p.)], dimethyl sulfoxide (i.p.), VA [400 mg/(kg-day), i.p.], SLY100 [100 mg/(kg-day), i.p.], VA + SLY50 [50 mg/(kg-day), i.p.], VA + SLY100 [100 mg/(kg-day), i.p.], and VA + SLY200 [200 mg/(kg-day), i.p.]. SLY was administered once daily for 8 days. One day after the first treatment of SLY, VA administration was started and continued for 7 days. The levels of serum creatinine and BUN were evaluated using ELISA, caspase enzyme activities and levels of MDA and NO in the kidney tissues were evaluated by the colorimetric methods. The serum BUN, creatinine, NO, MDA levels, and caspase activities were significantly higher in VA group than in control (p < 0.05). However, caspase activities were significantly lower in VA + SLY200 than in VA (p < 0.05). The MDA, serum BUN, and creatinine levels were significantly lower in VA + SLY (50, 100, and 200) groups than in VA group (p < 0.05). VA + SLY200 was found to be the most effective group based on the caspase activities; MDA, NO, serum BUN, creatinine levels; and histopathological findings.

Protective effects of curcumin on biochemical and molecular changes in sodium arsenite-induced oxidative damage in embryonic fibroblast cells.

The present study was aimed at determining the oxidative damage caused by sodium arsenite in 3T3 fibroblast cells and the possible protective role of curcumin (Cur) against sodium arsenite toxicity. Embryonic fibroblast cells were exposed to sodium arsenite (0.01, 0.1, 1, and 10 µM) in the presence and absence of Cur (2.5 µM) for 24 hours. Cell viability, cytotoxicity, lipid peroxidation, hydroxyl radical, hydrogen peroxide, antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase) and expression levels of antioxidant genes (superoxide dismutase, catalase, and glutathione peroxidase) were measured in embryonic fibroblast cells. Results demonstrated that sodium arsenite directly affects antioxidant enzymes and genes in 3T3 embryonic fibroblast cells and induces oxidative damage by increasing the amount of hydrogen peroxide, hydroxyl radical, and lipid peroxidation in the cell. Furthermore, the study indicated that Cur might be a potential ameliorative antioxidant to protect the fibroblast cell toxicity induced by sodium arsenite.

Serum activities of dipeptidyl peptidase-4 and adenosine deaminase in polycystic ovary syndrome: association with obesity.

Dipeptidyl peptidase-4 (DPP-4) plays a role in metabolic and inflammatory diseases. Increased adenosine deaminase (ADA) has been suggested to induce insulin resistance and inflammation. We measured serum DPP-4 and ADA activities. Serum ADA activity was significantly higher in PCOS group (p = .006), whereas there was no difference in serum DPP-4 activity between the groups (p > .05). When the study subjects were divided into four groups in terms of obesity; an increasing trend in serum ADA activity between the groups was observed and ADA activity was significantly higher in overweight and obese patients with PCOS than nonobese controls (p = .016), there were no significant differences between the other groups (p > .05). A positive correlation was found between ADA and BMI in the whole group (p = .022). Multivariate regression analyses revealed that significant determinants were diastolic blood pressure, ADA, and the presence of PCOS for DPP-4 (R2 = 0.344, F = 9.079, p < .001); the presence of PCOS and DPP-4 for ADA (R2 = 0.123, F = 6.302, p = .003). We demonstrated increased serum ADA activity as well as its association with obesity in PCOS, while there was no change in serum DPP-4 activity in women with PCOS.

Early effect of the fear of terrorism on a hospital's emergency department use and on the incidence of cardiovascular events: A Turkish multicenter study.

BACKGROUND: To our knowledge, the early effect of the fear caused by terrorism on human health, especially its effect on the number of visits to medical emergency departments (EDs), has not yet been studied. OBJECTIVES: To observe the effect of fear from terrorist alerts on the use of EDs and on the rate of cardiovascular (CV) and/or cerebrovascular events. SETTING: In Istanbul, Turkey, there was a terror alert on the weekend of 19 and 20 March 2016. In this multicenter retrospective study, we compared the data of patients from that weekend with those from the preceding and following weekends. PATIENTS: A total of 12 324 adult patients' records were included in this study: 4562 patients in the first weekend, 3627 patients in the second, terror alert weekend, and 4135 patients in the third weekend. MEASUREMENTS: The ED, CV, and cerebrovascular incidence rates of the above three groups were compared. RESULTS: The rate of ED use was the least in the weekend of the terror alert; the highest rate occurred during the weekend prior to it (female applications decreased more [P = 0.03]). The medical center that was the farthest from the crowded central places of the city and from the place where suicide bombing occurred was less affected by the decrease in use. CONCLUSIONS: Fear associated with terrorism may affect human health indirectly by preventing patients from reaching the necessary emergency healthcare facilities. This finding may be a pathfinder to decision-makers in such extraordinary emergency conditions. Further studies are needed in this field.

Expression of prostaglandin E2 receptor subtypes in human pterygium and normal conjunctiva: immunohistochemical study.

PURPOSE: In the present study, we aimed to evaluate the expression of EP receptors in primary and recurrent human pterygium tissues. METHODS: Pterygium samples were collected from 65 patients with primary pterygium and 16 patients with recurrent pterygium. Normal conjunctival tissues were collected from nasal interpalpebral area from 17 patients without systemic and any other ocular pathology. Expression of EP receptors was evaluated by immunohistochemistry. The median value for each receptor staining score (RSS) was determined in normal conjunctival specimens. In this study, RSS of > median value was defined as positive staining or high expression and ≤ median value as negative staining or weak expression in specimens. Chi-square test was used for statistical analysis, and p value of less than 0.05 was considered significant. RESULTS: Stromal expression of EP1 was significantly higher in primary and recurrent pterygium specimens compared to normal conjunctival tissues (p = 0.007 and p = 0.002, respectively). Epithelial expressions of EP2 and EP3 were significantly lower in primary pterygium specimens compared to normal conjunctival tissues (p = 0.005 and p < 0.0001, respectively), and stromal expressions were insignificant. Stromal expression of EP4 was significantly higher in primary and recurrent pterygium specimens compared to normal conjunctival tissues (p = 0.002 and p = 0.012, respectively). CONCLUSIONS: Expression of EP receptors has been up- or downregulated in primary and recurrent pterygium tissues, and these receptors may play a role in formation and recurrence of pterygium.

Pretreatment with paricalcitol attenuates level and expression of matrix metalloproteinases in a rat model of renal ischemia-reperfusion injury
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BACKGROUND: Ischemia-reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI). The inflammatory response that drives IRI involves upregulation of matrix metalloproteinases (MMPs), which results in proteolytic degradation of renal microvascular matrix. Evidence suggests a potential protective role of active vitamin D on ischemic injury by downregulating MMPs. In the present study, we aimed to determine the expression and level of MMP-2 and MMP-9 in renal IRI model and the potential beneficial effect of paricalcitol on both level and expression of MMPs and tubular injury caused by IRI. MATERIALS AND METHODS: 20 Wistar albino rats were divided into three groups: sham-operated, ischemia-reperfusion, and paricalcitol-pretreated. IRI model was induced by bilateral clamping of renal arteries for 45 minutes followed by 24 hours of reperfusion. The analysis of serum creatinine and levels of MMPs were performed after 24 hours of IRI. The effects of paricalcitol on the quantity and expression of MMP-2 and MMP-9 in renal tubular epithelial cells were investigated by enzyme-linked immunosorbent assay and immunohistochemistry, respectively. The pathological examinations were performed to score tubular damage by light microscopy. RESULTS: Creatinine levels decreased in the paricalcitol group, although this was not proven to be significant. Rats in the paricalcitol group showed significant decrease in both level and expression of MMPs and in tubular injury scores as compared to the IRI group. CONCLUSION: Paricalcitol may attenuate renal tubular injury caused by IRI by decreasing both level and expression of MMPs. Further studies are required to investigate the interplay between activated vitamin D and MMPs in AKI.
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Circulating Th17 cytokine levels are altered in Hashimoto's thyroiditis.

The disrupted autoimmune response in Hashimoto's thyroiditis (HT) has long been considered to be dominantly T helper type 1 (Th1) mediated. Recent advances in the field of immunology have introduced a new class of effector T cells, named 'Th17', which plays important roles in autoimmune disorders once thought to be merely Th1 mediated. We aimed to examine the levels of major Th17 cytokines in patients with HT in this study. We studied serum interleukin 17 (IL-17) and interleukin 23 (IL-23) levels in 46 newly diagnosed, untreated patients with HT (40 women and 6 men, aged 40.0 ± 11.8 years) divided into euthyroid (n=22) and hypothyroid (n=24) groups and compared them with age and sex matched 26 healthy euthyroid controls without HT (21 women and 5 men; aged 36.0 ± 12.9 years). Serum IL-17 and IL-23 levels were significantly different among euthyroid and hypothyroid HT patients and controls, with highest levels obtained in the euthyroid HT group (p=0.041 for IL-17 and p<0.001 for IL-23). TSH was negatively and FT4 was positively correlated with IL-17 (p=0.016 for TSH and p=0.004 for FT4) and IL-23 (p<0.001 for TSH and p=0.003 for FT4) levels. There were no correlations between thyroid volumes calculated on thyroid ultrasonography and IL-17 (p=0.630) or IL-23 (p=0.321) levels. In conclusion, the levels of IL-17, one of the major effector cytokines of the Th17 system, and IL-23, which had been implicated in the generation, survival and expansion of Th17 cells, are altered in HT. How thyroid hormone status and the course of disease affect Th17 system in chronic autoimmune thyroiditis needs to be determined with further studies.

RANKL/Osteoprotegerin System and Bone Turnover in Hashimoto Thyroiditis.

Hypothyroidism is associated with changes in bone metabolism. The impact of hypothyroidism and the associated autoimmunity on the mediators of bone turnover in Hashimoto's thyroiditis (HT) is not known. In this study, we assessed the levels of OPG, RANKL, and IL-6 along with markers of bone formation as osteocalcin (OC) and markers of bone resorption as type 1 collagen C telopeptide (CTX) and tartrate-resistant acid phosphatase isoform 5b (TRAcP 5b) in 30 hypothyroid and 30 euthyroid premenopausal HT patients and 20 healthy premenopausal controls. We found that TRAcP 5b (p = 0.006), CTX (p = 0.01), OC (p = 0.017), and IL-6 (p < 0.001) levels were lower in the hypothyroid group compared to euthyroid HT patients and controls. OPG levels were higher (p < 0.001) and RANKL levels were lower (p = 0.021) in hypothyroid and euthyroid HT patients compared to controls. TSH was negatively correlated with IL-6 (rho = -0.434, p < 0.001), OC (rho = -0.313, p = 0.006), TRAcP 5b (rho = -0.335, p = 0.003), and positively correlated with OPG (rho = 0.248, p = 0.029). RANKL/OPG ratio was independently associated with the presence of HT. In conclusion, bone turnover is slowed down by hypothyroidism in premenopausal patients with HT. Thyroid autoimmunity might have a unique impact on OPG/RANKL levels apart from the resultant hypothyroidism.