Kynurenine, Kynurenic Acid, Quinolinic Acid and Interleukin-6 Levels in the Serum of Patients with Autism Spectrum Disorder.

Background and Objectives: It is known that inflammatory processes play a role in the pathogenesis of autism spectrum disorder (ASD). It is also reported that immune activation induces the kynurenine pathway (KP), as known as the tryptophan destruction pathway. In our study, we aimed to investigate whether the serum levels of KP products and interleukin (IL)-6 activating indolamine 2-3 dioxygenase (IDO) enzyme are different in healthy developing children and children with ASD. Materials and Methods: Forty-three ASD children aged 2-9 were included in this study. Forty-two healthy developing children, similar to the patient group in terms of age and gender, were selected as the control group. Serum levels of kynurenic acid, kynurenine, quinolinic acid and IL-6 were analyzed using the ELISA method. ASD severity was evaluated with the Autism Behavior Checklist (ABC). Results: The mean age of children with ASD was 42.4 ± 20.5 months, and that of healthy controls was 48.1 ± 15.8 months. While the serum levels of kynurenic acid, kynurenine and interleukin-6 were higher in the group with ASD (p < 0.05), there was no significant difference (p > 0.05) in terms of the quinolinic acid level. There was no significant difference between the ABC total and subscale scores of children with ASD and biochemical parameters (p > 0.05). Conclusions: We conclude that these biomarkers must be measured in all ASD cases. They may be important for the diagnosis of ASD.

The Comparison of the Biological Rhythms of Patients with Fibromyalgia Syndrome with Biological Rhythms of Healthy Controls.

BACKGROUND Fibromyalgia syndrome (FMS) is a rheumatic disease characterized by diffuse body pain and decreased muscle function. The aim of the present study was to compare the biological rhythms of patients with fibromyalgia syndrome with the biological rhythms of healthy controls. MATERIAL AND METHODS This was a cross-sectional, single blind, and single center case-control study. The patients with fibromyalgia were evaluated using a Fibromyalgia Impact Questionnaire (FIQ), Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) Scale, Visual Analog Scale (VAS), Pittsburg Sleep Quality Index (PSQI) and Beck Depression Inventory (BDI). RESULTS The study included 77 female patients with FMS, and 32 healthy female individuals as the control group. We found that the patients in the FMS group achieved higher scores in VAS, BDI, PSQI, and the BRIAN scale than the patients in the control group (P<0.001). An evaluation of the relationship between FMS evaluation parameters and biological rhythm scores in patients with FMS revealed a significant positive correlation between total BRAIN and VAS, FIQ, BDI, and PSQI scores. When the relationship between FMS evaluation parameters and biological rhythm scores was evaluated in patients with FMS, a significant positive correlation was found between total BRAIN and VAS, FIQ, BDI, and PSQI scores (r=0.555, P<0.001; r=0.461, P<0.001; r=0.630, P<0.001; and r=0.551, P<0.001 respectively). CONCLUSIONS We consider that an evaluation of the biological rhythm of female patients with FMS, and appropriate treatment when required, would contribute significantly to the treatment and follow-up process of the patients.

Investigation of Therapeutic Effects of Erdosteine on Polycystic Ovary Syndrome in a Rat Model.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a serious endocrine disorder. In the present study, we investigated the therapeutic effects of erdosteine in letrozole-induced PCOS in rats. METHODS: Thirty-two Wistar albino female rats were grouped as control group (C), PCOS group (PCOS), PCOS-metformin group (PCOS+MET), and PCOS-erdosteine group (PCOS+Erd). PCOS was induced by administering letrozole; such rats presented with sex hormone disorder, abnormal estrous cycles determined by daily vaginal smear, large cystic follicles, and increasing fasting insulin levels. After induction of PCOS, metformin (500 mg/kg/day) and erdosteine (100 mg/kg/day) were given orally to the treatment groups for 30 days. Serum concentrations of glucose, total cholesterol, low- and high-density lipoprotein, triglyceride, as well as the total oxidant and antioxidant status, oxidative stress index, circulating estrone (E1), estradiol (E2), testosterone, and androstenedione were evaluated. The ovaries were graded histologically. RESULTS: Weights of ovarian tissues (p < 0.05) and the number of atretic follicles (p < 0.001) and cystic follicles (p < 0.01) decreased in the PCOS+Erd group; the corpus luteum number was significantly higher in the PCOS+Erd group (p < 0.01) as compared with the PCOS group. Lipid parameters (total-C, LDL-C, and TG), E1 (estrone), E1/E2 ratio, testosterone, and androstenedione significantly decreased, while HDL-C and E2 (estradiol) significantly increased in the PCOS+Erd group as compared with the PCOS group. Moreover glucose, insulin, and HOMA-IR were reduced with treatment of erdosteine (p > 0.05, p < 0.001, and p < 0.001, respectively). CONCLUSION: It is suggested that erdosteine may be used in the treatment of PCOS as an alternative to metformin. It appears that our findings might be supported by clinical and molecular studies.

The Presence of Demodex Folliculorum in Various Obese Groups According to BMI Levels.

BACKGROUND: This study aimed to detect the presence of the parasite Demodex folliculorum (DF) in various obese groups according to BMI Levels. MATERIALS AND METHODS: A total of 182 patients (40.8 ± 14.8 years, min-max age 19 - 73 years) were enrolled in the study, of those 65 (35.7%) were female and 117 (64.3%) were male. They had previously applied to Mustafa Kemal University (Faculty of Medicine, Endocrine Outpatient Clinic) during 2012. A standardized skin surface biopsy method was used to research the existence of DF. Patients were classified into four main groups, including: obese (n = 89), overweight (n = 31), normal (n = 32), and underweight (n = 30). RESULTS: There was no significant difference between groups in terms of age and sex. The total DF positivity was 19 (21.3%) in obese patients. Among those with positive DF, the mean BMI was 35.7 ± 12.1 kg/m(2), while those with negative DF had a mean BMI of 29.2 ± 9.2 kg/m(2). There was a significant difference between two groups (P = 0.002). Also, the underweight group has significantly higher DF positivity in comparison to the normal weight group. CONCLUSION: The DF positivity was significantly higher in obese patients in accordance with the physiopathologic nature of the disease.

Histopathologic and metabolic effect of ursodeoxycholic acid treatment on PCOS rat model.

The aim of this study was to determine the effect of ursodeoxycholic acid (UDCA) treatment on a polycystic ovary syndrome (PCOS) rat model. Thirty-two female Wistar-Albino rats were randomly divided into four groups as follows - group 1: sham group (n: 8), group 2: letrozole-induced PCOS group (n: 8), group 3: letrozole-induced PCOS plus metformin-treated (500 mg/kg) group (n: 8) and group 4: letrozole-induced PCOS plus UDCA (150 mg/kg)-treated group (n: 8). Histopathologic examination of the ovaries, circulating estrone (E1), estradiol (E2), testosterone, androstenedione, glucose, insulin and lipid profiles were evaluated. Histopathologic examination results revealed that groups 3 and 4 had significantly lower cystic and atretic follicles compared to group 2. Besides, group 4 had significantly higher antral follicles than group 2 (8.5 ± 2.9 versus 5.4 ± 1.1; p: 0.001). Furthermore, total testosterone (4.9 ± 2.8 versus 8.8 ± 2.9; p= 0.004) and insulin levels were significantly lower in group 4 compared to group 2 (1.7 ± 0.08 versus 2.1 ± 0.5; p = 0.02). However, lipid parameters, E1, E2, glucose and HOMA-IR were comparable between the groups. Our study results demonstrated that UDCA therapy improves ovarian morphology and decreases total testosterone and insulin levels.

Effect of colchicine on polycystic ovary syndrome: an experimental study.

PURPOSE: To investigate whether there is any therapeutic effect of colchicine on a rat model of polycystic ovary syndrome (PCOS). METHODS: Twenty-two Wistar-Albino rats were randomly assigned into four with 8 rats in each group: control group; PCOS only group; PCOS-metformin group and PCOS-colchicine group. PCOS was induced by gavage with letrozole once daily at the concentration of 1 mg/kg orally with 21 consecutive days. After PCOS model assessment, PCOS-metformin group was received metformin orally with 500 mg/kg and PCOS-colchicine group was received colchicine orally with 1 mg/kg for the 35 day. Histopathology of ovaries, circulating estrone (E1), estradiol (E2), total testosterone, androstenedione and c-reactive protein (CRP) levels were evaluated. RESULTS: cystic and atretic follicle number was significantly decreased, but CRP and hormone parameters were not significantly changed with colchicine treatment. CONCLUSION: Colchicine has provided histopathological improvement compared with metformin in PCOS rat model.

The Effect of Coenzyme Q10 (Ubiquinone) on Random Pattern Skin Flap Survival in Rat Model.

BACKGROUND: In this study, the effect of coenzyme Q10 (CQ10) on flap survival was investigated. METHODS: Fifty Wistar Albino rats were divided into 5 groups. The survival rates of the skin flaps were assessed 10 days after complete elevation of the flaps. Regions of survival and necrosis were drawn on transparent acetate sheets and scanned into a computer. Tissue samples were assessed histopathologically after staining with hematoxylin-eosin, vascular endothelial growth factor staining and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-Biotin Nick End-labeling staining. To evaluate the antioxidant effect of CQ10; malondialdehyde, nitric oxide levels were measured. RESULTS: Viable flaps area was found higher in groups 3 and 4 as compared to groups 1, 2, and 5. In terms of vascular proliferation, elevated angiogenesis was observed in pathological specimens of groups 3 and 4 as compared to groups 1, 2, and 5. Malondialdehyde levels in groups 3 and 4 were found to be significantly decreased as compared to groups 1, 2 and 5 (P < 0.05). Moreover, serum levels of CQ10 were found significantly increased in groups 3 and 4 (P < 0.05). CONCLUSIONS: In conclusion, CQ10 significantly improves flap viability in rat model, and the highest levels of serum CQ10 can be obtained by oral administration.

Agomelatine Protection in an LPS-Induced Psychosis-Relevant Behavior Model.

BACKGROUND The aim of this study was to investigate the effect of agomelatine in a psychosis-relevant behavior model. MATERIAL AND METHODS We used 18 adult male Wistar rats in this study. Twelve rats given LPS for endotoxemia were randomly divided into 2 groups (n=6). Group I was treated with 1 mL/kg 0.9% NaCl i.p. and Group II was treated with 40 mg/kg agomelatine. Six normal rats served as the control group and were not given LPS for endotoxemia. Cylindrical steel cages containing vertical and horizontal metal bars with top cover were used. Rats were put in these cages for the purpose of orientation for 10 min. Apomorphine was given to rats removed from cages, and then they were immediately put back in the cages for the purpose of observing stereotyped conduct. Brain HVA levels and plasma TNF-a levels were evaluated in tissue homogenates using ELISA. The proportion of malondialdehyde (MDA) was measured in samples taken from plasma for detection of lipid peroxidation similar to thiobarbituric acid reactive substances. RESULTS LPS induced-plasma TNF-α, brain TNF-α, and plasma MDA levels were significantly lower in the LPS+agomelatine group compared to the LPS+saline group (p<0.05). HVA levels and stereotype scores were significantly lower in the LPS+agomelatine group compared to the LPS+saline group (p <0.001). CONCLUSIONS Agomelatine reduced TNF-α, HVA, MDA levels, and the stereotype score in relevant models of psychosis. Our results suggest that the anti-inflammatory effect of agomelatine involved oxidant cleansing properties and that its effects on the metabolism of dopamine can play an important role in the model of psychosis.

The Antipsychotic Effects of Omega-3 Fatty Acids in Rats.

BACKGROUND: In humans, omega-3 fatty acids are necessary for cell membranes, brain function and nerve transmission continuation. When animals are exposed to a new environment-or as a result of an apomorphine application that creates an agonistic effect on D1 and D2 receptors-they display behavioral reactions like rearing and stereotypy. This study aims to reveal the possible antipsychotic and oxidative effects of omega-3 fatty acids by comparing with chlorpromazine, a conventional antipsychotic drug, through evaluating the novelty-induced rearing and apomorphine-induced stereotypic behaviors, as well as malondialdehyde and glutathione levels in rats. METHODS: Twenty-eight, adult, male, Wistar rats were used in the study. Briefly, 4 groups of rats (n = 7) were administered docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA) (300 mg/kg; DHA: 120 mg/kg + EPA: 180 mg/kg intraperitoneally [IP]), DHA + EPA (150 mg/kg; DHA: 60 mg/kg + EPA: 90 mg/kg IP), chlorpromazine (1 mg/kg, IP) and isotonic saline (1 mL/kg, IP). One hour later, apomorphine (2 mg/kg, subcutaneously) was administered to each rat. After the apomorphine administration, rats were observed for stereotypic behavior. RESULTS: This study shows that omega-3 fatty acids, "similar to antipsychotics," reversed the psychotic like effects, increase of oxidants and decrease of antioxidants that are composed experimentally in rats. CONCLUSIONS: The application of omega-3 fatty acids has antipsychotic effects and causes an oxidative imbalance. This study adds new evidence to the current literature regarding the possible antipsychotic effects of omega-3 fatty acids.

''The dermal internal brassiere flap,'' a new modification of inferior pedicle breast reduction technic.

BACKGROUND: The inferior pedicle mammaplasty is particularly applied to large breasts with a long sternal notch to nipple distance. The present study reports modifications developed to solve the bottoming-out deformity, the lack of upper pole fullness and the wound healing problems seen at the reverse T-zone, known disadvantages of the inferior pedicle reduction mammaplasty, and evaluates postoperative sensation. METHODS: A total of 110 patients with a mean age of 32 underwent the same technique. In this technique, two pairs of quadrangular and triangular flaps were planned from the skin of resection sites. The triangular dermal flaps and quadrangular flaps were suspended from the periosteum of the 2nd and 4th ribs, respectively. The distance from the nipple to inframammary fold was measured at the postoperative 1st month and 1st year. In the postoperative period, a nipple-inframammary fold distance increase of over 2 cm was determined as bottoming-out deformity. Sensation evaluations were performed by subjective and objective tests. RESULTS: The mean sternal notch to nipple distance was 35.00 cm. After operation, the mean distance between the sternal notch and the nipple was 20.00 cm. NAC examination revealed normal sensation in all patients. Whereas the preoperative mean areolar threshold value was 36.70 g/mm(2), the postoperative first-year mean areolar pressure threshold value was 35.50 g/mm(2) (p < 0.0001). The preoperative mean nipple pressure threshold value was 25.30 g/mm(2), whereas the postoperative first-year mean nipple pressure threshold value was 26.00 g/mm(2) (p = 0.5471). The postoperative first-month mean sternal notch to nipple distance value of the patients was 20.00 cm, whereas the postoperative first-year mean sternal notch to nipple distance value of the patients was 20.00 cm, (p = 0.0648). The postoperative first-month mean nipple to submammary fold distance value of the patients was 10.50 cm, the postoperative first-year mean nipple to submammary fold distance value of the patients was 11.00 cm (p < 0.0001) There were no patients determined as having bottoming-out deformity. No breast asymmetry was encountered at the late follow-up period. All patients, except the scarred ones, were satisfied with the results. CONCLUSION: In this study, we achieved an internal fascial reconstruction using a pair of triangular and quadrangular dermal flaps suspended to the rib periosteum. We believe that our modifications will contribute to decreasing the disadvantages of the inferior pedicle breast reduction technique. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A novel tumor suppressor gene in basal cell carcinoma: inhibition of growth factor-2.

In loss of heterozygosity (LOH) studies at the chromosome 4q22-35 region, it was shown that the amount of deletion was high in basal cell carcinoma (BCC). It has been proposed that genes located in this chromosomal region could be tumor suppressor genes in BCC. It has been thought that deletions in the ING2 gene located in the same region can play a role in the pathophysiology of BCC and that deletions occurring in this region may influence the level of ING2 expression in BCC. Tumoral and non-tumoral tissues from 75 patients with BCC (45 men and 30 women) were included to the study. Lesions were excised by a surgical margin of 0.5 cm. After excision, RNA was isolated from tumoral and non-tumoral tissue samples. ING2 messenger RNA (mRNA) expression level was determined in tumoral and non-tumoral tissues by the real-time polymerase chain reaction (RT-PCR). It was detected that ING2 mRNA expression level decreased in tumoral tissues when compared to non-tumoral tissues from BCC patients (p = 0.0001). It was found that expression levels of this gene were comparable among patients with primary, recurrent, or multiple BCC. It is thought that ING2 gene expression level could contribute to the development of BCC but not be associated with the stage and the prognosis of the tumor.