Gamma Knife Radiosurgery Modulates micro-RNA Levels in Patients with Brain Metastasis.

BACKGROUND: The relation between micro-RNA (miRNA) modulation and immune cell activity in high-dose radiation settings is not clearly understood. OBJECTIVE: To investigate the role of stereotactic radiosurgery (SRS) in (i) the regulation of tumorsuppressor and oncogenic miRNAs as well as (ii) its effect on specific immune cell subsets in patients with metastatic brain tumors (MBT). METHODS: 9 MBT patients who underwent gamma knife-based stereotactic radiosurgery (GKRS) and 8 healthy individuals were included. Serum samples were isolated at three-time intervals (before GKRS, 1 hour, and 1-month post-GKRS). Expressions of tumor-suppressor (miR-124) and oncogenic (miR-21, miR-181a, miR-23a, miR-125b, and miR-17) miRNAs were quantified by qPCR. The lymphocytic frequency (CD3+, CD4+, CD8+, CD56+, CD19+, and CD16+) was investigated by means of flow cytometry. RESULTS: The median age was 64 years (range: 50-73 years). The median prescription dose was 20Gy (range: 16Gy-24Gy), all delivered in a single fraction. The median overall survival and progression- free survival were 7.8 months (range: 1.7-14.9 months) and 6.7 months (range: 1.1-11.5 months), respectively. Compared to healthy controls, baseline levels of oncogenic miRNAs were significantly higher, while tumor-suppressing miRNA levels remained markedly lower in MBT patients prior to GKRS. Following GKRS, there was a reduction in the expression of miR-21, miR-17, and miR-181a; simultaneously, increased expression increased of miR-124 was observed. No significant difference in immune cell subsets was noted post GKRSIn a similar fashion. We noted no correlation between patient characteristics, radiosurgery data, miRNA expression, and immune cell frequency. CONCLUSION: For this specific population with MBT disease, our data suggest that stereotactic radiosurgery may modulate the expression of circulating tumor-suppressor and oncogenic miRNAs, ultimately enhancing key anti-tumoral responses. Further evaluation with larger cohorts is warranted.

Kisspeptin: a potential therapeutic target in patients with unexplained infertility?

BACKGROUND: Kisspeptin has recently emerged as a key regulator of the reproductive axis in women. Kisspeptin, acting centrally via the kisspeptin receptor, stimulates the secretion of the gonadotrophin-releasing hormone (GnRH). AIMS: To investigate serum kisspeptin levels in infertility patients for its clinical utilisation in management and understanding of the pathophysiology of infertility in a wide array of patients. METHODS: This prospective case-control study analysis involved 92 primary infertile women with PCOS, diminished ovarian reserve (DOR), unexplained infertility (UEI), and male factor infertility between 20 and 42 years of age. Serum samples were collected between the second and fifth day of the menstrual cycle. The kisspeptin level was determined using a human kisspeptin ELISA kit according to the manufacturer's procedure. RESULTS: The median value of serum kisspeptin in the PCOS infertility group was significantly higher than that in the UEI group (p = 0.011). There was a statistically significant (p = 0.015, r = -0.182) negative weak correlation found between serum kisspeptin levels and age. The optimal cutoff value obtained to differentiate the UEI from others (PCOS infertility + DOR + male factor infertility) according to the serum kisspeptin level was 214.3 ng/L with a sensitivity of 55% and specificity of 80.9%. CONCLUSIONS: Understanding the role of kisspeptin may lead to its use as a biomarker in infertility diagnosis in UEI patients and might guide the use of kisspeptin analogues in selected patients for infertility management.

Effect of Camellia sinensis, Hypericum perforatum and Urtica dioica on kidney and liver injury induced by carbon tetrachloride in rats.

This study is aimed to investigate the effects of Camellia sinensis (CS), Hypericum perforatum (HP) and Urtica dioica (UD) in kidney and liver injury induced by carbon tetrachloride (CCl4) in rats. Highly toxic CCl4 which is used as a solvent in industry comprises experimental toxicity in rats and is widely used in hepatotoxicity and other tissue injury models. The purpose of this investigation is to monitor blood and various tissues by biochemical and histopathological analysis for preventive effects of CS, HP and UD on oxidative stress induced by administration of CCl4 and to enlighten the probable mechanism. Fifty eight rats were divided into five groups; sham group (Group 1, untreated animals), control CCl4 treated group (Group 2), HP extract-treated group (Group 3), UD extract-treated group (Group 4), CS extract-treated group (Group 5). All rats were anaesthetized at the end of the experiment and the blood was collected from each rat. Afterwards, tissue specimens were obtained. The tissue specimens were immersed in 10% formaldehyde for 24 hours. After routine tissue processing, the liver, kidney and stomach were sectioned in 5µm thickness, stained in hematoxylin and eosin. The histological study was performed by using light microscope. The serum marker enzymes were found to be significantly increased in CCl4-induced liver and kidney damage when compared with the sham group (p<0.05). However, treatment with CS, HP, and UD extracts resulted in decreased activity of serum enzymes. Malondialdehyde (MDA) levels were decreased by 20.51±0.95, 27.98±1.58, and 32.39±3.1 nmol/g wet weight protein in kidney homogenates and 16.65±1.75, 17.22±0.71 and 18.92±71 nmol/g wet weight protein in liver homogenates in CS, HP and UD treated groups, respectively. Our results have shown that additive antioxidants like CS, HP and UD will aid in diminishing these deviations in cases of liver and kidney dysfunction.

Omentin-1 level in adolescents with polycystic ovarian syndrome.

BACKGROUND: Adipokines have been suggested to play an important role in the pathogenesis of polycystic ovarian syndrome (PCOS). Omentin is an adipokine secreted essentially by visceral adipose tissue with an insulin-sensitizing effect. Insulin resistance (IR) is a common feature of PCOS, therefore the aim of this study was to investigate omentin-1 level in adolescent girls with PCOS and its relationship with IR and androgens. METHOD: A total of 41 obese girls with PCOS, and 30 age- and body mass index (BMI)-matched obese girls without PCOS were enrolled in the study. The demographic, clinic and laboratory characteristics of the groups were compared. Additionally, bivariate correlation analysis of omentin-1 with BMI standard deviation score (BMI-SDS), insulin, glucose, homeostatic model assessment of IR (HOMA-IR), total and free testosterone was performed. RESULTS: In the PCOS group HOMA-IR, free and total testosterone were higher than in the control group. Omentin-1 was lower in the PCOS group compared with the controls (55.01 ± 7.99 ng/mL vs 59.10 ± 7.02 ng/mL, respectively; P = 0.027). Omentin-1 was inversely correlated with free testosterone (r = -0.527, P = 0.030) and BMI-SDS (r = -0.241, P = 0.046) but it was not correlated with total testosterone, HOMA-IR, glucose, insulin or serum lipids. CONCLUSION: Omentin-1 was lower in obese girls with PCOS and hyperandrogenism was associated with this condition.

The evaluation of antioxidant and anticancer effects of Lepidium Sativum Subsp Spinescens L. methanol extract on cancer cells.

In recent years, there is an increased research interest for plants which are natural sources of antioxidants. Lepidium sativum Subsp spinescens L., commonly found in South West Asia, is a plant known as a healthy nutritional source containing bio-molecules that carry anti-hypertensive, hypoglycemic, anti-asthmatic, antispasmodic, hepato-protective, chemoprotective, anti-inflammatory and anti-oxidant effects. In this study, we aimed to investigate the antioxidant content and activity of Lepidium sativum Subsp spinescens L. methanol extract on cancer cells. Methanol extract of dried Lepidium sativum Subsp spinescens L. was prepared. Total amount of phenolic compounds was determined by Slinkard and Singleton method using Folin-Ciocalteu reagent. Total flavonoid amount was determined according to Zhishen method. Antioxidant activity of the extract was evaluated by CUPRAC and ABTS radical scavenging activity assays. Cytotoxic effects of the plant extract on colon and endometrium cancer cells, and human peripheral lymphocyte cells were investigated in vitro by MTT and neutral red assays. Furthermore, the plant extract was investigated for necrotic effects by LDH assay; apoptotic activity by DNA ladder fragmentation, ELISA and acridine orange/ethidium bromide staining; and genotoxic effect by comet assay methods. Methanol extract of Lepidium sativum Subsp spinescens L. was found to have a high content of phenolic and flavonoid compounds. The extract showed significant antioxidant activity and also cytotoxic activity on colon and endometrium cancer cells in a concentration-dependent manner. Apoptotic activity and genotoxic effects were significantly increased, especially with 200 µg/ml concentrations at 48 hours incubation. In conclusion, it was determined that the extract evaluated in this study could be a natural source of antioxidants. Further molecular studies explaining chemo-preventive and chemotherapeutic effects on cancer cells are required to support anticancer efficacy of the plant.

Iron deficiency anemia and levels of oxidative stress induced by treatment modality.

BACKGROUND: The effects of iron deficiency anemia (IDA) and its treatment on plasma total antioxidant capacity (TAOC) were investigated. METHODS: Sixty patients with IDA and 20 healthy controls were divided into four subgroups: an oral (per os: PO) group (n = 20); an intramuscular (IM) group (n = 20); an intravenous (IV) group (n = 20); and the control group (n = 20). Blood samples were obtained from all patients before treatment, and at 24 h, 7 days, 6 and 13 weeks after initiation of IDA therapy. RESULTS: TAOC in the IDA group was low when compared with the control group (P < 0.001). Although TAOC at 24 h in the PO group was not different from the control group, the TAOC in the IM and IV groups was relatively lower (P < 0.001). The TAOC in the PO group at 7 days, and at 6 and 13 weeks was closest to the control group level. The mean TAOC in the IV group at 13 weeks was clearly lower relative to the PO and IM groups. CONCLUSIONS: Oxidative stress was minimally induced with oral therapy, while IM and IV therapies induced higher levels of oxidative stress, in increasing order of intensity.

A defect in the antioxidant defense system in schizophrenia.

OBJECTIVES: Several oxidants and antioxidants have been evaluated in schizophrenia. However, previous studies frequently focused on individual parameters. Determination of the total oxidant and antioxidant status may be more useful. Therefore, we aimed to evaluate both plasma total oxidant status (TOS) and total antioxidant status (TAS) together with the oxidative stress index (OSI) in schizophrenia patients for the first time in the literature. METHODS: A total of 60 schizophrenia patients and 40 healthy volunteers were included in the study. The Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression-severity scale (CGI-S) were used to evaluate the severity of schizophrenia in the patients. TOS and TAS were measured in plasma and the OSI was calculated for patients and controls. RESULTS: There was no difference between patients and controls with regard to TOS, but the patients' TAS and OSI were significantly lower and higher, respectively, than those of the controls. No difference was detected between the schizophrenia subtypes or between the patients on typical or atypical antipsychotic medications or a combination of the two with regard to oxidative parameters. There was a weak to moderately significant negative correlation between TAS and total, positive and general psychopathology PANSS scores. Finally, we found a weak to moderately significant negative correlation between the CGI-S score and TOS and between the CGI-S score and TAS. CONCLUSIONS: There is a defect in the antioxidant defense system in schizophrenia. Known oxidative stress that causes oxidative cell damage and thus contributes to the pathophysiology of schizophrenia may be mainly related to this defensive defect.

Paraoxonase and arylesterase activities in fibromyalgia.

We aimed to evaluate the association of serum paraoxonase and arylesterase activities and oxidative/antioxidative status in patients with fibromyalgia. Forty-two patients with fibromyalgia and 53 healthy controls were included in the study. Serum paraoxonase and arylesterase activities were measured spectrophotometrically. Oxidative and antioxidative status were evaluated by measuring serum lipid hydroperoxide (LOOH) levels, total antioxidant status (TAS) and free sulfhydryl groups (-SH = total thiol). Lipid parameters were determined by routine laboratory methods. Serum paraoxonase and arylesterase activities, and TAS were lower in patients with fibromyalgia than in controls (P < 0.001, for all), and the -SH level was also lower in the patient group (P = 0.03). LOOH levels were higher in the patient group than in controls (P = 0.01). Our results suggest that patients with fibromyalgia were exposed to oxidative stress, and paraoxonase and arylesterase activities were decreased in these patients. Patients with fibromyalgia might be prone to development of atherosclerosis with reduced paraoxonase and arylesterase activities.

Total antioxidant response in patients with schizophrenia.

There is a large amount of convincing data demonstrating that reactive oxygen species (ROS) are involved in initiation and development of many different forms of neuropsychiatric disorders. The levels of oxidants and antioxidants in schizophrenia have been evaluated. However, measurements of total antioxidant response (TAR) were not evaluated up to now. Therefore, the objectives of this study are to investigate plasma TAR levels in schizophrenia subtypes. A total of 76 patients with schizophrenia and 25 healthy volunteers were included in the study. Positive and Negative Syndrome Scale (SANS and SAPS, respectively) were applied to patients. TAR values were determined in the plasma of normal healthy controls and patients with schizophrenia. Plasma TAR levels of each schizophrenia subtype were significantly lower than healthy controls (P < 0.01 for disorganized, residual and undifferentiated subtypes and P < 0.01 for paranoid subtype). When intragroup comparisons were performed, paranoid subtype had higher plasma TAR levels compared to other subtypes (P < 0.01). Accordingly, as a whole group, patients with schizophrenia had lower plasma TAR levels compared to controls. Plasma TAR levels were significantly and negatively correlated with SANS scores, and duration of illness was evaluated but not related to other parameters. Consequently, the present study further emphasizes the growing consideration that free radical damage may have an important etiopathogenetic role on the development of schizophrenia and suggests that decreased plasma total antioxidant levels may be related to the progression of illness.

Relationship between levels of DNA damage in lymphocytes and histopathological severity of chronic hepatitis C and various clinical forms of hepatitis B.

BACKGROUND AND AIM: A significant proportion of cancer is attributable to DNA damage caused by chronic infection and inflammation. Because both hepatitis B and C viruses (HBV and HCV, respectively) cause chronic infection and inflammatory disease, the aim of the present study was to investigate whether there is a difference in peripheral DNA damage in patients with chronic HCV compared with patients with chronic HBV; and whether there is an association in the level of peripheral DNA damage with a natural history of HBV infection. METHODS: Twenty patients with chronic hepatitis C, 20 patients with chronic hepatitis B, 11 patients with cirrhosis secondary to hepatitis B, 12 inactive hepatitis B s antigen (HBsAg) carriers and 21 healthy subjects were included in the study. The DNA damage in lymphocytes was determined using the alkaline comet assay. RESULTS: Although the chronic hepatitis C group had similar levels of DNA damage compared with patients with cirrhosis due to hepatitis B (P > 0.05) and non-cirrhotic patients with chronic hepatitis B (P > 0.05), they had higher levels of DNA damage compared with inactive HBsAg carriers (P = 0.021) and controls (P = 0.001). Hepatitis B cirrhotic patients and patients with chronic hepatitis B had significantly higher levels of DNA damage than inactive HBsAg carriers (P = 0.002 and P = 0.012, respectively) and controls (both P = 0.001). Linear logistic regression analysis showed that chronic hepatitis C and HBV-related cirrhosis were discriminators in determining DNA damage in lymphocytes (beta 0.424 and P = 0.013, beta 0.393 and P = 0.016, respectively). CONCLUSIONS: Chronic hepatitis C, based on the severity of liver disease, or cirrhosis as an advanced form of HBV infection increase DNA damage in lymphocytes independently of confounding factors such as age, gender, body mass index and smoking habits.

Increased oxidative stress in children exposed to passive smoking.

BACKGROUND: Atherogenic process is accelerated with cigarette smoke that contains many oxidants and prooxidants, capable of producing free radical and enhancing the oxidative stress. We investigated oxidative and antioxidative status of children who had been exposed to passive smoking and compared with those of not exposed group. METHODS: One hundred forty-three school children aged 9-13 years, 61 of whom had never been exposed to passive smoking, and 82 of whom had been exposed to passive smoking at least 10 cigarette per day for at least last 1 year in their house, were enrolled in this study. Total antioxidative response (TAR) was measured to determine antioxidative status of plasma, and total peroxide concentration was measured to determine oxidative status of plasma. The ratio of TAR to total peroxide was accepted as an indicator of oxidative stress. RESULTS: TAR of plasma was significantly lower in children exposed to passive smoking than in those of not exposed group (p=0.018). Mean (S.D.) values were 1.49 (0.07) and 1.52 (0.08) mmol Trolox Equiv./l, respectively. In contrary, the mean (S.D.) total peroxide level of plasma was significantly higher in children exposed to passive smoking [13.06 (2.34) micromol H2O2/l] than in not exposed group [12.24 (1.74) micromol H2O2/l] (p=0.015). The mean (S.D.) oxidative stress index (OSI) value was significantly higher in the children exposed to passive smoking [0.87 (0.15)] than in not exposed group [0.80 (0.10)] (p=0.001). CONCLUSION: Children who are exposed to passive smoking are exposed to oxidative stress, which has been implicated in the etiopathogenesis of over 100 disorders including atherosclerosis.