Ljiljana Marina

Decreased glutathione levels and altered antioxidant defense in an animal model of schizophrenia: Long-term effects of perinatal phencyclidine administration

Perinatal phencyclidine (PCP) administration to rodents represents one of the more compelling animal models of schizophrenia. There is evidence that decreased glutathione (GSH) levels and oxidative stress mediated through free radicals in the central nervous system are involved in the pathophysiology of this disease. Limited data are available on the role of free radicals in neurotoxicity induced by NMDA-receptor antagonists. The aim of this study was to elucidate the long-term effects of perinatal phencyclidine administration on superoxide dismutase (SOD), catalase (CAT), gamma-glutamyl cisteine ligase (gamma-GCL), glutathione peroxidase (GPx), glutathione reductase (GR) and levels of lipid peroxides as well as GSH content. The Wistar rats were treated on the 2nd, 6th, 9th and 12th postnatal (PN) days with either phencyclidine (10mg/kg) or saline and sacrificed on PN70. The activities of antioxidant enzymes and level of lipid peroxides and GSH were determined in dorsolateral frontal cortex (dlFC), hippocampus, thalamus and caudate nucleus. Expression of SOD1 and SOD2 was determined by immunoblot. Region-specific changes of the measured parameters were observed. Decreased content of reduced GSH and altered activities of GR, GPx and SOD were determined in dlFC. In hippocampus, reduced GSH content and decreased activities of GPx and GR were accompanied with increased activity of gamma-GCL and increased level of lipid peroxides. gamma-GCL and GSH content were also decreased in caudate nucleus, while in thalamus major findings are increased levels of lipid peroxides and GR activity and decreased gamma-GCL activity. It can be concluded that perinatal PCP administration produces long-term alteration of antioxidant defense. Further studies are necessary in order to clarify role of redox dysregulation in the pathogenetic mechanism of schizophrenia.

Nondiabetic patients with either subclinical Cushing's or nonfunctional adrenal incidentalomas have lower insulin sensitivity than healthy controls: clinical implications.

OBJECTIVE The aim of this study was to estimate insulin sensitivity (IS) in nondiabetic patients with adrenal incidentalomas (AI): nonfunctional adrenal incidentalomas (NAI) and patients with AI and subclinical Cushings syndrome (SCS). METHODS Based on the inclusion criteria (normal fasting glucose levels, no previous history of impaired fasting glucose and/or diabetes, and no medications or concomitant relevant diseases) and the exclusion criteria (pheochromocytoma, overt hypercortisolism, hyperaldosteronism, adrenal carcinoma, metastasis of extra-adrenal tumors, extra-adrenal malignancies), 142 subjects were drawn from a series of patients with AI. The subjects were age-, sex- and body mass index (BMI)-matched: 70 with NAI (50 women and 20 men), 37 with AI and SCS (31 women and 6 men) and 35 healthy control (HC) subjects (30 women and 5 men). The oral glucose tolerance test (OGTT) and several indices of insulin sensitivity (IS) were used: homeostasis model assessment (HOMA), quantitative insulin sensitivity check index (QUICKI), triglycerides and glucose index (TyG), index of whole-body insulin sensitivity (ISI-composite) and glucose to insulin ratio (G/I). RESULTS There was a significant difference in IS between subjects with NAI and HC (HOMA, p=0.049; QUICKI, p=0.036; TyG, p=0.002; ISI-composite, p=0.024) and subjects with SCS and HC (AUC insulin, p=0.01; HOMA, p=0.003; QUICKI, p=0.042; TyG, p=0.008; ISI-composite, p=0.002). There was no difference in the tested indices of IS between subjects with NAI and SCS (p>0.05). However, subjects with SCS had a significantly higher prevalence of impaired glucose tolerance and higher area under the curve for glucose than subjects with NAI (p=0.0174). The linear regression analysis showed that 1 mg-DST cannot be used as a predictor of HOMA (R(2)=0.004, F=0.407, p=0.525). Significant relationship was found between 1 mg-DST and ISI-composite (R(2)=0.042, F=4.981, p=0.028) but this relationship was weak and standard error of estimate was high. The linear regression model also showed that ACTH cannot be used as a predictor of HOMA (R(2)=0.001, F=0.005, p=0.943) or ISI-composite (R(2)=0.015, F=1.819, p=0.187). CONCLUSIONS Insulin resistance is a major cardiovascular risk factor; therefore, the assessment of IS in patients with AI, even nonfunctional, has a valuable place in the endocrine workup of these patients.

Influence of obesity and hormone disturbances on sexuality of women in the menopause

Abstract Objective: To assess influence of obesity and hormone disturbances on sexuality in the menopause. Methods: The study included 73 menopausal women, who were divided into groups according to body mass index (BMI) ≥ 26.7 kg/m2. Anthropometric characteristics and blood pressure were measured. Blood was taken at 08:00 for hormones. All the participants filled in McCoy Female Sexual Questionnaire for the assessment of sexual life. Statistics: Student’s t-test, correlation, analysis of variance (ANOVA). Results: Follicle-stimulating hormone (FSH), luteinizing hormone (LH) and sex hormone-binding globulin (SHBG) were very significantly lower in obese compared to controls. E2 and systolic blood pressure were very significantly, while diastolic blood pressure significantly higher in obese compared to controls. Obese women had significantly decreased frequency of pain during sexual intercourse (3.48 ± 2.64 vs. 4.09 ± 2.81). Influence of age on frequency of sexual intercourse was very significant. Significant influence in interaction between BMI and age on frequency of sexual fantasies as well as significant influence of BMI on satisfaction with partner as lover is also found. Conclusion: Obesity has influence on different aspects of sexuality in the postmenopausal women. Our results suggest the need of awareness toward obesity and its impact on sexuality in the menopause.

Finger Length Ratios in Serbian Transsexuals

Atypical prenatal hormone exposure could be a factor in the development of transsexualism. There is evidence that the 2nd and 4th digit ratio (2D : 4D) associates negatively with prenatal testosterone and positively with estrogens. The aim was to assess the difference in 2D : 4D between female to male transsexuals (FMT) and male to female transsexuals (MFT) and controls. We examined 42 MFT, 38 FMT, and 45 control males and 48 control females. Precise measurements were made by X-rays at the ventral surface of both hands from the basal crease of the digit to the tip using vernier calliper. Control male and female patients had larger 2D : 4D of the right hand when compared to the left hand. Control males left hand ratio was lower than in control females left hand. There was no difference in 2D : 4D between MFT and control males. MFT showed similar 2D : 4D of the right hand with control women indicating possible influencing factor in embryogenesis and consequently finger length changes. FMT showed the lowest 2D : 4D of the left hand when compared to the control males and females. Results of our study go in favour of the biological aetiology of transsexualism.

Hot flush values of gonadotropins and estradiol in the menopause

* Accepted papers are articles in press that have gone through due peer review process and have been accepted for publication by the Editorial Board of the Serbian Archives of Medicine. They have not yet been copy edited and/or formatted in the publication house style, and the text may be changed before the final publication. Although accepted papers do not yet have all the accompanying bibliographic details available, they When the final article is assigned to volumes/issues of the journal, the Article in Press version will be removed and the final version will appear in the associated published volumes/issues of the journal. The date the article was made available online first will be carried over.

How to Prevent Cardiovascular Disorders: Influence of Gonadal Steroids on the Heart

In the ancient Rome, average life duration was 23 years; in Sweden at the end of the eighteenth century, 36.6 years for women and 33.7 for men; and in many European countries at the beginning of the twenty-first century, life expectancy was 72 and 76 years, respectively. The menopause (period in women’s life 1 year after the last menstruation until the end of life) and involutive hypoandrogenism in males (testosterone below 12 nmol/L and typical symptoms) are characterized by decrease of gonadal steroids and initiating of cardiovascular diseases (CVD). Rahman [1] found that women who entered early menopause (40–45 years) had 40% increase of heart disease. Meta-analysis confirmed these data (Table 16.1).

Endometrium receptivity in premature ovarian insufficiency – how to improve fertility rate and predict diseases?

Abstract More empathized approach is required and is obligatory to women with premature ovarian insufficiency (POI) interested for pregnancy. In order to improve fertility rate in POI patients our suggestions would be: (1) To decrease FSH value to 10–15 IU/L by increasing estrogen. Oocyte donation can be suggested after a minimum of six month interval from FSH between 10–15 IU/L and when no dominant follicles are found. (2) To perform oral glucose tolerance test (OGTT). Insulin sensitizing agents has to be included, when indicated, 3–6 month before pregnancy. (3) TSH has to be 1–2.5 mM/L during 3–6 months before pregnancy. (4) Tests for thrombophyllia (Leiden V, FII, MTHFR, PAI) have to be obligatory. They are less expensive than those repeated in vitro fertilizations. Therapy has to be included according to the indications. (5) In order to regulate disturbed immune response in POI patients with endometriosis oral contraceptive therapy is needed for atleast six months prior to the pregnancy. (5) Encourage the patients and advice them about healthy life style and eating habits. (6) Add other drugs, when they are indicated. Complex interplay between endocrine, immunological, haematological, and psychological factors are very often underdetected in POI patients. It is very important to find out the real time for oocyte donation after correcting all the disturbances, improving endometrium receptivity and reaching women’s acceptable psychological status. Untreated disturbances induce cardiovascular diseases, diabetes mellitus, thyroid diseases, coagulopathioes etc. 摘要 需要采取更有效的方法以帮助早发性卵巢功能不全（POI）妇女受孕。为了提高POI患者的生育率, 我们的建议是：（1）通过增加雌激素来降低FSH值到10-15IU/L。在至少6个月的时间内FSH介于10-15 IU/L且未发现优势卵泡, 建议接受赠卵。（2）进行口服葡萄糖耐量试验（OGTT）。在怀孕前3-6个月如果需要应用胰岛素增敏剂。（3）TSH在怀孕前3-6个月必须在1–2.5mM/L。（4）必须进行易栓症的检测（Leiden V, FII, MTHFR, PAI）。它们比重复体外受精要便宜。根据适应证进行必要的治疗。（5）为了调节POI患者因子宫内膜异位症而被干扰的免疫应答, 在怀孕前至少6个月需要口服避孕药。（5）鼓励病人并向他们建议健康的生活方式和饮食习惯。（6）如果需要应添加其他药物。在POI患者中, 内分泌、免疫、血液学和心理因素之间的复杂相互作用常常被低估。在纠正所有的干扰、改善子宫内膜容受性和达到妇女可接受的心理状态后, 及时找到卵子捐献的时间非常重要。未经治疗易诱发心血管疾病、糖尿病、甲状腺疾病和凝血功能障碍等。

Luteinizing hormone and insulin resistance in menopausal patients with adrenal incidentalomas: The cause‐effect relationship?

A high prevalence of insulin resistance (IR) has proven to manifest in patients with adrenal incidentalomas (AI). It has been demonstrated that an increase in IR is related to the size of tumourous masses; additionally, luteinizing hormone (LH)‐dependent adrenal pathologies are well documented in patients with LH‐responsive adrenal tumours occurring under conditions of physiologically elevated LH. We hypothesized that an association between LH and insulin might play a role in adrenal tumourigenesis and steroidogenesis.

Adipose Tissue and Menstrual Disturbances: Obesity Versus Anorexia Nervosa

Maintaining body homeostasis is a prerequisite for normal reproductive function, which is vital for the survival of the species and an important process of natural selection. Body weight is an independent regulator of the hypothalamic–pituitary–gonadal axis activity.

Gender-Specific Hypertension

It is well known that hypertension can be primary or secondary. However, among secondary causes of hypertension, gender-specific hypertension is one lately recognized.