The role of reactive oxygen species in testicular dysfunction associated with varicocele

OBJECTIVE: To determine the level of malondialdehyde (MDA), an indirect indicator of lipid peroxidation-induced injury by reactive oxygen species, in testicular biopsy specimens from infertile patients with and without varicocele. PATIENTS AND METHODS: Levels of MDA were measured in the testicular biopsy specimens from 25 infertile men (15 with varicocele, mean age 30.0 years, SD 5.7, range 23-45, and 10 without, mean age 28.7 years, SD 4.2, range 21-34). All patients were evaluated by a detailed history, physical examination, semen analysis (at least twice), serum follicle-stimulating hormone and free testosterone levels, testicular biopsy and contact imprint. Scrotal colour Doppler ultrasonography was used to confirm suspected varicocele. The level of MDA in testicular biopsy specimens was measured using the thiobarbituric acid test and the results expressed per unit tissue weight. RESULTS: As a causal factor for infertility, varicocele was identified in 15 men (60%), testicular failure in four (16%), idiopathic infertility in four (16%) and obstruction in two (8%). Of the 15 patients with varicocele, eight had bilateral varicocele and it was subclinical in three; the varicocele was grade I in four, grade II in six and grade III in two. The mean (SD) MDA level in the men with a subclinical varicocele was 15.7 (3.1) pmol/mg tissue, while in those with grade I-III varicocele it was 32.9 (12.25), 37.1 (12.25) and 86.9 (2.89) pmol/mg tissue, respectively. The levels in patients with grade III varicocele were significantly greater than in the other groups (P < 0.05). The mean MDA level in patients with or without varicocele was 38.3 (22.92) and 33.5 (18.93) pmol/mg tissue, respectively (P > 0.05). CONCLUSION: These results suggest that increasing levels of MDA are associated with higher grades of varicocele and support a possible rationale for controlled trials in infertile men with varicocele.     

Effects of <Emphasis Type="Italic">N</Emphasis>-acetylcysteine on regeneration following partial hepatectomy in rats with nonalcoholic fatty liver disease

Purpose  To investigate the effect of N-acetylcysteine on regeneration following partial hepatectomy in rats with nonalcoholic fatty liver disease (NAFLD). Methods   N-Acetylcysteine was given to seven rats with NAFLD (group 1); physiological saline was given to seven rats with NAFLD (group 2); and physiological saline was given to seven rats with a normal liver (group 3). We performed two-thirds hepatectomy in all rats and removed the remnant liver tissue 48 h later to measure the mitotic index (MI), proliferating cell nuclear antigen, glutathione (GSH), and malondialdehyde (MDA) levels. Results  Mitotic index values were significantly higher in group 1 than in groups 2 and 3, and higher in group 3 than in group 2. Proliferating cell nuclear antigen values were significantly higher in group 1 than in group 2, but no significant difference was found in comparison with group 3. Glutathione values in group 1 were significantly higher than in group 2 and MDA values in group 1 were lower than in group 2. There was no significant difference between groups 1 and 3 in GSH and MDA values, in both the two-thirds hepatectomy and 48-h tissues. Conclusions   N-Acetylcysteine enhanced regeneration after partial hepatectomy in rats with NAFLD. We believe that it exerted this effect through its influence on oxidative stress.     

General health status and intelligence scores of children of mothers with acromegaly do not differ from those of healthy mothers

Purpose

To determine the physical status and intelligence scores of children of acromegalic mothers and to compare them with those of children from mothers without acromegaly.

Methods

Six women with acromegaly who became pregnant under follow-up between 2010 and 2014 and their 16 children (group A) were assessed and compared with 16 children of healthy women (group B) and 15 children of women with prolactinoma (group C). The physical examinations of children were performed by the department of pediatric endocrinology and intelligence quotient (IQ) testing was undertaken by adult and pediatric psychiatry departments, using appropriate scales for their ages.

Results

Six of the 16 children (girls/boys: 7/9) were born after the diagnosis of acromegaly. Five of the 6 pregnancies occured when the patients were taking somatostatin analogs, none continued taking the drugs during pregnancy. The mean IQ of groups A, B, and C were 106.4 ± 12.5, 105.3 ± 12.5, and 103.2 ± 16.1 respectively (p > 0.05). The mean ages, birth percentiles, recent weight and height standard deviation scores were similar between groups (p > 0.05). Two siblings from group A and 1 child from group B were large for gestational age at birth. At recent follow-up, two children from group A were found tall for their age and one from group C was short for his age and was placed under the care of pediatric endocrinology clinic.

Conclusions

Pregnancies in acromegaly seems to be uneventful and the general health status and IQ scores of children from women with and without acromegaly were found similar.

     

Aromatase cytochrome P450 enzyme expression in human pituitary

Aromatase (P450AROM) converts testosterone to estrogen. This conversion could be important in normal physiology and estradiol-induced tumorigenesis in human pituitary. The objective of this study was to examine the expression of P450AROM in normal human pituitary and determine the gender difference. We examined aromatase expression in 19 normal human pituitary glands [13 males, 6 females, median age: 30 years (interquartile ranges, IQR: 23–63)] obtained from autopsy. We demonstrated aromatase gene expression levels by quantitative RT-PCR and aromatase protein with immunohistochemical staining in normal male and female human pituitary. Although median relative expression level of aromatase mRNA of male individuals [median ΔCt = 42.6 (IQR: 7.6–93.9)] was higher than the female individuals [median ΔCt = 3.9 (IQR:0–44.8)], we could not determine a significant gender difference in aromatase mRNA levels (p = 0.2). The difference between the aromatase protein density by immunohistochemistry was not significant between genders (p = 0.78). The aromatase levels were also not correlated with the age of the study subjects (p = 0.42 r = −0.21). The results indicate that aromatase enzyme is present in human pituitary. The amount and the density of the enzyme show a large variance among different individuals. Although higher mRNA expression was observed in male pituitary compared to female pituitary, there was no statistically significant difference for gender or age.     

Adhesion of rheumatoid peripheral blood and synovial fluid mononuclear cells to high endothelial venules of gut mucosa.

Mononuclear cells isolated from paired blood and synovial fluid of seven patients with rheumatoid arthritis showed cytoadherence to porcine Peyer's patch high endothelial venules using the Stamper-Woodruff method. A significantly greater proportion of binding was found among the synovial fluid lymphocytes. These would appear to be a population of cells that share adherence characteristics with cells known to be of gut mucosal origin, suggesting that in rheumatoid arthritis some lymphocytes derived from mucosa migrate to joints.     

Steroid pulse therapy for rheumatoid arthritis: effect on lymphocyte subsets and mononuclear cell adhesion

Eighteen patients with clinically active rheumatoid arthritis, satisfying the ARA criteria, were admitted to hospital for i.v. methylprednisolone pulse therapy. Studies of circulating lymphocyte subsets 1 h before and 24 h after pulsing were carried out together with studies on their adhesion to endothelium-containing lamina propria of porcine gut at various time points. Additionally, circulating VCAM-1 was estimated pre- and post-pulse by ELISA. We observed a marked fall (59%) in mononuclear cell adhesion 24 h post-pulse therapy (P < 0.001). Accompanying this was a significant, though slight, fall in circulating mononuclear cells (P < 0.01), mainly involving T cells. However, the degree of reduction in cell adhesion did not appear to reflect change in any particular circulating subset, but was more likely due to changes in adhesion molecule expression of several subsets. No significant change in circulating VCAM-1 was observed. It would appear, therefore, that the early beneficial effect of steroid pulsing in rheumatoid arthritis coincides with a demonstrable reduction in cell adhesion to gut. This may have implications for the pathogenesis of this disease.      

Reliability of the diagnostic tests for Cushing’s syndrome performed in a tertiary referral center

The study aimed to retrospectively evaluate the reliability of the diagnostic and location tests in Cushing’s Syndrome (CS). Eighty-seven patients diagnosed with CS between 1995 and 2007 by Endocrinology Metabolism Department of Cerrahpasa Medical School were included in the study. The control group consisted of 91 patients who presented to the outpatient clinic because of obesity. The diagnostic tests were as follows: 1 mg dexamethasone suppression test (DST), 24-h urinary free cortisol (UFC), midnight cortisol level (MCL), ACTH level and overnight 8 mg DST. The sensitivity and specificity of UFC were 81 and 66 % respectively for the cut-off point of 50 μg/day, whereas they were 64 and 76 % respectively for the cut-off point of 100 μg/day. For the cut-off value of 1.8/μg/dL for MCL and 1 mDST, the sensitivity rates were 100 and 98 %, while the specificity rates were 88 and 33 %, respectively. Among the location tests, the sensitivity and specificity of ACTH under 10 pg/mL for adrenal CS were 92 and 94 % respectively. The sensitivity and specificity of ACTH higher than 30 pg/mL for ACTH-dependent CS were 69 and 100 % respectively. The sensitivity rates of 8 mg DST for 50 and 60 % suppressions were 83 and 79 % respectively, whereas the specificity rates were 75 and 88 % respectively. 1 mg DST (cut-off <1.8 μg/dL) and UFC (50 μg/24 h) are appropriate tests for screening CS. Overnight 8 mg DST with 60 % suppression for Cushing’s Disease (CD) and ACTH levels <10 pg/mL for adrenal CS, ACTH levels >30 pg/mL for ACTH dependency were identified as the best tests for the differential diagnosis of the subtypes.