Metabolic and polycystic ovary syndromes in indigenous South Asian women with previous gestational diabetes mellitus

OBJECTIVE: To determine the risk of metabolic syndrome (MS) and polycystic ovary syndrome (PCOS) in a cohort of indigenous South Asian women with a recent history of gestational diabetes mellitus (GDM). DESIGN: Case-control study. SETTING: Department of Obstetrics & Gynaecology, University of Colombo, Sri Lanka. SAMPLE: Two hundred and seventy-four indigenous Sri Lankan women with previous GDM and 168 ethnically matched controls. Of these, 147 with previous GDM and 67 controls not taking hormonal contraception participated in an in-depth endocrine study. METHODS: Assessing the prevalence of MS and PCOS based on clinical features, biochemistry and ovarian ultrasound examination at 3 years postpartum. MAIN OUTCOME MEASURES: Prevalence of MS and PCOS. RESULTS: Women with previous GDM and controls were studied at a mean (range) of 34.6 (13.4-84.1) and 46.5 (17.5-78) months postpartum, respectively. Those with previous GDM had a larger mean +/- 95% confidence interval waist circumference (90.9 +/- 1.3 versus 81.2 +/- 2.8 cm, P = 0.0004) and were more likely to have hypertension (17.6 versus 7.4%, P = 0.001), glucose intolerance (51.7 versus 10.4%, P = 0.00001), hypertriglyceridaemia (16.3 versus 5.9%, P = 0.02) and a lower level of high-density lipoprotein (70 versus 56.7%, P = 0.04) than the controls. Of the women who had GDM, 72 (49%) had MS, 86 (58.5%) had polycystic ovaries and 59 (40%) had PCOS, significantly more than the control women-4 (6%), 9 (13%) and 2 (3%), respectively (P = 0.00001). CONCLUSIONS: The prevalence of MS and PCOS in indigenous Sri Lankan women 3 years postpartum is significantly higher in those with previous GDM compared with ethnically matched controls. This confirms an association between GDM and subsequent PCOS and MS.     

Bacterial vaginal flora in relation to changing oestrogen levels

Hormonal changes may be important in the onset and clearance of bacterial vaginosis. We studied vaginal flora and serum oestradiol levels of 55 women at baseline and during hormonal treatment. None developed bacterial vaginosis (BV) from normal vaginal flora, 69% of women had normal flora at baseline increasing to 91% following hormonal treatment. The mean oestradiol level with BV was 39.07 ng/L compared with 176.41 ng/L with normal flora. Non-smokers had a mean oestradiol level of 173.95 ng/L compared with 118.67 ng/L in smokers. Recombinant follicle-stimulating hormone resulted in a mean oestradiol rise of 113.9 ng/L. The mean rise was 330.4 ng/L with improved vaginal flora but only 15.1 ng/L in persistently abnormal or worsening flora. A rise in oestradiol in this group of women was associated with a significant reduction of abnormal flora. Reversion from BV to normal flora was associated with a greater rise in oestradiol than where abnormal flora persisted or worsened. This study supports a possible hormonal influence in the natural history of BV. The lower oestradiol levels in smokers may help explain their increased risk of BV.     

Sexual risk behavior and pregnancy in detained adolescent females: a study in Dutch detention centers

Background  

The purpose of this study was to investigate the lifetime prevalence of teenage pregnancy in the histories of detained adolescent females and to examine the relationship between teenage pregnancy on the one hand and mental health and sexuality related characteristics on the other.     

Transport of diclofenac by breast cancer resistance protein (ABCG2) and stimulation of multidrug resistance protein 2 (ABCC2)-mediated drug transport by diclofenac and benzbromarone

Diclofenac is an important analgesic and anti-inflammatory drug, widely used for treatment of postoperative pain, rheumatoid arthritis, and chronic pain associated with cancer. Consequently, diclofenac is often used in combination regimens and undesirable drug-drug interactions may occur. Because many drug-drug interactions may occur at the level of drug transporting proteins, we studied interactions of diclofenac with apical ATP-binding cassette (ABC) multidrug efflux transporters. Using Madin-Darby canine kidney (MDCK)-II cells transfected with human P-glycoprotein (P-gp; MDR1/ABCB1), multidrug resistance protein 2 (MRP2/ABCC2), and breast cancer resistance protein (BCRP/ABCG2) and murine Bcrp1, we found that diclofenac was efficiently transported by murine Bcrp1 and moderately by human BCRP but not by P-gp or MRP2. Furthermore, in Sf9-BCRP membrane vesicles diclofenac inhibited transport of methotrexate in a concentration-dependent manner. We next used MDCK-II-MRP2 cells to study interactions of diclofenac with MRP2-mediated drug transport. Diclofenac stimulated paclitaxel, docetaxel, and saquinavir transport at only 50 microM. We further found that the uricosuric drug benzbromarone stimulated MRP2 at an even lower concentration, having maximal stimulatory activity at only 2 microM. Diclofenac and benzbromarone stimulated MRP2-mediated transport of amphipathic lipophilic drugs at 10- and 250-fold lower concentrations, respectively, than reported for other MRP2 stimulators. Because these concentrations are readily achieved in patients, adverse drug-drug interactions may occur, for example, during cancer therapy, in which drug concentrations are often critical and stimulation of elimination via MRP2 may result in suboptimal chemotherapeutic drug concentrations. Moreover, stimulation of MRP2 activity in tumors may lead to increased efflux of chemotherapeutic drugs and thereby drug resistance.     

A novel diketopiperazine improves functional recovery given after the onset of 6-OHDA-induced motor deficit in rats

Background and purpose:

Cyclo-L-glycyl-L-2-allylproline (NNZ-2591), a modified diketopiperazine, is neuroprotective and improves long-term function after hypoxic-ischaemic brain injury in rats. The present studies were designed to examine both the neuroprotective and neurotrophic actions of NNZ-2591 on neurochemical and behavioural changes in a rat model of Parkinson''s disease.

Experimental approach:

To examine its protective effect, either NNZ-2591 (20 ng·day⁻¹) or saline was given intracerebroventricularly for 3 days starting 2 h after 6-hydroxydopamine (6-OHDA) induced unilateral striatal lesion. In a subsequent experiment either NNZ-2591 (0.2, 1 and 5 mg·day⁻¹, s.c.) or saline was administered daily for 14 days starting 2 weeks after the lesion. Behavioural and neurochemical outcomes were examined using the adjusting step test and immunohistochemical staining.

Key results:

Cyclo-L-glycyl-L-2-allylproline given 2 h after the lesion reduced the degree of motor deficit compared with the saline-treated group. Delayed treatment with NNZ-2591, initiated after the onset of motor deficit, significantly improved motor function from week 7 onwards compared with the saline-treated group. Neither treatment regime altered nigrostriatal dopamine depletion. NNZ-2591 significantly enhanced the expression of doublecortin-positive neuroblasts in the sub-ventricular zone.

Conclusions and implications:

These studies reveal that early treatment with NNZ-2591 protects against the motor deficit induced by 6-OHDA and that treatment initiated after the establishment of motor impairment significantly improves long-term motor function. These effects of NNZ-2591 on functional recovery were independent of dopamine depletion and also appeared not to be symptomatic as the improved motor function was long-lasting. NNZ-2591 has potential as a therapeutic agent for neurodegenerative disorders.     

Offense related characteristics and psychosexual development of juvenile sex offenders

Objective:  

This article reports on offense related characteristics and the psychosexual development in subgroups of juvenile sex offenders as measured by the Global Assessment Instrument for Juvenile Sex Offenders (GAIJSO). The predictive validity of these characteristics for persistent (sexual) offensive behavior in subgroups of juvenile sex offenders was investigated.     

Ascorbic acid treatment, similarly to fluoxetine, reverses depressive-like behavior and brain oxidative damage induced by chronic unpredictable stress

Reactive oxygen species (ROS) have been shown to play a role in the pathophysiology of depression. Taking into account that experimental chronic unpredictable stress (CUS) induces depressive-like behavior and that ascorbic acid has antidepressant-like effect in animals, the objective of this study was to investigate the influence of ascorbic acid on depressive-like behavior induced by CUS paradigm, serum corticosterone levels and markers of oxidative stress in cerebral cortex and hippocampus of mice. Animals were submitted to CUS procedure during 14 days. From the 8th to the 14th day mice received ascorbic acid (10 mg/kg) or fluoxetine (10 mg/kg, conventional antidepressant, positive control) once a day by oral route. On 15th day behavioral and biochemical parameters were analyzed. CUS exposure caused a depressive-like behavior evidenced by the increased immobility time in the tail suspension test and decreased time in which mice spent grooming in the splash test. Depressive-like behavior induced by CUS was accompanied by a significant increased lipid peroxidation (cerebral cortex and hippocampus), decreased catalase (CAT) (cerebral cortex and hippocampus) and glutathione reductase (GR) (hippocampus) activities and reduced levels of glutathione (cerebral cortex). Repeated ascorbic acid or fluoxetine administration significantly reversed CUS-induced depressive-like behavior and oxidative damage. No alteration was observed in locomotor activity, corticosterone levels and glutathione peroxidase (GPx) activity. These findings indicate a rapid and robust effect of ascorbic acid in reversing behavioral and biochemical alterations induced by CUS in mice, suggesting that this vitamin may be an alternative approach for the management of depressive symptoms.     

Critical appraisal of the revised Ghent criteria for diagnosis of Marfan syndrome

Radonic T, de Witte P, Groenink M, de Bruin‐Bon RACM, Timmermans J, Scholte AJH, van den Berg MP, Baars MJH, van Tintelen JP, Kempers M, Zwinderman AH, Mulder BJM. Critical appraisal of the revised Ghent criteria for diagnosis of Marfan syndrome. Marfan syndrome (MFS) is a connective tissue disorder with major features in cardiovascular, ocular and skeletal systems. Recently, diagnostic criteria were revised where more weight was given to the aortic root dilatation. We applied the revised Marfan nosology in an established adult Marfan population to define practical repercussions of novel criteria for clinical practice and individual patients. Out of 180 MFS patients, in 91% (n = 164) the diagnosis of MFS remained. Out of 16 patients with rejected diagnosis, four patients were diagnosed as MASS (myopia, mitral valve prolapse, borderline non‐progressive aortic root dilatation, skeletal findings and striae) phenotype, three as ectopia lentis syndrome and in nine patients no alternative diagnosis was established. In 13 patients, the diagnosis was rejected because the Z‐score of the aortic root was <2, although the aortic diameter was larger than 40 mm in six of them. In three other patients, the diagnosis of MFS was rejected because dural ectasia was given less weight in the revised nosology. Following the revised Marfan nosology, the diagnosis of MFS was rejected in 9% of patients, mostly because of the absence of aortic root dilatation defined as Z‐score ≥2. Currently used Z‐scores seem to underestimate aortic root dilatation, especially in patients with large body surface area (BSA). We recommend re‐evaluation of criteria for aortic root involvement in adult patients with a suspected diagnosis of MFS.