Effects of cyclic AMP and phorbol ester on transepithelial electrical resistance of Sertoli cell monolayers in two-compartment culture.

The effects of dibutyryl cyclic AMP [Bu)2cAMP) and phorbol ester (TPA), in the absence or presence of follicle-stimulating hormone (FSH) and/or testosterone, on the development of tight junctions by immature rat Sertoli cells (Sc) were investigated in vitro using the two-compartment culture system. The tight junction status was evaluated by repeated measurements of transepithelial electrical resistance (TER). Untreated cell monolayers developed stable TER of approximately 120 omega cm2 during 3 days of culture. Continuous presence of FSH (200 ng/ml) from day 1 onward significantly increased the TER up to approximately 300 omega cm2 after a transient (24-36 h) delay. The initial delay was prolonged to 3-4 days by the addition of 1-methyl-3-isobutylxanthine (MIX) (0.2 mM), whereas the subsequent increase of TER was significantly potentiated by the concomitant presence of testosterone (10 microM). Cholera toxin (CHT; 10 ng/ml) and forskolin (FR; 50 microM) mimicked these FSH effects. (Bu)2cAMP, at concentrations which maximally stimulated immunoactive inhibin secretion (100-500 microM), inhibited the initial TER increase and significantly decreased the TER level when added on days 1 and 5 of culture, respectively. In contrast, low concentrations of (Bu)2cAMP (4-20 microM) consistently stimulated the TER development, mimicking the stimulatory phase of FSH action. TPA (100 nM) alone had no effect on TER development, but potentiated the stimulatory effect of testosterone in a manner similar to FSH, CHT, FR or low concentrations of (Bu)2cAMP. These results demonstrate, for the first time, a concentration-dependent, dual effect of exogenous cAMP on the Sc function.(ABSTRACT TRUNCATED AT 250 WORDS)     

GCH1 mutation in a patient with adult-onset oromandibular dystonia

The authors report a mutation in exon 5 of GCH1 in a patient with adult-onset oromandibular dystonia and no obvious family history of dystonia. The patient responded positively to treatment with L-dopa. These findings demonstrate that GCH1 mutations must be considered even in patients with dystonic symptoms not typical of dopa-responsive dystonia.     

Vascular Structure and Function in Cancer Survivors after Hematopoietic Stem Cell Transplantation

This study examined the effects of hematopoietic cell transplantation (HCT) and associated preparative regimens on vascular structure and function. Measures of carotid artery stiffness and brachial artery endothelial-dependent dilation were obtained in patients who had survived ≥ 2 years after HCT for hematologic malignancy and were diagnosed at ≤21 years. HCT survivors (n?=?108) were examined: 66 received total body irradiation (TBI) alone or with a low-dose cranial radiation boost (TBI±LD-CRT), 19 received TBI plus high-dose cranial radiation (TBI+HD-CRT), and 23 received a chemotherapy-only preparative regimen (CHEMO). Siblings (n?=?83) were invited to participate as control subjects. Although endothelial-dependent dilation did not differ between siblings and HCT survivors, carotid cross-sectional compliance, cross-sectional distensibility, diameter compliance, and diameter distensibility were greater in siblings than HCT survivors. Comparing the HCT preparative regimens, carotid cross-sectional compliance, cross-sectional distensibility, diameter compliance, diameter distensibility, and incremental elastic modulus were significantly lower in the TBI+HD-CRT group compared with siblings or with TBI±LD-CRT and CHEMO treatment groups. Cross-sectional distensibility and diameter compliance were significantly lower in the TBI±LD-CRT group compared with siblings. TBI±LD-CRT and CHEMO groups did not differ from each other in these vascular measures. HCT preparative regimens containing TBI+HD-CRT resulted in greater arterial decrements, indicating increased risk for cardiovascular disease.     

Comparison of body fatness measurements by BMI and skinfolds vs dual energy X-ray absorptiometry and their relation to cardiovascular risk factors in adolescents

OBJECTIVE: To compare estimates of adiposity by dual emission X-ray absorptiometry (DXA), skinfolds and body mass index (BMI); and to evaluate the relation of these measures to cardiovascular risk in adolescents. DESIGN: In a cohort of adolescents participating in a longitudinal study of insulin resistance, Slaughter formulas were used to estimate adiposity from skinfolds and DXA was used to estimate adiposity as % body fat (%BF) and fat mass (FBM). BMI, blood pressure, lipids and insulin resistance were measured. SUBJECTS: Male and female, 11-17 y old (n=130). MEASUREMENTS: To compare DXA with two office-based methods of assessing fatness and cardiovascular risk. RESULTS: Slaughter estimates were highly correlated with DXA (%BF r=0.92, P=0.0001; FBM r=0.96, P=0.0001). Correlations were similar in heavy and thin children. BMI was also highly correlated with DXA (%BF r=0.85, P=0.0001; FBM r=0.95, P=0.0001), and these relations were stronger in heavy than thin children. BMI and the Slaughter formulas were similar to DXA in their relations to cardiovascular risk factors. CONCLUSIONS: Adiposity by BMI and Slaughter formulas are highly correlated with DXA and similarly related to cardiovascular risk factors. BMI is easy to obtain and is an acceptable method for initial office estimation of body fatness. BMI and skinfolds compare well with DXA in predicting adverse cardiovascular risk profile.     

Relation of circulating oxidized LDL to obesity and insulin resistance in children

Kelly AS, Jacobs DR Jr, Sinaiko AR, Moran A, Steffen LM, Steinberger J. Relation of circulating oxidized LDL to obesity and insulin resistance in children. Introduction: Circulating oxidized low‐density lipoprotein (LDL), a marker of oxidative stress, is associated with obesity, insulin resistance, metabolic syndrome, and cardiovascular disease in adults. However, little is known about its relation to insulin resistance and cardiovascular risk factors in children. The purpose of this study was to assess the relation of oxidative stress, measured by circulating oxidized LDL, with measures of adiposity and insulin resistance in children. Methods: Oxidized LDL, measures of body fatness (body mass index: BMI, percent body fat, waist circumference, percent trunk fat, abdominal visceral and subcutaneous fat), insulin resistance with euglycemic insulin clamp (Mlbm), blood pressure, and blood lipids were obtained in 78 children. Oxidized LDL was compared between normal weight children (BMI < 85th percentile) and overweight/obese children (BMI ≥ 85th percentile) and levels were evaluated for associations with body fatness and insulin resistance. Results: Oxidized LDL levels were significantly higher in overweight/obese vs. normal weight children (p < 0.0001). Oxidized LDL was significantly correlated with BMI, percent body fat, waist circumference, percent trunk fat, abdominal visceral fat, and abdominal subcutaneous fat (all p‐values <0.0001). Moreover, oxidized LDL was negatively correlated with Mlbm, even after adjustment for adiposity (p < 0.01). Conclusions: Oxidized LDL is significantly associated with adiposity and with insulin resistance, independent of body fatness, in children. Oxidative stress may be independently related to the development of insulin resistance early in life, especially in obese youth.     

Milestones in magnetic resonance imaging and transcranial sonography of movement disorders

Twenty‐five years ago, when this journal was initiated, imaging of movement disorders was in its infancy. Since that time, magnetic resonance imaging has become a standard technique that is routinely performed in patients with movement disorders in order to exclude secondary causes and in some instances to provide specific information that aids in making the diagnosis of a neurodegenerative condition. Transcranial sonography is a more recent advance and is now widely employed to aid in the diagnosis of Parkinson's disease and possibly in detecting individuals in the premotor phases of the disease. Investigations are currently under way to evaluate the value of this technique in other movement disorders. © 2011 Movement Disorder Society     

Hyperprolactinemia with prolonged amenorrhea reversed with bromocriptine in a menopausal woman

Bromocriptine treatment of the amenorrhea-galactorrhea syndrome with elevated prolactin levels is well recognized. The return of menses after 30 years in a menopausal woman with this syndrome is described. Lowering of both prolactin and follicle-stimulating hormone levels was found to occur after bromocriptine therapy.