Thyroid-stimulating hormone restores bone volume, microarchitecture, and strength in aged ovariectomized rats.

We show the systemic administration of low levels of TSH increases bone volume and improves bone microarchitecture and strength in aged OVX rats. TSH's actions are mediated by its inhibitory effects on RANKL-induced osteoclast formation and bone resorption coupled with stimulatory effects on osteoblast differentiation and bone formation, suggesting TSH directly affects bone remodeling in vivo. INTRODUCTION: Thyroid-stimulating hormone (TSH) receptor haploinsufficient mice with normal circulating thyroid hormone levels have reduced bone mass, suggesting that TSH directly affects bone remodeling. We examined whether systemic TSH administration restored bone volume in aged ovariectomized (OVX) rats and influenced osteoclast formation and osteoblast differentiation in vitro. MATERIALS AND METHODS: Sprague-Dawley rats were OVX at 6 months, and TSH therapy was started immediately after surgery (prevention mode; n = 80) or 7 mo later (restoration mode; n = 152). Hind limbs and lumbar spine BMD was measured at 2- or 4-wk intervals in vivo and ex vivo on termination at 8-16 wk. Long bones were subjected to microCT, histomorphometric, and biomechanical analyses. The direct effect of TSH was examined in osteoclast and osteoblast progenitor cultures and established rat osteosarcoma-derived osteoblastic cells. Data were analyzed by ANOVA Dunnett test. RESULTS: In the prevention mode, low doses (0.1 and 0.3 microg) of native rat TSH prevented the progressive bone loss, and importantly, did not increase serum triiodothyroxine (T3) and thyroxine (T4) levels in aged OVX rats. In restoration mode, animals receiving 0.1 and 0.3 microg TSH had increased BMD (10-11%), trabecular bone volume (100-130%), trabecular number (25-40%), trabecular thickness (45-60%), cortical thickness (5-16%), mineral apposition and bone formation rate (200-300%), and enhanced mechanical strength of the femur (51-60%) compared with control OVX rats. In vitro studies suggest that TSH's action is mediated by its inhibitory effects on RANKL-induced osteoclast formation, as shown in hematopoietic stem cells cultivated from TSH-treated OVX rats. TSH also stimulates osteoblast differentiation, as shown by effects on alkaline phosphatase activity, osteocalcin expression, and mineralization rate. CONCLUSIONS: These results show for the first time that systemically administered TSH prevents bone loss and restores bone mass in aged OVX rats through both antiresorptive and anabolic effects on bone remodeling.     

Prevalence of primary late-onset focal dystonia in the Belgrade population.

The aim of this cross-sectional study was to estimate the prevalence of different subtypes of idiopathic focal dystonia in the population of Belgrade (Serbia), Yugoslavia. On December 31, 2001, the crude prevalence of all studied types of dystonia (focal, segmental, and multifocal) in Belgrade was 13.6 per 100,000 population (11.8 per 100,000 for men and 15.2 per 100,000 for women). Type-specific prevalence for focal dystonia was 11.2 per 100,000. The prevalence for cervical dystonia, blepharospasm, writer's cramp and laryngeal dystonia were 5.9 per 100,000, 1.9 per 100,000, 1.9 per 100,000, and 1.1 per 100,000, respectively.     

ACTH-producing cells of 21-day-old rat fetuses after maternal dexamethasone exposure

Adrenocorticotrophic hormone (ACTH) is essential for developmental maturation of numerous organ systems during the fetal period and for adaptation to environmental challenges. Immunocytochemical and stereological methods were used in the present study to examine the effects of dexamethasone (Dx) administration during pregnancy on fetal rat pituitary ACTH-producing cells. Doses of 0.5, 0.5 and 1.0 mg Dx/kg body weight/day were given to the dams on 3 consecutive days starting on day 16 of gestation. Morphometric analysis of the ACTH-producing cells of fetuses at 21 days of gestation revealed significant inhibition by 24% and 27%, respectively, of cell volume and cell number after maternal Dx administration, whereas the volume of cell nuclei and volume density of ACTH-stained cells were insignificantly decreased. Immunocytochemical analysis showed reduced numbers, sizes and immunopositivity of ACTH cells of 21-day-old fetuses from Dx-treated dams as compared with the control group. Maternal Dx treatment in the period of intense differentiation of the hypothalamo-hypophyseal-adrenal system had an inhibitory effect on fetal function and proliferative activity of ACTH-producing cells at 21 days of gestation. Thus, inhibition of activity of fetal ACTH-producing cells may lead to adrenal suppression, modified activity of the hypothalamo-pituitary-adrenal axis and reduced body weight possibly causing lasting functional abnormalities.     

Antibodies against annexin A5: detection pitfalls and clinical associations

Antiphospholipid syndrome (APS) has been defined as a clinical and laboratory entity. Laboratory criteria include the presence of anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LA), collectively termed as antiphospholipid antibodies (aPL). However, there has been a rising interest in antibodies against so-called protein cofactors, particularly in beta(2)-glycoprotein I. In the early 90s, annexins were considered as target antigens for aPL, but at present the exact role of antibodies against annexins (aANX) remains puzzling. This review is concerned with annexin V or annexin A5 (ANXA5), a widespread member of the annexin family, and antibodies directed towards it. We have endeavoured to summarise essential information about the detection of anti-annexin V antibodies (aANXA5) and their clinical relevance. This review has also brought together some relevant published data concerning the structure, physiological role and therapeutic potential of ANXA5.     

Morphological and morphometric characteristics of choroid plexus psammoma bodies during the human aging

Psammoma bodies are one of many choroid plexus aging changes which origin is still enigma for the scientists. During our investigation psammoma bodies were studied on 30 postmortem brains by light microscopy. They stained red with HE, and were PAS and AB PAS positive. The largest number of lamellas were stained blue with Mallory's connective tissue stain, except peripheral and next to the center lamella which stained red. During the aging, psammoma bodies became larger and more irregular, which was followed with group area and perimeter, single psammoma body average area and average perimeter, average diameter and contour index increase. Psammoma bodies mearged in the second and the third age group and mearging process led to larger and more irregular structures formation. The results of this investigation suggest that psammoma bodies are more frequent in choroid plexus of healthy older people and during the aging they obtain larger dimensions, more irregular contours, which is the result of their mutual mearging.     

Expression of Daxx sensitizes Jurkat T-cells to the apoptosis-inducing effect of chemotherapeutic agents.

BACKGROUND: The role of Daxx, in particular its ability to promote or hinder apoptosis, still remains controversial. In order to elucidate the functional relevance of Daxx in the extrinsic signaling of malignant lymphocytes Jurkat T-cells were stably transfected with a Daxx-expressing vector or with the respective Daxx-negative control vector. RESULTS: Assessing first the impact of Daxx expression on the rate of proliferation we demonstrate that overexpression of Daxx alone is not sufficient to alter proliferation in neoplastic lymphocytes. Nevertheless, expression of Daxx down-regulates anti-apoptotic Bcl-2 and up-regulates pro-apoptotic BID. In addition, Daxx-overexpressing Jurkat cells exhibit a decreased expression of the pro-caspase-8, -10, -9 and -3 and a concomitant increase of the inhibitors of apoptosis proteins survivin, XIAP, cIAP-1 and -2. We further demonstrate, that upon incubation with various chemotherapeutic agents these Daxx-induced molecular alterations sensitize Jurkat T-cells to the apoptosis-inducing effects of specific chemotherapeutic agents. CONCLUSIONS: We here outline the molecular changes elicited by Daxx on major components of the apoptotic cascade of malignant lymphocytes and demonstrate the capacity of Daxx to sensitize these cells to the apoptosis-inducing effect of various chemotherapeutic agents.     

Urinary sucrose and fructose as biomarkers for sugar consumption.

The use of 24-hour urinary sucrose and fructose as potential biomarkers for sugars consumption was investigated in two studies of 21 healthy participants living in a volunteer suite where dietary intake was known and all specimens collected. The dose-response was assessed in 12 males using a randomized crossover design of three diets containing constant levels of 63, 143, and 264 g of sugars for 10 days each. Both sugars and sucrose intake were significantly correlated with the sum of sucrose and fructose concentration in urine (0.888; P < 0.001). To assess effects with volunteers consuming their habitual varying diets, seven males and six females were fed their usual diet (assessed beforehand from four consecutive self-completed 7-day food diaries) for 30 days under controlled conditions in the volunteer suite. The mean (+/-SD) calculated total sugars intake was 202 +/- 69 g/d, 41% from sucrose. Mean (+/-SD) urinary sucrose and fructose were 36.6 +/- 16.6 and 61.8 +/- 61.3 mg/d, respectively. The sum of sucrose and fructose in urine was significantly correlated with sugars (0.841; P < 0.001) and sucrose intake (0.773; P = 0.002). In the regression, 200 g of sugars intake predicted approximately 100 mg of sucrose and fructose in urine. The correlation between individual means of randomized 16 days of sugars intake and 8 days of sugars excretion data (as used in validation studies) remained as high as that obtained with the means of 30-day measurements and the regression estimates were very similar. Twenty-four-hour urinary sucrose and fructose could be grouped into a new category of biomarkers, predictive biomarkers, that can be used in studies determining the structure of dietary measurement error in free living individuals and to relate sugars intake to disease risk.     

20 Hz membrane potential oscillations are driven by synaptic inputs in collision-detecting neurons in the frog optic tectum

Although the firing patterns of collision-detecting neurons have been described in detail in several species, the mechanisms generating responses in these neurons to visual objects on a collision course remain largely unknown. This is partly due to the limited number of intracellular recordings from such neurons, particularly in vertebrate species. By employing patch recordings in a novel integrated frog eye-tectum preparation we tested the hypothesis that OFF retinal ganglion cells were driving the responses to visual objects on a collision course in the frog optic tectum neurons. We found that the majority (22/26) of neurons in layer 6 responding to visual stimuli fitted the definition of η class collision-detectors: they readily responded to a looming stimulus imitating collision but not a receding stimulus (spike count difference ∼10 times) and the spike firing rate peaked after the stimulus visual angle reached a threshold value of ∼20–45°. In the majority of these neurons (15/22) a slow frequency oscillation (f = ∼20 Hz) of the neuronal membrane potential could be detected in the responses to a simulated collision stimulus, as well as to turning off the lights. Since OFF retinal ganglion cells could produce such oscillations, our observations are in agreement with the hypothesis that ‘collision’ responses in the frog optic tectum neurons are driven by synaptic inputs from OFF retinal ganglion cells.     

Lung Function in Gypsies in Greece

The relationship between lung function and smoking and dietary habits was examined in 121 Gypsies (62 males, 59 females) who were 14-70 y of age and who lived in Greece. All were examined clinically, after which they all participated in spirometry tests. Half of the study group had abnormal (< 80% of predicted) forced vital capacity, 36.4% had abnormal (< 80% of predicted) forced expiratory volume in 1 sec, and 5% had serious lung function disturbances (forced vital capacity < 50% of predicted). Approximately 70% of subjects were smokers, and their diets were rich in alcohol and meat; they ate very few salads and oranges. Consequently, decreased lung function might be a major health problem in Gypsies in Greece. Organization of preventive health strategies should improve the overall health of this study group.