Two Randomized Trials of Low-Dose Calcium Supplementation in Pregnancy.

BACKGROUND: The World Health Organization recommends 1500 to 2000 mg of calcium daily as supplementation, divided into three doses, for pregnant persons in populations with low dietary calcium intake in order to reduce the risk of preeclampsia. The complexity of the dosing scheme, however, has led to implementation barriers. METHODS: We conducted two independent randomized trials of calcium supplementation, in India and Tanzania, to assess the noninferiority of a 500-mg daily dose to a 1500-mg daily dose of calcium supplementation. In each trial, the two primary outcomes were preeclampsia and preterm birth, and the noninferiority margins for the relative risks were 1.54 and 1.16, respectively. RESULTS: A total of 11,000 nulliparous pregnant women were included in each trial. The cumulative incidence of preeclampsia was 3.0% in the 500-mg group and 3.6% in the 1500-mg group in the India trial (relative risk, 0.84; 95% confidence interval [CI], 0.68 to 1.03) and 3.0% and 2.7%, respectively, in the Tanzania trial (relative risk, 1.10; 95% CI, 0.88 to 1.36) - findings consistent with the noninferiority of the lower dose in both trials. The percentage of live births that were preterm was 11.4% in the 500-mg group and 12.8% in the 1500-mg group in the India trial (relative risk, 0.89; 95% CI, 0.80 to 0.98), which was within the noninferiority margin of 1.16; in the Tanzania trial, the respective percentages were 10.4% and 9.7% (relative risk, 1.07; 95% CI, 0.95 to 1.21), which exceeded the noninferiority margin. CONCLUSIONS: In these two trials, low-dose calcium supplementation was noninferior to high-dose calcium supplementation with respect to the risk of preeclampsia. It was noninferior with respect to the risk of preterm live birth in the trial in India but not in the trial in Tanzania. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT03350516; Clinical Trials Registry-India number, CTRI/2018/02/012119; and Tanzania Medicines and Medical Devices Authority Trials Registry number, TFDA0018/CTR/0010/5).

Evaluation of the efficacy of different concentrations of nano-capsules containing Talaromyces flavus with two forms of powder and suspension in reducing the incidence of cotton Verticillium wilt.

Previous domestic and foreign studies have shown the significant effect of Talaromyces flavus on growth inhibition of some important plant pathogens including Verticillium dahliae, Fusarium oxysporum f. sp. lycopersici and Fusarium oxysporum f. sp. cucumerinum. In Iran, it is necessary to produce new formulations of this fungus based on modern technologies given the importance of attracting companies producing biological control agents and transferring the technical knowledge of mass production of formulations of these agents to them. In the present study, based on the method presented in the Pesticide Research Department of the Iranian Plant Protection Research Institute, two types of T. flavus formulations in the form of nano-capsules containing Talaromyces flavus with two forms of powder and suspension were prepared using nanotechnology. In the next step, during the greenhouse examination, the efficiency of each of these new formulations in concentrations of one to five per thousand for soil addition method and concentration of five per thousand for seed impregnation method (six treatments for each of the two new formulations) was compared with the registered formulation of Talaromin in two methods of seed impregnation and soil addition with healthy control and infected control to control cotton Verticillium wilt disease, in the form of a randomized complete block design with 16 treatments and 5 replications. After statistical analysis of the data obtained by Duncan's Multiple Range Test by MS TAT C software, the results showed that in terms of disease severity among treatments with the previous formulation (Talaromin) with each of the methods of soil addition and seed impregnation, there was no statistically significant difference between nano-suspension with each of the concentrations of one, four and five per thousand by the soil addition method and nano-powder with each of the concentrations of two and three per thousand by soil addition method, and the mentioned treatments were included in one statistical group in terms of disease severity with healthy control.

Gallic acid inhibits celecoxib-induced mitochondrial permeability transition and reduces its toxicity in isolated cardiomyocytes and mitochondria.

BACKGROUND: Mitochondria are the main target organelles through which drugs and chemicals exert their toxic effect on cardiomyocytes. The mitochondria-related mechanisms of celecoxib-induced cardiotoxicity have been extensively studied. Accumulated evidence shows natural molecules targeting mitochondria have proven to be effective in preventing cardiotoxicity. PURPOSE: In the present study, we examined the ameliorative effect of gallic acid (GA) against celecoxib-induced cellular and mitochondrial toxicity in isolated cardiomyocytes and mitochondria. RESEARCH DESIGN: The isolated cardiomyocytes and mitochondria were divided into various group, namely, control, celecoxib, celecoxib + GA (10, 50, and 100 µM). Several cellular and mitochondrial parameters such as cell viability, lipid peroxidation, succinate dehydrogenase (SDH) activity, reactive oxygen species (ROS) formation, mitochondrial membrane potential (MMP) collapse, and mitochondrial swelling were assessed in isolated cardiomyocytes and mitochondria. RESULTS: Our results showed that administration of celecoxib (16 µg/ml) induced cytotoxicity and mitochondrial dysfunction at 6 h and 1 h, respectively, which is associated with lipid peroxidation intact cardiomyocytes, mitochondrial ROS formation, MMP collapse, and mitochondrial swelling. The cardiomyocytes and mitochondria treated with celecoxib + GA (10, 50, and 100 µM) significantly and dose-dependently restore the altered levels of cellular and mitochondrial parameters. CONCLUSIONS: We concluded that GA through antioxidant potential and inhibition of mitochondrial permeability transition (MPT) pore exerted ameliorative role in celecoxib-induced toxicity in isolated cardiomyocytes and mitochondria. The data of the current study suggested that GA supplementation may reduce celecoxib-induced cellular and mitochondrial toxicity during exposure and may provide a potential prophylactic and defensive candidate for coxibs-induced mitochondrial dysfunction, oxidative stress, and cardiotoxicity.

A mini-review on sofosbuvir and daclatasvir treatment in coronavirus disease 2019.

Sofosbuvir and daclatasvir have been used successfully since 2013 for hepatitis C treatment. It has been shown by different studies that sofosbuvir can inhibit RNA polymerase of other positive-strand RNA viruses including Flaviviridae and Togaviridae. Homology between hepatitis C virus RNA polymerase and severe acute respiratory syndrome coronavirus 2 has also been established. The efficacy of sofosbuvir and daclatasvir as potential choices in treating patients with coronavirus disease 2019 and their recovery can be hypothesized.

Effectiveness of Thermostable Vaccine for Newcastle Disease Produced by the Razi Institute on Backyard Poultry in Iran during 2015.

Newcastle disease causes many economic losses to the poultry industry in most countries. This disease is endemic in Iran. Backyard poultry is considered the reservoir of Newcastle virus; however, there is either no vaccination program against Newcastle, or it is performed in a restricted manner. Commercial live vaccines are inactive and sensitive to temperature; moreover, vaccine delivery to villages and remote areas requires special equipment and high cost to maintain the cold chain. This study evaluated the effectiveness of a thermostable Newcastle vaccine produced by the Razi Institute (ND.TR.IR) on the backyard poultry. In four provinces, at least 4 villages were selected as the treatment group, and the same number was selected as the control group. At least, 30 birds were sampled in each village. In each group, blood samples were collected before vaccination and 2 weeks later, and the serum titer of the samples was examined with the haemagglutination inhibition test. The arithmetic mean and standard deviation of the sample titers at the rural level were compared using paired t-test before and after vaccination in each group. Moreover, Repeated Measures ANOVA was utilized to compare the vaccinated and control groups in terms of the titer changes before and after vaccination. In this study, 584 and 389 samples were taken from the treatment (53 households in 20 villages) and control groups (33 households in 14 villages). The mean serum titer values of Newcastle were 4.51±3.03 and 6.64±2.48 in the treatment group before and after vaccination, respectively (P<0.001). The increase in mean titer of the treatment group (2.31 log) was statistically higher than that in the control group (0.66 log) (P<0.001). Out of 584 birds, 517 (88.5%) ones had titer above 3 in the second turn in the treatment group. The thermostable vaccine (ND.TR.IR) produced by the Razi institute is suitable for backyard poultry, which immunizes them against Newcastle disease. Appropriate vaccination programs for backyard poultry should be made; moreover, vaccination of backyard poultry can be effective in preventing the circulation of the field viruses.

A Feasibility Study of IMRT of Lung Cancer Using Gafchromic EBT3 Film.

BACKGROUND: Intensity modulated radiation therapy (IMRT) is an advanced method for delivery of three dimensional therapies, which provides optimal dose distribution with giving multiple nonuniform fluency to the patient. The complex dose distribution of IMRT should be checked to ensure that the accurate dose is delivered. Today, film dosimetry is a powerful tool for radiotherapy treatment Quality Assurance (QA) and a good method to verify dose distribution in phantoms. OBJECTIVE: This study aimed to evaluate the accuracy of IMRT treatment planning system, Prowess Panther® software, with Gafchromic EBT3 films in a inhomogeneity phantom. MATERIAL AND METHODS: The IMRT plan was generated by Prowess Panther® treatment planning system (TPS) version 5.2 on a inhomogeneity phantom, then it was irradiated by ONCOR linear accelerator (Linac) with 6 (MV) photon beam energy. The Gafchromic EBT3 film located between the phantom has measured the dose distribution. To compare between TPS calculated doses and film measured doses, Gamma criteria 3%/3 mm, 4%/4 mm, 5%/5 mm, 6%/6 mm and 7%/7 mm Dose Difference (DD) and Distance to Agreement (DTA), respectively were used. RESULTS: Gammas passing rates for PTV are obtained 67.5% for 3%/3mm, 78.8% for 4%/4mm, 86.3% for 5%/5mm, 91.2% for 6%/6mm and 94.3% for 7%/7mm and for organs at risk is 72.4% for 3%/3mm, 82.8% for 4%/4mm, 89.8% for 5%/5mm, 93.3% for 6%/6mm and 95.4% for 7%/7mm (respectively DD/DTA). By increasing the range of criteria the capability increased. CONCLUSION: The results show that the use of EBT3 film in a inhomogeneity phantoms allows us to evaluate the dose differences between the EBT3 measured dose distribution and TPS calculated dose distribution .Hence, a result Prowess Panther® TPS can be used for IMRT technique treatment.

MHC class II deficiency: Report of a novel mutation and special review

The MHC II deficiency is a rare autosomal recessive primary immunodeficiency syndrome with increased susceptibility to respiratory and gastrointestinal infections, failure to thrive and early mortality. This syndrome is caused by mutations in transcription regulators of the MHC II gene and results in development of blind lymphocytes due to the lack of indicatory MHC II molecules. Despite homogeneity of clinical manifestations of patients with MHC II deficiency, the genetic defects underlying this disease are heterogeneous. Herein, we report an Iranian patient with MHC II deficiency harbouring a novel mutation in RFXANK and novel misleading clinical features. He had ataxic gait and dysarthria from 30 months of age. Epidemiology, clinical and immunological features, therapeutic options and prognosis of patients with MHC II are reviewed in this paper

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Calvarium mass as the first presentation of glioblastoma multiforme: A very rare manifestation of high-grade glioma.

Glioblastoma multiforme (GBM) is a high grade glial tumor, primarily located in cerebral hemispheres. The most common clinical presentations are slowly progressive neurological deficit such as motor weakness, seizure, and headaches that last less than three months. Calvarium and extra-axial invasion are very rare and generally occur after a brain biopsy or surgery, or secondary to radiotherapy of primary intra-axial glial tumors. We report a case of GBM with calvarium involvement in a 60-year-old man who presented with a frontal bump and left-sided clumsiness. Imaging studies revealed a tumoral lesion that destroyed the frontal bone with white matter involvement of the frontal lobe and extension into the corpus callosum. Histopathological examination of intra-axial and extra-axial lesions revealed pleomorphic high-grade tumor with large areas of necrosis and hemorrhage. Immunohistochemical (IHC) studies confirmed GBM that spread directly into the dura, galea, and calvarium (positive reaction for GFAP, S-100, CD68, OLIG2, and p53). The patient was treated with radiotherapy (60Gy/30 fractions) and concomitant temozolomide. Unfortunately, the patient died seven months after the initial diagnosis.

MHC class II deficiency: Report of a novel mutation and special review.

The MHC II deficiency is a rare autosomal recessive primary immunodeficiency syndrome with increased susceptibility to respiratory and gastrointestinal infections, failure to thrive and early mortality. This syndrome is caused by mutations in transcription regulators of the MHC II gene and results in development of blind lymphocytes due to the lack of indicatory MHC II molecules. Despite homogeneity of clinical manifestations of patients with MHC II deficiency, the genetic defects underlying this disease are heterogeneous. Herein, we report an Iranian patient with MHC II deficiency harbouring a novel mutation in RFXANK and novel misleading clinical features. He had ataxic gait and dysarthria from 30 months of age. Epidemiology, clinical and immunological features, therapeutic options and prognosis of patients with MHC II are reviewed in this paper.

Effects of enriched environment on alterations in the prefrontal cortex GFAP- and S100B-immunopositive astrocytes and behavioral deficits in MK-801-treated rats.

A plethora of studies have indicated that enriched environment (EE) paradigm provokes plastic and morphological changes in astrocytes with accompanying increments of their density and positively affects the behavior of rodents. We also previously documented that EE could be employed to preclude several behavioral abnormalities, mainly cognitive deficits, attributed to postnatal N-methyl-d-aspartate (NMDA) receptor antagonist (MK-801) treatment, as a rodent model of schizophrenia (SCH) aspects. Given this, the current study quantitatively investigated the number of cells, presumed to be astrocytes, expressing two astroglia-associated proteins (S100B and glial fibrillary acidic protein (GFAP)) by immunohistochemistry in the prefrontal cortex (PFC), along with anxiety and passive avoidance (PA) learning behaviors by utilizing elevated plus maze (EPM) and shuttle-box tests, in MK-801-treated male wistar rats submitted to EE and non-EE rats. Following a treatment regime of sub-chronic MK-801 (1.0mg/kg i.p. daily for five consecutive days from postnatal day (P) 6), S-100B-positive cells and anxiety level were markedly increased, while the GFAP-positive cells and PA learning were notably attenuated. The trend of diminished GFAP-immunopositive cells and elevated S100B-immunostained cells in the PFC was reversed in the SCH-like rats by exposure of animals to EE, commencing from birth up to the time of experiments on P28-85. Additionally, EE exhibited an ameliorating effect on the behavioral abnormalities evoked by MK-801. Overall, present findings support that improper astrocyte functioning and behavioral changes, reminiscent of the many facets of SCH, occur consequential to repetitive administration of MK-801 and that raising rat pups in an EE mitigates these alterations.

Sex-specific restoration of MK-801-induced sensorimotor gating deficit by environmental enrichment.

Despite ample evidence of N-methyl-D-aspartate (NMDA) receptor dysfunction in schizophrenia, no study has addressed the effects of enriched environment (EE) on sensorimotor gating deficits induced by postnatal NMDA receptor blockade. We evaluated the effect of EE on sensorimotor gating (measured by prepulse inhibition, PPI), or on sensorimotor gating deficit induced by the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) in both sexes of Wistar rats. Rats were injected with MK-801 (1 mg/kg) on postnatal days (P) 6-10. EE was provided from birth up to the time of experiments on P28-30 or P58-60. PPI data were collected at three prepulse intensities and then averaged to yield global PPI. MK-801 treatment reduced PPI significantly in both sexes. While EE per se had no significant effect on PPI, it restored MK-801-induced PPI deficit only in male rats. An extended period of EE did not influence PPI deficit in female rats. Our results indicate that postnatal exposure to MK-801 may exert long-lasting effects on neuronal circuits underlying sensorimotor gating. Sex-specific modulation of such effects by EE suggests sexually dimorphic mechanisms are involved.

Expression Profile of Human Fc Receptor-Like 1, 2, and 4 Molecules in Peripheral Blood Mononuclear Cells of Patients with Hashimoto's Thyroiditis and Graves' Disease.

Recently identified Fc receptor-like (FCRL) molecules are new members of the immunoglobulin superfamily dominantly expressed by B cells. Although FCRL expression patterns have been studied in normal and malignant cells, their biological functions and roles remain to be clearly identified in humans. Research has particularly focused on FCRL gene polymorphisms in autoimmune diseases, however, their involvement in the pathogenesis of autoimmune diseases is an interesting field for investigation. In the present study, we have investigated the gene expression profiles of FCRL1, 2, and 4 in 2 common thyroid diseases, Hashimoto's thyroiditis (HT) and Graves' disease (GD). FCRL1, 2, and 4 expressions were determined in peripheral blood samples of 55 HT patients, 40 GD patients and equal numbers of normal subjects by quantitative real-time PCR. Our results showed downregulation of FCRL1 and upregulation of FCRL2 transcripts in both HT and GD groups compared to healthy counterparts. Overexpression of FCRL4 was observed only in GD patients compared to controls. A significant correlation was observed between all FCRL gene expression levels in HT patients. Only FCRL2 and 4 had a correlation in GD patients. In addition, FCRL1, 2, and 4 gene expressions showed no correlations with the level of anti-thyroid peroxidase antibody (anti-TPO) or anti-thyroglobulin (anti-Tg) antibody from patients' sera. In conclusion, expressions of activating or inhibitory FCRL1, 2, and 4 showed significant alterations in HT and GD patients compared to healthy subjects.

Fabricating and characterising ZnO-ZnS-Ag2S ternary nanostructures with efficient solar-light photocatalytic activity.

ZnO-ZnS-Ag2S ternary nanostructures were prepared by a simple and low-cost chemical precipitation method. The sample was characterised by X-ray diffraction, energy-dispersive X-ray, UV-Vis-NIR, Raman and Fourier transform infrared spectroscopy. Morphology of the sample was studied by scanning electron microscopy and it was observed that ZnO nanoplates were covered with ZnS and Ag2S nanoparticles. A high resolution transmission electron microscope was used to obtain further information about the crystalline domains of the prepared ternary nanostructure. The Kramers-Kronig method and classical dispersion theory were utilised to study the optical properties of the sample in the far-infrared region. Photocatalytic activity of the prepared samples was also attained in the gas-solid phase by using a solar lamp (simulating outdoor lighting) and monitoring NOx degradation.

Maternal mobile phone exposure adversely affects the electrophysiological properties of Purkinje neurons in rat offspring.

Electromagnetic field (EMF) radiations emitted from mobile phones may cause structural damage to neurons. With the increased usage of mobile phones worldwide, concerns about their possible effects on the nervous system are rising. In the present study, we aimed to elucidate the possible effects of prenatal EMF exposure on the cerebellum of offspring Wistar rats. Rats in the EMF group were exposed to 900-MHz pulse-EMF irradiation for 6h per day during all gestation period. Ten offspring per each group were evaluated for behavioral and electrophysiological evaluations. Cerebellum-related behavioral dysfunctions were analyzed using motor learning and cerebellum-dependent functional tasks (Accelerated Rotarod, Hanging and Open field tests). Whole-cell patch clamp recordings were used for electrophysiological evaluations. The results of the present study failed to show any behavioral abnormalities in rats exposed to chronic EMF radiation. However, whole-cell patch clamp recordings revealed decreased neuronal excitability of Purkinje cells in rats exposed to EMF. The most prominent changes included afterhyperpolarization amplitude, spike frequency, half width and first spike latency. In conclusion, the results of the present study show that prenatal EMF exposure results in altered electrophysiological properties of Purkinje neurons. However, these changes may not be severe enough to alter the cerebellum-dependent functional tasks.

Regulation of luteinizing hormone receptor in hippocampal neurons following different long-lasting treatments of castrated adult rats.

The aim of this study was to investigate the effects of different Luteinizing hormone (LH) and steroid hormones levels on LH receptor (LHR) expression in the hippocampal cells. Rats (24 males and 24 females) were assigned to four groups: one control and three experimental [gonadectomy (GDX), gonadectomy + gonadotropin releasing hormone analogue (GDX+GnRHa) and GDX+GnRHa+estradiol (E2) or testosterone (T)] independently for each gender. All experimental rats were gonadectomized; then GnRHa was administrated to GDX+GnRHa group, and GnRHa plus steroid hormone to GDX+GnRHa+E2 or T group in both genders for four-month. LHR mRNA expression and its protein level in hippocampal cells were measured using QRT-PCR and Western blotting. Quantification of mRNA revealed a decrease in LHR transcripts level in GDX+GnRHa group of females. A significant change was observed between GDX groups and GDX+GnRHa+E2 or T versus GDX+GnRHa group in females. High levels of LH decreased significantly the immature isoform of LHR in GDX group compared to control group in both genders, but low LH concentrations in GDX+GnRHa group induced immature LHR isoform production only in females. Therefore increased LH concentration induces production of incomplete LHR transcripts in hippocampal cells and decreases immature LHR at the protein level. This implies that LH decreases the efficiency of translation through either producing non-functional LHR molecules or preventing their translation.

The effect of Lactobacillus reuteri on bone morphogenetic protein-7 and beta transforming growth factor gene expressions in streptozotocin-induced diabetic rat's kidneys.

Diabetes mellitus is a serious health problem in the world and about 20 to 40% of the patients are being affected with diabetic nephropathy. The anti diabetic property of Lactobacillus reuteri (L. reuteri) has been reported. The study designed to investigate the effect of L. reuteri on the expression of BMP-7 and TGF-beta genes, the two basic factors involved in diabetic nephropathy. This experimental study was carried out in two months. For this goal thirty male Wistar rats with 12 weeks old and 200 +/- 50 g weight was divided into 5 groups, each consisting six rats. (1) Non diabetic, (2) Untreated diabetic, (3) Diabetic rats fed with L. reuteri, (4) Diabetic rats treated with insulin (4-5 U/kg/day), (5) Non diabetic rat fed with L. reuteri. Diabetes in the was induced single intraperitoneal (i.p.) injection of streptozotocin (50 mg kg(-1) b. wt). The L. reuteri 1 x 10(8) Colony Forming Units (CFU) were administered via oral gavages. After two months rats were anesthetized and blood samples collected. Serum nitric oxide (NO) levels were determined by a chemiluminescence method using NO analyzer and serum glucose by glucose oxidize method. The expression of BMP-7 and TGF-beta genes in the rat's kidneys were determined by real time PCR. Results showed that BMP-7 gene expression was increased in diabetic rats that fed with L. reuteri, while TGF-beta gene expressions were decreased. Histopathological study showed that administration of L. reuteri (1 x 10(8) CFU/rat/day) significantly reduced kidney fibrosis and increased meaningfully NO levels in diabetic rats fed with L. reuteri. It was concluded that L. reuteri increase BMP-7 gene expression and may prevents from renal damage by oxidative stress by increasing antioxidant capacity.

Maternal exposure to the CB1 cannabinoid agonist WIN 55212-2 produces robust changes in motor function and intrinsic electrophysiological properties of cerebellar Purkinje neurons in rat offspring.

The cerebellum, which controls coordinated and rapid movements, is a potential target for the deleterious effects of drugs of abuse including cannabis (i.e. marijuana, cannabinoids). Prenatal exposure to cannabinoids has been documented to cause abnormalities in motor and cognitive development, but the exact mechanism of this effect at the cellular level has not been fully elucidated. Previous studies indicate that cannabinoids are capable of modulating synaptic neurotransmission. In addition to altering synaptic activity, cannabinoid exposure may also change intrinsic neuronal properties. In the present study several different approaches including behavioral assays, extracellular field potential recordings and whole-cell patch clamp recordings, were used to address whether maternal exposure to the CB1 cannabinoid receptor agonist WIN 55-212-2 (WIN) affects the intrinsic electrophysiological properties of Purkinje neurons. WIN treatment of pregnant rats produced a significant decrease in the rearing frequency, total distance moved and mobility of the offspring, but significantly increased the time of the righting reflex, the grooming frequency and immobility. Neuromotor function, as assessed in the grip test and balance beam test, was also significantly impaired in prenatally WIN-treated group. Prenatal exposure to WIN increased the amplitude of population spikes (PS) recorded from the cerebellar Purkinje cell layer of offspring following synaptic blockage. WIN treatment of pregnant rats also profoundly affected the intrinsic properties of Purkinje neurons in offspring. This treatment increased the firing regularity, firing frequency, amplitude of afterhyperpolarization (AHP), the peak amplitude of action potential and the first spike latency, but decreased significantly the time to peak and duration of action potentials, the instantaneous firing frequency, the rate of rebound action potential and the voltage "sag" ratio. These results raise the possibility that maternal exposure to cannabinoids may profoundly affect the intrinsic membrane properties of cerebellar Purkinje neurons of offspring by altering the membrane excitability through modulation of intrinsic ion channels.

Profound alterations in the intrinsic excitability of cerebellar Purkinje neurons following neurotoxin 3-acetylpyridine (3-AP)-induced ataxia in rat: new insights into the role of small conductance K+ channels.

Alterations in the intrinsic properties of Purkinje cells (PCs) may contribute to the abnormal motor performance observed in ataxic rats. To investigate whether such changes in the intrinsic neuronal excitability could be attributed to the role of Ca(2+)-activated K(+) channels (K(Ca)), whole cell current clamp recordings were made from PCs in cerebellar slices of control and ataxic rats. 3-AP induced profound alterations in the intrinsic properties of PCs, as evidenced by a significant increase in both the membrane input resistance and the initial discharge frequency, along with the disruption of the firing regularity. In control PCs, the blockade of small conductance K(Ca) channels by UCL1684 resulted in a significant increase in the membrane input resistance, action potential (AP) half-width, time to peak of the AP and initial discharge frequency. SK channel blockade also significantly decreased the neuronal discharge regularity, the peak amplitude of the AP, the amplitude of the afterhyperpolarization and the spike frequency adaptation ratio. In contrast, in ataxic rats, both the firing regularity and the initial firing frequency were significantly increased by the blockade of SK channels. In conclusion, ataxia may arise from alterations in the functional contribution of SK channels, to the intrinsic properties of PCs.

Bone status in professional cyclists.

Professional cycling combines extensive endurance training with non weight-bearing exercise, two factors often associated with lower bone mineral density (BMD). Therefore BMD was measured with dual-energy x-ray absorptiometry in 30 professional road cyclists (mean (SD) age: 29.1 (3.4) years; height: 178.5 (6.7) cm; weight: 71.3 (6.1) kg; %fat mass: 9.7 (3.2)%; VO (2)max: 70.5 (5.5) ml.kg (-1).min (-1)) and in 30 young healthy males used as reference (28.6 (4.5) years; 176.5 (6.3) cm; 73.4 (7.3) kg; 20.7 (5.8)%). Adjusting for differences in age, height, fat mass, lean body mass, and calcium intake by ANCOVA, professional cyclists had similar head BMD (p=0.383) but lower total body (1.135 (0.071) vs. 1.248 (0.104) g.cm (-2); p<0.001), arms (0.903 (0.075) vs. 0.950 (0.085), p=0.028), legs (1.290 (0.112) vs. 1.479 (0.138); p<0.001), spine (0.948 (0.100) vs. 1.117 (0.147) g.cm (-2); p<0.001), pelvis (1.054 (0.084) vs. 1.244 (0.142), p<0.001), lumbar spine (1.046 (0.103) vs. 1.244 (0.167), P<0.001), and femoral neck BMD (0.900 (0.115) vs. 1.093 (0.137), p<0.001) compared to reference subjects. Professional cycling appears to negatively affect BMD in young healthy and highly active males, the femoral neck being the most affected site (-18%) in spite of the elevated muscle contractions inherent to the activity.

Low bone mineral density and calcium intake in elite cyclists.

AIM: High physical activity is associated with larger bone mineral content (BMC) and density (BMD) in young males though competitive road cyclists have been reported to have similar or lower BMD than controls. METHODS: BMC and BMD were assessed in 73 highly trained (42 professional and 31 elite amateur) road cyclists (CYCLIST; age: 25.8+/-4.3 years; height: 179.7+/-6.3 cm; weight: 71.6+/-6.3 kg; %Fat mass: 9.5+/-3 %; VO(2max): 68.5+/-5.7 mlxkg(-1)xmin(-1)) and in 30 healthy males used as reference (REF: 28.3+/-4.5 years; 176.6+/-6.2 cm; 74.5+/-8.4 kg; 21.3+/-6.1%). RESULTS: Daily calcium intake estimated from a food-questionnaire was higher in CYCLIST than in REF (942+/-374 vs 753+/-315 mgxd(-1); P=0.008). Compared to REF, CYCLIST had lower L1-L4 BMD (1.004+/-0.125 vs 1.240+/-0.163 gxcm(-2); P<0.0001) and femoral neck BMD (0.986+/-0.132 vs 1.098+/-0.137; P<0.003). In CYCLIST, daily calcium intake is correlated with total BMC and BMD (r=0.27-0.26, P=0.02) and femoral BMD (r=0.35; P=0.002). Divided by tertiles (high, medium and low Ca), CYCLIST with high Ca (1320+/-382 mgxd(-1)) had lower lumbar BMD values (-6.68%; P=0.02) and tended to have lower femoral neck BMD (-4.77%; P=0.09) and radius UD BMD (-5.9%; P=0.07) than REF. CONCLUSIONS: There was no difference between medium Ca and high Ca for any BMC or BMD parameters. Differences between low Ca and high Ca could be detected only for Total BMC (-8.4%; P=0.01), Pelvis BMD (-7.4%; P=0.01) and femoral neck BMD (-9.9%; P=0.006).