Glutathione effects on vitamin D metabolism in control and streptozotocin diabetic rat

The circulating concentration of 1,25-dihydroxycholecalciferol [1,25-(OH)₂D₃] is a physiologic index of enzymatic activity of the renal 1-hydroxylase of 25-hydroxychole-calciferol (25-OH-D₃). Hydroxylation of 25-OH-D₃ and circulating 1,25-(OH)₂D₃ are decreased in the streptozotocin diabetic rat. We previously found that activity of another redox enzyme system, cytosolic superoxide dismutase, also decreased in streptozotocin diabetes, can be restored by treatment with glutathione. In the present experiment we tested the effect of glutathione treatment on vitamin D metabolism in control and diabetic rats. Enteral glutathione increased circulating 1,25-(OH)₂D₃ and decreased 25-OH-D₃ in both control and diabetic animals. These results suggest that exogenous glutathione increases 25-OH-D₃ 1-hydroxylation both under basal conditions in the normal animal and in diabetes-induced depression.     

Deep brain stimulation for Parkinson's disease dissociates mood and motor circuits: a functional MRI case study.

Behavioral disturbances have been reported with subthalamic (STN) deep brain stimulation (DBS) treatment in Parkinson's disease (PD). We report correlative functional imaging (fMRI) of mood and motor responses induced by successive right and left DBS. A 36-year-old woman with medically refractory PD and a history of clinically remitted depression underwent uncomplicated implantation of bilateral STN DBS. High-frequency stimulation of the left electrode improved motor symptoms. Unexpectedly, right DBS alone elicited several reproducible episodes of acute depressive dysphoria. Structural and functional magnetic resonance imaging (fMRI) imaging was carried out with sequential individual electrode stimulation. The electrode on the left was within the inferior STN, whereas the right electrode was marginally superior and lateral to the intended STN target within the Fields of Forel/zona incerta. fMRI image analysis (Analysis of Functional NeuroImages, AFNI) contrasting OFF versus ON stimulation identified significant lateralized blood oxygen level-dependent (BOLD) signal changes with DBS (P < 0.001). Left DBS primarily showed changes in motor regions: increases in premotor and motor cortex, ventrolateral thalamus, putamen, and cerebellum as well as decreases in sensorimotor/supplementary motor cortex. Right DBS showed similar but less extensive change in motor regions. More prominent were the unique increases in superior prefrontal cortex, anterior cingulate (Brodmann's area [BA] 24), anterior thalamus, caudate, and brainstem, and marked widespread decreases in medial prefrontal cortex (BA 9/10). The mood disturbance resolved spontaneously in 4 weeks despite identical stimulation parameters. Transient depressive mood induced by subcortical DBS stimulation was correlated with changes in mesolimbic cortical structures. This case provides new evidence supporting cortical segregation of motor and nonmotor cortico-basal ganglionic systems that may converge in close proximity at the level of the STN and the adjacent white matter tracts (Fields of Forel/zona incerta).     

多问病人一个问题改进全科医疗中抑郁症的诊断

在全科医疗诊断抑郁症时，在原有2个问题的筛查问卷基础上再增加一个问题（病人是否要求立即帮助解决抑郁症状），可增加筛查的特异性。Arroll及其同事报告了一个横向交叉诊断可靠性研究结果。该研究包括了新西兰6个诊所中19个全科医生和1000名以上连续病人。采用两个筛查问题再加一个问题的方法，全科医生正确诊断抑郁症率达到79％，对没有抑郁症者的正确评估率为94％。     

Lack of awareness of need to clean CFC-free metered-dose inhalers.

BACKGROUND: Chlorofluorocarbon (CFC)-free metered-dose inhalers (MDIs) were introduced into Australia in 1999. Device care instructions were modified (e.g., CFC-free salbutamol inhalers to be washed weekly), but this information was not communicated directly to health care professionals. OBJECTIVE: This pilot study aimed to assess the level of awareness of device care protocols for CFC-free MDIs by patients and their pharmacists. SETTING AND DESIGN: Purchasers of CFC-free MDIs were recruited from four community pharmacies. They were interviewed regarding information sources, knowledge of propellant change, and awareness of and adherence to device care protocols. The dispensing pharmacists were interviewed for knowledge of CFC-free device care. The primary outcome variable was awareness of the relevant device care protocol. RESULTS: Thirty-nine patients were interviewed. Most patients (77%) were aware of the change to CFC-free propellant. Only nine patients (23%) were aware of the need to wash the device holder, and four patients (10% of total) complied with the specified protocol. One of the ten dispensing pharmacists could describe correct device care protocols for the CFC-free MDIs. CONCLUSIONS: Although most patients are aware that MDIs are now CFC-free, there is a low level of awareness of the device care required for these inhalers, and a very low rate of compliance with recommended practice. Although the clinical impact of failing to wash the device holder is unclear, this added instruction may have substantial implications for patient satisfaction and medication delivery. Pharmaceutical manufacturers need to highlight to health care professionals any clinically important changes in device care instructions, so that appropriate information may be passed on to patients.     

The effect of mode of delivery on neonatal mortality in very low birthweight infants born in Victoria, Australia: Caesarean section is associated with increased survival in breech-presenting, but not vertex-presenting, infants

To determine whether the improved survival of very low birthweight (VLBW) infants (< 1500 g) born in Australia can be attributed to currently high rates of Caesarean section, we examined the associations between neonatal mortality and Caesarean section in singleton liveborn VLBW infants (500–1499 g) born during 1986–93 in Victoria, Australia, using data from the Victorian Perinatal Collection Unit. The infants included in this study had completed > 23 weeks of gestation, had no life-threatening malformations and had not been delivered by a repeat Caesarean without a trial of labour (n = 2763). For infants weighing 500–749 g, 750–999 g, 1000–1249 g and 1250–1499 g, the neonatal mortality rates were 56.1%, 25.7%, 13.0% and 4.3% respectively, and the Caesarean section rates were 33.1%, 42.3%, 54.8% and 55.8%. Nearly half of these births (n = 1269) were associated with one or more obstetric indications for Caesarean section (non-breech malpresentaion, fetal distress, prolapsed cord, placenta praevia, pre-eclampsia and hypertension). Overall, the odds ratio (OR) for neonatal death associated with Caesarean section was 0.92 [95% confidence interval 0.60–1.41], after adjustment for gestational age, birthweight, year of birth, type of hospital, presence or absence of labour, presentation and obstetric indications for Caesarean section. However, when the vertex-presenting (n = 1702) and breech-presenting (n = 746) infants were considered separately, the adjusted ORs for neonatal death were 1.98 [0.96–4.10] and 0.52 [0.29–0.96] respectively. For those infants without obstetric indications for Caesarean section, the adjusted ORs for neonatal death in vertex-presenting (n = 950) and breech-presenting (n = 446) infants were 3.80 [1.11–13.0] and 0.47 [0.23–0.6]. These recent population - based data support the view that Caesarean section does not enhance the neonatal survival of VLBW babies when obstetric complications are absent.     

Glial cell line-derived neurotrophic factor (GDNF) gene expression in the human brain: A post mortem in situ hybridization study with special reference to Parkinson's disease

Summary Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor for dopaminergic neurons. Since dopaminergic neurons degenerate in Parkinson's disease, this factor is a potential therapeutical tool that may save dopaminergic neurons during the pathological process. Moreover, a reduced GDNF expression may be involved in the pathophysiology of the disease. In this study, we tested whether altered GDNF production may participate in the mechanism of cell death in this disease. GDNF gene expression was analyzed by in situ hybridization using riboprobes corresponding to a sequence of the exon 2 human GDNF gene. Experiments were performed on tissue sections of the mesencephalon and the striatum from 8 patients with Parkinson's disease and 6 control subjects matched for age at death and for post mortem delay. No labelling was observed in either group of patients. This absence of detectable expression could not be attributed to methodological problems as a positive staining was observed using the same probes for sections of astroglioma biopsies from human adults and for sections of a newborn infant brain obtained at post-mortem. These data suggest that GDNF is probably expressed at a very low level in the adult human brain and its involvement in the pathophysiology of Parkinson's disease remains to be demonstrated. GDNF may represent a powerful new therapeutic agent for Parkinson's disease, however.     

Tritiated Uridine Uptake in the Retinal Ganglion Cell Layer of the Cat during Normal Development and after Visual Cortex Ablation

The short-term metabolic response of immature retinal ganglion cells to destruction of their target cells in the dorsal lateral geniculate nucleus (dLGN) was assessed in newborn cats. Retrograde degeneration of virtually all dLGN cells was induced by ablation of the 13 contiguous areas of visual cortex on the day of birth. The metabolic response of retinal ganglion cells to this loss of target cells in dLGN was determined by exposing the ganglion cell layer to tritiated uridine, a precursor of RNA. Control measurements were made from unoperated littermates. Following sectioning and processing of the retinae from both groups of kittens for autoradiography, silver grain densities overlying the cellular profiles in the ganglion cell layer were calculated. These calculations revealed levels of uridine incorporation at Postnatal Day 4 in both groups of kittens significantly higher than at either Postnatal Day 2 or 7, but no significant differences between the two groups on any day examined. These results show that the level of RNA synthesis in retinal ganglion cells increases temporarily during the first postnatal week and that this synthesis is unaffected by the death of target cells in the dLGN. The temporary increase may be related to the establishment of synaptic connections on retinal ganglion cells by their afferent bipolar and amacrine neurons in the inner nuclear layer.