脑室给予不同剂量的Capsazepine对LPS致大鼠发热过程的影响

目的在大鼠侧脑室内给予不同剂量的瞬时受体电位香草酸受体1(transient receptor potential vanilloid 1,TRPV1)拮抗剂Capsazepine,观察对LPS致热过程的影响。方法在侧脑室内预先给与3种剂量Capsazepine,随之腹腔给与LPS致热。在腹腔内埋植发射子遥测体温变化过程,同时应用荧光测定法检测下丘脑细胞内钙离子浓度的变化,Western blot方法检测TRPV1表达水平。结果随着Capsazepine剂量增大,LPS致大鼠发热水平升高,下丘脑细胞内钙离子浓度减少,TRPV1表达水平降低。结论 Capsazepine作用于大鼠下丘脑,可使LPS诱导的发热水平提高,此效应可能与TRPV1的作用有关。     

Magnitude and consequences of misclassification of incident hip fractures in large cohort studies: the Study of Osteoporotic Fractures and Medicare claims data

Summary

In the Study of Osteoporotic Fractures (SOF), 18.5 % of incident hip fractures identified in Medicare Fee-for-Service claims data were not reported to or confirmed by the cohort. Cognitive impairment was a modest risk factor for false-negative hip fracture ascertainment via self-report.

Introduction

Prospective cohort studies of fractures that rely on participant self-report to be the initial signal of an incident fracture could be prone to bias if a significant proportion of fractures are not self-reported.

Methods

We used data from the SOF merged with Medicare Fee-for-Service claims data to estimate the proportion of participants who had an incident hip fracture identified in Medicare claims that was either not self-reported or confirmed (by review of radiographic reports) in SOF.

Results

Between 1/1/1991 and 12/31/2007, 647 SOF participants had a hip fracture identified in Medicare claims, but 120 (18.5 %) were either not reported to or confirmed by the cohort. False-negative hip fracture ascertainment was associated with a reduced modified Mini-Mental State Exam (MMSE) score (odds ratio 1.31 per SD decrease, 95 % C.I. 1.06–1.63). Point estimates of associations of predictors of incident hip fracture were changed minimally when the misclassification of incident hip fracture status was corrected with use of claims data.

Conclusions

A substantial minority of incident hip fractures were not reported to or confirmed in the SOF. Cognitive impairment was modestly associated with false-negative hip fracture ascertainment. While there was no evidence to suggest that misclassification of incident hip fracture status resulted in biased associations of potential predictors with hip fracture in this study, false-negative incident fracture ascertainment in smaller cohort studies with limited power may increase the risk of type 2 error (not finding significant associations of predictors with incident fractures).     

Manufacturing of solid dispersions of poorly water soluble drugs by spray drying: Formulation and process considerations

Spray drying is an efficient technology for solid dispersion manufacturing since it allows extreme rapid solvent evaporation leading to fast transformation of an API-carrier solution to solid API-carrier particles. Solvent evaporation kinetics certainly contribute to formation of amorphous solid dispersions, but also other factors like the interplay between the API, carrier and solvent, the solution state of the API, formulation parameters (e.g. feed concentration or solvent type) and process parameters (e.g. drying gas flow rate or solution spray rate) will influence the final physical structure of the obtained solid dispersion particles. This review presents an overview of the interplay between manufacturing process, formulation parameters, physical structure, and performance of the solid dispersions with respect to stability and drug release characteristics.     

Ser67-phosphorylated inhibitor 1 is a potent protein phosphatase 1 inhibitor

Inhibitor 1 (I-1) is a protein inhibitor of protein phosphatase 1 (PP1), a major eukaryotic Ser/Thr phosphatase. Nonphosphorylated I-1 is inactive, whereas phosphorylated I-1 is a potent PP1 inhibitor. I-1 is phosphorylated in vivo on Thr(35) and Ser(67). Thr(35) is phosphorylated by cAMP-dependent protein kinase (A kinase), and Thr(35)-phosphorylated I-1 inhibits PP1. Until now the kinase that phosphorylates Ser(67) had not been identified and the physiological role of Ser(67) phosphorylation was unknown. In this study we detected a high level of kinase activity in brain extract when a glutathione S-transferase (GST) fusion I-1 mutant containing an Ala substituted for Thr(35) [GST-I-1(T35A)] was used as the substrate. GST-I-1(T35A) kinase and neuronal cdc2-like protein kinase (NCLK) in the brain extract could not be separated from each other by a series of sequential chromatographies. GST-I-1(T35A) kinase immunoprecipitated with anti-NCLK antibody from kinase-active column fractions. Purified NCLK-phosphorylated GST-I-1(T35A) and I-1 (0.7 mole of phosphate per mole of I-1). HPLC phosphopeptide mapping, amino acid sequencing, and site-directed mutagenesis determined that NCLK phosphorylates Ser(67) of I-1. NCLK-phosphorylated I-1 and I-1(T35A) inhibited PP1 with IC(50) values approximately 9.5 and 13. 8 nM, respectively. When compared, A kinase-phosphorylated I-1 was only approximately 1.2 times more inhibitory than NCLK-phosphorylated I-1. Our data indicate that NCLK is a potential in vivo I-1 kinase and that Thr(35) and Ser(67) phosphorylation independently activate I-1.     

EPI vaccination in Nepal

A number of surveys, small or large, have been undertaken by various agencies for coverage evaluation of immunization programs. The most commonly used design is the WHO-30 cluster sampling method. Other new methods are the Institute for Refresh Medical Statistics (IRMS) New Delhi method and the lot quality assurance sampling method. This paper describes the National Immunization Day (NID) method to evaluate the immunization coverage of the Expanded Program on Immunization (EPI) vaccines in the Sunsari district of Nepal. A total number of 3,332 respondents (69.4% females and 30.6% males) were interviewed regarding the immunization status of their children during NID. The children with complete immunization (BCG, measles and three doses of DPT and OPV) were 65.7%. The individual coverage by EPI vaccines (except OPV III and measles) was more than 80%. The result shows that there is positive relationship between immunization coverage and educational level of the respondents.     

Brain tumours in children

A 10 years old, female patient presented with symptoms of abnormal movement of the body for 5 years, deviation of mouth to left side for 12 days and difficulty in walking for 12 days. We report a very rare case of Brain Stem gliomas. Clinical and imaging findings were suggestive of Brain Stem gliomas. Key words: Brain tumors, Intracranial space occupying lesion.     

A rare case of pancreatic mediastinal pseudocyst.

Pancreatic pseudocysts are the most common cystic lesions of the pancreas, accounting for 75-80% of such masses. Pancreatic pseudocyst with mediastinal extension is a rare clinical entity and only a handful cases report on dysphagia associated with mediastinal pseudocyst formation.1 We present a case of pancreatic mediastinal pseudocyst that presented with palpitations and dysphagia. Demonstration of cystic lesion in relation to the pancreas on ultrasound and mediastinal extension of the cyst on CT suggested the diagnosis. Key words: pseudocyst, mediastinal cyst, pancreas.