Corticosteroids: way upstream

Background

In recent years, several lines of evidence have shown an increase in Parkinson's disease prevalence in rural environments where pesticides are heavily used. Although, the underlying mechanism for neuronal degeneration in sporadic PD remains unknown, mitochondrial dysfunction, oxidative stress and proteasomal dysfunction are proposed as contributing factors. In this study rats were chronically and continuously exposed to the pesticide, dichlorvos to identify the molecular mechanism of nigrostaital neuronal degeneration.

Result

Chronic dichlorvos exposure (2.50 mg/kg b.wt.s.c/daily for 12 weeks) caused nigrostriatal dopaminergic degeneration. The degenerative changes were accompanied by a loss of 60-80% of the nigral dopamine neurons and 60-70% reduction in striatal dopamine and tyrosine hydroxylase levels. Dichlorvos exposed animals also showed α -synuclein and ubiquitin positive inclusions along with swollen, dystrophic neurites and mitochondrial abnormalities like decreased complex I&IV activities, increased mitochondrial size, axonal degeneration and presence of electron dense perinuclear cytoplasmic inclusions in the substantia nigra of rats. These animals also showed evidence of oxidative stress, including increased mitochondrial ROS levels, decreased MnSOD activity and increased lipid peroxidation. Measurable impairments in neurobehavioral indices were also observed. Notable exacerbations in motor impairments, open field and catalepsy were also evident in dichlorvos exposed animals.

Conclusion

All these findings taken together indicate that chronic dichlorvos exposure may cause nigrostaital neurodegenaration and significant behavioral impairments.     

Les fractures ouvertes de jambe — La série de Clermont-Ferrand

The authors report a series of 9 cases over the period 1981–1992. Debridement was achieved in a single procedure in 44.5% of the cases, in 2 procedures in 33.3%, in more than 2 procedures in 22.2%. The closure of the wound was achieved by secondary sature in 77.8% of the cases and by a muscule flap in 22.2%. The fixation of the fracture was performed by an external fixator in all cases. Primary consolidation was obtained in 44.4% of the cases. A tibiofibular graft was needed in 4 cases. The mean time to consolidation was 23 months.     

Les fixateurs externes

The authors will highlight the advantages of external fixation in the treatment of open fractures of the leg. The first is stabilisation of the fracture site. It is obtained by using transfixion pins in multiple planes (the ideal being 2 planes between 60 and 90°). With flexible pins, stability is obtained by using multiple pins and fixing them to rings under tension. The second advantage is to allow secondary reduction and encourage consolidation by compression, distraction or dynamisation (according to Ilizarov). The third advantage is to leave the adjacent joint free which is sometimes difficult with epiphyseal and metaphyseal fractures even with the newer fixators. Preserving muscle function is sometimes difficult and depends on pin position. The fourth advantage is to be able to obtain skin cover although the use of flaps may be compromised by the pin tracks. The ideal therefore in open fractures of the leg is to fix the fracture site by pins at a distance from the fracture, to obtain skin cover after the fracture has been stabilised and then complete the assembly of the fixator.     

分叉病变支架置入术国际注册研究[BISCOR]初步结果

一、背景分叉病变血管成形术一直是个困扰医学界的难题。没有现成的严格治疗标准可以依据。大多数技术不是复杂耗时就是成功率低 ,且伴有早期和后期并发症。二、目标我们对因血管分叉病变 (侧支血管直径 >2mm)进行支架置入术的情况进行了注册研究。所用支架类型具有最佳的柔软性 ,较小外径、较小的横梁宽度和较大的侧孔 ,适于直接扩张 ,在不弯曲远端支架末端的情况下容易进入侧支血管 ,大多数情形下无需双导丝技术和对吻球囊。三、方法以调查问卷的形式收集了自 2 0 0 1年 6月 1日起在所有侧支血管直径 >2mm的分叉病变中使用Coroflex 支架…     

Preparation and Characterization of Novel Poly(methylidene Malonate 2.1.2.)-Made Nanoparticles

Poly(methylidene malonate 2.1.2.) (PMM 2.1.2.) nanoparticles were prepared in phosphate buffer through emulsion polymerization of monomeric units; the kinetics of the reaction was monitored by spectrophotometry at 400 nm. Average nanoparticle sizes, molecular weights, and biodegradability of this potential drug carrier were determined under various conditions. As previously demonstrated for other similar monomers, i.e. IHCA or IBCA, pH influenced the physico-chemical characteristics of the nanoparticles obtained. Ethanol release from the ester-bearing side chains indicated that the polymers were susceptible to hydrolysis when incubated in basic pH or in rat plasma. A secondary degradation pathway, yielding formaldehyde through a reverse Knoevenagels reaction, was minimal. Cytotoxicity studies of this new vector, in vitro, against L929 fibroblast cells demonstrated that PMM 2.1.2. nanoparticles were better tolerated than other poly(alkylcyanoacrylate) (PACA) carriers. Pharmacokinetic studies were also carried out to observe the fate of ¹⁴C-labelled PMM 2.1.2. nanoparticles after intravenous administration to rats. Forty eight hour post-injection, more than 80% of the radioactivity was recovered in urine and faeces. The body distribution of the polymer was estimated by measuring the radioactivity associated with liver, spleen, lung and kidneys. Five minutes after injection, a maximum of 24 ± 2% of the total radioactivity was detected in the liver and less than 0.4% in the spleen. The liver-associated radioactivity decreased according to a biphasic profile and less than 8% of the total radioactivity remained after 6 days.     

Diversity and functional plasticity of eukaryotic selenoproteins: identification and characterization of the SelJ family

Selenoproteins are a diverse group of proteins that contain selenocysteine (Sec), the 21st amino acid. In the genetic code, UGA serves as a termination signal and a Sec codon. This dual role has precluded the automatic annotation of selenoproteins. Recent advances in the computational identification of selenoprotein genes have provided a first glimpse of the size, functions, and phylogenetic diversity of eukaryotic selenoproteomes. Here, we describe the identification of a selenoprotein family named SelJ. In contrast to known selenoproteins, SelJ appears to be restricted to actinopterygian fishes and sea urchin, with Cys homologues only found in cnidarians. SelJ shows significant similarity to the jellyfish J1-crystallins and with them constitutes a distinct subfamily within the large family of ADP-ribosylation enzymes. Consistent with its potential role as a structural crystallin, SelJ has preferential and homogeneous expression in the eye lens in early stages of zebrafish development. A structural role for SelJ would be in contrast to the majority of known selenoenzymes. The unusually highly restricted phylogenetic distribution of SelJ, its specialization, and the comparative analysis of eukaryotic selenoproteomes reveal the diversity and functional plasticity of selenoproteins and point to a mosaic evolution of the use of Sec in proteins.     

膀胱嗜铬细胞瘤5例的术前护理

0　引言　膀胱嗜铬细胞瘤是极少见的肿瘤 ,其典型的临床症状是排尿时或排尿后出现头痛、心慌、面色苍白、多汗和血压升高 ,B超、CT和尿 VMA检查可明确诊断 ,我科共收治膀胱嗜铬细胞瘤 5例 ,就其术前护理特点总结如下 .1　临床资料　本组 5 (男 3,女 2 )例 ,年龄 2 6～ 5 6岁 .5例测尿 VMA,4例显著高于正常 ,5例均通过膀胱镜检获得定位诊断 ,3例分别位于膀胱前、顶壁 ,2例分别位于膀胱颈及三角区 ,病体最大为 7cm× 8cm× 7cm,最小为直径 2 cm,2例经活检术前确诊 .病史 2 0 d～ 1a,5例均出现排尿时头晕、心慌及血压升高 ,3例伴有无痛性肉…     

Neurosecretory granule release and endocytosis during prolonged stimulation of the rat neurohypophysis in vitro

The nature of the readily releasable pool of neurohypophysial hormone and the recapture of membrane which occurs after hormone release have been investigated using a radioimmunoassay and stereological analysis of electron micrographs. Prolonged stimulation of the rat neurohypophysis in vitro with high potassium ion concentration (high-K⁺) gives rise to hormone release which declines with time. A second increase in hormone release is observed when veratridine (an agent which increases intracellular Ca²⁺ concentration independent of K⁺-produced depolarization) is added to the high-K⁺ containing medium at the time when the decline in hormone release has occurred. There is a depletion of neurosecretory granules from the nerve endings associated with both phases of hormone release and the time course of granule release and hormone release are similar. There is no quantitative change in the microvesicle population either during the high-K⁺-or the veratridine-stimulated release. There is, however, a large increase in the volumetric density occupied by endocytotic vacuoles associated with both phases of release, and the time course of the appearance of vacuoles closely parallels that of the decrease in the granules.These findings indicate that the hormone in both the ‘readily releasable’ pool mobilized by high-K⁺ and that in the pool released by veratridine is contained within granules and that therefore the decline in hormone release during prolonged stimulation is unlikely to be due to the exhaustion of a readily releasable pool of granules defined by their position within the nerve endings. They also indicate that, in the neurohypophysis, vacuoles are the major route for membrane retrieval after hormone release and that microvesicles are unlikely to arise from the division of vacuoles.