Mice lacking alpha-synuclein have an attenuated loss of striatal dopamine following prolonged chronic MPTP administration

The functional role of alpha-synuclein in the pathogenesis of Parkinson's disease (PD) is not fully understood. Systemic exposure of alpha-synuclein-deficient mice to neurotoxins provides a direct approach to evaluate how alpha-synuclein may mediate cell death in a common murine model of PD. To this end, wild-type and homozygous alpha-synuclein knock-out mice were treated with sub-chronic and prolonged, chronic exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In the sub-chronic model, wild-type and alpha-synuclein knock-out mice were treated for five consecutive days with MPTP (1-25 mg/kg, s.c.) or vehicle, and sacrificed 3 days following the last injection. The prolonged, chronic model consisted of two injections of MPTP (1-20 mg/kg, s.c.) per week for 5 weeks, with co-administration of probenecid (250 mg/kg, i.p.), and animals were sacrificed 3 weeks following the last injection. Sub-chronic administration of MPTP caused a dramatic, dose-dependent decrease in striatal dopamine (DA) concentrations, while an attenuated response was observed in alpha-synuclein knock-out mice. Similarly, prolonged, chronic administration of MPTP produced a dose-dependent decrease in striatal DA concentrations, and a corresponding loss of striatal vesicular monoamine transporter (VMAT-2) protein in wild-type mice. However, mice lacking alpha-synuclein had an attenuated loss of striatal DA concentrations, while no loss of striatal VMAT-2 protein was observed. Both sub-chronic and prolonged, chronic administration of MPTP caused an increase in the 3,4-dihydroxyphenylacetic acid (DOPAC) to DA ratio in wild-type mice, but not in mice lacking alpha-synuclein. Despite attenuated toxicity, elevated lactate concentrations were observed in alpha-synuclein knock-out mice following prolonged, chronic MPTP administration. The results of this study provide evidence that alpha-synuclein null mice have an attenuated response to the toxic effects of MPTP exposure, even over prolonged periods of time and that the biochemical sequela of a protracted insult to nigrostriatal DA neurons are distinct between mice with and without alpha-synuclein expression.     

D2 lymphadenectomy in the management of gastric cancer

Background Gastric carcinoma is a significant cause of death in Ireland. Surgery offers the best option of cure, but the five-year survival following resection remains dismal at 10–15%. Experience from Japan and from some Western units suggest that an extended (D2) lymphadenectomy in association with gastrectomy increases the prospect of cure, but concern about the morbidity and mortality of this operation and lack of evidence from randomised studies has limited its acceptance. Aims This study reports the experience of a specialist upper gastrointestinal unit with D2 gastrectomy in a four-year audit. Methods Sixty-two resections were performed for gastric cancer. Results Nineteen patients were deemed unsuitable for the D2 procedure and underwent a more limited lymphadenectomy (DO or D1). Forty-three patients underwent D2 resection, 12 with an oesophagogastrectomy, 22 with total gastrectomy and nine with a sub-total distal resection. Eight patients undergoing D2 resection had extended resections, five with splenectomy and three with a distal pancreatectomy. Post-operative complications occurred in 31% of patients. Thirty-day and 90-day mortality were zero. Median survival was 822 days in the D2 group (range 120–1,320). Conclusions These results show that a D2 gastrectomy can be performed with a low morbidity and mortality and a median survival of greater than two years.     

ENDOTHELIAL CELL CULTURE AND SEEDING OF PROSTHETIC VASCULAR GRAFTS: AN EXPERIMENTAL STUDY

Current synthetic vascular prostheses do not acquire lining of vascular endothelium in humans or dogs. Endothelial seeding of vascular grafts has been proposed as a means of reducing the thrombogenicity of these grafts. We examined feasibility of cultivating endothelial cells (EC) by tissue culture technique and their subsequent seeding onto small diameter polytetra fluoroethylene (PTFE) grafts. Twenty adult dogs underwent common carotid artery interposition with 4 mm PTFE grafts. Ten dogs received seeded and the remaining ten received unseeded grafts. Grafts were removed at 4 and 12 weeks and their gross/morphological features compared. Cumulative patency rates for seeded grafts were 70% as compared to unseeded ones 30%. Seeded grafts were completely surfaced with a mono-layer of endothelium by 4 weeks. Small graft patency appears to be related to the establishment of an endothelial surface, the development of which is clearly facilitated by seeding with autogenous endothelium.KEY WORDS: Endothelial cell seeding, Vascular grafts     

Cloning of cDNA coding for connective tissue activating peptide III from a human platelet-derived lambda gt11 expression library

We report here the cloning of the cDNA coding for platelet connective tissue-activating peptide-III (CTAP-III) from a lambda gt11 expression library prepared using messenger RNA (mRNA) isolated from human platelets. The open reading frame of the clone coded for a protein with 128 amino acid residues. Since the precursor of CTAP-III, platelet basic protein (PBP is 94 amino acids long, the 5'-translated region of the cDNA codes for a leader sequence 34 amino acids long. This leader sequence, like the sequence of mature CTAP-III, shows significant homology to the sequence of platelet factor 4 (PF4), the only other platelet specific alpha-granule protein cloned until now, from a human erythroleukemic (HEL) cell line-derived cDNA library. These leader sequences are probably critical for targeting such proteins to the alpha-granule. Northern blot hybridization with platelet and megakaryocyte mRNA shows a single species mRNA of approximately 0.8 kb, suggesting that the corresponding cDNA is full length. The cloning of platelet specific CTAP-III provides additional evidence for the platelet specificity of the cDNA library used.     

Noradrenergic innervation to the VMN or MPN is not necessary for lordosis.

The purpose of the present study was to determine the importance of noradrenergic neurons terminating in the ventromedial nucleus (VMN) and medial preoptic nucleus (MPN) of the hypothalamus for lordosis behavior in ovariectomized, estrogen/progesterone-treated female rats. Seven days following bilateral injections of the noradrenergic neurotoxin 5-amino-2,4-dihydroxy-alpha-methylphenylethylamine (5-ADMP) into the ventral noradrenergic bundle (VNAB), norepinephrine (NE) concentrations (ng/mg protein) were reduced to 30-35% of control in the VMN and MPN. 5-ADMP-induced lesions of the VNAB also reduced lordosis quotients in these animals, and this effect was reversed by intracerebral ventricular administration of the alpha 1-adrenergic receptor agonist phenylephrine. These results indicate that neurotoxin-induced disruption of noradrenergic neurons in the VNAB is associated with a deficit in sexual receptivity in female rats. To determine if the reduction in sexual receptivity following 5-ADMP-induced lesions of the VNAB resulted from loss of noradrenergic neuronal projections specifically to the VMN or MPN, lordosis quotients were determined in ovariectomized, estrogen/progesterone-treated rats in which noradrenergic terminals in these hypothalamic nuclei were selectively lesioned. Injection of 5-ADMP directly into either the VMN or MPN reduced NE concentrations to 17% of control in these hypothalamic nuclei, but failed to alter lordosis. Furthermore, injection of phenylephrine into either the VMN or MPN of VNAB-lesioned rats failed to reinstate lordosis to the levels comparable to sham-lesioned controls. Taken together, these results indicate that noradrenergic neurons terminating in either the VMN or MPN are not essential for gonadal steroid induction of sexual receptivity in ovariectomized female rats.     

腘绳肌腱重建前交叉韧带移植肌腱的固定

目的:腘绳肌腱重建前交叉韧带曾出现过多种固定器材,分析近年来关于腘绳肌腱重建前交叉韧带的文献资料,了解肌腱固定方式的发展趋势。资料来源:通过计算机检索Medline1995-01/2006-09有关腘绳肌腱重建前交叉韧带移植肌腱固定方式的文献,检索词为“anteriorcruciate ligament,reconstruction,hamstring”,限定文章语言种类为English;另外检索中文期刊全文数据库2000-01/2006-03有关腘绳肌腱重建前交叉韧带移植肌腱固定方式的文献,检索词为“前交叉韧带,重建术,腘绳肌腱”,限定文章语言种类为中文。资料选择:选取有关腘绳肌腱重建前交叉韧带的文章,纳入标准:①随机或自身前后对照的临床研究。②观点明确。③有关于固定方式的评论。排除标准:①综述。②重复性研究。资料提炼:共检索到60篇关于腘绳肌腱重建前交叉韧带的文章,选择其中符合标准的33篇进行综合分析。资料综合:固定方式经历了一个由皮质骨外固定到骨隧道内固定的演变过程,Transfix是目前较为理想的固定方式,肌腱结嵌压固定是最新出现的一种固定方式,其临床效果尚需进一步验证。在固定位置的选择上,多数学者认为应该遵循等距重建。通过对固定方式的比较发现,隧道内固定能减轻术后骨隧道的扩大程度。结论:腘绳肌腱重建前交叉韧带的固定方法越来越趋于隧道内固定,并朝着利于腱骨愈合、减轻骨隧道扩大的方向发展。在固定位置的选择上,学者们尚无统一的意见,其趋势可能是向解剖固定发展。