The vascular effects of different arginase inhibitors in rat isolated aorta and mesenteric arteries

Background and purpose

Arginase and nitric oxide (NO) synthase share the common substrate L-arginine, and arginase inhibition is proposed to increase NO production by increasing intracellular levels of L-arginine. Many different inhibitors are used, and here we have examined the effects of these inhibitors on vascular tissue.

Experimental approach

Each arginase inhibitor was assessed by its effects on isolated rings of aorta and mesenteric arteries from rats by: (i) their ability to preserve the tolerance to repeated applications of the endothelium-dependent agonist acetylcholine (ACh); and (ii) their direct vasorelaxant effect.

Key results

In both vessel types, tolerance (defined as a reduced response upon second application) to ACh was reversed with addition of L-arginine, (S)-(2-boronethyl)-L-cysteine HCl (BEC) or N^G-Hydroxy-L-arginine (L-NOHA). On the other hand, N^ω-hydroxy-nor-L-arginine (nor-NOHA) significantly augmented the response to ACh, an effect that was partially reversed with L-arginine. No effect on tolerance to ACh was observed with L-valine, nor-valine or D,L, α-difluoromethylornithine (DFMO). BEC, L-NOHA and nor-NOHA elicited endothelium-independent vasorelaxation in both endothelium intact and denuded aorta while L-valine, DFMO and nor-valine did not.

Conclusions and implications

BEC and L-NOHA, but not nor-NOHA, L-valine, DFMO or nor-valine, significantly reversed tolerance to ACh possibly conserving L-arginine levels and therefore increasing NO bioavailability. However, both BEC and L-NOHA caused endothelium-independent vasorelaxation in rat aorta, suggesting that these inhibitors have a role beyond arginase inhibition alone. Our data thus questions the interpretation of many studies using these antagonists as specific arginase inhibitors in the vasculature, without verification with other methods.     

Severe Acute Pancreatitis: The Life After

Background  The present study reports functional and morphological changes noted over long-term follow-up in patients with severe acute pancreatitis. Methods  Thirty patients who had completed at least 6 months after recovery were included. Fecal fat, urinary d-xylose, blood sugar, C-peptide, pancreatic changes, and recurrences were studied. Results  Etiology was gallstones (12), alcohol (10), both gallstone and alcohol (3), and idiopathic (5). Five patients were managed conservatively while 25 underwent surgery. Mean follow-up was 31.3 months. Exocrine and endocrine insufficiencies were noted in 12 (40%) and were more common in no-necrosis group compared to necrosis group (p = 0.04 and 0.28, respectively) and infected compared to sterile pancreatitis (45% vs. 25%, p = 0.55 and 50% vs. 12%, p = 0.15, respectively). Higher frequency was noted in nonvisualized, partly visualized, and dilated segment of duct. Significant proportion (8/12) had both exocrine and endocrine abnormalities and their incidence decreased as duration of follow-up increased. Urinary d-xylose excretion was abnormal in 16% and noted >1 year postrecovery. Thirty percent required >1 readmission and pain was the commonest cause. Conclusions  Forty percent had functional abnormality; 16% had mucosal absorption abnormality while 30% required >1 readmission. Exocrine and endocrine insufficiencies were more prevalent in first year, and a significant proportion had both. A trend for higher functional insufficiency was observed in infected necrosis, complete or incomplete visualization of main pancreatic duct (MPD), dilated segment of MPD, and pseudocyst.     

Evaluation of gall bladder carcinoma with dynamic magnetic resonance imaging and magnetic resonance cholangiopancreatography

The objective of this study is to evaluate the efficacy of dynamic MRI with magnetic resonance cholangiopancreatography (MRCP) in the preoperative assessment of gall bladder carcinoma. Magnetic resonance imaging and MRCP were carried out in 15 patients with gall bladder carcinoma before surgery and the imaging findings correlated with surgical and pathological findings. Gall bladder carcinoma manifested as focal or diffuse wall thickening in 73% (11/15) and as a mass replacing the gall bladder in 27% (4/15). All tumours showed enhancement in the early phase, which persisted into the delayed phase. The sensitivity and specificity of MRI with MRCP in detecting hepatic invasion, lymph node metastasis and bile duct invasion was 87.5 and 86%, 60 and 90%, and 80 and 100%, respectively. Magnetic resonance imaging correctly diagnosed duodenal invasion in only 50% and in none of the two patients with peritoneal metastasis. In conclusion, dynamic MRI with MRCP is an accurate and a reliable method of showing gall bladder carcinoma and in assessing its local and regional extent as part of preoperative assessment.     

Organization, expression and polymorphism of the human persyn gene

Persyn is a recently identified member of the synuclein family with a distinct pattern of expression during pre- and postnatal development of the mouse peripheral and central nervous systems. As with other synucleins, persyn is believed to be involved in the pathogenesis of human neurodegenerative diseases. However, in contrast to other synucleins, high levels of persyn mRNA expression were also found in advanced breast carcinomas, suggesting an involvement of the encoded protein in breast tumour progression. Here we have used an antibody specific to human persyn to demonstrate that the level of this protein is increased in ageing cerebral cortex and in breast tumours. We cloned, characterized and sequenced the human persyn genomic locus and localized it to the long arm of chromosome 10 in the q23.2-q23.3 region. Sequence information was used to search for specific mutations in the protein coding regions of persyn mRNA and the persyn gene in breast tumours and tumour cell lines. No tumour-specific mutations were found, but two linked polymorphisms in the coding region were detected, both in mRNA and exons III and IV of the gene. These results suggest that development of breast tumours correlates with overexpression of the wild-type persyn protein. Detailed characterization of the human persyn locus is important for further studies of the involvement of persyn in neurodegeneration and malignancy.      

内固定基础上应用骨形态发生蛋白人工骨与自体髂骨植骨治疗骨质疏松性髋骨折的效果比较

目的:比较采用骨形态发生蛋白人工骨植骨加骨折内固定与自体髂骨植入加骨折内固定治疗骨质疏松性转子间骨折的效果。方法:选择2003-10/2005-10桂林医学院附属医院骨科收治的Ⅲ、Ⅳ、V型骨质疏松性转子间骨折患者51例,均知情同意。实验分组:随机将病例分为2组,骨形态发生蛋白人工骨植入组26例,自体髂骨植入组25例。实验干预:采用股骨上段外侧切口,DHS或加防旋钉内固定,骨形态发生蛋白人工骨由处理后的牛松质骨与成品重组人骨形态发生蛋白2按一定比例复合而成,骨折固定后在骨折缺损处、内侧及骨折周围植骨,骨形态发生蛋白人工骨组采用骨形态发生蛋白人工骨植入,自体髂骨组取自体髂骨植入。实验评估:术后定期随访,比较二组患者的基本情况、临床效果和影像学结果(骨折愈合情况和颈干角的变化)。随访时关节功能评定参照采用黄公怡等提出的标准,分为优、良、可、差4级。髋内翻分类标准为颈干角<100°。结果:术后随访1年,51例患者全部进入结果分析。①术后X射线片观察:骨形态发生蛋白人工骨组临床愈合时间短于自体髂骨组[(94.50±22.45),(116.96±15.90)d,P<0.01];骨形态发生蛋白人工骨组术后1年颈干角大于自体髂骨组[(127.19±3.23)°,(120.4±5.22)°,P<0.01]。②髋关节功能及不良事件和副反应:骨形态发生蛋白人工骨组术后以1年髋关节功能优良率优于自体髂骨组(P<0.05);骨形态发生蛋白人工骨组髋内翻、下肢短缩(>2cm)的发生率均低于自体髂骨组[髋内翻(n):4,7;下肢短缩(n):3,5,P均<0.01];钉退出二组差异均无显著性意义(P>0.05)。结论:伴有骨质疏松的转子间骨折患者,采用骨形态发生蛋白人工骨植骨优于自体髂骨植骨,可缩短骨折愈合期,减少髋内翻等并发症的发生率,提高术后髋关节功能优良率,提示骨形态发生蛋白人工骨能替代自体髂骨植骨治疗骨质疏松性转子间骨折。     

Onset of acute psychotic states in India: a study of sociodemographic,seasonal and biological factors

This is a comparative study of patients with acute-onset, non-affective, non-organic, remitting psychoses and with non-remitting or schizophrenic psychoses in India. Two groups of patients with acute remitting and non-remitting or schizophrenic psychoses were compared with regard to the following variables: month of onset of psychosis; presence of stress, particularly fever, within 4 weeks preceding the onset of psychosis; childbirth within 12 weeks preceding the onset of psychosis; gender differences. It was found that the acute remitting psychoses showed an overrepresentation of females, a higher frequency of associated stress preceding the onset of psychosis, more often had onset during the summer months, i.e. between May and September, and had fever and childbirth preceding the onset of psychosis in a significantly higher proportion of patients, compared to acute non-remitting psychoses or schizophrenia. The implications of the findings which point towards biological factors in the aetiology of acute remitting psychoses are discussed.     

Reductions in neural activity underlie behavioral components of repetition priming

Repetition priming is a nonconscious form of memory that is accompanied by reductions in neural activity when an experience is repeated. To date, however, there is no direct evidence that these neural reductions underlie the behavioral advantage afforded to repeated material. Here we demonstrate a causal linkage between neural and behavioral priming in humans. fMRI (functional magnetic resonance imaging) was used in combination with transcranial magnetic stimulation (TMS) to target and disrupt activity in the left frontal cortex during repeated classification of objects. Left-frontal TMS disrupted both the neural and behavioral markers of priming. Neural priming in early sensory regions was unaffected by left-frontal TMS--a finding that provides evidence for separable conceptual and perceptual components of priming.