Glucagon-induced somatostatin release from perifused rat hypothalamus: calcium dependency and effect of cysteamine treatment

Somatostatin (SRIF) release from rat hypothalamus was investigated in vitro with a perifusion system. Glucagon (1 microM) and high potassium concentrations (56 mM) stimulated SRIF release in a calcium-dependent manner. Pretreatment of the rat with cysteamine (30 mg/100 g body weight, 7 h earlier) significantly reduced SRIF release from the hypothalamus in glucagon- and high potassium-stimulated states as well as in the basal state. SRIF release from rat hypothalamus was also stimulated by both dibutyryl cyclic AMP (1 mM) and theophylline (3 mM). These results suggest that glucagon, acting in a calcium-dependent manner and possibly through the adenylate cyclase-cyclic AMP system, stimulates SRIF release from rat hypothalamus and that cysteamine treatment reduces releasable SRIF in the hypothalamus.     

A Randomized Clinical Trial of Topical Cysteamine Disulfide (Cystamine) versus Free Thiol (Cysteamine) in the Treatment of Corneal Cystine Crystals in Cystinosis

In nephropathic cystinosis, corneal cystine crystals cause severe photophobia and corneal erosions. Topical cysteamine dissolves these crystals, but cannot be marketed because it rapidly oxidizes to the disulfide form, cystamine, at room temperature. Since cystamine itself could be used commercially, we compared the efficacy of cystamine and cysteamine with respect to cystine crystal dissolution in a randomized, double-masked clinical trial. One eye each of 14 patients with cystinosis was randomized to either cystamine or cysteamine, 0.5%, with 0.01% benzalkonium chloride; the companion eye was treated with the alternate preparation. Corneal crystals were photographed and a density score was assigned to each slide based on 13 standard slides. After 8–20 months, 6 patients showed significant reduction of the corneal crystal score in only one eye. In each case, the improved eye was the cysteamine-treated eye. Theoretically, cysteamine should dissolve both intracellular and extracellular crystals, whereas cystamine should dissolve only intracellular crystals because it must first be reduced to the free thiol by the cytoplasmic-reducing environment. Hence, the lack of efficacy of the disulfide cystamine suggests that some corneal cystine crystals in cystinosis patients are extracellular, and that another form of stable, topical cysteamine must be developed for cystinosis patients.     

脑梗死与血管活性物质及同型半胱氨酸的相互关系

目的　探讨脑梗死患者颈动脉病变 ,血管活性物质 [一氧化氮 (NO)、内皮素 (ET 1) ]及同型半胱氨酸 (Hcy)的相互关系。方法　选择 14 9例高血压患者 ,按有无缺血性脑卒中分为 2组 ,A组 :高血压并发缺血性脑卒中组 (74例 )。B组 :单纯高血压病组 (75例 ) ,对上述患者测定血清中NO、ET 1、Hcy值 ,颈动脉超声。结果　缺血性脑卒中组Hcy、ET 1生成增加 ,NO生成减少 ,差异有显著性 (P <0 .0 5 )。颈动脉斑块的发生A组较B组明显增多 ,差异有显著性 (P <0 .0 5 )。结论　高Hcy加重了高血压对血管壁的损伤 ,使血管内皮细胞中NO生成减少 ,ET 1生成增加 ,斑块的形成增加 ,从而促进了血管内血栓的形成 ,增加了缺血性脑卒中发生的危险性     

Effects of Cysteamine Pretreatment and Hypothalamic Periventricular Nucleus Lesion on the Cold-Stimulated Thyrotropin Responses to Intracerebroventricular 5-Hydroxytryptamine in Male Rats

The hypothalamic somatostatinergic system was devitalized in male rats by intracerebroventricular (icv) cysteamine (CSH) pretreatment (250 μg/rat/day into the third ventricle) on 4 consecutive days or by a limited lesion of the hypothalamic periventricular nucleus (PeVNx). The acute effect of icv serotonin (5-HT) on the cold-stimulated thyrotropin (TSH) and prolactin responses were studied in these animals. The experiments were performed 24 h after the last saline or CSH infusions and 7 days after the sham- or PeVN-lesions. CSH and PeVNx decreased the hypothalamic somatostatin content by 44% to 57% and 19% to 28%, respectively. PeVNx did not affect hypothalamic thyrotropin-releasing hormone content. 5-HT infusion (9 μg/rat icv) into the anterior third ventricle elevated, although not significantly, TSH levels in both saline- or CSH-pretreated rats. 5-HT infusion into the anterior third ventricle did not affect TSH in sham-operated rats. However, 5-HT augmented the cold-stimulated TSH levels after PeVNx compared to sham-lesion. Inversely, 5-HT infusion (9 μg/rat) into the posterior third ventricle inhibited TSH secretion irrespective of the pretreatment or lesion. The inhibitory action of 5-HT on TSH was significantly suppressed by CSH. 5-HT infusions elevated serum prolactin levels irrespective of the infusion site, pretreatment or lesion. 5-HT infusion into both the anterior and the posterior third ventricle decreased rectal temperature in saline-pretreated, sham- and PeVN-lesioned rats. The hypothermie effect of 5-HT was weakened by CSH. The hypothalamic levels of noradrenaline, dopamine and their metabolites were not significantly affected by CSH and PeVNx. 5-HT infusion into the anterior third ventricle decreased hypothalamic dopamine content in both saline- and CSH-pretreated rats. However, such an effect was not seen in sham- or PeVN-lesioned animals. Although CSH is an inhibitor of dopamine-β-hydroxylase, this activity was not reflected in serum TSH or prolactin levels. The results support our hypothesis of the site-dependent action of icv 5-HT or TSH secretion. The elevation of TSH levels may arise from the inhibition of somatostatin release from rostral anterior hypothalamus. The inhibition of TSH secretion may result from the inhibition of thyrotropin-releasing hormone release from more caudal periventricular structures of the hypothalamus.     

复方胃利散抗大鼠消化性溃疡的作用

目的考察复方胃利散(compound Weili powder,FFWLP)对动物实验性溃疡模型的影响。方法建立乙醇致大鼠胃溃疡模型,幽门结扎型大鼠胃溃疡模型,盐酸半胱氨酸致大鼠十二指肠溃疡模型及乙酸致大鼠十二指肠溃疡模型。结果复方胃利散对乙醇致大鼠胃溃疡有保护作用;对幽门结扎致大鼠胃溃疡有保护作用;对乙酸、盐酸半胱氨酸致大鼠十二指肠溃疡有明显的治疗作用,并能降低胃液酸性,显著升高十二指肠溃疡模型大鼠的肠黏膜PGE2含量。结论复方胃利散有很好的抗消化性溃疡的作用。     

Effects of compound U74500A in animal models of gastric and duodenal ulceration

Pretreatment with U74500A (up to 0.65 mg/100 g) failed to affect gastric lesions induced by 100% EtOH gavage in Sprague-Dawley rats. Topical application of U74500A did not reduce lesions induced by 40% EtOH inex vivo gastric chamber preparations. However, pretreatment of rats with U74500A (0.65 g/100 gper os) reduced the incidence and severity of experimental duodenal ulcer induced by cysteamine HCl, and duodenal ulcer induced by cysteamine-HCl plus GABA. These results show U74500A to have powerful and specific antiduodenal ulcer actions. Pharmacologic analysis of organ-bath preparations of the small intestine show this compound to reduce intestinal contractility to applied cholinergic and serotonergic agonists. However, relaxations induced by electrical or nicotinic ganglionic stimulation were unaffected. U74500A itself caused concentrationdependent contractions.     

Autoradiographic study on healing process of cysteamine-induced duodenal ulcer in rat

The healing process of cysteamine-induced duodenal ulcer was studied by [³H]thymidine autoradiography. After the development of ulcer in the duodenum, cell proliferation was markedly activated not only in the crypts but also in the Brunner's glands near the ulcer. In the initial stages of ulcer healing, they both contributed to form the surface covering regenerating epithelium. Granulation tissue also proliferated at the base of the ulcer. In later stages of ulcer healing, new crypts were formed in the floor of the ulcer. New villi regenerated from these crypts and Brunner's glands regenerated by proliferationin situ. The ulcer base then was completely covered with new villi and granulation tissue was replaced by dense fibrous connective tissue. The present study suggested that the Brunner's glands, together with the crypts of Lieberkühn, play an important role in the healing process of cysteamine-induced duodenal ulcer.     

Sulfhydryl drugs reduce neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridime (MPTP) in the mouse

Summary Striatal levels of dopamine and its metabolites 3-methoxy-4-hydroxy-phenylacetic acid (DOPAC) and homovanillic acid (HVA) decreased 7 days after subcutaneous injection of MPTP (20 mg/kg) to the mouse. Striatal GSH contents decreased and GSSG/GSH ratios increased one hour after subcutaneous administration of MPTP. Pretreatments of both cysteamine (200 mg/kg, s.c.) and dimercaprol (20 mg/kg, i.m.) reduced the MPTP-induced decreases in striatal dopamine, DOPAC and HVA, and also prevented the MPTP-induced decreases in GSH levels and increases in GSSG/GSH ratios. On the other hand, injection of cysteamine did not modify the MPTP-induced decreases in striatal levels of dopamine and its metabolites when it was done 2 hours after MPTP administration. Moreover, pretreatment of cysteamine did not affect striatal concentrations of MPP⁺ in MPTP-treated mice. These results suggest that sulfhydryl drugs such as cysteamine and dimercaprol may reduce neurotoxity of MPTP probably via changes in redox cycle of glutathione in the brain.     

生长抑素与GABA对大鼠海马CA1区长时程增强的影响(英文)

目的:研究生长抑素(SS)和GABA对大鼠海马长时程增强(LTP)的影响.方法:采用穿梭箱主动回避反应(AAR)法和以海马CA1区群体峰电位(PS)为LTP的指标. 结果:AAR习得达标鼠,PS增幅达100％以上;海马内注射(ih)SS(1 g L~(-1))后,PS增幅大于120％;ih SS耗竭剂半胱胺(Cys,20gL~9-1))后,PS不出现(n=8)或PS增幅不及10％(n=3);ih GABA(200g L~(-1))后,PS增幅小于30％,且有拮抗SS增强LTP的效应. 结论:SS有易化LTP的作用,而GABA则有相反的效应,二者共同参与调控海马突触传递的信息,从而影响学习和记忆.