Augmentation of cysteamine-induced ulceration of rat duodenum by systemically administered γ-aminobutyric acid (GABA)

Subcutaneous administration of a single dose of -aminobutyric acid (GABA, 10 mg/100 g) in conjunction with a pretreatment dose of aminooxyacetic acid (AOAA 2.5 mg/100 g subcutaneously) to prevent the degradation of GABA, significantly augmented the incidence and intensity of cysteamine HCl-induced duodenal ulceration in rats. This effect of GABA could be reduced by the GABA receptor antagonist, bicuculline (30 g/100 g subcutaneously). These results suggest peripheral GABA receptors can modulate cysteamine HCl-induced duodenal ulcer.     

大鼠背侧海马生长抑素在青霉素致癎中的作用

目的　观察大鼠海马内生长抑素在癫中的作用。方法　14肽生长抑素(SS14)或半胱胺微量注入背侧海马,在大鼠感觉运动皮质记录脑电功率,应用推挽灌流结合放免法测定青霉素致后背侧海马内生长抑素免疫反应物质(SLI)含量的变化。结果　致后0.5hSLI含量显著增加,可持续4h。SLI含量的上升程度与致后感觉运动区脑电相对功率增加呈正相关。单侧背海马内注入SS140.03nmol使大鼠感觉运动区出现棘尖波,行为上表现样活动。单侧背海马内注入SS耗竭剂半胱胺30μg减少SLI含量30%左右,原先致剂量青霉素所诱发的癫程度减轻。结论　背侧海马SS可能参与致     

碳纳米管和纳米金自组装固定GOD的葡萄糖传感器的研究

目的：研制一种新型的葡萄糖传感器，用于临床检验患者的血糖浓度。方法：通过单层膜自组装技术将多壁碳纳米管、纳米金及葡萄糖氧化酶（GOD）固定到金电极上，用循环伏安法和线性扫描法考察传感器的组装特性、响应电流的性质、对葡萄糖浓度的响应特性。结果：对葡萄糖浓度进行定量分析，线性范围为10-1400mg／L．相关系数R^2=0．9909，检测限为0．0001mg／L。取3支电极测试4例不同浓度的标准样，结果RSD〈2％，在4℃干态保存30d后．响应电流仍然保持在80％，取106名糖尿病患者的临床血清进行检测，符合要求。结论：用多壁碳纳米管和纳米金固定葡萄糖氧化酶研制的葡萄糖传感器能用于临床检验。     

A randomized,double‐blind,placebo‐controlled trial evaluating cysteamine in Huntington's disease

Background : Cysteamine has been demonstrated as potentially effective in numerous animal models of Huntington's disease. Methods : Ninety‐six patients with early‐stage Huntington's disease were randomized to 1200 mg delayed‐release cysteamine bitartrate or placebo daily for 18 months. The primary end point was the change from baseline in the UHDRS Total Motor Score. A linear mixed‐effects model for repeated measures was used to assess treatment effect, expressed as the least‐squares mean difference of cysteamine minus placebo, with negative values indicating less deterioration relative to placebo. Results : At 18 months, the treatment effect was not statistically significant — least‐squares mean difference, ‐1.5 ± 1.71 (P = 0.385) — although this did represent less mean deterioration from baseline for the treated group relative to placebo. Treatment with cysteamine was safe and well tolerated. Conclusions : Efficacy of cysteamine was not demonstrated in this study population of patients with Huntington's disease. Post hoc analyses indicate the need for definitive future studies. © 2017 International Parkinson and Movement Disorder Society     

Endogenous glutathione and platelet function in platelet concentrates stored in plasma or platelet additive solution

Platelet function was studied in platelet concentrates by assay of the thrombin-induced release of endogenous serotonin and presence of the swirling phenomenon in relation to endogenous glutathione (GSH) and cysteine. In platelets stored in plasma, addition of cysteamine resulted in only a moderate fall in GSH after 5 days of storage, from an average of 14.91 to 11.46 nmol per 109 platelets. Exogenously added GSH had no effect, and addition of buthionine sulfoximine (BSO) resulted in almost complete depletion of GSH, to an average of 0.65 nmol per 109 platelets. Addition of cysteamine or GSH resulted in increased endogenous cysteine whereas BSO had no effect. In platelets stored in a platelet additive solution (T-sol), complete depletion of GSH was found in the presence of cysteamine, GSH and BSO. Endogenous serotonin was unchanged during storage both in plasma and in additive solution (2.8 nmol per 109 platelets). Despite almost total depletion of endogenous GSH, the thrombin-induced release of serotonin after 5 days' storage was significantly affected only in the presence of BSO in platelets stored in additive solution (mean values 72.3% vs. 63.3% of endogeneous serotonin, P < 0.05). Similarly, addition of cysteamine or GSH had no significant effect on swirling but BSO reduced the swirling score after 5 days' storage in platelet additive solution compared with plasma. After 10 days' storage, there was a significant reduction in swirling in the concentrates where BSO was added (P < 0.05).     

利津县中青年人血压、血清同型半胱氨酸水平及其与体重指数的相关性调查

目的了解中青年血压、血清同型半胱氨酸（HCY）水平及其与体重指数的相关性,为探讨高血压、高HCY血症的发生与超重肥胖的关系提供依据。方法2012年1月至2013年10月,按照随机原则在利津县第二人民医院抽取20～55岁健康查体者750名,进行调查。结果调查750人,超重的233人,超重率为31．07％;肥胖的91人,肥胖率为12．13％;高血压128例,检出率为17．07％;高HCY血症73例,检出率为9．73％。324名超重与肥胖者的体重指数与收缩压、舒张压、血清HCY水平的相关系数分别为0．639、0．515、0．497,相关均有统计学意义（P〈O．01）。结论利津县中青年健康查体者超重率、肥胖率与高血压及高HCY血症检出率均较高,血压、血清HCY水平与体重指数呈较高的正相关关系。     

A systematic literature review of cysteamine bitartrate in the treatment of nephropathic cystinosis

Objectives: To summarize available clinical evidence for cysteamine bitartrate preparations in the treatment of nephropathic cystinosis as identified through a systematic literature review (SLR).

Methods: We searched MEDLINE, MEDLINE In-Process and Embase using Ovid with a predefined search strategy through 19 January 2016. All publicly available clinical reports on the use of delayed-release (DR) cysteamine bitartrate (Procysbi¹) or immediate-release (IR) cysteamine bitartrate (Cystagon²) in patients with cystinosis were included.

Results: We identified a total of 103 publications and 10 trial records. Of these, 9 studies describe DR cysteamine bitartrate (n?=?267 patients), 42 describe IR cysteamine bitartrate (n?=?1,427 patients) and in 53 studies the exact preparation was not specified (n?=?906 patients). The vast majority of the studies used a non-randomized study design, with randomized clinical trials (RCTs) being scarce (1 study comparing DR and IR formulation) and case reports (n?=?49) being the most common study design representing 47% of the total.

Conclusion: A substantial evidence base for cysteamine bitartrate in the treatment of nephropathic cystinosis was identified. However, the majority of the evidence was of relatively low quality, with evidence levels of 3 or 4.     

Pharmacokinetics of cysteamine bitartrate following gastrointestinal infusion

AIMS: Although cysteamine was first used in the treatment of cystinosis in 1976 and approved by the FDA as cysteamine bitartrate (Cystagon) in 1994, surprisingly little pharmacological data are available for this compound. Cysteamine and its related drugs are currently being evaluated for the treatment of Huntington's and Parkinson's disease. The aim of te study was to understand the pharmacokinetics of cysteamine bitartrate following gastrointestinal infusion. METHOD: Cysteamine bitartrate was delivered through a naso-enteric catheter into the stomach (n = 8), small intestine (n = 8) and caecum (n = 4) of normal subjects. Plasma cysteamine concentrations were determined using LC-MS/MS. RESULTS: The rate and extent of drug absorption were assessed by comparing AUC(0, infinity), C(max) and t(max), among the gastrointestinal infusion sites. Total cysteamine exposure, expressed as area under the curve (AUC(0, infinity)) was greatest when the drug was infused into the small intestine (4331.3 +/- 1907.6 min x microM) followed by stomach (3901.9 +/- 1591.9 min x microM) and caecum (3141.4 +/- 1627.6 min x microM). Cysteamine infusion into the small intestine resulted in the most rapid rise to maximal plasma concentrations (t(max) = 21 +/- 0.56 min); t(max) was delayed to 50 +/- 26 min and 64 +/- 26 min after gastric and caecal infusion, respectively. The maximum cysteamine plasma concentration (C(max)) was reached after infusion of the drug into the small intestine (51 +/- 21 microM), which was higher than plasma C(max) concentrations after gastric (39 +/- 16 microM) and caecal infusion (23 +/- 15 microM). CONCLUSIONS: The pharmacokinetic data generated help extend our understanding of cysteamine.