脑室注射催产素对大鼠胃和十二指肠溃疡的作用

INTRODUCTION Central neurons that synthesize oxytocin are locatedin the supraoptic(SON) and paraventricular nuclei(PVN) of the hypothalamus. Magnocellular neurons inboth nuclei project to the posterior pituitary gland,     

Mechanisms for the cytotoxicity of cysteamine.

The major aim of this study was to quantitatively assess the contribution of H2O2 generation to the cytotoxicity induced by cysteamine. Cysteamine produces H2O2 at levels that correlate with its toxicity between 23 and 160 microM. A maximum of 6.9 microM H2O2 is generated by 625 microM cysteamine. When compared to the toxicity of exogenous H2O2, cysteamine-derived peroxide accounted for 57% of its toxicity. This corresponded to the percent toxicity due to 23 to 91 microM cysteamine. The remaining 43% toxicity appears to involve the inhibition of glutathione peroxidase, because activity of both the cellular and purified enzyme were inhibited by 200 microM cysteamine concentrations. CCRF-CEM cells have no catalase activity, so the inhibition of glutathione peroxidase may sensitize these cells to the less than toxic levels of peroxide generated by this aminothiol. Cysteamine also stimulated the production of cellular glutathione in a manner that was not related to its H2O2 generation. The production of glutathione did not influence toxicity but may reflect the accumulation of cysteamine to levels that inhibit glutathione peroxidase.     

醋氨己酸锌对半胱胺大鼠溃疡模型的影响

用半胱胺在大鼠上引起非弥散性和弥散性十二指肠溃疡，并以雷尼替丁作为对照，研究了醋氨己酸锌对溃疡的预防作用和治疗作用。弥散性十二指肠溃疡有一个较长的愈合过程，在用醋氨己酸锌治疗５０ｄ后，溃疡受到极明显的抑制。对非弥散性十二指肠溃疡也表现了极好的预防作用。另外，对醋氨己酸锌各个剂量溃疡愈合的形态学也进行了比较，发现在不同的剂量时显示不同的损伤修复及愈合情况，明显地加速了受损处的上皮细胞、十二指肠腺及平滑肌细胞的增殖。     

Preclinical and clinical studies with cysteamine and pantethine related to the central nervous system

Vécsei, László and Erik Widerlöv: Preclinical and Clinical Studies with Cysteamine and Pantethine Related to the Central Nervous System. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1990, : 835–862.

1. 1. Cysteamine is formed by degradation of coenzyme A (CoA) and causes somatostatin (SS), prolactin and noradrenaline depletion in the brain and peripheral tissues.

2. 2. Cysteamine influences several behavioral processes, like active and passive avoidance behavior, open-field activity, kindled seizures, pain perception and SS-induced barrel rotation.

3. 3. Cysteamine has several established (cystinosis, radioprotection, acetaminophen poisoning) and theoretical (Huntington's disease, prolactinsecreting adenomas) indications in clinical practice.

4. 4. Pantethine is a naturally occurring compound which is metabolized to cysteamine.

5. 5. Pantethine depletes SS, prolactin and noradrenaline with lower efficacy compared to that of cysteamine.

6. 6. Pantethine is well tolerated by patients and has been suggested to treatment of atherosclerosis. The other possible clinical indications (alcoholism, Parkinson's disease, instead of cysteamine) are discussed.

大鼠实验性十二指肠粘膜损伤对胃及十二指肠电活动的影响

本文观察了半胱胺诱发的大鼠实验性十二指肠粘膜损伤对胃和十二指肠电活动的影响。实验经口给半胱胺,以诱发大鼠十二指肠粘膜损伤。离体条件下,以胃和十二指肠电慢波频率和振幅为指标,观察了胃十二指肠各部位的电活动变化。实验结果表明:由半胱胺诱发的大鼠十二指肠粘膜损伤对离幽门括约肌(以下简称PS)上1.5cm和PS下0.5cm, 1.0cm及2.0cm处的电慢波频率具有明显的加快作用,而对PS上0.5cm和1.5cm处的电慢波振幅具有明显的减低作用,但对十二指肠各部位的电慢波振幅均无明显的影响。     

Autophagy-mediated chemosensitization by cysteamine in cancer cells

Cysteamine (CS) has many biomedical and clinical applications because of its excellent water solubility, low cytotoxicity and good biocompatibility. A previous study by Brawer et al. reported the occurrence of many Gomori inclusion bodies in CS-treated astrocytes, which would suggest the induction of autophagy. Here we provided a comprehensive line of evidence demonstrating that CS caused autophagosome accumulation in cancer cells. CS exerted a biphasic effect on the autophagy process, increasing the formation of autophagosomes in the early phase and blocking the autophagic degradation in a later phase. Furthermore, we showed that CS sensitized doxorubicin-elicited chemotherapeutic killing in HeLa, B16 melanoma and doxorubicin-resistant MCF-7 cells and also enhanced chemotherapeutic efficacy of doxorubicin in a mouse melanoma model. Finally, we demonstrated that the chemosensitizing effect of CS was at least partly dependent on its ability to modulate autophagy. Our results revealed a novel biological function for CS in enhancing the chemotherapeutic effect of doxorubicin through autophagy modulation and pointed to the potential use of CS in adjunct cancer chemotherapy.     

Follow-up and treatment of adults with cystinosis in the Netherlands.

BACKGROUND: Cystinosis is a rare autosomal recessive disease, caused by intracellular cystine accumulation due to a defect in the lysosomal cystine carrier. Treatment with cysteamine favours the transport of cystine out of the lysosomes, diminishes organ damage, and postpones the progression of renal failure. The extra-renal deposition of cystine continues after renal transplantation, leading to later complications. The objective of this study was to evaluate the follow-up, the occurrence of late complications, the social status, and the adequacy of cysteamine treatment in adult patients with cystinosis. METHODS: The medical histories of 10 adult cystinosis patients aged 19-36 years were studied. The impairment of thyroid function, central nervous system, endocrine pancreas, and ocular manifestations, as well as treatment with cysteamine were evaluated. RESULTS: Eight patients received in total 12 renal grafts, one patient was dialysed and one received conservative treatment for chronic renal failure. Extra-renal complications were noted in six patients, loss of visual acuity in four, hypothyroidism in three, diabetes mellitus in one, cerebral atrophy and epilepsy in one, and swallowing difficulties in two patients. Ophthalmic control was not performed in two patients, thyroid function was not controlled in two and glycaemia not controlled in two patients. Seven patients received 2100-4000 mg cysteamine per day in 2 (n=2), 3 (n=1), 4 (n=3), or 6 (n=1) doses. Cystine concentration in leukocytes was measured once or twice a year in eight patients and was within the recommended range only in three patients. CONCLUSION: A high rate of extra-renal complications in adults with nephropathic cystinosis was found. Optimizing the cysteamine therapy may attenuate these complications. Better communication between paediatric and 'adult's' nephrologists is needed to improve follow-up and treatment of grown-up cystinosis patients.     

桉柠蒎肠溶软胶囊联合吸入用乙酰半胱氨溶液治疗慢性阻塞性肺疾病的效果

目的：探究桉柠蒎肠溶软胶囊联合吸入用乙酰半胱氨溶液治疗慢性阻塞性肺疾病（COPD）的临床效果。方法：选择厦门市同安区中医医院2020年6月至2022年2月收治的60例COPD患者,按用药不同分为两组,每组30例,其中对照组患者给予吸入用乙酰半胱氨溶液进行治疗,观察组则实施桉柠蒎肠溶软胶囊联合吸入用乙酰半胱氨溶液进行治疗,比较两组患者治疗效果。结果：与对照组比较,观察组患者总有效率更高,治疗后第1秒用力呼气量（FEV1）、第1秒用力呼气量占用力肺活量比值（FEV1/FVC）均高于对照组,临床症状消失时间短于对照组,慢性阻塞性肺疾病评估测试量表（CAT）评分低于对照组,差异具有统计学意义（P <0.05）;两组患者不良反应比较差异无统计学意义（P> 0.05）。结论：桉柠蒎肠溶软胶囊联合吸入用乙酰半胱氨溶液治疗COPD患者,在获得较好的临床效果的同时不增加不良反应,安全性较高,能有效改善患者肺功能、呼吸情况。     

Cysteamine in renal transplantation: A report of two patients with nephropathic cystinosis and the successful re‐initiation of cysteamine therapy during the immediate post‐transplant period

Nephropathic cystinosis is a rare disorder causing the accumulation of intracellular cystine crystals in tissues. The damage to the proximal tubules of the kidneys results in Fanconi syndrome, and patients with cystinosis experience the progression of chronic kidney disease, resulting in the need for kidney transplantation. Treatment of cystinosis with cysteamine has proven to be effective; however, it has many gastrointestinal side effects that are concerning for transplant specialists during the immediate post‐transplant period. Transplant specialists routinely discontinue cysteamine therapy for up to six weeks to ensure proper immunosuppressant absorption. This practice is worrisome because it communicates the acceptability of lapses of cysteamine treatment to patients. It may be better to re‐initiate cysteamine therapy shortly after transplantation while the patient is followed more closely by the transplant team. This report presents two pediatric patients with nephropathic cystinosis who successfully restarted cysteamine therapy in the immediate post‐transplant period without issue in regard to immunosuppression absorption or gastrointestinal side effects. These cases challenge current practice of discontinuing cysteamine therapy during kidney transplantation, and immediate re‐initiation of cysteamine therapy in cystinosis patients post‐transplant should be considered.