Cimetidine is critical in CNS disorders

There are many CNS disorders with imbalance of dopamine in brain. Cimetidine adversely increases serum level of the prolactin and leads to activate feedback control to decrease prolactin release and intensifies synthesis and secretion of dopamine. Thus, cimetidine can be critical in CNS disorders.     

Determination of the Superoxide Dismutase-Like Activity of Cimetidine-Cu(II) Complexes

Using the direct method of pulse radiolysis to determine the superoxide dismutase like activity of copper(II) cimetidine complexes, it was found that the reaction rate constant with O^?₂, k_cat, was (8.5 ± 0.5) × 10⁸ M^?1s^?1 independent of the cimetidine concentrations present in excess of 50–200 μM over the metal. The results suggest that either the 1:1 ligand to metal complex does not catalyze O^?₂ dismutation at a comparable rate to that of the 2:1 complex, or that the stability constant of the last species is much higher than that determined earlier by Kimura el al.,¹ and only the 2:1 species is present in the solutions. With the indirect methods of cytochrome c and NBT for determining the ability of these complexes to catalyze O^?₂ dismutation, these compounds exhibited a much lower SOD activity. and k_cat was determined to be (5.0 ± 0.3) × 10⁶ and (7.± 0.4) × 10¹ M^?1s^?1. respectively using the two assays.     

玉屏风颗粒联合西咪替丁对过敏性紫癜患儿临床疗效及外周血免疫学指标的影响

目的:探讨玉屏风颗粒联合西咪替丁对过敏性紫癜患儿临床疗效及外周血免疫学指标的影响。方法:选取2017年1月至2019年12月我院68例过敏性紫癜患儿为研究对象,根据随机化原则将受试儿进行分组,其中对照组34例患儿仅接受西咪替丁治疗,研究组45例患儿在对照组的基础上口服玉屏风颗粒治疗,比较两组的治疗效果、治疗前后外周血免疫学指标水平变化及用药安全性。结果:研究组临床治疗总有效率显著高于对照组(P<0.05),治疗前两组各免疫学指标及各炎性因子水平比较无统计学差异(P>0.05),治疗后两组各免疫学指标及各炎性因子水平较治疗前均明显降低,且研究组显著低于对照组(P<0.05),两组治疗期间不良反应发生率无差异(P>0.05)。结论:玉屏风颗粒联合西咪替丁可有效改善患儿的临床症状及外周血免疫学指标,疗效安全显著,值得在过敏性紫癜患儿治疗中应用及推广。     

Cimetidine enhances the protective effect of GST DNA vaccine against Schistosoma japonicum

Cimetidine (CIM), a histamine-2-receptor antagonist, has a long history of safe use in gastric acid-mediated gastrointestinal disorders. In this study, we used CIM, as an adjuvant, with pEGFP-Sj26 GST (the recombinant plasmid containing enhanced green fluorescent protein gene and the gene encoding 26 kDa glutathione S-transferase of Schistosoma japonicum) DNA vaccine to immunized mice and attempted to enhance the protective effect against S. japonicum. The results showed that the reduction rate of worm and egg burdens in the pEGFP-Sj26GST plus CIM group were 79.0% and 68.4%, respectively, significantly higher than that in pEGFP-Sj26GST alone group (27.0% and 22.5%, P < 0.01). Compared with the pEGFP-Sj26GST alone group, mice immunized with pEGFP-Sj26GST plus CIM showed an elevated level of IFN-γ and IL-12 and a low level of IL-10 in splenocytes, while the levels of IL-4 and IL-5 showed no difference between the two groups. Our data also demonstrated that the percentage of CD4⁺CD25⁺ regulatory T cells (Tregs) was significantly decreased in the spleens of mice immunized with pEGFP-Sj26GST plus CIM. All these findings suggest that CIM as a potential schistosome DNA vaccine adjuvant can enhance the protective effect of pEGFP-Sj26GST vaccine.     

Protective effects of cimetidine on radiation-induced micronuclei and apoptosis in human peripheral blood lymphocytes

The radioprotective effects of cimetidine, which has been used clinically as an antagonist of H 2 receptor, on radiation-induced micronuclei and apoptosis in human peripheral blood lymphocytes (PBL) prepared from healthy donors were studied. Cells were treated with cimetidine before or after X-irradiation, and then cytokinesis-blocked micronucleus assay and flow cytometry for measurement of phosphatidylserine externalization were utilized to evaluate the radiation-induced cytogenetic damage and apoptosis. The protective effect of pre-irradiation treatment of cimetidine on radiation-induced micronuclei was dependent on the concentration. The maximum protection rates of cimetidine (1 mM) on frequencies of micronuclei were 38.8 and 30.2% for cells treated before and after X-irradiation (5 Gy), respectively. Protective effects of pre- and post-irradiation treatment with cimetidine on radiation-induced early apoptosis and decreased activity of caspase-3 were observed. A study of electron paramagnetic resonance-spin trapping with 5,5'-dimethyl-1- N -oxide revealed that the rate constant of cimetidine with radiation-induced OH radicals is about 4.5 ×10 9 l/mol/s. Cimetidine did not significantly increase the intracellular concentration of glutathione. These results suggest that cimetidine suppresses radiation-induced micronuclei and apoptosis via OH radical scavenging and an intracellular antioxidation mechanism. Cimetidine appears to be a useful candidate for the future development of post-irradiation radioprotectors.     

Simple high-performance liquid chromatographic method to analyze serum creatinine has several advantages over the Jaffé picric acid reaction as demonstrated with a cimetidine dose response in rhesus monkeys

A simple method for creatinine determination was developed using high-performance liquid chromatography (HPLC) to more accurately monitor serum creatinine levels in experimental animal models when compared to the Jaffé method. The new HPLC procedure will replace the traditional Jaffé method for rhesus monkey kidney function studies. We developed an isocratic method using a polymeric, hydrophilic, silica-based strong cation-exchange bed with a 5.0 mmol/l lithium acetate matrix, pH 4.9, which isolates creatinine with no detectable impurities as determined by three-dimensional ultraviolet–visible spectral analysis. Sample preparation includes deproteination with acetonitrile, evaporation, and resolubilization in mobile phase followed by quantitation with UV detection at 234 nm. Extraction efficiency across the measured range was 96±2%. From numerous extracted rhesus monkey creatinine curves (n=38) a slope of 251 100±756 (95% CI) and an intercept of 675.6±712.7 (95% CI) was calculated. Extraction efficiency and peak purity tests with human plasma were cross-compared with rhesus monkey serum producing equivalent results. An average of 120 samples can be run daily.     

西咪替丁对坏死性小肠结肠炎小鼠炎症免疫反应、肠道微生物的影响

摘要 目的：探讨与分析西咪替丁对坏死性小肠结肠炎（NEC）小鼠炎症免疫反应、肠道微生物的影响。方法：将建模成功的坏死性小肠结肠炎小鼠36只随机平分为三组-模型组、西咪替丁1组、西咪替丁2组,每组12只,每组每日分别灌胃生理盐水0.1mL、胃西咪替丁0.1 mL、胃西咪替丁0.2 mL,持续应用14 d,观察小鼠炎症免疫反应、肠道微生物变化情况。结果：西咪替丁1组、西咪替丁2组治疗第7 d、第14 d的体重都显著高于模型组（P<0.05）,西咪替丁2组与西咪替丁1组对比有显著提高（P<0.05）。西咪替丁1组、西咪替丁2组治疗第14 d的肠组织白介素-2含量低于模型组（P<0.05）,白介素-10含量高于模型组（P<0.05）,西咪替丁2组与西咪替丁1组对比有显著差异（P<0.05）。西咪替丁1组、西咪替丁2组治疗第14 d的粪便双歧杆菌、乳酸杆菌相对表达水平显著高于模型组（P<0.05）,大肠埃希菌相对表达水平显著低于模型组（P<0.05）,西咪替丁2组与西咪替丁1组对比有显著差异（P<0.05）。西咪替丁1组、西咪替丁2组治疗第14 d的肠组织CaMKIV、CREM蛋白相对表达水平都显著低于模型组（P<0.05）,西咪替丁2组与西咪替丁1组对比也显著降低（P<0.05）。结论：西咪替丁在坏死性小肠结肠炎小鼠的应用能调节炎症免疫反应平衡,促进小鼠体重恢复正常,还可降低肠组织CaMKIV、CREM蛋白相对表达水平,从而改善小鼠肠道微生物状况,且具有剂量依赖性。     

Effect of Histamine H2 Receptor Antagonists on the Secretion of Cerebrospinal Fluid in the Cat

Following a recent report that epithelial cells of the choroid plexus possess histamine H2 receptors, the effect of cimetidine and ranitidine, histamine H2 receptor antagonists, on the secretion and electrolyte content of CSF was examined. Fifty cats were divided into one control (n = 6) and six experimental groups. CSF was collected by puncture of the cisterna magna following pentobarbital anesthesia, and its volume, concentrations of Na+, K+, Cl-, and pH were determined. Cimetidine or ranitidine (50, 20, or 10 mg/kg) was injected intravenously 2 h after the start of the test, and their concentrations were measured in hourly blood samples and in 30-min aliquots of CSF in the 50 mg/kg experimental groups. Whereas the secretion of CSF did not change over 6 h in the control group, it decreased significantly by 30-60 min after injection of cimetidine or ranitidine and remained low for the following 6 1/2 h in all experimental groups except the 10-mg ranitidine group. Peak cimetidine and ranitidine concentrations in CSF in the 50-mg experimental groups were noted 60 and 90 min, respectively, after intravenous injection. CSF electrolyte concentrations and pH did not change during the test in any group. We conclude that intravenous cimetidine or ranitidine can significantly reduce CSF secretion in the cat, possibly by competitive inhibition of the histamine effect on H2 receptors located on the choroid plexus epithelial cell, or by a direct effect on the capillaries of the choroid plexus.     

Inhibition of prostaglandin E2 formation and histamine action in cancer immunotherapy

The activity of cell-mediated defense systems is stimulated by consecutive formation of interleukin-1 (IL-1), interleukin-2 (IL-2) and interferon (IFN). The system is inhibited by interleukin-4 (IL-4) and also by prostaglandin E₂ (PGE₂) and histamine, which are released when the immune system is activated. The inhibition is strong in cancer patients, because PGE₂ is formed in many cancer cells and its formation is stimulated by IL-1. The release of histamine is also stimulated by IL-1. Tus PGE₂ and histamine are feedback inhibitors of cell-mediated immunity. This inhibition can be abolished by inhibitors of the cyclo-oxygenase (e. g. indomethacin) and H-2 receptor antagonists (e. g. cimetidine). This may offer a new option to stimulate the immune system to kill cancer cells.     

A lyophilized aqueous extract of<Emphasis Type="Italic"> Maytenus ilicifolia</Emphasis> leaves inhibits histamine-mediated acid secretion in isolated frog gastric mucosa

Lyophilized aqueous extract of Maytenus ilicifolia leaves (LAEMIL) is commonly used in Brazilian folk medicine in the treatment of dyspepsia as well as gastric ulcers. We have investigated the effect and the possible mechanism of action of the LAEMIL on acid secretion in isolated frog gastric mucosa incubated in an Ussing chamber. It was observed that LAEMIL (7–28 mg%) as well as cimetidine (125–4,000 M), a well-known histamine H₂ receptor antagonist, decreased basal acid secretion in a concentration-dependent manner. Similarly to cimetidine (190 M), LAEMIL (21 mg%) also inhibited gastric acid secretion induced by increasing concentrations of histamine (50–800 M). The EC₅₀ values for histamine alone and histamine in the presence of LAEMIL or cimetidine were 94.6 M (71.1–125.9 M), 244.9 M (209.4–286.4 M) and 142.2 M (23.6–855.0 M), respectively. LAEMIL, histamine and cimetidine were effective on acid secretion only when added to the serosal surface of the mucosa. Furthermore, simultaneous addition of LAEMIL and cimetidine at concentrations, per se, ineffective, caused a 16% reduction in the basal acid secretion [from 8.3±0.3 to 6.9±0.2 Eq g^–1 (15 min)^–1, n=4]. Although effects such as inhibition of histamine biosynthesis and/or histamine release can not be ruled out, our data suggest that LAEMIL, like cimetidine, reduces acid secretion in the isolated frog gastric mucosa by antagonising histamine H₂ receptors.Abbreviations LAEMIL Lyophilized aqueous extract of Maytenus ilicifolia leaves - Hist Histamine - Cim Cimetidine