新型丝素蛋白水凝胶携载西咪替丁预防酒精引起的小鼠急性胃溃疡

目的：探讨新型丝素蛋白（SF）水凝胶携载西咪替丁（CMD）预防酒精引起的小鼠急性胃溃疡的作用。方法：提取制备SF，构建西咪替丁-丝素蛋白（CMD-SF）水凝胶体系。将8 周龄SPF级C57BL/6 雄性小鼠随机分为4 组，对照组、CMD组、CMD-SF溶液组、CMD-SF水凝胶组，每组8 只。通过扫描电镜观察CMDSF水凝胶的显微结构，再通过FT-IR分析判别CMD-SF水凝胶的成胶状态，缓释实验检测CMD-SF水凝胶体系对于CMD的缓释效果。体内实验中，通过HE染色观察各组组织病理学变化，PAS染色检测胃黏液分泌状态，SOD、MDA试剂盒检测氧化应激反应相关指标水平，caspase3免疫组化染色观察各组组织细胞凋亡情况。结果：扫描电镜成像以及FT-IR检测结果均证明CMD-SF水凝胶制备成功。缓释实验证明，在72 h时，CMD-SF水凝胶体系中CMD的累积释放量约为45.4%，而CMD组以及CMD-SF溶液组中的CMD累积释放量超过70.0%。HE染色、PAS染色以及caspase3免疫组化和免疫印迹结果显示，与对照组、CMD组和CMD-SF溶液组相比，CMDSF水凝胶组预防酒精引起的急性胃溃疡的发生、降低胃黏膜损伤的效果更为显著。同时，对比于对照组SOD[（0.21±0.05）U/g prot]和MDA[（4.51±0.94）nmol/mg prot]水平，CMD-SF水凝胶组的SOD水平升至（0.61±0.11）U/g prot，MDA水平降至（2.42±0.38）nmol/mg prot，能有效缓解氧化应激反应。结论：CMD-SF水凝胶能延长CMD停留于胃黏膜表面的时间，有效预防酒精引起的急性胃溃疡的发生，其机制可能与抑制氧化应激反应，从而降低细胞凋亡，防止组织损伤相关。     

Reducing meal-stimulated acid secretion versus reducing nocturnal acid secretion for healing of duodenal ulcer

Both meal-stimulated and nocturnal acid secretions have been shown to be abnormally increased in patients with duodenal ulcer. The relative efficacy of an acid-reducing regimen aimed specifically at controlling postprandial acid secretion compared with one that controls nocturnal acid secretion is, however, not known. The endoscopic healing rates at weeks 2, 4, 6, 8, 10, and 12 of three cimetidine regimens with identical total daily dose—bedtime (1200 mg), mealtime (400 mg three times a day with meals), and reference (200 mg three times a day with meals and 600 mg at bedtime)—were compared in a randomized study on 141 patients with endoscopically proven duodenal ulcer. Evaluating endoscopists were blinded to patients' form and duration of treatment and their clinical progress; patients were unaware of the comparative design of the study. Life-table analysis for the 12 weeks of observation revealed that the mealtime regimen resulted in significantly (P<0.05) better healing rates than either the bedtime or the reference regimen. The differences were accounted for largely by the significantly (P<0.04) better healing rate at two weeks with the mealtime regimen (68%) than with either the bedtime (47%) or the reference (45%) regimen. These findings indicate that a regimen that aims at controlling meal-stimulated acid secretion achieves a faster healing rate than one that aims at controlling nocturnal acid secretion in the treatment of duodenal ulcer, and they suggest that postprandial acid secretion plays a greater role than nocturnal acid secretion in the pathophysiology of this condition.This study was supported by the Peptic Ulcer Research Fund (311/041/0372), and by grants (311/030/8009/31, 311/030/8010/12, 335/041/0006, 311/030/8010/69) of the University of Hong Kong.     

更昔洛韦联合西咪替丁治疗轮状病毒肠炎的疗效观察

目的:观察更昔洛韦联合西咪替丁治疗轮状病毒肠炎的效果。方法:167例轮状病毒肠炎患儿随机分成更昔洛韦联合西咪替丁治疗组(A组)60例、病毒唑治疗组(B组)52例、对照组(C组)55例。三组病例均给予补液,维持水、电解质、酸碱平衡等综合治疗。结果:更昔洛韦联合西咪替丁治疗组(A组)、病毒唑治疗组(B组)、对照组(C组)的治疗总有效率分别为96.6%、82.7%、78.2%,其中A组显著高于B组、C组(P均<0.05)。结论:更昔洛韦联合西咪替丁治疗轮状病毒肠炎,效果佳且安全,两者有协同作用。     

喜炎平联合西米替丁治疗小儿轮状病毒肠炎75例

目的探讨喜炎平联合西米替丁治疗小儿轮状病毒肠炎的疗效及安全性。方法将2009年10月至2010年2月185例确诊为轮状病毒肠炎的住院患儿随机分为3组,对照组55例采用综合治疗及利巴韦林注射液10～15mg/（kg·d）静脉滴注抗病毒;治疗A组55例加用喜炎平注射液2mg/（kg·d）,用5%葡萄糖注射液稀释静脉滴注,疗程5～7d;治疗B组75例在治疗A组的基础上加用西米替丁注射液10～15mg/（kg·d）,用生理盐水稀释静脉滴注,疗程5～7d。结果治疗B组总有效率为96.00%,较治疗A组和对照组明显提高,发热、呕吐、呼吸道感染等全身症状消失时间为（1.68±0.77）d,粪便性状及次数恢复正常时间为（2.66±1.06）d,均较治疗A组和对照组明显缩短（P〈0.05或P〈0.01）。结论喜炎平联合西米替丁治疗小儿轮状病毒肠炎,可缩短病程、提高治愈率,疗效确切,值得推广。     

兰索拉唑对离体壁细胞酸分泌的影响

目的应用兔离体壁细胞为模型,研究兰索拉唑体外抑酸效果.方法应用细胞淘洗与连续密度梯度离心相结合的方法分离兔胃黏膜壁细胞,以14C氨基比林摄取为酸分泌指标,观察西咪替丁及兰索拉唑对离体壁细胞组胺诱导的酸分泌的影响.结果壁细胞纯度达80%以上进行实验,兰索拉唑能明显抑制离体壁细胞组胺诱导的酸分泌,对组胺刺激酸分泌的50%抑制量(IC50)为9.59×10-8mol/L,明显高于H2受体拮抗剂(3.70×10-5mol/L).结论兰索拉唑对兔离体壁细胞组胺诱导的酸分泌具明显的抑制作用,效果优于西咪替丁;本研究为国内开展新的抑酸剂基础与临床研究提供了新方法.     

Favorable response to combination treatment of cimetidine,cyclooxygenase‐2 inhibitor and renin‐angiotensin system inhibitor in metastatic renal cell carcinoma: Report of three cases

Abstract: We report three cases of metastatic renal cell carcinoma (RCC) in which combination treatment of cimetidine, cyclooxygenase‐2 inhibitor and renin‐angiotensin system inhibitor (angiotensin converting enzyme inhibitor or angiotensin II type 1 receptor antagonist) (CCA therapy) was effective. Case 1: A 47‐year‐old man who had a 12‐cm right renal tumor with multiple pulmonary and hepatic metastases refused cytokine therapy for economic reasons and received CCA therapy. All of the metastases showed partial remission, which continued for 12 months. Case 2: A 62‐year‐old man with multiple pulmonary and mediastinal lymph node metastases from clear cell RCC refractory to interferon‐α and interleukin‐2 started CCA therapy. Partial remission has been maintained for 16 months. Case 3: A 64‐year‐old man with pulmonary metastases from clear cell RCC discontinued interferon‐α treatment due to its side effects after six months and received CCA therapy. Pulmonary metastases showed partial remission for 31 months. The CCA therapy could be an alternative treatment for metastatic RCC patients unfit for cytokine therapy.     

甲氰咪胍对非酒精性脂肪性肝炎大鼠脂质过氧化作用的影响

目的：探讨甲氰咪胍对非酒精性脂肪性肝炎（NASH）大鼠脂质过氧化作用的影响。方法：雄性SD大鼠30只，随机分为3组，正常对照组、模型组、甲氰咪胍组，正常组普通饲料喂养，模型组喂高脂饮食，甲氰咪胍组在高脂饮食12w后给予甲氰咪胍灌胃治疗。16w末处死各组大鼠，测定血清转氨酶（ALT、AST）、血脂（TC、TG）、肝匀浆丙二醛（MDA）含量、超氧化物歧化酶（SOD）活性，同时测定细胞色素P450（CYP450）和细胞色素2E1（CYP2E1）含量，光镜下观察肝组织学改变。结果：与正常组比较，模型组大鼠血清TG、TC水平，肝组织脂质过氧化产物MDA含量明显增高，而抗氧化物SOD活性明显降低，肝脏的脂肪变性程度和炎症活动度均显著增高，细胞色素P450和CYP2E1含量显著增高。甲氰咪胍组各项指标较模型组有明显改善（P〈0．05）。结论：甲氰咪胍通过抑制CYP2E1表达与其密切相关的脂质过氧化作用，改善NASH大鼠脂肪变性，减轻炎症反应。     

An improved method to evaluate secretory activity of isolated gastric glands and cells

The accumulation of [¹⁴C]aminopyrine (AP) is a valuable and widely used method to probe acid secretion of gastric glands and parietal cells. Usually, the dry weight of glands is used to normalize the AP accumulation ratio, and since the nonhomogeneity of the suspension makes it impossible to evenly distribute glands by simple pipetting, it is necessary to scrupulously dry and weigh each and every experimental sample. Thus, massive, time-consuming procedures of tube drying and weighing are involved. Moreover, the weighing of 1 mg dried gland samples in a 1-g Eppendorf tube introduces considerable sample variance. Here, we present a modified protocol to simplify the AP accumulation method by introducing a generic ³H labeling of protein for normalization. Freshly isolated glands were treated with high specific activity ³H-labeled succinimidyl propionate (³H-succ, 60 Ci/mmol) for 10 min at room temperature during the normal isolation/washing procedure. This reagent reacts with primary amines, and even at normal cell pH the efficiency of reaction (25–30%) is more than adequate. The ³H-labeled glands are then processed normally with simultaneous monitoring of ³H (representing gland amount) and AP (representing the extent of acid accumulation) in separate energy windows of a liquid scintillation counter. Dose- and time-dependent efficiency of ³H labeling were evaluated. The relations between labeling and gland protein and dry weight were linear. No detrimental effects of reagent were noted in the useful range of 1–3 nM ³H-succ. Although some limited sample weighing or protein determination must be made for each batch of ³H-labeled glands, this method avoids massive tube weighings and provides the convenience of double label counting with a highly reproducible method for normalizing data.     

Possible Role of Histamine in Rheumatoid Arthritis

Basophilocytes from patients with rheumatoid arthritis (RA) responded to leukocyte nuclei from normal persons with histamine release; a similar histamine release induced by the nuclear components RNA and DNA has been demonstrated previously. A role of histamine in RA is also supported by the findings of clinical improvement during treatment with H₁ and H₂ antihistamines in six of 12 patients with RA in active phase, whereas four showed definite deterioration.