Do Statins have a Role in Reduction/Prevention of Post‐PCI Restenosis?

The pathophysiology of post‐PCI restenosis involves neointimal formation that consists of three phases: thrombosis (within 24 h), recruitment (3–8 days), and proliferation, which starts on day 8 of PCI. Various factors suggested to be predictors/risks for restenosis include C‐reactive protein (CRP), inflammatory mediators (cytokines and adhesion molecules), oxygen radicals, advanced glycation end products (AGEs) and their receptors (RAGE), and soluble RAGE (sRAGE). The earlier noted factors produce thrombogenesis, vascular smooth muscle cell proliferation, and extracellular matrix formation. Statins have pleiotropic effects. Besides lowering serum cholesterol, they have various other biological effects including antiinflammatory, antithrombotic, CRP‐lowering, antioxidant, antimitotic, and inhibition of smooth muscle cell proliferation. They inhibit matrix metalloproteinase and cyclooxygenase‐2, lower AGEs, decrease expression of RAGE and increase levels of serum sRAGE. They also increase the synthesis of nitric oxide (NO) by increasing endothelial NO synthase expression and activity. Preprocedural statin therapy is known to reduce peri‐ and post‐PCI myonecrosis and reduce the need for repeat revascularization. There is evidence that statin‐eluting stents inhibit in‐stent restenosis in animal models. It is concluded that because of the above attributes of statins, they are suitable candidates for reduction of post‐PCI restenosis and post‐PCI myonecrosis. The future directions for the use of statins in reduction of post‐PCI restenosis and myonecrosis have been discussed.     

Pathophysiology of gastroesophageal reflux disease

The gastroesophageal junction is structurally complex and functionally designed to ensure the acid secreted by the most proximal gastric mucosa flows towards the stomach and not up onto the oesophageal squamous mucosa. The pattern and mechanism of reflux vary with the severity of reflux disease and this probably represents different ends of a spectrum rather than distinct pathophysiological mechanisms. Nearly all patients with severe reflux disease have hiatus hernia, however, a substantial proportion of patients with mild reflux disease do not, and this may be a result of intermittent or partial hiatus hernia undetectable by current available tools. The acid pocket is an area of post-prandial unbuffered gastric acidity immediately distal to the gastroesophageal junction and which is enlarged in patients with hiatus hernia. The acid pocket provides a reservoir of acid available to reflux when the intrinsic sphincter fails. Central obesity is an important factor in the aetiology of reflux and does this by the increased abdomino-thoracic pressure gradient inducing hiatus hernia and increasing the rate of flow of reflux when sphincter opens. Central obesity also induces short segment intrasphincteric reflux and thereby columnar metaplasia of the most distal oesophagus.     

Gastrointestinal radiation injury:Symptoms,risk factors and mechanisms

Ionising radiation therapy is a common treatment modality for different types of cancer and its use is expected to increase with advances in screening and early detection of cancer.Radiation injury to the gastrointestinal tract is important factor working against better utility of this important therapeutic modality.Cancer survivors can suffer a wide variety of acute and chronic symptoms following radiotherapy,which significantly reduces their quality of life as well as adding an extra burden to the cost of health care.The accurate diagnosis and treatment of intestinal radiation injury often represents a clinical challenge to practicing physicians in both gastroenterology and oncology.Despite the growing recognition of the problem and some advances in understanding the cellular and molecular mechanisms of radiation injury,relatively little is known about the pathophysiology of gastrointestinal radiation injury or any possible susceptibility factors that could aggravate its severity.The aims of this review are to examine the various clinical manifestations of post-radiation gastrointestinal symptoms,to discuss possible patient and treatment factors implicated in normal gastrointestinal tissue radiosensitivity and to outline different mechanisms of intestinal tissue injury.     

急性心房颤动模型心房肌超微结构改变及替米沙坦对其影响

目的观察急性心房颤动(简称房颤)模型心房肌细胞超微结构的改变及替米沙坦对其干预作用。方法30只新西兰纯种大白兔随机分为:假手术对照组、非给药模型组和给药模型组。用快速心房起搏法建立兔房颤模型,利用透射电镜观察房颤形成8 h后心房肌细胞超微结构改变。结果与假手术对照组比较,非给药模型组心房肌细胞超微结构有明显变化,如心肌细胞肌原纤维排列紊乱、线粒体肿胀、细胞器明显减少、细胞染色质凝集类似凋亡改变等,而给药模型组变化较轻。结论房颤时心房肌的组织细胞学会发生重构,血管紧张素受体阻滞剂类药物可拮抗房颤时的组织细胞重构。     

Change in pharmacological effect of endothelin receptor antagonists in rats with pulmonary hypertension: Role of ETB-receptor expression levels

Background and purposeThe endothelin (ET) system is activated in pulmonary arterial hypertension (PAH). The therapeutic value of pharmacological blockade of ET receptors has been demonstrated in various animal models and led to the current approval and continued development of these drugs for the therapy of human PAH. However, we currently incompletely comprehend what local modifications of this system occur as a consequence of PAH, particularly in small resistance arteries, and how this could affect the pharmacological response to ET receptor antagonists with various selectivities for the receptor subtypes. Therefore, the purposes of this study were to evaluate potential modifications of the pharmacology of the ET system in rat pulmonary resistance arteries from monocrotaline (MCT)-induced pulmonary arterial hypertension.Experimental approachET-1 levels were quantified by ELISA. PreproET-1, ET_A and ET_B receptor mRNA expressions were quantified in pulmonary resistance arteries using Q-PCR, while protein expression was evaluated by Western blots. Reactivity to ET-1 of isolated pulmonary resistance arteries was measured in the presence of ET_A (A-147627), ET_B (A-192621) and dual ET_A/B (bosentan) receptor antagonists.Key resultsIn rats with PAH, plasma ET-1 increased (p < 0.001) while pulmonary levels were reduced (p < 0.05). In PAH arteries, preproET-1 (p < 0.05) and ET_B receptor (p < 0.001) gene expressions were reduced, as were ET_B receptor protein levels (p < 0.05). ET-1 induced similar vasoconstrictions in both groups. In arteries from sham animals, neither bosentan nor the ET_A or the ET_B receptor antagonists modified the response. In arteries from PAH rats, however, bosentan and the ET_A receptor antagonist potently reduced the maximal contraction, while bosentan also reduced sensitivity (p < 0.01).Conclusions and implicationsThe effectiveness of both selective ET_A and dual ET_A/B receptor antagonists is markedly increased in PAH. Down-regulation of pulmonary resistance arteries ET_B receptor may contribute to this finding.     

Pathogenesis and pathophysiology of anemia in HIV infection

 Anemia occurs frequently among patients seropositive for human immunodeficiency virus (HIV), but its multifactorial origin complicates its differential diagnosis and adequate treatment. In addition, the etiology of anemia in HIV infection often remains unclear. In recent years several attempts have been undertaken to elucidate the mechanisms leading to HIV-associated anemia. Direct infection of erythroid progenitors has been discussed, but could not be proven. Furthermore, soluble factors like HIV proteins and cytokines have been suggested to inhibit growth of hematopietic cells in the bone marrow of HIV-infected patients. However, so far no statements can be made whether these factors are directly involved in myelosuppression or mediate their effect by inhibiting growth-factor synthesis. Opportunistic complications represent the underlying cause for anemia in a large number of HIV-infected patients. Next to this rather obvious reason for anemia, iatrogenic anemia induced by myelosuppressive drugs is also very common. It is of note, however, that modern dosages of <600 mg zidovudine (ZDV) daily rarely cause anemia. Instead, other drugs that can induce anemia itself or by enhancing ZDV plasma concentrations must be considered important contributing factors. Deficiency of vitamin B12, folate and iron are frequently reported in HIV patients. However, specific investigations revealed appropriate storage amounts of these micronutrients. Supplementation may be beneficial in some patients, but often fails to reverse anemia in this population. In anemic HIV patients reticulocytopenia is a consistent finding. Additionally, inadequately low endogenous erythropoietin concentrations have been repeatedly reported. Thus, it is speculated that a blunted erythropoietin feedback mechanism contributes substantially to the pathogenesis of anemia in HIV patients. Received: 16 September 1997 / Accepted: 25 September 1997     

Association between microRNA polymorphisms and chronic pancreatitis

BackgroudMicroRNAs play important roles in the development and progression of many human diseases. mir-146a could significantly suppress the induction of proinflammatory cytokines IL-1β, IL-6, TNF-α, NF-κB and chemokine MCP-1, which might play important roles in chronic pancreatitis. This study was conducted to evaluate the association between mir-146a rs2910164, a functional polymorphism in the pre-mir-146a, and chronic pancreatitis risk.MethodsThe rs2910164 genotypes were determined in 165 patients with chronic pancreatitis and 200 healthy controls who were frequency matched for age and gender. One single nucleotide polymorphism (rs2910164) was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RLFP).ResultsThe frequency of individuals who carried [G] allele was significantly higher in cases (62.7%) than in controls (53.7%, p = 0.015), which resulted in a statistically significant pathogenic effect associated with this variant allele (OR: 1.448, CI: 1.076–1.950; p = 0.015). The GC and GG genotypes showed strong and significant increased risk for complication of chronic pancreatitis (OR = 3.668, 95%CI = 1.233–10.916, p = 0.019; OR = 5.667, 95%CI = 1.852–17.336, p = 0.002). The individuals carrying G allele confer a lower expression level of mature mir-146a.ConclusionThese findings suggest that the mir-146a rs2910164 may contribute to genetic susceptibility to chronic pancreatitis, and that mir-146a might be involved in chronic pancreatitis development.     

机械通气困难撤机/延迟撤机的病理生理学因素与解决策略

随着有创机械通气在临床上的广泛使用,救治了大量的危重症患者,但也有较多使用有创通气的患者由于各种原因导致撤机困难,严重影响患者的预后和生活质量.该文将从机械通气困难撤机/延迟撤机的病理生理学角度,阐述临床上困难撤机/延迟撤机的相关要点,总结并提出对应的处理措施.     

Colon ischemia: A comprehensive review

The clinical and endoscopic features of colon ischemia (CI) are non-specific. CI is correctly identified at the time of presentation in only 9% of patients is. The true incidence is likely underestimated because many mild cases resolve spontaneously without medical treatment. Furthermore, since most cases of CI are transient, and no specific cause is detected they are often considered to be “idiopathic”. In the setting of severe CI correct diagnosis and prompt recognition and therapy as well as identification of underlying causes are crucial for a favourable outcome. Although less severe, mild cases may present with similar symptoms, the prognosis and management are completely different and managed conservatively rather than with surgery. Unfortunately, data from most studies and current guidelines do not provide recommendations on the long-term management of CI or about the need for endoscopic follow-up to detect the development chronic, recurrent and/or ischemic colonic strictures. In this review, we focus on the definition of CI, its aetiology, and patterns of presentation. We highlight the pharmacological and/or endoscopic management as determined severity of disease that allow for improved outcomes. Prompt recognition and treatment using a multidisciplinary approach are essential for successful management of severe CI because mortality rates are significantly higher when the diagnosis is delayed.     

对氧磷对血管内皮细胞的损伤作用及机制探讨

目的为探讨有机磷酸酯对血管内皮细胞和血管内皮功能是否有直接的损伤作用。方法用不同浓度的对氧磷分别与大鼠离体血管环和培养的人脐静脉单层内皮细胞共孵不同的时间,以乙酰胆碱引起的血管内皮依赖性舒张反应和单层内皮细胞通透性等为观察指标,检测对氧磷对血管内皮的损伤作用。结果对氧磷（36.3nmol/L-36.3μmol/L）与血管环共孵,呈浓度和时间依赖性地显著抑制乙酰胆碱诱导的内皮依赖性舒张反应,而对硝普钠引起的非内皮依赖性舒张反应没有明显的影响。对氧磷与内皮细胞共孵不同的时间,呈浓度和时间依赖性地显著增加单层内皮细胞的通透性。对氧磷在损伤血管内皮的同时也导致了血管组织及细胞培养液中一氧化氮浓度和超氧化物歧化酶活性的降低、脂质过氧化代谢产物丙二醛浓度的升高。加入左旋精氨酸能部分拮抗对氧磷对血管内皮功能的损伤作用,用阿托品预处理则不影响对氧磷的作用。结论该研究提示对氧磷对血管内皮细胞有直接损伤作用,其机制可能与对氧磷诱发氧化应激,进而导致脂质过氧化反应发生和增加内皮细胞的通透性有关。