肛门直肠功能紊乱在消化科就诊患者中占有相当比例,其中包括各种器质性和功能性疾病.大便失禁属于排便功能紊乱的一种,是消化科医师常遇到的棘手问题,尤其在高龄患者、危重病人及截瘫病人中发病率居高不下[1].大便失禁可分为完全失禁和不完全失禁:大便完全失禁指不能随意控制粪便及气体的排出;而大便不完全失禁指可控制干便排出,却不能控制稀便和气体排出.疾病本身虽不能致命,却会带给患者难言的身心痛苦和生活不便,乃至造成人格变化,值得重视.但由于既往认识不足及诊断方法缺乏,迄今这些问题仍被忽视。

Fecal incontinence

Focal cerebral ischemia is associated with expression of both inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), enzymes whose reaction products contribute to the evolution of ischemic brain injury. We tested the hypothesis that, after cerebral ischemia, nitric oxide (NO) produced by iNOS enhances COX-2 activity, thereby increas- ing the toxic potential of this enzyme. Cerebral ischemia was produced by middle cerebral artery occlusion in rats or mice. Twenty-four hours after ischemia in rats, iNOS-immunore- active neutrophils were observed in close proximity (<20 mm) to COX-2-positive cells at the periphery of the infarct. In the olfactory bulb, only COX-2 positive cells were observed. Cerebral ischemia increased the concentration of the COX-2 reaction product prostaglandin E2 (PGE2) in the ischemic area and in the ipsilateral olfactory bulb. The iNOS inhibitor aminoguanidine reduced PGE2 concentration in the infarct, where both iNOS and COX-2 were expressed, but not in the olfactory bulb, where only COX-2 was expressed. Postischemic PGE2 accumulation was reduced significantly in iNOS null mice compared with wild-type controls (C57BLy6 or SV129). The data provide evidence that NO produced by iNOS inf lu- ences COX-2 activity after focal cerebral ischemia. Pro- inf lammatory prostanoids and reactive oxygen species pro- duced by COX-2 may be a previously unrecognized factor by which NO contributes to ischemic brain injury. The patho- genic effect of the interaction between NO, or a derived specie, and COX-2 is likely to play a role also in other brain diseases associated with inf lammation.

Interaction between inducible nitric oxide synthase and cyclooxygenase-2 after cerebral ischemia (middle cerebral artery occlusionyaminoguanidineyNS-398ygene expressionyinducible nitric oxide synthase null mice)

Background—Coronary spasm plays an important role in the pathogenesis of ischemic heart diseases in general. However, the precise mechanism(s) responsible for coronary spasm remains to be elucidated, and we examined the molecular genetics of coronary spasm. Methods and Results—We searched for the possible mutations in the endothelial nitric oxide synthase (eNOS) gene in patients with coronary spasm. In this study, we demonstrate the existence of 3 linked mutations in the 5′-flanking region of the eNOS gene (T−786→C, A−922→G, and T−1468→A). The incidence of the mutations was significantly greater in patients with coronary spasm than in the control group (P<0.0001). Multiple logistic regression analysis with forward stepwise selection using the environmental risk factors and the eNOS gene variant revealed that the most predictive independent risk factor for coronary spasm was the mutant allele (P<0.0001). As assessed by luciferase reporter gene assays, the T−786→C mutation resulted in a significant reductio...

T−786→C Mutation in the 5′-Flanking Region of the Endothelial Nitric Oxide Synthase Gene Is Associated With Coronary Spasm

Ghrelin is a novel GH-releasing peptide that may also induce vasodilation and a positive energy balance through GH-independent mechanisms. However, the hemodynamic, renal, and hormonal effects of ghrelin in patients with chronic heart failure (CHF) remain unknown. Accordingly, 12 patients with CHF were given an iv infusion of human ghrelin (0.1 microg/kg.min) or placebo. Ghrelin significantly decreased mean arterial pressure (-9 mm Hg, P < 0.05) without a significant change in heart rate. Ghrelin significantly increased cardiac index (+25%, P < 0.05) and stroke volume index (+30%, P < 0.05), although it did not significantly alter mean pulmonary arterial pressure or pulmonary capillary wedge pressure. Infusion of ghrelin induced a marked increase in serum GH level (15-fold), associated with slight increases in circulating epinephrine, ACTH, cortisol, and PRL. Infusion of ghrelin did not significantly alter urine volume, urinary sodium excretion, or creatinine clearance. These hemodynamic, renal and hormonal parameters remained unchanged during placebo infusion. In summary, iv infusion of ghrelin, a potent GH-releasing peptide, had beneficial hemodynamic effects in patients with CHF in the absence of renal effects.

Hemodynamic, Renal and Hormonal Effects of Ghrelin Infusion in Patients With Chronic Heart Failure

Circadian and seasonal rhythms are a fundamental feature of all living organisms and their organelles. Biological rhythms are responsible for daily food intake; the period of hunger and satiety is controlled by the central pacemaker, which resides in the suprachiasmatic nucleus (SCN) of the hypothalamus, and communicates with tissues via bidirectional neuronal and humoral pathways. The molecular basis for circadian timing in the gastrointestinal tract (GIT) involves interlocking transcriptional/translational feedback loops which culminate in the rhythmic expression and activity of a set of clock genes and related hormones. Interestingly, it has been found that clocks in the GIT are responsible for the periodic activity (PA) of its various segments and transit along the GIT; they are localized in special interstitial cells, with unstable membrane potentials located between the longitudinal and circular muscle layers. The rhythm of slow waves is controlled in various segments of the GIT: in the stomach (about 3 cycles per min), in the duodenum (12 cycle per min), in the jejunum and ileum (from 7 to 10 cycles per min), and in the colon (12 cycles per min). The migrating motor complex (MMC) starts in the stomach and moves along the gut causing peristaltic contractions when the electrical activity spikes are superimposed on the slow waves. GIT hormones, such as motilin and ghrelin, are involved in the generation of MMCs, while others (gastrin, ghrelin, cholecystokinin, serotonin) are involved in the generation of spikes upon the slow waves, resulting in peristaltic or segmental contractions in the small (duodenum, jejunum ileum) and large bowel (colon). Additionally, melatonin, produced by neuro-endocrine cells of the GIT mucosa, plays an important role in the internal biological clock, related to food intake (hunger and satiety) and the myoelectric rhythm (produced primarily by the pineal gland during the dark period of the light-dark cycle). This appears to be an endocrine encoding of the environmental light-dark cycle, conveying photic information which is used by organisms for both circadian and seasonal organization. Motor and secretory activity, as well as the rhythm of cell proliferation in the GIT and liver, are subject to many circadian rhythms, mediated by autonomic cells and some enterohormones (gastrin, ghrelin and somatostatin). Disruption of circadian physiology, due to sleep disturbance or shift work, may result in various gastrointestinal diseases, such as irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD) or peptic ulcer disease. In addition, circadian disruption accelerates aging, and promotes tumorigenesis in the liver and GIT. Identification of the molecular basis and role of melatonin in the regulation of circadian rhythm allows researchers and clinicians to approach gastrointestinal diseases from a chronobiological perspective. Clinical studies have demonstrated that the administration of melatonin improves symptoms in patients with IBS and GERD. Moreover, our own studies indicate that melatonin significantly protects gastrointestinal mucosa, and has strong protective effects on the liver in patients with non-alcoholic steatohepatitis (NASH). Recently, it has been postulated that disruption of circadian regulation may lead to obesity by shifting food intake schedules. Future research should focus on the role of clock genes in the pathophysiology of the GIT and liver.

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Gut clock: implication of circadian rhythms in the gastrointestinal tract

Our objective was to investigate the effects of chronic unpredictable mild stress (CUMS) with or without selective serotonin reuptake inhibitor (fluoxetine) and anti-oxidant (resveratrol) on testicular functions and oxidative stress in rats. Fifty male rats were divided into 2 groups; control and CUMS. CUMS group was further subdivided into 4 subgroups administered water, fluoxetine, resveratrol and both. Sucrose intake, body weight gain, serum corticosterone, serotonin and testosterone levels, sperm count and motility, testicular malondialdehyde, superoxide dismutase (SOD), catalase, glutathione (GSH), and gene expression of steroidogenic acute-regulatory (StAR) protein and cytochrome P450 side chain cleavage (P450scc) enzyme were evaluated. CUMS decreased sucrose intake, weight gain, anti-oxidants (SOD, catalase, GSH), testosterone, serotonin, StAR and cytochrome P450scc gene expression, sperm count and motility and increased malondialdehyde and corticosterone. Fluoxetine increased malondialdehyde, sucrose intake, weight gain, serotonin and decreased anti-oxidants, StAR and cytochrome P450scc gene expression, sperm count and motility, testosterone, corticosterone in stressed rats. Administration of resveratrol increased anti-oxidants, sucrose intake, weight gain, serotonin, StAR and cytochrome P450scc gene expression, testosterone, sperm count and motility, and decreased malondialdehyde and corticosterone in stressed rats with or without fluoxetine. In conclusion, CUMS induces testicular dysfunctions and oxidative stress. While treatment of CUMS rats with fluoxetine decreases the depressive behavior, it causes further worsening of testicular dysfunctions and oxidative stress. Administration of resveratrol improves testicular dysfunctions and oxidative stress that are caused by CUMS and further worsened by fluoxetine treatment.

/pdf/effect-of-fluoxetine-and-resveratrol-on-testicular-functions-pzuwwc8ekt.pdf

Effect of fluoxetine and resveratrol on testicular functions and oxidative stress in a rat model of chronic mild stress-induced depression

Indomethacin (IND) is a non-steroid anti-inflammatory agent that is known to induce severe gastric mucosal lesions. In this study, we investigated the protective effect of selenium (SEL), grape seed extract (GSE), and both on IND-induced gastric mucosal ulcers in rats. Sprague–Dawley rats (200–250 g) were given SEL, GSE, and both by oral gavage for 28 days, and then gastric ulcers were induced by oral administration of 25 mg/kg IND. Malondialdehyde (MDA), non-enzymatic (reduced glutathione, GSH) and enzymatic (superoxide dismutase, catalase, and glutathione peroxidase) antioxidants, prostaglandin E2 (PGE2) in gastric mucosa, and serum tumor necrosis factor alpha (TNF-α) were measured. Moreover, gastric ulcer index and preventive index were determined. Indomethacin increased the gastric ulcer index, MDA, TNF-α, and decreased PGE2 and non-enzymatic (GSH) and enzymatic (superoxide dismutase, catalase, and glutathione peroxidase) antioxidants. Pretreatment with SEL, GSE, and both significantly decreased the gastric ulcer index, MDA, and TNF and increased antioxidants and PGE2. Histopathological observations confirm the gastric ulcer index and biochemical parameters. Selenium and GSE have a protective effect against IND-induced gastric ulcers through prevention of lipid peroxidation, increase of GSH, activation of radical scavenging enzymes, PGE2 generation, and anti-inflammatory activity. Co-administration of GSE and SEL is more effective than GSE or SEL alone.

Effect of selenium and grape seed extract on indomethacin-induced gastric ulcers in rats

Gastro-Esophageal Reflux Disease (GERD) defined as a condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications Many drugs are used for the treatment of GERD such as omeprazole (a proton pump inhibitor) which is a widely used antiulcer drug demonstrated to protect against esophageal mucosal injury Melatonin has been found to protect the gastrointestinal mucosa from oxidative damage caused by reactive oxygen species in different experimental ulcer models The aim of this study is to evaluate the role of exogenous melatonin in the treatment of reflux disease in humans either alone or in combination with omeprazole therapy 36 persons were divided into 4 groups (control subjects, patients with reflux disease treated with melatonin alone, omeprazole alone and a combination of melatonin and omeprazole for 4 and 8 weeks) Each group consisted of 9 persons Persons were subjected to thorough history taking, clinical examination, and investigations including laboratory, endoscopic, record of esophageal motility, pH-metry, basal acid output and serum gastrin Melatonin has a role in the improvement of Gastro-esophageal reflux disease when used alone or in combination with omeprazole Meanwhile, omeprazole alone is better used in the treatment of GERD than melatonin alone The present study showed that oral melatonin is a promising therapeutic agent for the treatment of GERD It is an effective line of treatment in relieving epigastric pain and heartburn However, further studies are required to confirm the efficacy and long-term safety of melatonin before being recommended for routine clinical use QA13NCT00915616

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The potential therapeutic effect of melatonin in Gastro-Esophageal Reflux Disease.

High fat diet (HFD) is a common cause of metabolic syndrome and type 2 diabetes mellitus. Published data showed that HFD and subsequent dyslipidemia are major triggers for oxidative stress. Forty-eight male Sprague–Dawley rats, weighing 170–200 g, were divided into six groups: control, control with vitamin E (100 mg/kg/day, i.p.), control with simvastatin (SIM) (10 mg/kg of body weight/day), HFD, HFD with vitamin E, and HFD with SIM. Standard and high cholesterol diets were given for 15 weeks and SIM and vitamin E were added in the last 4 weeks. In all rats, serum vitamin E, total cholesterol (TC), triglycerides (TG), low (LDL) and high (HDL) density lipoproteins, alanine (ALT) and aspartate (AST) transaminases, alkaline phosphatase (ALP), and gamma glutamyl transpeptidase (GGT) as well as cardiac and hepatic thiobarbituric acid-reactive substances (TBARS) and antioxidants (reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT)) were measured. Also, electrocardiogram (ECG) was recorded. HFD significantly increased QTc interval, heart rate (HR), serum TC, TG, LDL, ALT, AST, ALP, GGT, liver TG, and cardiac and hepatic TBARS but decreased antioxidants and HDL, while SIM decreased HR, liver TG, serum TC, TG, and LDL and increased HDL in HFD rats. Vitamin E had no effect. Moreover, SIM and vitamin E decreased QTc interval, serum ALT, AST, ALP, GGT, and cardiac and hepatic TBARS and increased antioxidants in HFD rats. Histopathological observations confirm the biochemical parameters. SIM and vitamin E slow progression of hypercholesterolemia-induced oxidative stress in liver and heart and improve their functions.

Simvastatin and vitamin E effects on cardiac and hepatic oxidative stress in rats fed on high fat diet

The prevalence of insulin resistance syndrome increases during menopause with the overproduction of reactive oxygen species and impairment of the free radical scavenger function. Therefore, we inve...

Amr M. Abbas

Papers

Effect of fluoxetine and resveratrol on testicular functions and oxidative stress in a rat model of chronic mild stress-induced depression

Effect of selenium and grape seed extract on indomethacin-induced gastric ulcers in rats

The potential therapeutic effect of melatonin in Gastro-Esophageal Reflux Disease.

Simvastatin and vitamin E effects on cardiac and hepatic oxidative stress in rats fed on high fat diet

Effects of 17β-estradiol and antioxidant administration on oxidative stress and insulin resistance in ovariectomized rats.