Role of dietary phospholipids and phytosterols in protection against peptic ulceration as shown by experiments on rats.

Geographically the prevalence of duodenal ulceration is related to the staple foods in the diet in regions of developing countries where the diet is stable. It is higher in regions where the diet is based on milled rice, refined wheat or maize, yams, cassava, sweet potato, or green bananas, and is lower in regions where the staple diet is based on unrefined wheat or maize, soya, certain millets or certain pulses. Experiments on rat gastric and duodenal ulcer models showed that it was the lipid fraction in staple foods from low prevalence areas that was protective against both gastric and duodenal ulceration, including ulceration due to non-steroidal anti-inflammatory drugs (NSAIDs). It also promoted ulcer healing. The lipid from the pulse, Dolichos biflorus, horse gram which was highly protective was used to identify the fractions with protective activity in the lipid. The protective activity lay in the phospholipid, sterol and sterol ester fractions. In the phospholipid fraction phosphatidyl choline (lethicin) and phosphatidyl ethanolamine (cephalin) were predominant. In the sterol fraction the sub-fractions showing protective activity contained ß-sitosterol, stigmasterol, and an unidentified isomer of ß-sitosterol. The evidence from animal models shows that certain dietary phospholipids and phytosterols have a protective action against gastroduodenal ulceration, both singly and in combination. This supports the protective role of staple diets in areas of low duodenal ulcer prevalence and may prove to be of importance in the prevention and treatment of duodenal ulceration and management of recurrent ulcers. A combination of phospholipids and phytosterols could also play an important role in protection against ulceration due to NSAIDs.

Cystamine induces AIF-mediated apoptosis through glutathione depletion.

Cystamine and its reduced form cysteamine showed protective effects in various models of neurodegenerative disease, including Huntington's disease and Parkinson's disease. Other lines of evidence demonstrated the cytotoxic effect of cysteamine on duodenal mucosa leading to ulcer development. However, the mechanism for cystamine cytotoxicity remains poorly understood. Here, we report a new pathway in which cystamine induces apoptosis by targeting apoptosis-inducing factor (AIF). By screening of various cell lines, we observed that cystamine and cysteamine induce cell death in a cell type-specific manner. Comparison between cystamine-sensitive and cystamine-resistant cell lines revealed that cystamine cytotoxicity is not associated with unfolded protein response, reactive oxygen species generation and transglutaminase or caspase activity; rather, it is associated with the ability of cystamine to trigger AIF nuclear translocation. In cystamine-sensitive cells, cystamine suppresses the levels of intracellular glutathione by inhibiting γ-glutamylcysteine synthetase expression that triggers AIF translocation. Conversely, glutathione supplementation completely prevents cystamine-induced AIF translocation and apoptosis. In rats, cysteamine administration induces glutathione depletion and AIF translocation leading to apoptosis of duodenal epithelium. These results indicate that AIF translocation through glutathione depletion is the molecular mechanism of cystamine toxicity, and provide important implications for cystamine in the neurodegenerative disease therapeutics as well as in the regulation of AIF-mediated cell death.

Deep-sea water containing selenium provides intestinal protection against duodenal ulcers through the upregulation of Bcl-2 and thioredoxin reductase 1.

Deep-sea water (DSW), which is rich in micronutrients and minerals and with antioxidant and anti-inflammatory qualities, may be developed as marine drugs to provide intestinal protection against duodenal ulcers. We determined several characteristics in the modified DSW. We explored duodenal pressure, oxygenation, microvascular blood flow, and changes in pH and oxidative redox potential (ORP) values within the stomach and duodenum in response to tap water (TW, hardness: 2.48 ppm), DSW600 (hardness: 600 ppm), and DSW1200 (hardness: 1200 ppm) in Wistar rats and analyzed oxidative stress and apoptosis gene expressions by cDNA and RNA microarrays in the duodenal epithelium. We compared the effects of drinking DSW, MgCl2, and selenium water on duodenal ulcers using pathologic scoring, immunohistochemical analysis, and Western blotting. Our results showed DSW has a higher pH value, lower ORP value, higher scavenging H2O2 and HOCl activity, higher Mg2+ concentrations, and micronutrients selenium compared with TW samples. Water infusion significantly increased intestinal pressure, O2 levels, and microvascular blood flow in DSW and TW groups. Microarray showed DSW600, DSW1200, selenium water upregulated antioxidant and anti-apoptotic genes and downregulated pro-apoptotic gene expression compared with the TW group. Drinking DSW600, DSW1200, and selenium water but not Mg2+ water significantly enhanced Bcl-2 and thioredoxin reductase 1 expression. Bax/Bcl-2/caspase 3/poly-(ADP-ribose)-polymerase signaling was activated during the pathogenesis of duodenal ulceration. DSW drinking reduced ulcer area as well as apoptotic signaling in acetic acid-induced duodenal ulcers. DSW, which contains selenium, provides intestinal protection against duodenal ulcers through the upregulation of Bcl-2 and thioredoxin reductase 1.

[Glycoproteins of mucus of gastric and duodenal wall surface during ulcerogenesis and the impact of fenugreek].

The comparative evaluation of qualitative and quantitative composition of glycoproteins of gastric and duodenal wall surface layer of protective mucus in the normal, at the modeling of ulcers in rats and at the introduction to animals with ulcerative lesions of fenugreek extract carried out. It was shown in control (normally) the general level of glycosylation of glycoproteins gastric mucus is 1.7 times more than the duodenum. Under acute stress model ulceration in the stomach mucus decrease in hexosamine (1.4 times), galactose (2.2 times), fucose (1.3-fold) and an increase in NANA (3.6 times) observed. Under cysteamine model ulceration in duodenal mucus increase galactose (2.7 times), NANA (2.4 times), fucose (1.8-fold) but significant decrease in the amount of hexosamines 3 times compared to the control occurred. It was proved the protective effect of fenugreek extract to the wall surface mucus of the stomach and duodenum mucosa under conditions modeling ulceration in rats.

Anti-inflammatory and carbonic anhydrase restoring actions of yam powder (Dioscorea spp) contribute to the prevention of cysteamine-induced duodenal ulcer in a rat model.

Increased acid output, accompanied with a defective defense system, is considered a fundamental pathogenesis of duodenal ulcer (DU). However, relapse of DU occurs despite proton pump inhibitors and H2 receptor antagonists, hence imposing the enforcement of the defense system. Dried powder of the yam tuber (Dioscorea spp) has been used in traditional folk medicine as a nutritional fortification. We hypothesized that dried-yam powder would prevent DU through improvement of anti-inflammatory actions and carbonic anhydrase (CA) activity. Therefore, we investigated the preventive effects of dried-yam powder against the cysteamine-induced DU and elucidated the underlying mechanisms. Duodenal ulcers were induced in Sprague-Dawley rats by intragastric administration of 500 mg/kg cysteamine-HCl. The dried-yam powder was used as a pretreatment before the cysteamine-HCl. The number and size of DU were measured. The expressions of inflammation mediators were checked in duodenal tissues, and the expressions of CAs and malondialdehyde levels were also examined. Cysteamine provoked perforated DU, whereas dried-yam powder significantly prevented DU as much as pantoprazole and significantly reduced the incidence of perforation. The messenger RNA expressions of cyclooxygenase-2 and inducible nitric oxide synthase were remarkably decreased in the yam group compared with the cysteamine group, and the serum levels of proinflammatory cytokines including interleukin-1ß, interleukin-6, and tumor necrosis factor were significantly attenuated in the yam group. Cysteamine significantly decreased the expression of CAs, whereas yam treatment significantly preserved the expressions of CA IX, XII, and XIV. In conclusion, dried-yam powder exerts a significant protective effect against cysteamine-induced DU by lowering the activity of inflammatory cytokines and free radicals and restoring the activity of CAs, except in CA IV.

[The influence of melatonin included in the combined treatment of antichelicobaterial therapy on immunohistochemical characteristics of gastric epitheliocytes from patients with duodenal ulcer].

The study included 100 patients with duodenal ulcer (DU), 30 with chronic non-atrophic gastritis (CNAG), 30 with chronic atrophic gastritis (CAG) and 12 practically healthy subjects. All patients with DU and CNAG had morphologically confirmed H. pylori infection. The patients with DU were divided into 2 groups each including age-matched subjects with endoscopically, morphologically, immunohistochemically identical characteristics. Those of group 1 underwent eradication of H. pylori by a traditional 7-day procedure including the use of omeprazole (20 mg BID), claritromycin (500 mg BID) and amoxicillin (1000 mg BID). In group 2 this scheme was supplemented by melatonin (3 mg before bedtime). Patients of group 1 continued to use omeprazole and those in group 2 omeprazole + melatonin till the end of the second month. Healthy subjects and patients with CAG served as controls. All patients underwent FGDS on weeks 2 and 4, immunohistochemical study was conducted to detect endothelin-1 and melatonin-positive cells, apoptotic activity of mucosal epitheliocytes from gastric antrum was determined before and 6 weeks after the onset of therapy. It was shown that introduction of melatonin in the scheme of eradication therapy increases efficacy of H. pylori elimination and accelerates DU cicatrization. Two-month therapy with omeprazole + melatonin more effectively normalizes immunohistochemical parameters (endothelin-1 and melatonin-positive cells) and epitheliocyte apoptotic activity, than omeprazole alone.

[Clinical and morphological substantiation of SMC-peloidotherapy for the management of duodenal pathology].

This study included 112 patients presenting with duodenal ulcer disease and 65 ones with chronic duodenitis treated with the use of sinusoidal modulated current (SMC) electrophoresis in combination with peloidotherapy (peat muds of the Uva health resort, Republic of Udmurtia). This treatment was shown to produce positive effect on the proliferative activity of duodenal epithelium.

Prophylactic role of a herbomineral drug "Thamira parpam" against cysteamine-induced oxidative stress in liver and duodenum of rats.

Copper is known as Gunma Kaalan in Siddha literature, which means that the drug is effective for healing ulcers. The herbomineral drug "Thamira parpam" is prepared by calcining the purified copper foils with rock salt, lime juice, bracteated birth wort juice, and Alangium root decoction according to Siddha medicine. Our study investigated the possible role of Thamira parpam (TP) in the management of cysteamine-induced duodenal ulcers. Cysteamine (400 mg kg(-1) body weight(-1), two doses at 4 h interval) orally given to rats resulted in high ulcer index, increased TBARS with concomitant depletion of antioxidants such as superoxide dismutase, glutathione, glutathione peroxidase, and inflammatory markers cathepsin D, and myeloperoxidase (p < 0.01). Herbomineral drug TP (0.5, 1, and 2 mg/kg, p.o.) challenged with cysteamine attenuated the elevation of TBARS and imbalance of antioxidants. In the increases in liver inflammatory markers, tissue histopathology changes were not severe in TP treatment. Positive control omeprazole (25 mg/kg, body weight, orally) showed considerable protection against anomaly in biochemical parameters and tissue histology. Hence, our results indicate that the attenuation of oxidative stress by the herbomineral drug in experimentally induced damage to liver and duodenum of rats could be mediated by free radical quenching property.

[The effectiveness of SCENAR therapy in complex treatment of duodenal ulcer, and the mechanisms of its action].

A new technique of low-frequency modulated electric current therapy, SCENAR therapy, was used in treatment of 103 patients with duodenal ulcer (DU). The influence of SCENAR therapy on the main clinical and functional indices of a DU relapse was studied. It was shown that SCENAR therapy, which influences disturbed mechanisms of adaptive regulation and self-regulation, led to positive changes in most of the parameters under study. Addition of SCENAR therapy to the complex conventional pharmacotherapy fastened ulcer healing, increased the effectiveness of Helicobacter pylori eradication, and improved the condition of the gastroduodenal mucosa.

An extensive metabolizer with recurrent ulcer responding to high dose of lansoprazole.

A 51-year-old man underwent surgery for duodenal ulcer in 1983. Ulcer recurred several times. Recently, the patient was receiving 30 mg/day of lansoprazole. On June 15, 2001 hemorrhagic recurrent ulcer was diagnosed. Analysis of CYP2C19 enzyme genotype indicated that the patient was a heterozygous extensive metabolizer, suggesting that 30 mg/day of lansoprazole did not produce effective concentrations of drug in the serum. The dose of lansoprazole was increased to 60 mg/day, and intragastric pH monitoring revealed that a pH > or = 3 was maintained for 99.8% of a 24-hour period, as compared with a previous value of 88.3%. After 3 weeks of treatment, endoscopic examination showed that a red scar had formed at the ulcer site.

[Energetic aspects of adaptation processes and rehabilitation]. / Energeticheskie aspekty adaptatsionnykh protsessov i vosstanovitel'noe lechenie.

The study of energy metabolism and phenotypical adaptation in patients with ulcer disease has revealed deficiency of energy metabolism and defective phenotypical adaptation in the form of its tension or failure of adaptive processes. Sanatorium treatment with oral intake of mineral water, mineral baths, fangotherapy, limontar-electrophoresis and millimetric waves promoted normalization of energy metabolism and adaptive processes. Impact of different physiotherapeutic factors on energy metabolism and adaptation of the organism is described.

Involvement of nitric oxide in the gastroprotective effects of an aqueous extract of Pfaffia glomerata (Spreng) Pedersen, Amaranthaceae, in rats.

The plants belonging to Pfaffia genus are used in folk medicine to treat gastric disturbances. This study examined the effects of an aqueous extract of Pfaffia glomerata (Spreng) Pedersen (AEP) on the gastrointestinal tract. Wistar rats were pretreated orally (p.o.) with the AEP (125, 250, 500 and 1000 mg.kg(-1)) before induction of ulcers by hypothermic restraint stress (HRS, 3 h restraint stress at 4 degrees C), ethanol (ET, 70%; 0.5 ml/animal; p.o.) or indomethacin (IND, 20 mg.kg(-1); s.c.). Control animals received water (C) or ranitidine (60 mg.kg(-1)) p.o. The AEP protected rats against HRS and ET-induced ulcers, but was not able to protect the gastric mucosa against IND-induced ulcers. When injected into the duodenal lumen, the AEP reduced total acidity and both basal and histamine-stimulated acid secretion in pylorus-ligated rats. In addition, gastric secretion from AEP-treated animals exhibited increased concentrations of nitrite and nitrate. Treatment of animals with L-NAME (120 mg.kg(-1), p.o.) prevented both the reduction of total acidity and the increase in NOx levels promoted by AEP treatment. In conclusion, AEP effectively protected the gastric mucosa and inhibited gastric acid secretion in rats, probably by involving the histaminergic pathway and an enhanced production of nitric oxide in the stomach.

[SMC-electrophoresis of peat mud in the treatment of patients with duodenal ulcer in outpatient care unit]. / Opyt lecheniia bol'nykh iazvennoi bolezn'iu dvenadtsatiperstnoi kishki CMT-élektroforezom torfianoi lechebnoi griazi v usloviiakh dnevnogo statsionara.

To study collagen metabolism in reparative regeneration of duodenal ulcer in response to peat mud electrophoresis of Uva sanatorium using sinusoidal modulated currents (SMC) as monotherapy in a day hospital, 82 duodenal ulcer patients in exacerbation or attenuation were examined. They received SMC-electrophoresis of peat mud diluted by sulfate sodium-calcium mineral water Uvinskaya of moderate mineralization. The dynamics of clinico-endoscopic and morphological picture of the disease was controlled with fibrogastroduodenoscopy with target biopsy of the periulcer zone and antral stomach, investigation of secretory and acid-producing function of the stomach, hormone profile and collagen metabolism. Positive changes were found attributed to favourable shifts in the hormone status and normalization of collagen metabolism in duodenal mucosa.

Effect of xiaokuiling prescription on the expression of HSP72, HSP B in gastric mucosa of patients with Helicobacter pylori-associated duodenal ulcer.

In order to investigate the mechanism of Xiaokuiling prescription (XKL) in the treatment of Helicobacter pylori (HP)-associated duodenal ulcer (DU) and the pathophysiologic role of heat shock proteins (HSPs) in the healing of ulcer, the expression of HSP72 and HSP B in gastric mucosa was detected by using SABC immunohistochemistry method and processed by micro-image analysis system. The method of Western blotting was used to measure the contents of HSP72 and HSP B in the tissue emulsion of gastric mucosa. The results were as follows: (1) HSP72 expression of the gastric mucosa in the treated group was obviously increased as compared with that in the control group (P < 0.05); (2) HSP B expression of the gastric mucosa in the treated group was significantly decreased as compared with that in the control group (P < 0.01). It was suggested that the increased expression of HSP72 and the elimination of HP might be related to the mechanism of action of XKL. HSPs might play an pathological and physiological role in the process of healing of gastric ulcer.

[Actovegin treatment of duodenal ulcer associated with ischemic heart disease and diabetes mellitus]. / Lechenie aktoveginom bol'nykh iazvennoi bolezn'iu dvenadtsatiperstnoi kishki, sochetannoi s ishemicheskoi bolezn'iu serdtsa i sakharnym diabetom.

Actovegin, a deproteinized hemoderivative, was used to correct bioenergetic defects of duodenal mucosa, to reduce inflammatory-cell infiltration, to stimulate blood supply of patients with duodenal ulcer associated with ischemic heart disease or diabetes mellitus. As shown by the results obtained in 194 patients (119 males and 75 females), adjuvant actovegin in patients with duodenal ulcer associated with ischemic heart disease and diabetes mellitus stimulates the ulcer healing, prolongs the recurrence-free interval. It can be used both in outpatient departments and specialized hospitals.

[Relationship of cytokines and cold-heat syndrome differentiation in patients of duodenal ulcer].

OBJECTIVE: To explore the relationship of cytokines and Cold-Heat Syndrome in patients of duodenal ulcer. METHODS: Cold-Heat Syndrome Differentiation was done in 48 patients of duodenal ulcer, and the levels of interleukin-8 (IL-8), interleukin-6 (IL-6), tumor necrosis factor (TNF), malonyldialdehyde (MDA), marrow peroxidase (MPO) in gastric mucosa biopsy were measured and compared with those of 10 normal subjects. RESULTS: Levels of IL-8, TNF, MPO and MDA in Heat Syndrome were higher than those in Cold Syndrome (P < 0.05), while IL-6 level showed no significant relationship with Cold-Heat Syndrome. CONCLUSION: Cytokines IL-8, TNF, MPO and MDA are correlated with Cold-Heat Syndrome in duodenal ulcer patients and which might be one of the molecular mechanisms of Cold-Heat Syndrome Differentiation.

[A comparative evaluation of the action of kvamatel and omez on the glutathione system in different sections of the digestive system in experimental duodenal ulcer]. / Sravnitel'naia otsenka deistviia kvamatela i omeza na sistemu glutationa razlichnykh otdelov pishchevaritel'noi sistemy pri éksperimental'noi iazve dvenadtsatiperstnoi kishki.

Experiments on male albino rats demonstrated significant changes in the content of oxidized and reduced glutathione in the tissues of the liver, pancreas, stomach, duodenum, and small intestine in acetate ulcer of the duodenum. Experimental therapy with quamatel and particularly with omez led to activation of the glutathione system in the tissues under and in this way increased their resistance to the ulcerogenic effect.

[Clinical and experimental study of faeces trogopterus on protection of gastric mucosa].

The cure rate of Faeces Trogopterus in treating duodenal ulcer for six weeks was 70.59% and the total effective rate of which was 91.18%. The Shay model of rats was used. The result revealed that Faeces Trogopterus could protect the gastric mucosa. These results preliminarily indicated the mechanism of this drug was inhibiting gastric secretion and regulating gastric mucosal blood flow so as to enhance mucosal defense.

[Dynamics of prostaglandin E content in patients with duodenal ulcer various treatment regimens]. / Dinamika soderzhaniia prostaglandina E u bolnykh iazvennoi bolezníu dvenadtsatiperstnoi kishki pri razlichnykh vidakh lecheniia.

PGE levels were measured in duodenal ulcer patients treated by H2-blockers of histamine receptors of hyperbaric oxygenation (HBO). Histadyl is shown to cause a marked decrease in gastric juice PGE concentrations in contrast to HBO that raised PGE levels close to normal values. It is thought necessary to administer long-term maintenance therapy after cicatrisation of the ulcer lesion with the drugs improving local microcirculation and stimulating bicarbonates production in gastric mucosa, synthetic prostaglandins analogues, in particular.

Duodenal ulcer is associated with low dietary linoleic acid intake.

It has been suggested that the falling incidence and virulence of duodenal ulcer is related to increased dietary polyunsaturated essential fatty acid intake. The adipose fatty acid profile, which closely reflects dietary intake, was measured in 35 men with chronic duodenal ulcer and 35 matched control men. The mean percentage of linoleic acid in adipose tissue was significantly lower in the ulcer group (10.0 (0.7) v 12.3 (0.7)%, p less than 0.01) and this difference was found in both smokers and non-smokers. This finding suggests that the diets of duodenal ulcer patients are deficient in linoleic acid and this could be of aetiological importance.