Hepatotrophic factors reduce hepatic fibrosis in rats

CONTEXT: Hepatic fibrosis occurs in response to several aggressive agents and is a predisposing factor in cirrhosis. Hepatotrophic factors were shown to stimulate liver growth and to restore the histological architecture of the liver. They also cause an improvement in liver function and accelerate the reversion of fibrosis before it progresses to cirrhosis. OBJECTIVE: To test the effects of hepatic fibrosis solution composed by amino acids, vitamins, glucose, insulin, glucagon and triiodothyronine on hepatic fibrosis in rats. METHODS: Fibrosis was induced in rats by gastric administration of dimethylnitrosamine (10 mg/kg) for 5 weeks. After liver biopsy, the rats received either hepatotrophic factors solution (40 mg/kg/day) or saline solution for 10 days by intraperitoneal injection. Blood samples and liver fragments were collected for hepatic function analysis, standard histopathology evaluation, and morphometric collagen quantification. RESULTS: Rats in the hepatotrophic factors group showed a decrease of the histopathological components of fibrosis and an increase of their hepatic mass (12.2%). There was no development of neoplasic lesions in both groups. Compared with the saline group, the hepatotrophic factors group also had a decrease of blood levels of hepatic-lesion markers (AST, ALT) and a decrease of collagen content in the portal spaces (31.6%) and perisinusoidal spaces (42.3%), as well as around the hepatic terminal vein (57.7%). Thus, hepatotrophic factors administration in the portal blood promoted a regenerative hepatic response, with an overall reduction of the volumetric density of collagen, improved hepatic function, and a general improvement in the histopathological aspects of fibrosis. CONCLUSION: Taken together, these results suggest the potential therapeutic use of this hepatotrophic factors solution to treat chronic liver diseases.

Modulatory effect of Byrsonima basiloba extracts on the mutagenicity of certain direct and indirect-acting mutagens in Salmonella typhimurium assays

Byrsonima basiloba A. Juss. species is a native arboreal type from the Brazilian ""cerrado"" (tropical American savanna), and the local population uses it to treat diseases, such as diarrhea and gastric ulcer. It belongs to the Malpighiaceae family, and it is commonly known as ""murici."" Considering the popular use of B. basiloba derivatives and the lack of pharmacological potential studies regarding this vegetal species, the mutagenic and antimutagenic effect of methanol (MeOH) and chloroform extracts were evaluated by the Ames test, using strains TA97a, TA98, TA100, and TA102 of Salmonella typhimurium. No mutagenic activity was observed in any of the extracts. To evaluate the antimutagenic potential, direct and indirect mutagenic agents were used: 4 nitro-o-phenylenediamine, sodium azide, mitomycin C, aflatoxin B(1), benzo[a] pyrene, and hydrogen peroxide. Both the extracts evaluated showed antimutagenic activity, but the highest value of inhibition level (89%) was obtained with the MeOH extract and strain TA100 in the presence of aflatoxin B(1). Phytochemical analysis of the extracts revealed the presence of n-alkanes, lupeol, ursolic and oleanolic acid, (+)-catechin, quercetin- 3-O-alpha-L-arabinopyranoside, gallic acid, methyl gallate, amentoflavone, quercetin, quercetin-3-O-(2 ''-O-galloyl)-beta-D-galactopyranoside, and quercetin-3-O-(2 ''-O-galloyl)-alpha-L-arabinopyranoside.

Quadruple therapy with furazolidone for retreatment in patients with peptic ulcer disease

AIM: To establish the efficacy and safety of a 7-d therapeutic regimen using omeprazole, bismuth suticitrate, furazolidone and amoxicillin in patients with peptic ulcer disease who had been previously treated with other therapeutic regimens without success. METHODS: Open cohort study which included patients with peptic ulcer who had previously been treated unsuccessfully with one or more eradication regimens. The therapeutic regimen consisted of 20 mg omeprazole, 240 mg colloidal bismuth subcitrate, 1000 mg amoxicillin, and 200 mg furazolidone, taken twice a day for 7 d. Patients were considered as eradicated when samples taken from the gastric antrum and corpus 12 wk after the end of treatment were negative for Helicobacter pylori (H pylori) (rapid urease test and histology). Safety was determined by the presence of adverse effects. RESULTS: Fifty-one patients were enrolled. The eradication rate was 68.8% (31/45). Adverse effects were reported by 31.4% of the patients, and these were usually considered to be slight or moderate in the majority of the cases. Three patients had to withdraw from the treatment due to the presence of severe adverse effects. CONCLUSION: The association of bismuth, furazolidone, amoxicillin and a proton-pump inhibitor is a valuable alternative for patients who failed to respond to other eradication regimens. It is an effective, cheap and safe option for salvage therapy of positive patients. (C) 2008 The WJG Press. All rights reserved.

A perivascular epithelioid cell tumor of the stomach: An unsuspected diagnosis

Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasia and currently well recognized as a distinct entity with characteristic morphological, immunohistochemical and molecular findings. We report a case of PEComa arising in the antrum of a 71-year-old female with melena. The tumor, located predominantly in the submucosa as a well delimited nodule, measured 3.0 cm in diameter and was completely resected, with no evidence of the disease elsewhere. Histologically, it was composed predominantly of eosinophilic epithelioid cells arranged in small nests commonly related to variably sized vessels, with abundant extracellular material, moderate nuclear variation and discrete mitotic activity. No necrosis, angiolymphatic invasion or perineural infiltration was seen. Tumor cells were uniformly positive for vimentin, smooth muscle actin, desmin and melan A. Although unusual, PEComa should be considered in the differential diagnosis of gastric neoplasia with characteristic epithelioid and oncocytic features and prominent vasculature: (C) 2010 Baishideng. All rights reserved.

Mucin pattern reflects the origin of the adenocarcinoma in Barrett's esophagus: a retrospective clinical and laboratorial study

Background: Mucin immunoexpression in adenocarcinoma arising in Barrett's esophagus (BE) may indicate the carcinogenesis pathway. The aim of this study was to evaluate resected specimens of adenocarcinoma in BE for the pattern of mucins and to correlate to the histologic classification. Methods: Specimens were retrospectively collected from thirteen patients who underwent esophageal resection due to adenocarcinoma in BE. Sections were scored for the grade of intestinal metaplasia. The tissues were examined by immunohistochemistry for MUC2 and MUC5AC antibodies. Results: Eleven patients were men. The mean age was 61 years old (varied from 40 to 75 years old). The tumor size had a mean of 4.7 +/- 2.3 cm, and the extension of BE had a mean of 7.7 +/- 1.5 cm. Specialized epithelium with intestinal metaplasia was present in all adjacent mucosas. Immunohistochemistry for MUC2 showed immunoreactivity in goblet cells, while MUC5AC was extensively expressed in the columnar gastric cells, localizing to the surface epithelium and extending to a variable degree into the glandular structures in BE. Tumors were classified according to the mucins in gastric type in 7/13 (MUC5AC positive) and intestinal type in 4/13 (MUC2 positive). Two tumors did not express MUC2 or MUC5AC proteins. The pattern of mucin predominantly expressed in the adjacent epithelium was associated to the mucin expression profile in the tumors, p = 0.047. Conclusion: Barrett's esophagus adenocarcinoma shows either gastric or intestinal type pattern of mucin expression. The two types of tumors developed in Barrett's esophagus may reflect the original cell type involved in the malignant transformation.

Study of the patency of different peritoneal drains used prophylactically in bariatric surgery

AIM: To compare the performance of different types of abdominal drains used in bariatric surgery. METHODS: A vertical banded Roux-en-Y gastric bypass was performed in 33 morbidly obese patients. Drainage of the peritoneal cavity was performed in each case using three different types of drain selected in a randomized manner: a latex tubular drain, a Watterman tubulolaminar drain, and a silicone channeled drain. Drain permeability, contamination of the drained fluid, ease of handling, and patient discomfort were evaluated postoperatively over a period of 7 d. RESULTS: The patients with the silicone channeled drain had larger volumes of drainage compared to patients with tubular and tubulolaminar drains between the third and seventh postoperative days. In addition, a lower incidence of discomfort and of contamination with bacteria of a more pathogenic profile was observed in the patients with the silicone channeled drain. CONCLUSION: The silicone channeled drain was more comfortable and had less chance of occlusion, which is important in the detection of delayed dehiscence. (C) 2009 The WJG Press and Baishideng. All rights reserved.

Evaluation of gastrointestinal motility in awake rats: a learning exercise for undergraduate biomedical students

Souza MA, Souza MH, Palheta RC Jr, Cruz PR, Medeiros BA, Rola FH, Magalhaes PJ, Troncon LE, Santos AA. Evaluation of gastrointestinal motility in awake rats: a learning exercise for undergraduate biomedical students. Adv Physiol Educ 33: 343-348, 2009; doi: 10.1152/advan.90176.2008.-Current medical curricula devote scarce time for practical activities on digestive physiology, despite frequent misconceptions about dyspepsia and dysmotility phenomena. Thus, we designed a hands-on activity followed by a small-group discussion on gut motility. Male awake rats were randomly submitted to insulin, control, or hypertonic protocols. Insulin and control rats were gavage fed with 5% glucose solution, whereas hypertonic-fed rats were gavage fed with 50% glucose solution. Insulin treatment was performed 30 min before a meal. All meals (1.5 ml) contained an equal mass of phenol red dye. After 10, 15, or 20 min of meal gavage, rats were euthanized. Each subset consisted of six to eight rats. Dye recovery in the stomach and proximal, middle, and distal small intestine was measured by spectrophotometry, a safe and reliable method that can be performed by minimally trained students. In a separate group of rats, we used the same protocols except that the test meal contained (99m)Tc as a marker. Compared with control, the hypertonic meal delayed gastric emptying and gastrointestinal transit, whereas insulinic hypoglycemia accelerated them. The session helped engage our undergraduate students in observing and analyzing gut motor behavior. In conclusion, the fractional dye retention test can be used as a teaching tool to strengthen the understanding of basic physiopathological features of gastrointestinal motility.

Ultra-Deep Sequencing Reveals the microRNA Expression Pattern of the Human Stomach

Background: While microRNAs (miRNAs) play important roles in tissue differentiation and in maintaining basal physiology, little is known about the miRNA expression levels in stomach tissue. Alterations in the miRNA profile can lead to cell deregulation, which can induce neoplasia. Methodology/Principal Findings: A small RNA library of stomach tissue was sequenced using high-throughput SOLiD sequencing technology. We obtained 261,274 quality reads with perfect matches to the human miRnome, and 42% of known miRNAs were identified. Digital Gene Expression profiling (DGE) was performed based on read abundance and showed that fifteen miRNAs were highly expressed in gastric tissue. Subsequently, the expression of these miRNAs was validated in 10 healthy individuals by RT-PCR showed a significant correlation of 83.97% (P<0.05). Six miRNAs showed a low variable pattern of expression (miR-29b, miR-29c, miR-19b, miR-31, miR-148a, miR-451) and could be considered part of the expression pattern of the healthy gastric tissue. Conclusions/Significance: This study aimed to validate normal miRNA profiles of human gastric tissue to establish a reference profile for healthy individuals. Determining the regulatory processes acting in the stomach will be important in the fight against gastric cancer, which is the second-leading cause of cancer mortality worldwide.

Laser Phototherapy for Stevens-Johnson Syndrome: A Case Report

Background and Objective: Stevens-Johnson syndrome (SJS) is a life-threatening dermatosis characterized by epidermal sloughing and stomatitis. We report the case of a 7-year-old boy in whom laser phototherapy (LPT) was highly effective in reversing the effects of an initial episode of SJS that had apparently developed in association with treatment with phenobarbital for a seizure disorder. The patient was first seen in the intensive care unit (ICU) of our institution with fever, cutaneous lesions on his extremities, trunk, face, and neck; mucosal involvement of his genitalia and eyes (conjunctivitis); ulcerative intraoral lesions; and swollen, crusted, and bleeding lips. He reported severe pain at the sites of his intraoral and skin lesions and was unable to eat, speak, swallow, or open his mouth. Materials and Methods: Trying to prevent and minimize secondary infections, gastric problems, pain, and other complications, the patient was given clindamycin, ranitidine, dipyrone, diphenhydramine (Benadryl) drops, and morphine. In addition, he was instructed to use bicarbonate solution and Ketoconazole (Xylogel) in the oral cavity. Because of the lack of progress of the patient, the LPT was selected. Results: At 5 days after the initial session of LPT, the patient was able to eat gelatin, and on the following day, the number and severity of his intraoral lesions and his labial crusting and swelling had diminished. By 6 days after his initial session of LPT, most of the patient's intraoral lesions had disappeared, and the few that remained were painless; the patient was able to eat solid food by himself and was removed from the ICU. Ten sessions of LPT were conducted in the hospital. The patient underwent three further and consecutive sessions at the School of Dentistry, when complete healing of his oral lesions was observed. Conclusion: The outcome in this case suggests that LPT may be a new adjuvant modality for SJS complications.

Viability of Lactobacillus acidophilus in synbiotic guava mousses and its survival under in vitro simulated gastrointestinal conditions

The effects of refrigeration, freezing and substitution of milk fat by inulin and whey protein concentrate (WPC) on Lactobacillus acidophilus La-5 viability and resistance to gastric and enteric simulated conditions in synbiotic guava mousses effects were investigated. Refrigerated mousses supplemented with WPC presented the best probiotic viability. ranging from 7.77 to 6.24 log cfu/g during 28 days of storage. The highest probiotic populations, above 7.45 log cfu/g, were observed for all frozen mousses during 112 days of storage. Decreased L acidophilus survival during the in vitro gastrointestinal simulation was observed both for refrigerated and frozen mousses. Nonetheless, for the refrigerated mousses, the addition of inulin enhanced the probiotic survival during the in vitro assays in the first week of storage. L acidophilus survival in simulated gastrointestinal fluids was also improved through freezing. The frozen storage may be used to provide increased shelf-life for synbiotic guava mousses. Even though the protective effect of inulin and WPC on the probiotic microorganism tested was shown to be more specific for the refrigerated products, the partial replacement of milk fat by these ingredients may also help, as it improves the nutritional value of mousses in both storage conditions. (C) 2009 Elsevier B.V. All rights reserved.

Evaluation of the role of environmental factors in the human gastrointestinal tract on the behaviour of probiotic cultures of Lactobacillus casei Shirota and Lactobacillus casei LC01 by the use of a semi-dynamic in vitro model

This study evaluated the influence of gastrointestinal environmental factors (pH, digestive enzymes, food components, medicaments) on the survival of Lactobacillus casei Shirota and Lactobacillus casei LC01, using a semi-dynamic in vitro model that simulates the transit of microorganisms through the human GIT. The strains were first exposed to different simulated gastric juices for different periods of time (0, 30, 60 and 120 min), and then to simulated intestinal fluids for zero, 120, 180 and 240 min, in a step-wise format. The number of viable cells was determined after each step. The influence of food residues (skim milk) in the fluids and resistance to medicaments commonly used for varied therapeutic purposes (analgesics, antiarrhythmics, antibiotics, antihistaminics, proton pump inhibitors, etc.) were also evaluated. Results indicated that survival of both cultures was pH and time dependent, and digestive enzymes had little influence. Milk components presented a protective effect, and medicaments, especially anti-inflammatory drugs, influenced markedly the viability of the probiotic cultures, indicating that the beneficial effects of the two probiotic cultures to health are dependent of environmental factors encountered in the human gastrointestinal tract.

Evaluation of gastroprotective activity of Plinia edulis (Vell.) Sobral (Myrtaceae) leaves in rats

Plinia edulis, an arboreous species popularly known as ""cambuca"", is native to the Brazilian Atlantic Rain Forest. Despite its traditional uses, no reports are available on the safety of this utilization or on the relationship between the antiulcer activity of its extract and its phytochemical compounds. This paper reports on the investigation of the acute toxicity and gastroprotective effect of the aqueous ethanol extract of leaves of Plinia edulis on HCl/ethanol-induced ulcers. In order to correlate the secondary metabolites and the efficacy of the crude drug in traditional medicine, the extract was submitted to chromatographic fractionation after solvent partition. The extract did not show acute toxicity in mice treated with 5 g/kg p.o.. but exhibited significant antiulcer activity in rats at doses of 100, 200, and 400 mg/kg p.o., more active than the reference drug lansoprazole. The ethyl acetate fraction yielded P-amyrin, oleanolic acid, ursolic acid, and maslinic acid, which were identified based on spectrometric analyses. Since antiulcerogenic activity is not restricted to one class of compounds in plants, the triterpenoids isolated in the extract can be associated with the observed effect. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Antinociceptive and anti-inflammatory properties of 7-hydroxycoumarin in experimental animal models: potential therapeutic for the control of inflammatory chronic pain

Objectives In the present study we investigated the anti nociceptive, anti-inflammatory and antipyretic effects of 7-hydroxycoumarin (7-HC) in animal models. Methods The effects of oral 7-HC were tested against acetic acid-induced writhing, formalin test, tail flick test, complete Freund`s adjuvant (CFA)-induced hypemociception, carrageenan-induced paw oedema, lipopolysaccharide-induced fever and the rota rod test. Key findings 7-HC (3-60 mg/kg) produced a dose-related antinociception against acetic acid-induced writhing in mice and in the formalin test. In contrast, treatment with 7-HC did not prevent thermal nociception in the tail flick test. A single treatment with 7-HC, 60 mg/kg, produced a long-lasting antinociceptive effect against CFA-induced hypernociception, a chronic inflammatory pain stimulus. Notably, at 60 mg/kg per day over 4 days the administration of 7-HC produced a continuous antinociceptive effect against CFA-induced hypernociception. 7-HC (30-120 mg/kg) produced anti-inflammatory and antipyretic effects against carrageenan-induced inflammation and lipopolysaccharide-induced fever, respectively. Moreover, 7-HC was found to be safe with respect to ulcer induction. In the rota rod test, 7-HC-treated mice did not show any motor performance alterations. Conclusions The prolonged antinociceptive and anti-inflammatory effects of 7-HC, in association with its low ulcerogenic activity, indicate that this molecule might be a good candidate for development of new drugs for the control of chronic inflammatory pain and fever.

Evaluation of antiulcer activity of the main phenolic acids found in Brazilian Green Propolis

Aim of the study: In a previous study, our group described the gastric protective effect of the hydroalcoholic extract of Brazilian green propolis. The main compounds found in Brazilian green propolis include phenolic acids, such as: caffeic, ferulic, p-coumaric and cinnamic acids. This study was therefore carried out to evaluate the antiulcerogenic property of the main phenolic acids found in Brazilian Green Propolis. Material and methods: The anti-ulcer assays were performed using the following protocols: nonsteroidal-antinflammatory drug (NSAID)-induced ulcer, ethanol-induced ulcer, and stress-induced ulcer. The effects of the phenolic acids on gastric content volume, pH and total acidity, using the pylorus ligated model, were also evaluated. Results: It was observed that treatment using doses of 50 and 250 mg/kg of caffeic, ferulic, p-coumaric and cinnamic acids and positive controls (omeprazol or cimetidine) significantly diminished the lesion index, the total area of the lesion and the percentage of lesion in comparison with the negative control groups. In addition, the percentage of ulcer inhibition was significantly higher in the groups treated with the different phenolic acids, cimetidine or omeprazol, in all the protocols used, compared with the negative control groups. In the model to determine gastric secretion, using ligated pylorus, treatment with phenolic acids and cimetidine reduced the volume of gastricjuice and total acidity and significantly increased the gastric pH (p < 0.05), compared with the control group, with the exception of the group treated with 50 mg/kg of p-coumaric acid, in which no significant difference was observed, compared with the control. In relation to the acute toxicity, none sign of toxicity was observed when phenolic acids, used in this study, were administered for rats in dose of 2000 mg/kg. Conclusions: In conclusion, the results of this study show that caffeic, ferulic, p-coumaric and cinnamic acids display antiulcer activity. (c) 2008 Elsevier Ireland Ltd. All rights reserved.