Preliminary studies of Mammea americana L. (Guttiferae) bark/latex extract point to an effective antiulcer effect on gastric ulcer models in mice

Plant extracts are some of the most attractive sources of new drugs and have shown promising results for the treatment of gastric ulcers. Several folk medicinal plants and herbs have been used to treat gastrointestinal disorders, including gastric ulcers. Mammea americana L. (Guttiferae) fruit is very common in the diet of the population of northern South America. Our research interest in this plant arose because of its potential medicinal value as a tonic and against stomachache, as used in folk medicine. In this paper we evaluated three different extracts (ethanolic/EtOH, methanolic/MeOH and dichloromethane/DCM) obtained from M. americana L., for their ability to protect the gastric mucosa against injuries caused by necrotizing agents (0.3 M HCI/60% EtOH), hypothermic restraint stress, nonsteroidal anti-inflammatory drugs (NSAID, indomethacin) and pylorus ligation. In the HCI/EtOH-induced gastriculcer model, EtOH and DCM extracts demonstrated significant inhibition of the ulcerative lesion index by 54% (12.0 +/- 2.6 mm) and 86% (3.7 +/- 1.8 mm), respectively, in relation to the control value (26.0 +/- 1.4 mm) (p < 0.000 1). In the NSAID/cholinomimetic-induced lesion model, both EtOH and DCM extracts showed antiulcerogenic effects with significant reduction in the damage to these gastric lesions of 36% (8.3 +/- 2.0 mm) and 42% (7.5 +/- 1.4 mm), respectively, as compared to the control group (13.0 +/- 0.9 mm) (p < 0.0001). In the gastric ulcer induced by hypothermic-restraint stress, both extracts also showed significant activity, and inhibited the gastric lesion index by 58% and 75%, respectively. The EtOH and DCM extracts also changed gastric juice parameters as well as those of cimetidine, decreased gastric acid secretion significantly (p < 0.0001), increased pH values and promoted reduced acid output (p < 0.0001). In all gastric-ulcer-induced models, MeOH extract did not show any significant antiulcerogenic activity, nor did it change gastric-juice parameters (p > 0.05). The results suggest that EtOH and DCM extracts obtained from M. americana possess excellent antisecretory and/or gastrotective effect in all gastric ulcer models. These results suggest that the antiulcerogenic compound(s) present in M. americana may be clustered in the apolar fraction, which will be investigated by our group for the probable mechanisms of action. (c) 2004 Elsevier GmbH. All rights reserved.

Response to Treatment in a Prospective Cohort of Patients with Large Ulcerated Lesions Suspected to Be Buruli Ulcer (Mycobacterium ulcerans Disease)

Background: The World Health Organization (WHO) advises treatment of Mycobacterium ulcerans disease, also called Buruli ulcer'' (BU), with a combination of the antibiotics rifampicin and streptomycin (R+S), whether followed by surgery or not. In endemic areas, a clinical case definition is recommended. We evaluated the effectiveness of this strategy in a series of patients with large ulcers of >= 10 cm in longest diameter in a rural health zone of the Democratic Republic of Congo (DRC).Methods: A cohort of 92 patients with large ulcerated lesions suspected to be BU was enrolled between October 2006 and September 2007 and treated according to WHO recommendations. The following microbiologic data were obtained: Ziehl-Neelsen (ZN) stained smear, culture and PCR. Histopathology was performed on a sub-sample. Directly observed treatment with R+S was administered daily for 12 weeks and surgery was performed after 4 weeks. Patients were followed up for two years after treatment.Findings: Out of 92 treated patients, 61 tested positive for M. ulcerans by PCR. PCR negative patients had better clinical improvement than PCR positive patients after 4 weeks of antibiotics (54.8% versus 14.8%). For PCR positive patients, the outcome after 4 weeks of antibiotic treatment was related to the ZN positivity at the start. Deterioration of the ulcers was observed in 87.8% (36/41) of the ZN positive and in 12.2% (5/41) of the ZN negative patients. Deterioration due to paradoxical reaction seemed unlikely. After surgery and an additional 8 weeks of antibiotics, 98.4% of PCR positive patients and 83.3% of PCR negative patients were considered cured. The overall recurrence rate was very low (1.1%).Interpretation: Positive predictive value of the WHO clinical case definition was low. Low relapse rate confirms the efficacy of antibiotics. However, the need for and the best time for surgery for large Buruli ulcers requires clarification. We recommend confirmation by ZN stain at the rural health centers, since surgical intervention without delay may be necessary on the ZN positive cases to avoid progression of the disease. PCR negative patients were most likely not BU cases. Correct diagnosis and specific management of these non-BU ulcers cases are urgently needed.

Transplante pancreato-duodenal em ratos com microcirurgia. A téchnica e os resultados após 12 anos de experimentação

In this study we present the technical details, adaptations and modifications of the original procedure of pancreaticoduodenal transplantation in rats described by Lee et al. in 1972. We also present the results and technical failures observed in a follow-up of 12 years. From March, 1982 to December, 1994, we performed in the Laboratory of Surgical Technique and Experimental Surgery of Faculty of Medicine, Botucatu - UNESP, Brazil, 665 duodenopancreatectomies in donor rats and 592 surgeries for revascularization of the pancreatic graft in recipient animals. The observed percentage of technical failures in donor rats was 11% due to bleeding and/or vascular complications, irregular flushing of the graft with saline and respiratory insufficiency. In recipients of grafts, we observed a percentage of technical failures of 22,5% due to porto-caval thrombosis, vascular bleeding, pancreatitis and graft ischemia. In both surgeries, the successful results are directly related to the technical performance of the surgeon and the cares in the postoperative period.

Genetic alterations in benign lesions: Chronic gastritis and gastric ulcer

Aim: To investigate the occurrence of chromosome 3, 7, 8, 9, and 17 aneuploidies, TP53 gene deletion and p53 protein expression in chronic gastritis, atrophic gastritis and gastric ulcer, and their association with H pylori infection. Methods: Gastric biopsies from normal mucosa (NM, n = 10), chronic gastritis (CG, n = 38), atrophic gastritis (CAG, n = 13) and gastric ulcer (GU, n = 21) were studied using fluorescence in situ hybridization (FISH) and immunohistochemical assay. A modified Giemsa staining technique and PCR were used to detect H pylori. An association of the gastric pathologies and aneuploidies with H pylori infection was assessed. Results: Aneuploidies were increasingly found from CG (21%) to CAG (31%) and to GU (62%), involving mainly monosomy and trisomy 7, trisomies 7 and 8, and trisomies 7, 8 and 17, respectively. A significant association was found between H pylori infection and aneuploidies in CAG (P = 0.0143) and GU (P = 0.0498). No TP53 deletion was found in these gastric lesions, but p53-positive immunoreactivity was detected in 45% (5/11) and 12% (2/17) of CG and GU cases, respectively. However, there was no significant association between p53 expression and H pylori infection. Conclusion: The occurrence of aneuploidies in benign lesions evidences chromosomal instability in early stages of gastric carcinogenesis associated with H pylori infection, which may confer proliferative advantage. The increase of p53 protein expression in CG and GU may be due to overproduction of the wild-type protein related to an inflammatory response in mucosa. © 2006 The WJG Press. All rights reserved.

Diferentes procedimentos na determinação de indicadores internos para estimativa de produção fecal e fluxo duodenal de matéria seca em bovinos

Times of in situ incubation (144 and 288h) for determination of internal markers IADF and INDF and the effects of differents procedures (wash or not the nylon bag every 72h incubation) was evaluated in samples of diet, duodenal digesta and cattle feces. The duodenal flow dry matter and fecal production utilizing the internal markers to compare with the external marker chromium oxide there was estimated. The animals were fed with sorgum silage, concentrate or urea. In this experiment, a latin square design was used, in a factorial scheme (two times of incubation × two processing nylon bag). No was observed effect of the incubation time or processing in the internal markers INDF and IADF concentration and the in situ incubation after 144h is adequate to reproduce the indigestible markers fraction in samples. For fecal production estimation, the external marker chromium oxide presented similar result (1.26 kg day-1) as the total fecal collection (1.49 kg day-1). Both the internal markers overestimate the duodenal flow dry matter when compared with the external marker chromium oxide.

Effects of the ethyl acetate fraction of Alchornea triplinervia on healing gastric ulcer in rats

Alchornea triplinervia (Spreng.) Muell. Arg (Euphorbiaceae) is a medicinal plant commonly used by people living in the Cerrado region of Brazil to treat gastrointestinal ulcers. We previously described the gastroprotective action of methanolic extract (ME) of Alchornea triplinervia and the ethyl acetate fraction (EAF) in increasing of prostaglandin E 2 (PGE 2) gastric levels in the mucosa. In this work we evaluated the effect of EAF in promoting the healing process in rats with acetic acid-induced gastric ulcers. In addition, toxicity was investigated during treatment with EAF. After 14 days of treatment with EAF, the potent stimulator of gastric cell proliferation contributed to the acceleration of gastric ulcer healing. Upon immunohistochemical analysis, we observed a pronounced expression of COX-2, mainly in the submucosal layer. The 14-day EAF treatment also significantly increased the number of neutrophils in the gastric mucosa regeneration area. The EAF induced angiogenesis on gastric mucosa, observed as an increase of the number of blood vessels supplying the stomach in rats treated with EAF. Oral administration for 14 days of the ethyl acetate fraction from Alchornea triplinervia accelerated the healing of gastric ulcers in rats by promoting epithelial cell proliferation, increasing the number of neutrophils and stimulation of mucus production. This fraction, which contained mainly phenolic compounds, contributed to gastric mucosa healing. © 2011 by the authors; licensee MDPI, Basel, Switzerland.

Desempenho e morfometria duodenal de frangos de corte submetidos a diferentes níveis de energia e programas de alimentação de 42 a 57 dias de idade

This experiment was conducted to evaluate the use of different energy levels and amino acid recommendations on performance, carcass yield and intestinal morphometry of broilers from 42 to 57 days of age. We used 1,600 one-day old male broilers (Cobb 500) in a completely randomized design arranged in a 2x4 factorial scheme with 3,200 and 3,600 kcal ME/kg and four different feed programs. The metabolizable energy levels and the feed programs did not determine significant differences in carcass characteristics for choosing a level of energy or a feed program, thus the energy level and the recommendations of amino acids that determine the highest cost-benefit ratio should prevail. It was observed that 3,600 kcal ME/kg resulted in some improvement on performance and morphometry of the intestinal mucosa, also the fractioning of digestible amino acid requirements during two periods resulted in worse performance and intestinal villi height.

Essential oils from medicinal and aromatic plants: A review of the gastroprotective and ulcer-healing activities

Gastric ulcer is an excoriated area of the gastric mucosa. It is among the predominant gastrointestinal chronic diseases. The essential oils represent an important part of the traditional pharmacopoeia in many countries and have been successfully used for gastroprotection and ulcer healing. Thus, this review presents the experimental activity of essential oils traditionally used in the gastric ulcer prevention and treatment, considering their families, part of the plant studied, bioassays, and their mechanisms of gastroprotection and ulcer healing, with the aim of stimulating novel studies in the search for a new phytomedicine to treat gastric diseases. © 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de Pharmacologie et de Thérapeutique.

Serum Metalloproteinases 2 and 9 as Predictors of Gait Status, Pressure Ulcer and Mortality after Hip Fracture

Introduction: The aim of this study is to evaluate the serum activity of metalloproteinases (MMPs) -2 and -9 as predictors of pressure ulcer (PU), gait status and mortality 6 months after hip fracture. Methods: Eighty-seven patients over the age of 65 admitted to the orthopedic unit from January to December 2010 with hip fracture were prospectively evaluated. Upon admission, patient demographic information, including age, gender and concomitant diseases, was recorded. Blood samples were taken for analysis of MMP -2 and -9 activity by gel zymography and for biochemical examination within the first 72 hours of the patient's admission, after clinical stabilization. The fracture pattern (neck, trochanteric or subtrochanteric), time from admission to surgery, surgery duration and length of hospital stay were also recorded. Results: Two patients were excluded due to the presence of pathological fractures (related to cancer), and three patients were excluded due to the presence of PU before admission. Eighty-two patients, with a mean age of 80.4 ± 7.3 years, were included in the analysis. Among these patients, 75.6% were female, 59.8% had PU, and 13.4% died 6 months after hip fracture. All patients underwent hip fracture repair. In a univariate analysis, there were no differences in serum MMP activity between hip fracture patients with or without PU. In addition, the multiple logistic regression analysis models, which were adjusted by age, gender, length of hospital stay and C-reactive protein, showed that the pro-MMP-9 complexed with neutrophil gelatinase-associated lipocalin form (130 kDa) was associated with gait status recovery 6 months after hip fracture. Conclusions: In conclusion, serum pro-MMP-9 is a predictor of gait status recovery 6 months after hip fracture. © 2013 Gumieiro et al.

Marjolin's ulcer in two horses with hereditary equine regional dermal asthenia

Two Quarter Horse mares with hereditary equine regional dermal asthenia (HERDA) were diagnosed with metastatic squamous cell carcinoma (SCC) associated with chronic nonhealing wounds. The lesions were similar to the development of SCC from chronic nonhealing ulcers, known as Marjolin's ulcers in humans. The horses showed recurrent skin wounds in the saddle and paralumbar regions and were confirmed by molecular techniques as having HERDA. Both horses were maintained as research animals for prolonged periods and received regular veterinary care and wound treatment. Both horses were ultimately euthanized because of their chronic progressive wounds, coupled with declining health. At necropsy, the nonhealing wounds were found to be complicated by infiltrative SCC; both horses had metastasis to lungs. Chronically inflamed, recurrent skin wounds that heal slowly and incompletely as a consequence of HERDA are proposed as a major pathogenetic factor in tumorigenesis. Consistent findings with respect to proliferation index (Ki-67) and mutations of p53 tumor suppressor gene were confirmed by immunohistochemistry in one horse. SCC consistent with Marjolin's ulcer has been previously suggested in association with chronic ulcers or burn scars in horses, but this is the first report of an association with chronic poor healing wounds in HERDA horses. © 2013 Elsevier Inc.

Atividade antiulcerogênica e avaliação dos mecanismos de ação anticerogênicos do β-Mirceno

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação dos mecanismos de ação antiulcerogênica e antidiarrêica dos extratos e partições obtidos a partir das folhas de Byrsonima intermedia A. Juss (Malphighiaceae)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Clinical and pathological importance of vacA allele heterogeneity and cagA status in peptic ulcer disease in patients from North Brazil

We have examined the prevalence of gene cagA and vacA alleles in 129 patients, 69 with gastritis and 60 with peptic ulcer diseases from North Brazil and their relation with histopathological data. vacA and cagA genotype were determined by polymerase chain reaction. Hematoxylin-eosin staining was used for histological diagnosis. 96.6% of the patients were colonized by Helicobacter pylori strains harboring single vacA genotype (nont-mixed infection). Among them, 11.8% had subtype s1a, 67.8% had subtype s1b, and 17% subtype s2. In regard to the middle region analysis, m1 alleles were found in 75.4% and m2 in 21.2% of patients. The cagA gene was detected in 78% patients infected with H. pylori and was associated with the s1-m1 vacA genotype. The H. pylori strains, vacA s1b m1/cagA-positive, were associated with increased risk of peptic ulcer disease and higher amounts of lymphocytic and neutrophilic infiltrates and the presence of intestinal metaplasia. These findings show that cagA and vacA genotyping may have clinical relevance in Brazil.

Avaliação do efeito protetor e cicatrizante do extrato hidroalcóolico de folhas de Solanum paniculatum L. frente á úlceras pépticas

Pós-graduação em Biologia Geral e Aplicada - IBB