Relationship among oxidative DNA damage, gastric mucosal density and the relevance of cagA, vacA and iceA genotypes of Helicobacter pylori

The aim of this study was to evaluate the relationship among oxidative DNA damage, density of Helicobacter pylori and the relevance of cagA, vacA and iceA genotypes of H. pylori. Gastric epithelial cells were isolated from 24 uninfected patients, 42 H. pylori infected patients with gastritis, and 61 patients with gastric cancer. Oxidative DNA damage was analyzed by the Comet assay, the density of H. pylori was measured by real-time polymerase chain reaction (PCR), and allelic variants of cagA, vacA and iceA were identified using the PCR. Infected patients by Helicobacter pylori cagA(+), vacAs1 m1 and iceA1 genotype showed higher levels of oxidative DNA damage than infected patients with H. pylori cagA(-), vacAs2 m2 and iceA2 genotypes and uninfected patients. Density of H. pylori did not influence oxidative DNA damage. Our results indicate that H. pylori genotype is more relevant than density for oxidative DNA damage.

Influence of Helicobacter pylori infection on the expression of MLH1 and MGMT in patients with chronic gastritis and gastric cancer

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of Helicobacter pylori infection on IL-8, IL-1 and COX-2 expression in patients with chronic gastritis and gastric cancer

Objective. Helicobacter pylori infection is related to gastric cancer development, and chronic inflammation is presumed to be the main cause. The aim of the present study was to evaluate the influence of H. pylori cagA, vacA, iceA, and babA genotypes on COX-2, IL-1, and IL-8 expression. Material and methods. of the 217 patients included in the study, 26 were uninfected, 127 had chronic gastritis and were H. pylori-positive, and 64 had gastric cancer. Bacterial genotypes were evaluated by polymerase chain reaction (PCR), and the expression values were determined by quantitative real-time PCR and immunohistochemistry. Results. An association was found between the infection with cagA, vacA s1m1 strains and gastric cancer development. Regarding the 3' region of the cagA gene, we also found an association between the infection with cagA EPIYA-ABCCC strains and clinical outcome. Higher levels of IL-8, IL-1, and COX-2 were detected in gastric mucosa from infected patients with chronic gastritis, and they were also associated with the infection by cagA, vacA s1m1 strains. The IL-8 and IL-1 levels decrease significantly from chronic gastritis to gastric cancer, while the relative expression remained unaltered when COX-2 expression was analyzed among patients with gastritis and cancer. Conclusions. Since inflammatory response to H. pylori infection plays an important role in cellular proliferation and gastric mucosal damage, the up-regulation of IL-1, IL-8, and COX-2 in patients with chronic gastritis has an important clinical implication in gastric carcinogenesis.

Effects of Helicobacter pylori Infection on the Expressions of Bax and Bcl-2 in Patients with Chronic Gastritis and Gastric Cancer

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Treatment of venous ulcers with surgical adhesives derived from snake venom

A Brazilian dictionary states that "ulcer", from the Latin word ulcuserise, is a superficial lesion on skin or mucous membrane characterized by an inflammatory process and loss of tissue. Ulcers are a relatively frequent problem that may be worsen by infection or long-time duration. In these cases, they can represent a serious public health issue, since the increased case number contributes to the burden on the public health service. In recent decades, wound treatment has advanced in technological and scientific aspects regarding both development of new products and techniques. Ongoing research in this area is providing new products for wound treatment. Among newly tested substances that have presented successful results is fibrin glue, a snake venom derivative that promotes reduction of infection and edema as well as bleeding control and pain decrease. Thus, the present study aimed to evaluate fibrin glue effects on ulcers of venous origin in 24 patients that were divided into two groups. The first one (G1) consisted of 11 patients treated without the adhesive while the second group (G2) was composed of 13 persons who were under therapy with the adhesive. The results of this study revealed that patients treated with fibrin glue evolved to a satisfactory healing when compared to the other group. Therefore, fibrin glue is an appropriate alternative for treating leg ulcers with several advantages: easy application, less pain, early hospital discharge, not transmiting diseases, lower cost than the adhesive currently available in Brazil and, finally, it is a Brazilian technology.

Venous ulcer: clinical characteristics and risk factors

BackgroundLower limb venous ulceration ranks among the 10 most common medical problems in Western countries and has significant socioeconomic impact. The aim of this study was to identify the risk factors for unhealed, recurrent, and large ulcers and to characterize patients with active or recently healed venous ulcers.MethodsWe identified 97 patients and assessed 103 ulcerated limbs in 90 patients. All patients underwent clinical examination, arterial and venous system evaluation, ankle-brachial index determination, and ultrasound of the affected limb. Clinical characteristics included age, gender, race, ulcer duration, time since first episode, history of recurrence, localization of ulcer, ulcer area, eczema, ochre dermatitis, lipodermatosclerosis, pain, body mass index, and medical history data. Risk factors were identified by univariate analysis and estimated odds ratios.ResultsWe assessed 90 patients (103 limbs) with active or healed venous leg ulcers, of whom 84.4% were Caucasian and 68.9% were female. Mean age was 56.0 +/- 13.3 years. Ulcers had remained unhealed for < 1 year in 40.7%. Lipodermatosclerosis, lower limb hyperpigmentation, edema, and eczema were seen in 96.7%, 95.6%, 94.4%, and 51.1% of patients, respectively. Pain was a frequent symptom in 74.4%. Body mass index was assessed in 85 patients: 30.6% were slightly, 36.5% moderately, and 7% severely obese. Patient age > 60 years (odds ratio [OR] 4.0), extensive lipodermatosclerosis (OR 8.7), and previous history of ulceration (OR 19.9) were risk factors for unhealed ulcers. Time since first ulcer episode >= 2 years (OR 29.2) and incompetence of venous systems (OR 1.6) were risk factors for recurrence.ConclusionsLongstanding and large ulcers and recurrences are the main problems encountered by venous ulcer patients. Severe lipodermatosclerosis, previous ulcer history, and time since first ulcer episode >= 2 years are significant risk factors.

Abordagem de pacientes com úlcera da perna de etiologia venosa

Úlceras venosas são comuns na população adulta, causando significante impacto social e econômico devido a sua natureza recorrente e ao longo tempo decorrido entre sua abertura e cicatrização. Quando não manejadas adequadamente, as úlceras venosas têm altas taxas de falha de cicatrização e recorrência. Apesar da elevada prevalência e da importância da úlcera venosa, ela é freqüentemente negligenciada e abordada de maneira inadequada. Esta revisão discute abordagem diagnóstica e terapêutica das úlceras venosas. O diagnóstico clínico baseia-se em história e exame físico, com ênfase nos sinais e sintomas associados e palpação dos pulsos dos membros inferiores. A ultra-sonografia Doppler deve ser utilizada para determinar o índice pressórico entre o tornozelo e o braço, e exames não invasivos, como o duplex scan, devem ser realizados para avaliar o sistema venoso superficial, profundo e perfurante. Para abordagem terapêutica são fundamentais os diagnósticos clínico e laboratorial corretos, além do diagnóstico e tratamento adequados das complicações das úlceras crônicas. Os esforços devem ser direcionados para a cicatrização da úlcera e, posteriormente, para evitar as recidivas. O grande avanço no conhecimento da fisiopatogenia das úlceras venosas tem permitido o desenvolvimento de novas modalidades de tratamento clínico e cirúrgico.

Tratamento da úlcera corneana experimental com membrana amniótica

Objetivo: Avaliar a evolução da úlcera de córnea experimental tratada com enxerto de membrana amniótica (MA) homóloga. Métodos: Foram utilizados 18 coelhos, divididos em dois grupos experimentais: úlcera corneana (G1) e úlcera corneana tratada com enxerto de MA (G2). A ulceração corneana foi induzida na córnea toda, com álcool absoluto e lâmina de bisturi. Os animais foram sacrificados em três momentos experimentais: 7 dias (M1), 15 dias (M2) e 30 dias (M3) após a indução da ulceração. Os defeitos corneanos foram avaliados com fotodocumentação por analisador de imagem Luzex-F e exames histopatológicos, comparando-se os resultados por meio da análise de variância. Resultados: O resultado do exame morfométrico mostrou desepitelização maior em G2 no M1; a opacidade corneana foi mais intensa na área central da córnea, sendo significativamente maior em G1 no M3. Os neovasos corneanos também foram mais intensos em G1. A avaliação histopatológica revelou ulceração epitelial em dois animais de G1 no M2 e em dois de G2 no M1; o edema estromal foi mais intenso em G1, assim como a presença de neovasos. Conclusão: O uso de MA homóloga no tratamento da úlcera corneana experimental não acelerou a cicatrização, porém preveniu o edema estromal e a formação de neovascularização corneana. A cicatrização se mostrou mais deficiente na área central da córnea.

Esophageal and gastric biopsies in symptomatic children and adolescents. Should both be performed?

This study investigated the relationship among the histological diagnosis of esophagitis and gastritis in children and adolescents with gastroesophageal reflux disease (GERD) and/or dyspepsia. Records of 366 patients submitted to endoscopic biopsies were reviewed. Two groups were analyzed: G1 n=258 with esophageal and gastric biopsies, G2 n=108 with gastric biopsies only. For total subjects median age (range) was 8.5y (2mo-19.9y). Helicobacter pylori infection was detected in 30.6 %, median age 12.5y for H pylori-infected and 5.5y for uninfected children. Histological esophagitis was found in 216/258 (83.7 %) and gastritis in 95/258 (36.8 %) of G1. Both biopsies were normal for 13.6 % cases. Normal gastric biopsies were associated with esophagitis in 128/ 163 (78.5 %) of G1, but gastritis was associated with normal esophageal biopsies in only 7/95 (7.4 %) (0<.001). Histological gastritis was found in 80/108 (74.1 %) of G2 patients. Therefore, for symptomatic children both biopsies are indicated.

Relationship of IL-1 and TNF-alpha polymorphisms with Helicobacter pylori in gastric diseases in a Brazilian population

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Epstein-Barr virus infection and gastric carcinoma in São Paulo State, Brazil

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus, and most people have serological evidence of previous viral infection at adult age. EBV is associated with infectious mononucleosis and human cancers, including some lymphomas and gastric carcinomas. Although EBV was first reported in lymphoepithelioma-like gastric carcinoma, the virus was also found in conventional adenocarcinomas. In the present study, 53 gastric carcinomas diagnosed in São Paulo State, Brazil, were evaluated for EBV infection by non-isotopic in situ hybridization with a biotinylated probe (Biotin-AGACACCGTCCTCACCACCC GGGACTTGTA) directed to the viral transcript EBER-I, which is actively expressed in EBV latently infected cells. EBV infection was found in 6 of 53 (11.32%) gastric carcinomas, mostly from male patients (66.7%), with a mean age of 59 years old. Most EBV-positive tumors were in gastric antrum. Two EBV-positive tumors (33.3%) were conventional adenocarcinomas, whereas four (66.7%) were classified as lymphoepithelioma-like carcinomas. EBV infection in gastric carcinomas was reported elsewhere in frequencies that range from 5.6% (Korea) up to 18% (Germany). In Brazil, a previous work found EBV infection in 4 of 80 (5%) gastric carcinomas, whereas another study found 4.7 and 11.2% of EBV-positive gastric carcinomas of Brazilians of Japanese origin or not, respectively. In the present study, the frequency of EBV-positive gastric carcinomas is similar to that reported in other series, and the clinicopathologic characteristics of these EBV-positive tumors are in agreement with the data in the literature.

Gastric proliferative lesions induced by duodenogastric reflux in rats

OBJETIVO: Avaliar as lesões proliferativas que se desenvolvem na mucosa gástrica de ratos Wistar após modelo específico de refluxo duodeno-gástrico. MÉTODOS: Foram utilizados 75 ratos adultos machos divididos em três grupos experimentais: o grupo I (controle) submetido a gastrotomia na parede posterior do estômago glandular (25 animais); o grupo II (RDG), foi submetido a gastrojejunoanastomose látero-lateral na parede posterior do estômago glandular (25 animais) e o grupo III (RDG-P) submetido a gastrojejunoanastomose látero-lateral na parede posterior do estômago glandular, com secção e fechamento da alça (25 animais). Os animais foram observados durante 36 semanas, após o que foram realizados estudos macroscópicos e microscópicos da anastomose gastrojejunal, da região pré-pilórica e região escamosa do estômago. RESULTADOS: Os animais do Grupo I não apresentaram nenhum tipo de lesão. No grupo II observou-se 40% de lesões do tipo hiperplasia adenomatosa na anastomose e 12% de hiperplasia escamosa. No grupo III obteve-se 40% de hiperplasia adenomatosa na mucosa pré-pilórica, 72 % de hiperplasia adenomatosa na mucosa da anastomose, 20% de hiperplasia escamosa e 12 % de adenocarcinoma. CONCLUSÕES: O refluxo duodeno-gástrico induz a alta freqüência de lesões proliferativas na mucosa adjacente à anastomose gastrojejunal ou na mucosa pré-pilórica e o adenocarcinoma é um evento raro neste modelo experimental.

Biopatologia do Helicobacter pylori

A infecção pelo Helicobacter pylori (H. pylori) induz inflamação persistente na mucosa gástrica com diferentes lesões orgânicas em humanos, tais como gastrite crônica, úlcera péptica e câncer gástrico. Os fatores determinantes desses diferentes resultados incluem a intensidade e a distribuição da inflamação induzida pelo H. pylori na mucosa gástrica. Evidências recentes demonstram que cepas do H. pylori apresentam diversidade genotípica, cujos produtos acionam o processo inflamatório por meio de mediadores e citocinas, que podem levar a diferentes graus de resposta inflamatória do hospedeiro, resultando em diferentes destinos patológicos. Cepas H. pylori com a ilha de patogenicidade cag induzem resposta inflamatória mais grave, através da ativação da transcrição de genes, aumentando o risco para desenvolvimento de úlcera péptica e câncer gástrico. O estresse oxidativo e nitrosativo induzido pela inflamação desempenha importante papel na carcinogênese gástrica como mediador da formação ou ativação de cancerígenos, danos no DNA, bem como de alterações da proliferação celular e da apoptose.