Marcos Antonio Pereira de Lima

The relationship between Helicobacter pylori genes cagE and virB11 and gastric cancer

BACKGROUND The association between Helicobacter pylori gene diversity and gastric cancer has been poorly reported, although it is one of the important ways to explain the gastric pathogenesis. The aim of this study was to investigate the frequency of cagE and virB11 genes in H. pylori isolated from patients with gastric cancer and to analyze the histology profiles. MATERIALS AND METHODS The presence of H. pylori and subtypes (cagE and virB11) was detected by PCR from the genomic DNA of 101 patients who had been diagnosed with gastric cancer. The cases were grouped according to the presence/absence of the genes studied and were analyzed in relation to histopathological parameters. RESULTS H. pylori infection was detected in 94 out of 101 (93.1%) gastric carcinomas. The cases were categorized into the following groups: cagE+/virB11+, cagE+/virB11-, cagE-/virB11+, and cagE-/virB11-. Frequencies were: 50% (47/94) cagE+/virB11+, 3.2% (3/94) cagE+/virB11-, 10.6% (10/94) cagE-/virB11+, and 36.2% (34/94) cagE-/virB11-. Tumors in the gastric antrum were predominant. An exception was the cagE-/virB11- group, in which tumors had a tendency to be located in the gastric cardia; the majority of the cardia tumors (56% (14/25)) were in this group. Intestinal histology type was the most frequent, but the cagE+/virB11- group only had diffuse tumors. H. pyloricagE+/virB11+ occurred most frequently (except at stage III), and was present at all gastric cancer stages. CONCLUSIONS This study is the first to include a relevant number of gastric cancer cases with H. pylori infection, reporting the frequency and relationship of cagE and virB11 genes and the genesis of this tumor. The presence of these cag pathogenicity island genes shows that they are important factors for the pathogenesis and malignancy of gastric cancer related to H. pylori.

Clinical and Epidemiological Aspects of Scorpionism in the World: A Systematic Review.

OBJECTIVE Scorpion stings are registered worldwide, but the incidence and the features of the envenomations vary depending on the region. The aim of this review was to summarize the epidemiological, clinical, diagnostic, and therapeutic data worldwide regarding humans stung by scorpions. METHODS A systematic review of the literature was conducted through the online databases of the Virtual Health Library (VHL), which hosts Medline and the Latin American and Caribbean Center on Health Sciences Informational (LILACS) database. We selected articles published between January 1, 2002 and July 31, 2014. RESULTS Scorpion envenomation reports were found throughout the world, mainly in subtropical and tropical regions. The clinical manifestations were sympathetically and parasympathetically mediated, depending on the species of scorpion. Some of the most common severe complications of scorpionism included respiratory distress syndrome, pulmonary edema, cardiac dysfunction, impaired hemostasis, pancreatitis, and multiple organ failure. Scorpion envenomation could be classified as mild, moderate, and severe, and the therapeutic approach was based on the case severity. The treatment comprised 3 components: symptomatic measures, vital functions support, and injection of antivenom. Moreover, the time that elapsed between the sting and administration of the appropriate medical care was extremely important to the patients prognosis. CONCLUSIONS The large number of scorpion stings worldwide is concerning and reaffirms the need for new prevention measures and policies to reduce the incidence, prevalence, morbidity, and mortality rates from these poisonous arachnids.

Association between Epstein-Barr virus (EBV) and cervical carcinoma: A meta-analysis

OBJECTIVES Human papillomavirus (HPV) has been implicated as a major factor in cervical carcinogenesis. However, many pieces of evidence gathered over the last two decades suggest Epstein-Barr virus (EBV) plays a secondary role in this process. The purpose of the present meta-analysis was to determine whether the presence of EBV infection increases the risk of cervical carcinoma. METHODS Based on 25 articles, the analysis yielded a 33.44% overall pooled prevalence of EBV. RESULTS The pooled prevalence was higher in patients with carcinoma (43.63%) than in healthy patients (19.0%) or patients with cervical intraepithelial neoplasia 1 (CIN1) (27.34%) or CIN2/3 (34.67%). Co-infection with EBV and HPV displayed a similar pattern. EBV infection was significantly and positively associated with lesion grade in cervical epithelia and was more prevalent in malignant lesions. Moreover, cervical carcinoma occurred four times as often among EBV positive women as in women without EBV infection (OR=4.01 [1.87-8.58]; p<0.001). CONCLUSIONS The existence of EBV(+)HPV(-) carcinomas, the confirmed expression of latent oncoproteins (EBNA1, EBNA2, LMP1) and EBERs in tumor cells, and the association of EBV with the integration of high-risk-HPV DNA in malignant specimens point to EBV as a co-factor (so far underestimated) in the genesis and/or progression of cervical carcinoma. However, further studies are necessary before the link between EBV and cervical carcinoma can be established.

Relationship between EBV infection and expression of cellular proteins c-Myc, Bcl-2, and Bax in gastric carcinomas.

Background Epstein-Barr virus (EBV) has been related to tumorigenesis in about 10% of all gastric carcinomas. Several studies have demonstrated strong evidence of its involvement in this process, but most of the mechanisms used by the virus to control this process are still unknown. Previous studies in vitro have indicated a relationship between the virus and some cellular genes involved in processes such as proliferation and apoptosis. Objective The aim of the present study was to investigate a possible EBV-induced tumorigenic pathway involving the cellular proteins Bcl-2, Bax, and c-Myc. Study Design One hundred patients of gastric carcinoma, obtained from 2 hospitals in Fortaleza, Brazil were assessed for the presence of EBV by in situ hybridization, for the expression of Bcl-2, Bax, and c-Myc (nuclear and cytoplasmic staining) proteins by immunohistochemistry techniques, and for the apoptotic index. Results EBV was detected in 8 (8%) patients showing strong staining situated in the nuclei of the tumor cells, 6 of them displaying a diffuse pattern, and 2 demonstrating a focal pattern of staining. The correlation with the immunohistochemistry results demonstrated that none of the EBV-positive cases exhibited Bcl-2 staining. On the other hand, Bax and c-Myc (nuclear) proteins demonstrated a significant positivity index and staining scores (labeling index and H-score) in the EBV-positive group; however, the values were lower than those obtained in the EBV-negative group, notably for c-Myc nuclear protein. In contrast, the cytoplasmic staining of c-Myc protein revealed slightly higher staining values in the EBV-positive group. The balance between Bcl-2 and Bax proteins demonstrated that the majority of the evaluated cases exhibited apoptosis orientation; however, in 62.5% of the EBV-positive cases neither protein was observed. The average apoptotic index was 4.58%, demonstrating a slightly lower average in the EBV-positive group. Conclusions EBV is not related to the overexpression of Bcl-2 and c-Myc (nuclear) in gastric carcinomas; however, the results point to a possible EBV involvement with the transport mechanisms of the nuclear membrane, resulting in cytoplasmic c-Myc accumulation. The suppression of Bax expression could represent an alternative viral mechanism for inhibition of apoptosis.

Association between human papillomavirus (HPV) and the oral squamous cell carcinoma: a systematic review

The human papillomavirus (HPV) is an epitheliotropic agent whose high-risk genotypes have a well-established link with the development of cervical cancer. Although the relation of HPV to the oral squamous cell carcinoma (OSCC) has been studied since the beginning of the 1980s, its role in the oral carcinogenesis and the probable underlying molecular mechanisms are still not fully elucidated. We performed a systematic review of the worldwide scientific literature, published until the preparation of the present paper, concerning the association of HPV with OSCC, scrutinizing the samples, prevalence levels, the techniques utilized and relevant findings of the studies. The results showed that HPV is associated with approximately one quarter of OSCCs. Another interesting feature is the distinct pattern of infection in these oral tumors, including the participation of genotypes that are uncommon in cervical malignant lesions, such as HPV-38, 44, 53 and 70. Equally interesting is the possibility of carcinogenic action without the occurrence of viral integration, verified by the high expression of messenger ribonucleic acid (mRNA) of E6 and E7 from high-risk genotypes in cases whose virus remain in the episomal form. These findings support the assumption of HPV involvement in the genesis of OSCC, whereas warn about the possibility of unexpected viral behaviors that sometimes are not perceived or understood due to the technological limitations of the time and to the shortage of studies with the adequate approaches.

Differential expression of MYC in H. pylori- related intestinal and diffuse gastric tumors

Evidence suggests that the carcinogenic process guided by Helicobacter pylori is related to the expression of cell cycle and apoptosis proteins as BCL-2, BAX, and MYC. However, the literature is conflicting regarding the expression frequency in the histological subtypes and did not consider cagA gene presence. To investigate the expression of these proteins considering the histological subtypes of gastric cancer associated with H. pylori (cagA), a total of 89 cases were used. H. pylori infection and cagA status were determined by PCR. Immunodetection was performed for MYC, BCL-2, and BAX proteins. H. pylori was found in 95.5% of the patients, among them, 65.8% were cagA(+). Nuclear MYC was detected in 36.4%, BAX in 55.7%, while BCl-2 in just 5%. Nuclear MYC staining was significantly lower in the intestinal than diffuse subtype (p = 0.008) and was related with the presence of H. pylori cagA(+). Additionally, most of the few cases cytoplasmic MYC positive were in the intestinal subtype. In diffuse tumors, although most nuclear MYC positive cases were cagA(+), it was not significant. No difference was observed between BCL-2 or BAX expression considering the presence of cagA gene in the histological subtypes. It seems that MYC could be relevant for the diffuse tumorigenic pathway associated with H. pylori and possibly influenced by the presence of cagA gene, while in intestinal tumors, the tumorigenic pathway does not occur through the MYC expression.

Detecção do vírus Epstein-Barr (EBV) em adenocarcinomas gástricos procedentes dos estados do Ceará e de São Paulo

INTRODUCTION: The Epstein-Barr virus (EBV) has been associated with approximately 10% of gastric adenocarcinomas, which represents more than 50,000 cases/year worldwide. Despite the studies undertaken in several countries, some clinical-pathological aspects remain contentious. OBJECTIVE: The objective of this study was to analyze clinical-pathological features of gastric adenocarcinomas from two Brazilian states, Sao Paulo and Ceara, by correlating them with EBV detection. MATERIALS AND METHODS: One hundred ninety-two gastric adenocarcinoma cases were selected from hospitals in Sao Paulo and Ceara, of which 160 were submitted to RNA in situ hybridization for EBV detection. RESULTS: Eleven (6.9%) out of 160 cases were EBV-positive with intense nuclear staining in tumor cells. Among these, two cases also showed stained infiltrating lymphocytes. There was no staining in normal or preneoplastic tissue. Sao Paulo and Ceara yielded the respective results: 3/60 (5%) and 8/100 (8%). In both states, EBV was more prevalent among elder male patients with little to moderately differentiated intestinal tumors in advanced stage. Ceara cases substantiated a relative increase in EBV(+) tumors located in the cardia, whereas Sao Paulo cases presented an increase in the gastric corpus. CONCLUSION: The frequency of EBV(+) tumors is similarly described in the literature. Among our findings, the elevated percentage of EBV(+) tumors in the gastric corpus, which was observed in Sao Paulo cases, is unprecedented in the literature.

An Update On Rodent Model Studies In Diabetic Neuropathy: A Brief Communication

The diseases of the peripheral nerves are quite common and diversified, are directly related to several factors, ranging from the imbalance related to good nutrition and adequate needs of nutrients, going to the injuries caused by drugs or mechanisms external to the human organism. Diabetes is a complex syndrome that affects and kills millions of people worldwide. We demonstrated through the experimental model of diabetes using STZ@ in single intraperitoneal dose of 60 mg / kg, that both a purely motor nerve can be directly affected as well as a special afferent nerve (cranial nerve), this comparison showed us that there is a possibility of having a new type of mixed type neuropathy, this may be related to the amount of the dose involved, such as the time of disease progression, but more studies need to be done for definitive confirmation. We can extrapolate the original results to understand the mechanisms of diabetes in humans, although it does not yet have an experimental model of type II diabetes, more related to eating disorders, the STZ application simulates the effects of type I or insulin dependent diabetes, with more serious and deleterious effects mainly the more distal portions of the nerves. Prevention and food control are very important, especially those related to the mechanisms that involve carbohydrate metabolism and its peripheral resistance. The original results commented here are relevant for the continuous study of this serious but old illness, but quite current in the medical and therapeutic clinic. Keywords: Experimental Model of Diabetes; Sensory and Motor Peripheral Nerves; Peripheral Nerve Injuries; Neuropathies; STZ; Rats.

Epstein-Barr virus-associated gastric carcinoma in Brazil: comparison between in situ hybridization and polymerase chain reaction detection

Epstein-Barr virus (EBV) has been associated with 10% of gastric carcinomas. The aim of this study was to determine the frequency of EBV in gastric carcinomas in Brazil assessed by in situ hybridization (ISH) and PCR, which would contribute to the characterization of the clinical and pathological aspects of EBV-associated gastric carcinomas. One hundred and ninety-two gastric carcinoma cases were collected at hospitals in two Brazilian states. Seventy-three out of 151 cases were PCR(+), while 11/160 cases were ISH(+). Nine out of eleven ISH(+) cases displayed a diffuse staining pattern and 2 out of 11 a focal pattern. Both techniques showed that the EBV(+) cases were characterized by their association with males, older patients, lower gastric region, intestinal type, advanced stage and poorly to moderately differentiated tumors. The concordance between the two techniques was 55.8% (Cohens kappa index = 0.034). Four cases were ISH(+)/PCR(-), while 49 cases were PCR(+)/ISH(-). Only two cases showed stained lymphocytes by ISH and one of them was PCR(-). The observed discrepancy between the two techniques could not be explained just by the elevated accuracy of PCR. ISH(+)/PCR(-) carcinomas may be encountered if EBV is not present in the whole tumor tissue or if there are polymorphisms in the sequences of the viral genome amplified. On the other hand, the high frequency of PCR(+) results associated with the absence of ISH staining in lymphocytes and/or tumors cells suggests that the virus may be present in tumor cells or other cell types without expressing EBER1, the target of the ISH technique.