Epstein-Barr virus-positive gastric cancer: a distinct molecular subtype of the disease?

Abstract: Approximately 90% of the world population is infected by Epstein-Barr virus (EBV). Usually, it infects B lymphocytes, predisposing them to malignant transformation. Infection of epithelial cells occurs rarely, and it is estimated that about to 10% of gastric cancer patients harbor EBV in their malignant cells. Given that gastric cancer is the third leading cause of cancer-related mortality worldwide, with a global annual incidence of over 950,000 cases, EBV-positive gastric cancer is the largest group of EBV-associated malignancies. Based on gene expression profile studies, gastric cancer was recently categorized into four subtypes; EBV-positive, microsatellite unstable, genomically stable and chromosomal instability. Together with previous studies, this report provided a more detailed molecular characterization of gastric cancer, demonstrating that EBV-positive gastric cancer is a distinct molecular subtype of the disease, with unique genetic and epigenetic abnormalities, reflected in a specific phenotype. The recognition of characteristic molecular alterations in gastric cancer allows the identification of molecular pathways involved in cell proliferation and survival, with the potential to identify therapeutic targets. These findings highlight the enormous heterogeneity of gastric cancer, and the complex interplay between genetic and epigenetic alterations in the disease, and provide a roadmap to implementation of genome-guided personalized therapy in gastric cancer. The present review discusses the initial studies describing EBV-positive gastric cancer as a distinct clinical entity, presents recently described genetic and epigenetic alterations, and considers potential therapeutic insights derived from the recognition of this new molecular subtype of gastric adenocarcinoma.

Helicobacter pylori genotyping from positive clotests in patients with duodenal ulcer

Even though the seroprevalence of H. pylori may be high in the normal population, a minority develops peptic ulcer. Colonization of the gastric mucosa by more pathogenic vacA strains of H. pylori seems to be associated with enhanced gastric inflammation and duodenal ulcer. H. pylori genotyping from positive CLOtests was developed to determine the vacA genotypes and cagA status in 40 duodenal ulcer patients and for routine use. The pathogenic s1b/ m1/ cagA genotype was the most frequently occurring strain (17/42.5%); only two (5%) patients presented the s2/ m2 genotype, the less virulent strain. Multiple strains were also detected in 17 (42.5%) patients. Multiple strains of H. pylori colonizing the human stomach have been underestimated, because genotyping has been performed from cultures of H. pylori. We concluded that genotyping of H. pylori from a positive CLOtest had the advantages of reducing the number of biopsies taken during endoscopy, eliminating the step of culturing H. pylori, and assuring the presence of H. pylori in the specimen being processed.

Antimicrobial activity of bergenin from Endopleura uchi (Huber) Cuatrec

Endopleura uchi (Huber) Cuatrec. is an Amazon species traditionally used as treatment for inflammations and female disorders. Bergenin was isolated from ethyl acetate fraction of bark of E. uchi by using column chromatography over sephadex LH-20 and then silica gel 60 flash. Its structure was identified on the basis of its NMR spectra. The antimicrobial activity of bergenin and fractions of methanol extract of E. uchi were evaluated against ATCC microorganisms (Escherichia coli, Salmonella enteritidis, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus, Candida albicans, C. guilliermondii, Aspergillus flavus, A. nidulans). Clinically isolated strains of all of these microorganisms, along with C. tropicalis, A. niger, Shigella sonnei, Serratia marcenses and Klebsiella pneumoniae were also evaluated. The growth inhibition caused by bergenin, extracts and fractions of E. uchi against ATCC microorganisms were similar to the inhibition to microorganisms clinically isolated. The ethyl acetate fraction and the isolate bergenin inhibit the growth of the yeasts C. albicans, C. tropicalis, and C. guilliermondii, but present lower activity against filamentous fungi Aspergillus flavus, A. nidulans, A. niger, and did not inhibit the Gram positive and Gram negative bacteria. The activity of the ethyl acetate fraction and bergenin are in agreement wit its high concentration found in bark extract of E. uchi. Moreover, the selective activity against three Candida species helps to understand its traditional use against infections that affect women.

Selective serotonin-reuptake inhibitor and norepinephrine dopamine reuptake inhibitor antidepressants do not affect natural killer cell activity in vitro

OBJECTIVE: This study aims to evaluate the citotoxic activity of two commonly used anti-depressants: paroxetine and bupropion. We also evaluated the in vitro natural killer activity (NKA) after incubating the blood samples with the antidepressants. METHODS: Peripheral blood samples from 15 healthy volunteers were collected and the mononuclear cells (PBMCs) were isolated and incubated for 24h with (or without = control cells) paroxetine and bupropion, in concentrations of 30, 100 and 1000 ng/ml. After the incubation period in both groups, the amount of dead cells was calculated using trypam blue technique. NKA was evaluated using the classic51Cr release assay. CONCLUSIONS: PBMCs dead cells occurred in both groups and in proportion to all pharmacological concentrations. Nevertheless, the NKA was not affected, even with the reduction in the number of effective cells.

Cognitive processes affect the gait of subjects with Parkinson’s and Alzheimer’s disease in dual tasks

Objective To investigate the relation between gait parameters and cognitive impairments in subjects with Parkinson’s disease (PD) and Alzheimer’s disease (AD) during the performance of dual tasks. Methods This was a cross-sectional study involving 126 subjects divided into three groups: Parkinson group (n = 43), Alzheimer group (n = 38), and control group (n = 45). The subjects were evaluated using the Timed Up and Go test administered with motor and cognitive distracters. Gait analyses consisted of cadence and speed measurements, with cognitive functions being assessed by the Brief Cognitive Screening Battery and the Clock Drawing Test. Statistical procedures included mixed-design analyses of variance to observe the gait patterns between groups and tasks and the linear regression model to investigate the influence of cognitive functions in this process. A 5% significant level was adopted. Results Regarding the subjects’ speed, the data show a significant difference between group vs task interaction (p = 0.009), with worse performance of subjects with PD in motor dual task and of subjects with AD in cognitive dual task. With respect to cadence, no statistical differences was seen between group vs task interaction (p = 0.105), showing low interference of the clinical conditions on such parameter. The linear regression model showed that up to 45.79%, of the variance in gait can be explained by the interference of cognitive processes. Conclusion Dual task activities affect gait pattern in subjects with PD and AD. Differences between groups reflect peculiarities of each disease and show a direct interference of cognitive processes on complex tasks.

Doppler echocardiographic evaluation of HIV-positive patients in different stages of the disease

OBJETIVE: To evaluate by Doppler echocardiography (DE) early abnormalities of ventricular function in HIV-positive patients, as well as other cardiac abnormalities that can be detected by this method, with special emphasis on mitral valve flow. METHODS: 84 HIV- positive patients, 59 with CD4 cell count >500/mm³ (Group A) and 25 with CD4 cell count <500/mm³ (Group B), were analyzed. CD4 cells were counted and matched with structural data and systolic and diastolic function of the left ventricle (LV), as analyzed by DE. The results were compared with those obtained in 47 healthy individuals (Group C). RESULTS: 8% of patients in Group B had mild pericardial effusion; 31.5% showed decreased systolic function of the LV, and 12% had moderate mitral regurgitation. A wave velocity from the mitral inflow was different among the 3 groups, being higher in Group B, where the deceleration time of the E wave of the mitral inflow and the E/A ratio were significantly lower with a normal value of the isovolumic relaxation time (IVRT). CONCLUSION: HIV-positive patients with a CD4 cell count >500/mm³ had no abnormalities by DE. Patients with a more advanced infection (those with a CD4 cell count <500/mm³), had a significantly abnormal LV systolic function and a higher incidence of pericardial effusion and mitral regurgitation. Mitral valve inflow by Doppler did not indicate diastolic dysfunction.

Oxygen therapy, continuous positive airway pressure, or noninvasive bilevel positive pressure ventilation in the treatment of acute cardiogenic pulmonary edema

OBJECTIVE: To compare the effects of 3 types of noninvasive respiratory support systems in the treatment of acute pulmonary edema: oxygen therapy (O2), continuous positive airway pressure, and bilevel positive pressure ventilation. METHODS: We studied prospectively 26 patients with acute pulmonary edema, who were randomized into 1 of 3 types of respiratory support groups. Age was 69±7 years. Ten patients were treated with oxygen, 9 with continuous positive airway pressure, and 7 with noninvasive bilevel positive pressure ventilation. All patients received medicamentous therapy according to the Advanced Cardiac Life Support protocol. Our primary aim was to assess the need for orotracheal intubation. We also assessed the following: heart and respiration rates, blood pressure, PaO2, PaCO2, and pH at begining, and at 10 and 60 minutes after starting the protocol. RESULTS: At 10 minutes, the patients in the bilevel positive pressure ventilation group had the highest PaO2 and the lowest respiration rates; the patients in the O2 group had the highest PaCO2 and the lowest pH (p<0.05). Four patients in the O2 group, 3 patients in the continuous positive pressure group, and none in the bilevel positive pressure ventilation group were intubated (p<0.05). CONCLUSION: Noninvasive bilevel positive pressure ventilation was effective in the treatment of acute cardiogenic pulmonary edema, accelerated the recovery of vital signs and blood gas data, and avoided intubation.

Helminths of introduced house sparrows (Passer domesticus) in Brazil: does population age affect parasite richness?

Species introductions have altered host and parasite diversity throughout the world. In the case of introduced hosts, population age appears to be a good predictor of parasite richness. Habitat alteration is another variable that may impact host-parasite interactions by affecting the availability of intermediate hosts. The house sparrow (Passer domesticus (Linnaeus, 1758)) is a good model to test these predictions. It was introduced in several parts of the world and can be found across rural-urban gradients. A total of 160 house sparrows from Porto Alegre, state of Rio Grande do Sul, Brazil, were necropsied. Thirty house sparrows (19 %) were parasitized with at least one out of five helminth species (Digenea: Tamerlania inopina Freitas, 1951 and Eumegacetes sp.; Eucestoda: Choanotaenia passerina (Fuhrmann, 1907) Fuhrmann, 1932; Nematoda: Dispharynx nasuta (Rudolphi, 1819) Stiles & Hassall, 1920 and Cardiofilaria pavlovskyi Strom, 1937). Overall, there was no difference in prevalence and intensity of infection of any parasite species, parasite richness and community diversity between adult males and females and adults and juveniles. The number of infected sparrows among seasons, the richness of helminths and the abundance of species were also similar between rural and urban landscapes. Only the prevalence of C. passerina varied seasonally (p=0.0007). A decrease in the number of parasite species from the original range of P. domesticus (13) to its port of entrance in Brazil, the city of Rio de Janeiro (nine), to Porto Alegre (five) is compatible with the hypothesis that host population age is a good predictor of parasite richness.

Estudo bacteriológico de escarros de leprosos-tuberculosos em tratamento com a Estreptomicina

Fourteen samples of sputum from fourteen lepers with pulmonary tuberculosis, were treated by PETROFF method and its sediments were smeared on LOEWENSTEIN medium and incubated at 37°C. These fourteen patients are under treatment by Streptomycin. They are advanced cases of active leprosy associated with pulmonary tuberculosis, according to X ray diagnosis. Between 15 to 45 days thirteen out of fourteen (92,85%) sputa gave cultures of acid-fast bacilli with all characteristics of KOCH'S bacillus, eugonic type. Nine out of thirteen positive cases produced eugonic colonies in all ten tubes smeared with each sample. These facts proved that Streptomycin did not affect the pulmonary flora. Three out of fourteen patients died within two months after positive cultures of KOCH'S bacillus. New fact - Three out of those thirteen positive patients gave non-chromogenic cultures, eugonic type, associated with chromogenic ones, quite similar to cultures of acid-fast bacilli isolated previously by the author from leprous material. One of the three patients who died showed in smear of fresh sputum only characteristics globies (globies of MARCHOUX not globi of NEISSER) of HANSEN'S Bacillus. Probably he died from leprous-pneumonia. The eugonic type cultures are being inoculated in guinea-pigs and the choromogenic ones, similar to leprosy-culture, will be inoculated in white rats and mice.

Serological Evidence of HTLV-I and HTLV-II Coinfections in HIV-1 Positive Patients in Belém, State of Pará, Brazil

The occurrence of HTLV-I/II and HIV-1 coinfections have been shown to be frequent, probably in consequence of their similar modes of transmission. This paper presents the prevalence of coinfection of HTLV among HIV-1 infected and AIDS patients in Belém, State of Pará, Brazil. A group of 149 patients attending the AIDS Reference Unit of the State Department of Health was tested for the presence of antibodies to HTLV-I/II using an enzyme immunoassay and the positive reactions were confirmed with a Western blot that discriminates between HTLV-I and HTLV-II infections. Four patients (2.7%) were positive to HTLV-I, seven (4.7%) to HTLV-II and one (0.7%) showed an indeterminate pattern of reaction. The present results show for the first time in Belém not only the occurrence of HTLV-II/HIV-1 coinfections but also a higher prevalence of HTLV-II in relation to HTLV-I. Furthermore, it also enlarges the geographical limits of the endemic area for HTLV-II in the Amazon region of Brazil.

Parasite Genotypically Related to a Monoxenous Trypanosomatid of Dog's Flea Causing Opportunistic Infection in an HIV Positive Patient

An HIV positive patient presenting a clinical picture of visceral leishmaniasis co-infection was submitted to a bone marrow aspiration after admission to hospital. Amastigotes forms were seen in the bone marrow aspirate and the parasite grew in culture as promastigotes. Molecular analyses showed that the flagellates isolated did not belong to the genera Leishmania, Trypanosoma or Sauroleishmania. It was not possible to establish infection in laboratory animals. In vitro culture of mouse peritoneal macrophages revealed the invasion of the host cells by the flagellates and their killing 48 hr after infection. Opportunistic infection with an insect trypanosomatid was suspected. Further hybridization analyses against a pannel of different monoxenous and heteroxenous trypanosomatids showed kDNA cross-homology with Leptomonas pulexsimulantis a trypanosomatid found in the dog's flea