Dialyzable leukocyte extract suppresses the activity of essential transcription factors for HIV-1 gene expression in unstimulated MT-4 cells.

The human immunodeficiency virus type 1 (HIV-1) contains regulatory regions in its long terminal repeat (LTR) implicated in the control of viral gene expression. We previously demonstrated that Dialyzable Leukocyte Extract (DLE), a preparation derived from immune leukocytes, is able to inhibit HIV-1 replication in MT-4 cell cultures. Here, we examined the effect of DLE on the activation of NF-kappaB and Sp1 transcription factors. NF-kappaB activity was completely suppressed after seven days of treatment with 2.5 U/mL of DLE, with a parallel large reduction in the amounts of Sp1 complexes. These findings correlate with the maximum inhibitory effect on HIV-1 replication described in a previous report. IkappaBalpha and NF-kappaB p65(RelA) gene expression are not regulated by DLE in MT-4 cells. Although up to day, the precise molecular mechanism of DLE biological activity in HIV-1 infection remains unclear, this report presents data that indicate a potential downregulatory effect of DLE on HIV-1 gene expression.

Alcohol consumption and gastric cancer in Mexico.

This paper presents an assessment of alcohol consumption, including the popular Mexican liquor tequila, in relation to the incidence of gastric cancer. We conducted a population-based case-control study in Mexico City, with 220 gastric cancer cases and 752 population-based controls. A food frequency questionnaire was used to measure consumption of alcohol and other dietary items. Grams of ethanol were estimated by the Food Intake Analysis System 3.0 software. After adjustment for known risk factors, wine consumption was positively associated with the risk of developing gastric cancer (OR=2.93; CI 95% 1.27-6.75) in the highest category of wine consumption, corresponding to at least 10 glasses of wine per month, with a significant trend (p=0.005). This association remained among intestinal (OR=2.16; CI 95% 0.68-6.92, p-value for trend=0.031 ) and diffuse (OR=4.48; CI 95% 1.44-13.94, p-value for trend=0.018 ) gastric cancer cases. A borderline significant trend between GC risk and total ethanol intake was observed (p=0.068). Consumption of beer and distilled alcoholic beverages including brandy, rum, and tequila was not associated with GC risk. The results indicate the need to focus on the study of the potential effects of different types of wine, with emphasis on components other than ethanol regarding the incidence of gastric cancer, even among populations with moderate to low levels of alcohol consumption.

[Helicobacter pylori infection and gastric cancer in Mexico. A challenge for prevention and population control]. / Infección por Helicobacter pylori y cáncer gástrico en México. Un reto para la prevención y el control poblacional.

The International Agency for Research on Cancer (IARC) of the WHO has recognized a cause-effect relationship between Helicobacter pylori (Hp) infection and gastric cancer of such magnitude that the presence of this infection increases the risk of gastric cancer approximately four times. Gastric cancer is currently the second cause of mortality due to malignant neoplasms in Mexico City. This article explores the association between Hp infection and gastric cancer incidence through an epidemiological study including 109 gastric cancer patients and 177 hospital controls in Mexico City. The study estimates that, in the population studied, Hp infection was present in 87.2% of the cases, compared with 82.5% of the controls. The odds ratio of having gastric cancer if infected with Hp was 1.44 IC95% 0.7-2.8. In addition, it was calculated that with eradication of Hp infection in the general population, gastric cancer incidence would decrease by at least 26.6%. An improvement of the actual sanitary conditions along with the development of an effective vaccine for Hp infection and the existence of increasingly effective treatments to eradicate the bacteria are the necessary next step for populational prevention and control of gastric cancer.

Inhibition of in vitro HIV infection by dialysable leucocyte extracts.

Dialysable Leucocyte Extract (DLE) is a low molecular weight dialysable material of disrupted peripheral human leucocytes with widespread effects on the immune system. We described the in vitro anti-HIV activity of DLE as well as its three chromatographic fractions (Fa, Fb and Fc). To determine the levels of inhibition on HIV replication by DLE we infected MT-4 cell cultures, using the Bru viral isolate at 0.05, 0.1, 0.5 and 1 m.o.i. Previously, MT-4 cells cultures were treated with DLE or fractions at non-toxic concentrations. Reverse transcriptase (RT) activity and p24 antigen were evaluated in culture supernatants at seven days postinfection. No effect was observed when MT-4 cells were incubated with DLE for 3 h. Whereas inhibition of HIV production was observed when MT-4 cells were pre-treated for a longer period of time. DLE inhibited p24 production and RT activity more than 50% at 0.1 m.o.i. More than 80% of inhibition was observed for all doses of DLE tested at 0.05 m.o.i. Higher viral doses (m.o.i. 0.5 and 1) were used to assess the antiviral activity of DLE fractions. Fraction Fb inhibits viral production more than 80%. Otherwise, fractions Fa and Fc did not show inhibitory effect for any viral dose used. These results indicate that DLE is able to modulate cell susceptibility to viral infection in vitro.

Dialysable leucocyte extract (DLE) reduces lipopolysaccharide-induced tumour necrosis factor secretion in human leucocytes.

Dialysable leucocyte extract (DLE), obtained from lysed leucocytes, provide clinical effectiveness in a broad spectrum of diseases. Tumour necrosis factor (TNF) is raised in AIDS patients leading to an increase in human immunodeficiency virus (HIV) replication in vitro [1,2], whereas progression to AIDS in asymptomatic HIV infected individuals is retarded under treatment with DLE. In the present study we tested the DLE effect in vitro on both TNF biological activity (cytotoxicity) in L929 cells and its induction by lipopolysaccharide (LPS) in human monocytes as well as in whole blood from healthy donors. When monocytic cells were simultaneously exposed to LPS and DLE during a period of 5 1/2 hours, the induction of TNF was strongly diminished. The same inhibitory effect of DLE on TNF induction was observed when LPS was added to the culture medium prior to DLE. No significant effect of DLE on TNF-mediated cytotoxicity, even in the presence of the highest concentrations of DLE tested, was detected. DLE treatment of whole human blood regulates responses to LPS: simultaneous in vitro exposure to endotoxin provokes a remarkable decrease (4- and 1.6-fold) of TNF release. In pre-incubation experiments, TNF production was largely reduced or completed abrogated. These results could, in part, explain the in vivo observed effect, when under treatment with this extract, the progression to AIDS of HIV-infected individuals was retarded. The results suggest that "natural' substances like DLE may be important immunomodulators in inflammatory diseases.