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Biomedical subjects

E Alvarez

Publications and source records attributed to E Alvarez.

At least 145 records · Page 8Linked to original sources
PubMed1996

Metabolism and action of benzamide riboside in Chinese hamster ovary cells.

Benzamide riboside (3-(1-deoxy-beta-D-ribofuranosyl)benzamide, BR) a new analog of nicotinamide riboside, is toxic to Chinese hamster ovary cells and inhibits guanine nucleotide synthesis in a manner comparable to that of tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide). Adenosine kinase deficient cells demonstrate slight resistance but retain the ability to form the NAD analog, benzamide adenine dinucleotide (BAD). HPLC analysis of BAD containing cells is described. A BR resistant cell line was isolated that demonstrates cross-resistance to both tiazofurin and 6-aminonicotinamide, suggesting a common metabolic step; enzymatic analysis indicates reduced levels of NAD pyrophosphorylase in these cells. BR toxicity was only partially reversed or prevented by the presence of guanosine, suggesting either that BR inhibits guanine salvage to some extent or, more probably, that BR can, at high concentration, inhibit cell growth by another mechanism in addition to inhibition of guanine nucleotide synthesis. Cells incubated with BR for several hours retain the ability to salvage exogenously provided guanosine. The demonstration that BAD can be phosphorylated by NAD kinase, presumably to form BADP, suggests that this metabolite may be formed in cells and may have inhibitory activity at high concentrations of BR.

Animals↗
PubMed1996

[Interferon alfa in the treatment of chronic hepatitis C: course of 24 versus 48 weeks. Results of a randomized trial].

UNLABELLED: The aim of this trial was to investigate if a more prolonged course of interferon (IFN) is able to increase the long-term benefit in patients with chronic hepatitis C. Forty-four patients with active chronic hepatitis and antibodies to HCV were randomly assigned to receive IFN-alfa 2b 3 MU t.i.w. during 24 weeks (group I, n 23) or during 48 weeks (group II, n 21). In the evaluation of results, complete response was considered when the ALT values returned to normality during the treatment; and sustained response, when the ALT values persisted below normal range during at least 6 months post therapy. Histologic changes were compared by using the Histological Activity Index, or Knodell score. Viremia status was evaluated for the study of HCV RNA (by nested-RT-PCR). RESULTS: There were no significant differences between both groups before treatment, in terms of age, sex, ALT, or histologic findings (11 patients in group I, and 7 in group II had cirrhosis). Complete response was found in 9 patients (39.1%) from group I; in 11 (52.4%) from group II (NS). Basal histologic findings were identified as the only predictive factor of complete and sustained response, by logistic regression analysis. Considering only noncirrhotic patients, complete response was seen in 58.3% in patients from group I, 71.4% in group II. Sustained response was obtained in 4 patients from group I, (17.4%), 7 from group II (33.3%) (NS). Post IFN liver biopsies were performed in 23 patients (12 from group I, 11 from group II). In group I patients, there were no significant changes. In group II, Knodell score was found to be significantly decreased post IFN [pre IFN, median 10, range 3-15; post IFN, median 6, range 2-14] (p < 0.05). HCV RNA was absent in serum during the follow-up post IFN in 2 patients from group I, in 3 from group II. The results of this study show that a 48 weeks course of IFN has a trend to achieve a higher sustained response than the usual regime (but non significant); and it produces a decrease in the histologic activity. The best predictive factor of positive response was the absence of cirrhosis in our study (although we did not evaluate viral factors, such as genotypes or HCV viremia levels).

Adult↗
PubMed1996

[Immunobiological characterization of murine LB leukemia and the LBC cell line].

LB leukemia is a nonimmunogenic T cell tumor which spontaneously arose in a BALB/c mouse; efforts to induce immunological rejection of the leukemic cells have always failed. The leukemic cells grow rapidly and progressively in the syngeneic host invading spleen, lymph nodes and liver. A cell line (LBC) was developed from the original tumor. Both the original tumor and the cell line have been characterized as expressing the Thy 1+, CD3-, CD25+, MHC class I+, class II-, CD4- (original tumor), CD4+ (cell line), CD8+, gp70-, J11d.2+ phenotypes. Immunization of syngeneic mice with irradiated LBC cells induced cytotoxic T lymphocytes as well as anti-LBC antibodies which reacted with components of 14, 16 and 27 kDa present on LB tumor cells, LBC cell line and normal thymocytes but not on normal lymph node cells. Immunization of syngeneic mice with LBC cells partially protected them against subsequent challenge with the original tumor cells. The effect of sera from tumor-bearing mice and the super-natants from short term cultures were studied on cell proliferation. An inhibitory activity was demonstrated in these fluids, which was abrogated by addition of exogenous IL-2. ELISA showed the presence of soluble IL-2R alpha chain both in the conditioned medium as well as in the serum, which was demonstrated to be responsible for the inhibitory activity. The soluble IL-2R was produced by LB leukemic cells and exerted the inhibitory activity blocking cell proliferation and modulating immune response by binding to free IL-2. Using reverse-transcription PCR, mRNA for IL-2 was found to be present in tumor cells. Our findings indicate that LB cell proliferation is mediated by an autocrine pathway involving endogenous IL-2 generation, despite the fact that these cells are not dependent on exogenous IL-2 to grow in culture. The relationship between tumorigenicity and expression of MHC class II was also investigated. In vitro treatment with IFN-gamma failed to induce the expression of class II antigens in LBC cell line. Therefore these cells were tri-transfected by a liposome-mediated protocol with 1-A alpha d, I-A beta d genes and pSV2neo. Cells were selected to grow in medium containing Genetecin (G418) and surviving transfectants were cloned. Three I-A+ clones were obtained (LBCT) and were used to induce a specific CTL response against tumor cells. Syngeneic mice inoculated with 10(3) LBCT cells failed to develop a tumor while the DT50 of mice injected with 10(6) LBCT cells was three times the value for mice injected with LBC cells (I-A-). It is suggested that neoexpression of MHC class II molecules enhances anti-tumor response by transforming tumor cells into professional antigen-presenting cells, which may be used to improve tumor-specific immunity in the autologous host.

Animals↗
PubMed1995

Decrease in free-radical production with age in rat peritoneal macrophages.

The respiratory-burst reaction has been studied in rat peritoneal macrophages of different ages (3, 12 and 24 months) using phorbol 12-myristate 13-acetate (PMA) to stimulate NADPH oxidase. Production of O2-. and H2O2 decreased with age (about 50 and 75% respectively); however, no difference in NADPH oxidase activity was found. NO. production was also reduced with age (40%). Furthermore, a progressive and significant decrease in the pentose phosphate flux was detected as a function of age in control and PMA-stimulated macrophages. The NADPH/NADP+ ratio decreased with age in control and PMA-stimulated macrophages. Glucose uptake was lower in middle-aged (12 months) and old (24 months) animals but no differences were found between these groups.

Aging↗
PubMed1995

Evaluation of myocardial cell damage by In-111-monoclonal antimyosin antibodies in patients under chronic tricyclic antidepressant drug treatment.

BACKGROUND: The capability of chronic tricyclic antidepressant drug (TAD) treatment to elicit myocardial damage has been a subject of debate. Lack of an adequate noninvasive method to detect such damage has prevented an in-depth study. METHODS AND RESULTS: A prospective study with In-111-monoclonal antimyosin antibodies was undertaken in a series of 21 young patients with major depression on TADs and a control group of 19 healthy subjects. A heart-to-lung ratio (HLR) of antimyosin uptake was used to discriminate normal from abnormal scans. HLR in healthy subjects was 1.39 +/- 0.08. Patients on imipramine (HLR, 1.41 +/- 0.09) or clomipramine (HLR, 1.44 +/- 0.06) showed normal studies. Those under amitriptyline had a higher HLR (1.58 +/- 0.12) compared with nonamitriptyline or normal groups (P < .05). None of the 15 patients on imipramine or clomipramine showed abnormal HLR, while 3 of 6 on amitriptyline did (P < .01). In these 3 patients, uptake decreased or disappeared after drug withdrawal. Ejection fraction was normal in every patient. CONCLUSIONS: Monoclonal antimyosin antibody studies are normal in imipramine- and clomipramine-treated patients. Antibody uptake in those under amitriptyline treatment, which disappears after drug withdrawal, would suggest early evidence of myocardial toxicity.

Adult↗
PubMed1995

Sympathetic sudomotor function and aging.

Many studies have reported the influence of aging on different portions of the autonomic nervous system components but only partially for the sympathetic cholinergic system. We evaluated postganglionic sudomotor function in 196 healthy subjects, 104 women and 92 men, by determining sweat gland density (SGD) per square centimeter of skin, on the dorsum of the hand and foot, with the impression mold technique. The age range was from 5 to 84 years. A significant decrease of SGD was observed in both hand and foot in relation to age (P < 0.001). The ANOVA analysis of foot data shows that age is the only significant factor for SGD reduction. In the hand, both sex and body surface area are significant covariates with age. The dorsum of the foot is the most appropriate place to examine sweating in studies of aging. The lower normal limits for SGD in the foot are 213/cm2 for subjects younger than 30 years, 199/cm2 for those from 30 to 59 years, and 123/cm2 for subjects over 59 years old.

Adolescent↗
PubMed1995

Putative Leishmania hybrids in the Eastern Andean valley of Huanuco, Peru.

During an outbreak of tegumentary leishmaniasis that developed in the 1990s in the Eastern Andean valley of Huanuco, Peru, the coexistence of Andean (uta) and sylvatic leishmaniases was suspected for ecological and geographical reasons, and sympatric sampling was carried out. Seven human isolates of Leishmania were characterized by multilocus enzyme electrophoresis, random amplification of polymorphic DNA and molecular karyotyping. The three methods identified 3 isolates as L. braziliensis, and 4 isolates as putative hybrids with characters of L. braziliensis and L. peruviana. Data from Huanuco are compared to previous results from other areas endemic for uta. Biological and epidemiological implications are discussed.

Animals↗
PubMed1995

Fortification of sugar with iron sodium ethylenediaminotetraacetate (FeNaEDTA) improves iron status in semirural Guatemalan populations.

A 32-mo-long, double-blind field study involving one highland control community receiving only vitamin A-fortified sugar and three vitamin A- and FeNaEDTA-sugar-fortified communities, two in the lowlands and one in the highlands of Guatemala, was undertaken to test the effectiveness of this approach in controlling iron deficiency. The communities' population ranged between 1200 and 17000. Sugar fortified with 1 g FeNaEDTA and 15 mg retinol as retinyl palmitate/kg was stable, did not segregate, and was well accepted by the communities. The impact of fortification on iron nutrition was estimated at 8, 20, and 32 mo of intervention. All pregnant women and subjects with severe anemia received supplements or treatment and were excluded from the analysis. Iron stores in the fortified communities increased significantly except for women 18-48 y of age in one lowland community and > 49 y in the highland community. Iron stores in the control community remained unchanged except for a rise among adult males.

Adolescent↗
PubMed1995

Pretreatment with 1,25(OH)2D3 protects from Cytoxan-induced alopecia without protecting the leukemic cells from Cytoxan.

The authors previously demonstrated that pretreatment with 1,25(OH)2D3 protects from Cytoxan-induced alopecia in the rat model. The current study was designed to investigate whether 1,25(OH)2D3 protects the transplantable rat chloroleukemia (C51) cells from the cytotoxic effects of Cytoxan. In vitro, 4-hydroperoxycyclophosphamide had a dose-dependent cytotoxic effect on C51 cells. In separate experiments, preincubation with 1,25(OH)2D3 did not protect the C51 cells from the cytotoxic effects of 4-hydroperoxycyclophosphamide. In vivo, 4 groups of 10 5-day-old rats were treated as follows: Groups 1 and 2 received 0.2 micrograms of 1,25(OH)2D3 topically in ethanol daily starting on day 5 through day 10. Groups 3 and 4 received ethanol topically similarly. On day 7, all rats received 1 x 10(5) C51 cells intraperitoneally. On day 11, groups 1 and 3 received 35 mg/kg Cytoxan intraperitoneally. All rats in groups 2 and 4 were dead of leukemia by day 34. In groups 1 and 3, only 1 of 10 and 2 of 10 rats died of leukemia, respectively. Alopecia developed in all rats in group 3. In contrast, all rats in group 1 were protected from Cytoxan-induced alopecia. These results indicate that, in vivo, pretreatment with 1,25(OH)2D3 does not protect the rat chloroleukemia cells from the cytotoxic effect of Cytoxan, while protecting from Cytoxan-induced alopecia.

Alopecia↗
PubMed1995

Induction of anti-tumour immunity in syngeneic mice by a leukaemic cell line.

Induction of anti-tumour immunity in syngeneic mice by LBC cell line derived from a non-immunogenic T cell leukaemia was studied. The immunization of BALB/c mice with LBC irradiated cells induced in them anti-tumour spleen cells, cytotoxic T lymphocytes and anti-LBC antibodies. The anti-LBC antibodies reacted with components of 14, 16 and 27 kDa present on LB tumour cells, LBC cell line and normal thymocytes, but not with normal lymph node cells. Furthermore, immunization of the autologous hosts with LBC cells partially protected them against subsequent challenge with the original LB leukaemic cells. These findings demonstrate that culture conditions induced modifications in the antigenic properties of the leukaemic cells, allowing LBC cells to stimulate an immune response directed against components expressed at early stages during T cell maturation. These results also suggest that the immune response is responsible for the prolongation of the survival time of the mice inoculated with the parental leukaemic cells.

Animals↗
PubMed1995

[Severe complications of percutaneous hepatic biopsy in patients with orthotopic liver transplantation].

The incidence and type of complications appearing following the performance of liver biopsies were analyzed in the first 166 liver transplants in our hospital. The presence of a severe complications was defined if a patient presented hemoperitoneum, pneumothorax, hemothorax, post biopsy infection or symptomatic puncture of abdominal organs other than the liver. Four hundred thirty-eight liver biopsies were carried out in 129 patients with a mean of 3.4 biopsies per patient. The severe complications were observed in 7 (1.6%), all of which were bleeding episodes. Four hemothorax requiring the placement of a thoracic drainage tube were observed. In two cases thoracotomy was required with death occurring in one patient. Three hemoperitoneum were also seen requiring laparotomy in one and transfusion in the remaining two patients. Out of the non transplanted patients, four presented severe complications (0.7%), 50% of which were hemoperitoneum. No patient presented hemothorax and no deaths were reported. The authors conclude that the incidence of severe post liver biopsy complications in transplanted is low, similar to that reported in non transplanted patients. Nonetheless, there does appear to be a higher incidence of bleeding complications in the transplanted patients.

Biopsy↗
PubMed1995

[Epithelioid hemangioendothelioma: a rare indication for liver transplantation?].

A clinical case of epithelioid hemangioendothelioma without extrahepatic involvement treated with liver transplantation is presented. The patient remains alive 42 months thereafter without tumor recurrence. A review of cases reported to date was carried out with special reference being made to the therapy undertaken and the follow-up.

Adult↗
PubMed1995

[Cholestatic hepatitis caused by glybenclamide in a patient with hepatitis C virus].

We report the case of a 68-year-old male HVC+ diagnosed as cholestatic hepatitis induced by glybenclamide, following a non-insulin dependent diabetes mellitus treatment. When the drug was discontinued normal analytic parameters were obtained. However, HVC may induce more cholestatic and cytolysic changes on the hepatitis due to glybenclamide. When reviewing the literature only one similar case has been previously reported, although several disturbances in liver function tests have been described in other reports. Routine biochemical tests including liver function are indicated in patients receiving antidiabetic agents in order to make an early diagnosis of liver toxicity.

Aged↗
PubMed1995

[Extracorporeal membrane oxygenation in adult respiratory distress syndrome. Experience in 2 patients].

We report two female patients with adult respiratory distress syndrome and severe respiratory failure in whom extracorporeal membrane oxygenation was used. Its indication was due to a bad response to conventional treatment with mechanical ventilation and high levels of positive end expiratory pressure. A 2.0 or 2.2 m2 membrane oxygenator in a veno-venous circuit with systemic anticoagulation was used, maintaining mechanical ventilation. In the first patient, the procedure was done early and was successful, increasing hemoglobin saturation from 39 to 87%. The patient was withdrawn from the procedure 48 hours later and died one week later due to a septic shock. The second patient was connected to the procedure after three weeks of respiratory distress syndrome and no increase in arterial oxygenation was achieved. The patient died due to an intracranial hemorrhage, probably hastened by systemic anticoagulation. The real benefits of extracorporeal membrane oxygenation are not defined yet.

Adult↗