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Biomedical subjects

E Alvarez

Publications and source records attributed to E Alvarez.

At least 19 recordsLinked to original sources
PubMed1997

Randomised, double-blind, placebo-controlled trial of pindolol in combination with fluoxetine antidepressant treatment.

BACKGROUND: Major depression affects more than 5% of the population and is a serious health and economic problem. Antidepressants have a slow onset of action and are effective in less than two-thirds of patients. The biochemical effects of selective serotonin reuptake inhibitors may be limited by the negative feedback from serotonin autoreceptors. Pindolol is an antagonist of both serotonin autoreceptors and beta-adrenoceptors. We studied the effect of the addition of pindolol to fluoxetine antidepressant treatment. METHODS: Of 132 eligible patients with major depression, 111 were randomly assigned to treatment with fluoxetine (20 mg daily) and either placebo or pindolol (7.5 mg daily). Patients were assessed twice a week for the first 3 weeks of active treatment and then once a week until the end of the study (42 days). Hamilton and Montgomery-Asberg depression-rating scales were used to assess depression severity. FINDINGS: The proportion of patients who responded to treatment with fluoxetine and pindolol was greater than that with fluoxetine and placebo (41/55 [75%] vs 33/56 [59%], [90% CI 1.1-30.1], p = 0.04). The proportion of patients who achieved a sustained response was also greater in the fluoxetine and pindolol group than in the fluoxetine and placebo group (38/55 [69%] vs 27/56 [48%] [5.9-35.9], p = 0.03). The number of days to reach a sustained response was lower in the fluoxetine and pindolol group than in the fluoxetine and placebo group (median 19 vs 29 days, p = 0.01), however, there was no difference in the time-to-onset of clinical improvement when stringent conditions were used (15 vs 18 days, p = 0.20). INTERPRETATION: The addition of pindolol to fluoxetine antidepressant treatment increases the effectiveness of fluoxetine therapy. Further work is needed to resolve whether the time to clinical improvement benefits from this combination and whether the increase in efficacy occurs with other antidepressants.

Adult↗
PubMed1997

Predicting outcome of lithium added to antidepressants in resistant depression.

This study was conducted to assess the predictive value of different variables including the response to dexamethasone suppression test (DST), in 105 patients with resistant depression after the addition of lithium (600 to 800 mg/day) for 4 weeks to antidepressant medication. Clinical remission was observed in 57 patients and no improvement in 48. A dramatic and rapid relief of depression occurred in 12 patients. Variables with significant or marginally significant differences between responders and non-responders were included in a stepwise logistic regression model. Weight loss (P = 0.0013) and depressive psychomotor activity (P = 0.045) in the Newcastle diagnostic index (NDI) scale, and overall score of the Hamilton Rating Scale for Depression (HRSD) before adding the lithium (P = 0.0039) were significantly associated with clinical remission. The difference in post-DST cortisol plasma levels between both groups was marginally significant. The logistic equation resulted in a sensitivity of 78% and a specificity of 65% and total correct classification of the lithium-added response of 72%. The clinical profile of patients who improve with the addition of lithium may include significant weight loss, psychomotor retardation and possibly, poor control of cortisol secretion. Partial remission before adding lithium as well as endogenomorphic traits according to NDI may also be considered additional criteria for response.

Adolescent↗
PubMed1997

Interleukin 2 exerts autocrine stimulation on murine T-cell leukaemia growth.

As it has been suggested that an autocrine mechanism may control tumour cell growth, in this work cells from a spontaneous murine T lymphocyte leukaemia (LB) expressing the interleukin-2 receptor (IL-2R) (CD25) were evaluated in vitro for IL-2-mediated autocrine growth. Cells grew readily in culture and proliferation was enhanced by the addition of recombinant IL-2 but inhibited by monoclonal antibodies against either IL-2 or IL-2 receptor, in the absence of exogenous IL-2. Cyclosporin A also inhibited LB cell growth. However, when exogenous IL-2 was added together with cyclosporin A, cell proliferation proved similar to controls. Using reverse transcription polymerase chain reaction (PCR), mRNA for IL-2 was found to be present in tumour cells. Our findings support the hypothesis that LB tumour 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.

Animals↗
PubMed1997

Influence of dietary sulfur level on growth performance and digestive function in feedlot cattle.

Using ammonium sulfate, three levels of dietary S (.15, .20, and .25%, DM basis) were evaluated in a finishing trial with 108 yearling crossbred heifers (384 kg). The basal diet contained (DM basis) 4% alfalfa hay, 6% sudangrass hay, 74% steam-flaked corn, 4% yellow grease, 6% cane molasses, and 6% protein-mineral supplement. Increasing dietary S decreased ADG (quadratic effect, P < .10), DMI (linear effect, P < .10), feed efficiency (quadratic effect, P < .10), diet NE (quadratic effect, P < .10), and longissimus muscle area (linear effect, P < .05). Six Holstein steers (218 kg) with cannulas in the rumen and proximal duodenum were used to evaluate treatment effects on characteristics of digestion. Treatment effects on ruminal and total tract digestion of OM and N were small (P > .10). However, ruminal digestion of ADF and starch was slightly lower (quadratic effect, P < .10), and postruminal digestion of ADF and starch was correspondingly greater (quadratic effect, P < .05) with supplemental S. Dietary S level did not influence (P > .10) ruminal synthesis of microbial N. Increasing dietary S did not influence (P > .10) ruminal pH or lactic acid. Increasing S decreased molar proportions of acetate (quadratic effect, P < .10) and increased molar proportions of propionate (linear effect, P < .10). We conclude that S in excess of .20% of dietary DM may have detrimental effects on growth performance and dietary NE. Excessive dietary S may also compromise carcass merit by decreasing longissimus muscle area.

Animals↗
PubMed1997

Combined small bowel and reduced liver transplantation in pigs.

PURPOSE: Small bowel transplantation is a last resort treatment for intestinal insufficiency. Although the disorder is occasionally associated with chronic hepatopathy of variable severity, it may require simultaneous liver transplantation. We present a new model of heterotopic small bowel and reduced partial liver transplantation to an infrahepatic site. SUBJECTS AND METHODS: "Mini-pig" breed pigs weighing 28 to 35 kg were divided into four experimental transplant groups: intestine only (IO) without immunosuppression (group 1A, n = 11); IO with immunosuppression (group 1B, n = 10); intestine + reduced liver (IRL) without immunosuppression (group 2A, n = 12); IRL with immunosuppression (group 2B, n = 10). RESULTS: Overall mortality from technical causes (first 3 days) was 23/43 animals (53.4%). All animals in group 1A displayed rejection, which was the main cause of death. Rejection occurred in 1 animal in each of the other three groups. CONCLUSIONS: Heterotopic small bowel-reduced liver transplant is a multivisceral model that has the technical advantage of not requiring hepatectomy, and the immunological advantages of delayed appearance of acute rejection and the possibility of reducing immunosuppression during the first postoperative days.

Animals↗
PubMed1997

Synthesis and evaluation of new Reissert analogs as HIV-1 RT inhibitors. 2. Benzo[f]quinoline and pyridine derivatives.

The synthesis and preliminary evaluation of new benzo[f]quinoline and pyridine derivatives, obtained by application of the Reissert method and its modifications, as HIV-1 RT inhibitors and anti-infectives are presented. The most active products against HIV-1 RT wild type are the ethyl 2-cyano-1,2-dihydrobenzo[f]quinoline-1-carboxylate 2b, propyl 2-cyano-1,2-dihydrobenzo[f]quinoline-1-carboxylate 2c, and 2-cyano-1-(2'-furoyl)-1,2-dihydrobenzo[f]quinoline 2n, which maintain their activity against the mutant type P236L, resulting inactive against the Y181C type. Using the data previously obtained by our research team for analogous series derived from quinoline as reference, the compounds which have now been obtained present an increase in the cytotoxic character attributable to the introduction of a benzene ring fused with the quinoline base nucleus, as well as a decrease of the activity as HIV-1 RT inhibitors when the quinoline benzenic ring is eliminated.

Anti-HIV Agents↗
PubMed1997

Synthesis and evaluation of new Reissert analogs as HIV-1 reverse transcriptase inhibitors. 1. Quinoline and quinoxaline derivatives.

The synthesis and preliminary evaluation of new quinoline and quinoxaline derivatives (obtained by applying the original Reissert method, conveniently modified) as HIV-1 Reverse Transcriptase (RT) inhibitors are presented in this paper; likewise, the first structure-activity relationships are also proposed. Propyl 2-cyano-1(2H)-quinolin-carboxylate 2e, isopropyl 2-cyano-1 (2H)-quinolincarboxylate 2f, butyl 2-cyano-1 (2H)-quinolincarboxylate 2g and isobutyl 2-cyano-1 (2H)-quinolincarboxylate 2h have been selected as lead compounds. These compounds are active against the HIV-1 RT mutant type P236L (2f, IC50 = 1.2 microM) and present activity as anti-infective agents in HLT41acZ-1IIIB cells, showing no cytotoxicity at the active concentrations.

Anti-HIV Agents↗
PubMed1996

Influence of the age and sex on respiratory burst of human monocytes.

The respiratory burst reaction has been studied in monocytes from men and women of different age. Phorbol myristate acetate (PMA) was used to stimulate NADPH oxidase. Superoxide anion production was found to be dependent on age and sex (it decreased 45% in men and 70% in women during aging).

Adult↗
PubMed1996

Nitric oxide and superoxide anion production decrease with age in resident and activated rat peritoneal macrophages.

Superoxide anion and nitric oxide production have been studied in resident and activated peritoneal macrophages of 3-, 12-, and 24-month-old rats. Some key enzymes involved in the metabolism of glucose were also studied in relation to aging. Production of O2 and NO was reduced in all cases in middle-aged (12 months) and old (24 months) animals. Malic enzyme and citrate synthase activity shows a progressive reduction with age. Hexoquinase, pyruvate quinase, and lactate dehydrogenase activities decrease sharply from 3 to 12 months with no significant change between 12 and 24 months. Taken as a whole, the results of enzyme activity suggest that aging may reduce the capacity for glucose utilization in macrophages.

Aging↗
PubMed1996

Autonomic profile of subjects prone to fainting.

Syncope is the most common form of fainting that may occur at least once during a life-time in up to one-third of the general population. In 50% of patients the cause remains unknown. In an attempt to identify subtle disturbances of the autonomic nervous system, we examined 70 subjects, aged from 14 to 39 years, who suffered from recurrent neurally mediated syncope. We performed a battery of non-invasive tests assessing cardiovagal, sympathetic cholinergic and sympathetic adrenergic function. We compared the results with a group of 30 healthy, non-fainting subjects matched for age and sex. Basal records were similar in both groups. Patients had preserved cardiovagal function. The multivariate cluster analysis allowed us to find a homogeneous group of cases (46%) that simultaneously presented: greater fall in systolic and diastolic blood pressure after standing, increased 15:30 ratio, exaggerated absolute heart rate rise in response to standing and subclinical reduced sudomotor function in the foot. The results suggest the existence of a subclinical autonomic profile, with subtle sympathetic postganglionic impairment, evident in lower limbs. These findings may contribute to proving the existence of different types of neurally mediated syncope, all different in their onset and mechanism but with a common final manifestation: syncopal loss of consciousness.

Adolescent↗
PubMed1996

Expression of the glucagon-like peptide-1 receptor gene in rat brain.

Evidence that glucagon-like peptide-1 (GLP-1) (7-36) amide functions as a novel neuropeptide prompted us to study the gene expression of its receptor in rat brain. Northern blot analysis showed transcripts of similar size in RINm5F cells, hypothalamus, and brain-stem. First-strand cDNA was prepared by using RNA from hypothalamus, brainstem, and R1Nm5F cells and subsequently amplified by PCR. Southern blot analysis of the PCR products showed a major 1.4-kb band in all these preparations. PCR products amplified from hypothalamus were cloned, and the nucleotide sequence of one strand was identical to that described in rat pancreatic islets. In situ hybridization studies showed specific labeling in both neurons and glia of the thalamus, hypothalamus, hippocampus, primary olfactory cortex, choroid plexus, and pituitary gland. In the hypothalamus, ventromedial nuclei cells were highly labeled. These findings indicate that GLP-1 receptors are actually synthesized in rat brain. In addition, the colocalization of GLP-1 receptors, glucokinase, and GLUT-2 in the same areas supports the idea that these cells play an important role in glucose sensing in the brain.

Animals↗
PubMed1996

Colocalization of glucagon-like peptide-1 (GLP-1) receptors, glucose transporter GLUT-2, and glucokinase mRNAs in rat hypothalamic cells: evidence for a role of GLP-1 receptor agonists as an inhibitory signal for food and water intake.

This study was designed to determine the possible role of brain glucagon-like peptide-1 (GLP-1) receptors in feeding behavior. In situ hybridization showed colocalization of the mRNAs for GLP-1 receptors, glucokinase, and GLUT-2 in the third ventricle wall and adjacent arcuate nucleus, median eminence, and supraoptic nucleus. These brain areas are considered to contain glucose-sensitive neurons mediating feeding behavior. Because GLP-1 receptors, GLUT-2, and glucokinase are proteins involved in the multistep process of glucose sensing in pancreatic beta cells, the colocalization of specific GLP-1 receptors and glucose sensing-related proteins in hypothalamic neurons supports a role of this peptide in the hypothalamic regulation of macronutrient and water intake. This hypothesis was confirmed by analyzing the effects of both systemic and central administration of GLP-1 receptor ligands. Acute or subchronic intraperitoneal administration of GLP-1 (7-36) amide did not modify food and water intake, although a dose-dependent loss of body weight gain was observed 24 h after acute administration of the higher dose of the peptide. By contrast, the intracerebroventricular (i.c.v.) administration of GLP-1 (7-36) amide produced a biphasic effect on food intake characterized by an increase in the amount of food intake after acute i.c.v. delivery of 100 ng of the peptide. There was a marked reduction of food ingestion with the 1,000 and 2,000 ng doses of the peptide, which also produced a significant decrease of water intake. These effects seemed to be specific because i.c.v. administration of GLP-1 (1-37), a peptide with lower biological activity than GLP-1 (7-36) amide, did not change feeding behavior in food-deprived animals. Exendin-4, when given by i.c.v. administration in a broad range of doses (0.2, 1, 5, 25, 100, and 500 ng), proved to be a potent agonist of GLP-1 (7-36) amide. It decreased, in a dose-dependent manner, both food and water intake, starting at the dose of 25 ng per injection. Pretreatment with an i.c.v. dose of a GLP-1 receptor antagonist [exendin (9-39); 2,500 ng] reversed the inhibitory effects of GLP-1 (7-36) amide (1,000 ng dose) and exendin-4 (25 ng dose) on food and water ingestion. These findings suggest that GLP-1 (7-36) amide may modulate both food and drink intake in the rat through a central mechanism.

Animals↗
PubMed1996

Evaluation of congenital dysautonomia other than Riley-Day syndrome.

We report on four children, from different families, who suffer from a congenital autonomic disorder, presumably inherited. Three of them have a sensory neuropathy but do not fit any described hereditary sensory and autonomic neuropathy. All four were examined along with some of their immediate family members. We assessed the cardiovagal, sympathetic adrenergic and sympathetic cholinergic functions with a battery of non-invasive tests. Results demonstrated that sudomotor and cardiovascular orthostatic regulation exhibited the greatest abnormalities, pointing to a predominant impairment of sympathetic components, both cholinergic and adrenergic. The overall examination showed a heterogeneous group of congenital dysautonomia, exclusive of Riley-Day or other recognized hereditary sensory and autonomic neuropathies. We emphasize the importance of studying whole family groups to diagnose subclinical impairment and to provide correct genetic counselling.

Adolescent↗
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↗