Search PubMedSearch

Biomedical subjects

A Suárez

Publications and source records attributed to A Suárez.

At least 19 recordsLinked to original sources

Glucocorticoids increase IL-10 expression in multiple sclerosis patients with acute relapse.

High doses of glucocorticoids (GCs) are widely employed to treat acute attacks in relapsing-remitting multiple sclerosis (MS) patients. Their beneficial effects are partially due to their capacity to regulate the cytokine network. In the present work, we have examined the effect of GCs on the production of the immunosuppressor cytokine IL-10. Blood samples from MS patients suffering an acute relapse were obtained immediately before initiating therapy and after receiving a daily dose of 1 g intravenous methylprednisolone (MP) for four days. Levels of IL-10 mRNA in PBMC were semiquantified by RT-PCR, whereas protein concentration in serum and in cell culture supernatant was measured by ELISA. Our results show that 7 out of the 9 patients studied displayed increased IL-10 mRNA expression as well as higher serum IL-10 concentration following steroid treatment. In contrast, mRNA expression of two inflammatory cytokines, TNFalpha and IFNgamma, decreased following steroid therapy. In vitro experiments employing normal PBMC showed that methylprednisolone (MP) upregulated IL-10 expression as determined by measuring mRNA levels, flow cytometry of intracytoplasmic protein concentration, and the amount of secreted protein. Peak responses of secreted IL-10 by PBMC cultured cells treated with MP were obtained at 48 h. The effect was steroid-specific as IL-10 expression reversed to baseline levels in the presence of the glucocorticoid receptor antagonist RU486. Contrary to the effect of MP on the spontaneous expression of IL-10, this drug downregulated LPS-induced IL-10 synthesis. In fact, the concentration of IL-10 in LPS-induced IL-10 secretion from normal PBMC decreased upon addition of MP to cell cultures. Thus, it seems that MP exerts an opposite effect on the spontaneous and LPS-induced IL-10 production. Our studies indicate that GCs may control inflammatory responses by upregulating production of the immunosuppressor cytokine IL-10.

Acute Disease

Detection of a t(8;21)(q22;q22) in a case of M5 acute monoblastic leukemia.

Although the translocation (8;21) is the single most common structural rearrangement reported in acute myeloblastic leukemia (AML), it is rarely seen in AML FAB type M5. We describe a case of a 51-year-old male with a diagnosis of acute monoblastic leukemia (AML M5b with hemophagocytic component) whose karyotype showed at (8;21)(q22;22). To our knowledge, this is the first report of this translocation in an AML M5b. The t(8;21) has been associated with a good prognosis, but our patient suffered a fast and fatal evolution.

Chromosomes, Human, Pair 21

Glucocorticoids inhibit IL-4 and mitogen-induced IL-4R alpha chain expression by different posttranscriptional mechanisms.

BACKGROUND: A high level of expression of IL-4Ralpha chain on the surface of lymphocytes has been described in certain allergic and inflammatory autoimmune diseases. Progression of these diseases are usually controlled by steroid treatment. One mechanism by which these drugs exert their antiinflammatory and immunosuppressive effects is by widely repressing or enhancing the production of cytokines and their receptors. OBJECTIVES: The effect of glucocorticoids on IL-4Ralpha chain expression has not been previously studied, and this is the aim of the present report. For this purpose, human lymphocytes were induced to express IL-4Ralpha chain by means of protein kinase C (PKC) activation with phorbol myristate acetate (PMA) or by triggering the Janus kinase-Stat pathway with IL-4 in the presence or absence of pharmacologic doses of dexamethasone. METHODS: IL-4Ralpha cell surface expression was studied by flow cytofluorometry. The levels and stability of mRNA were assessed by Northern blot analysis. The effect of dexamethasone on the IL-4Ralpha rate of transcription was determined by nuclear run-on experiments. RESULTS: Dexamethasone significantly downregulated PMA-induced IL-4Ralpha mRNA and protein levels in total peripheral blood mononuclear cells and in isolated T cells. The mechanism involved a posttranscriptional regulation of IL-4Ralpha expression because dexamethasone decreased the PMA-induced IL-4Ralpha mRNA half-life. However, we found that PMA did not influence the transcription rate of IL-4Ralpha gene, irrespective of the presence or absence of dexamethasone. This immunosuppressor also diminished the IL-4-induced IL-4Ralpha expression on the surface of isolated T and B lymphocytes but, interestingly, without modifying mRNA levels that indicates that dexamethasone downregulated IL-4-dependent IL-4Ralpha expression by acting at a translational or posttranslational level. In fact, we observed that the drug did not affect IL-4-induced IL-4Ralpha gene transcription rate nor did it shorten mRNA half-life. The effect of dexamethasone on the IL-4Ralpha was steroid specific because it was totally reversed by the glucocorticoid receptor antagonist RU486. CONCLUSION: Our results support that dexamethasone may influence the course of allergic and inflammatory diseases by downregulating the expression of IL-4Ralpha.

Cells, Cultured

Tamoxifen does not improve survival of patients with advanced hepatocellular carcinoma.

To discover whether tamoxifen is able to extend the survival of patients with advanced hepatocellular carcinoma, we included 80 patients with cirrhosis and advanced hepatocellular carcinoma in a multicenter, double-blind, placebo-controlled trial in order to analyze the influence of treatment with tamoxifen on survival. The patients were randomized to receive tamoxifen, 40 mg/day (group 1), or placebo (group 2). Both groups were similar in age, sex, etiology of cirrhosis, biochemical, hematologic and hormonal parameters, morphology of the tumor (nodular vs multinodular or massive), Child-Pugh's score, and Okuda's stage. The 1-year survival rate was similar in both groups (30% in group 1 vs 37.8% in group 2; p = 0.31). Tamoxifen treatment was well tolerated by the patients. We conclude that tamoxifen does not extend the survival of patients with cirrhosis and advanced hepatocellular carcinoma.

Adult

Hepatitis G virus infection in Spanish patients with hepatocellular carcinoma.

AIMS/BACKGROUND: To establish the rate of infection with a newly discovered Flaviviridae family member hepatitis G virus (HGV) -- in Spanish patients with hepatocellular carcinoma (HCC), chronic alcoholic liver disease (CALD) with cirrhosis, or hepatitis C virus (HCV)-induced chronic hepatitis (CH). METHODS: The presence of HGV-RNA was assessed in sera of 117 patients divided in three groups: group 1: 40 patients with HCC (35 men, mean age 62.7 years, SD 10.9 years); group 2: 41 patients with chronic alcoholic liver disease (CALD) (36 men, mean age 52.5 years, SD 9.8 years); group 3: 36 patients with HCV-induced CH (27 men, mean age 35.8 years, SD 8.5 years). Serum samples were tested for HGV-RNA by specific reverse transcriptase-polymerase chain reaction (RT-PCR). Serological markers of hepatitis B virus (HBV) and HCV were investigated in all patients and were negative in CALD patients, as a prerequisite for their inclusion in the study. All patients in group 1 were also tested for HBV-DNA. RESULTS: Rates of HGV-RNA positivity were, respectively, 47%, 10% and 28% in groups 1, 2 and 3. Differences were significant between groups 1 and 2 (p=0.00017) and groups 2 and 3 (p= 0.042), but not between groups 1 and 3 (p=0.079). CONCLUSIONS: HGV infection is common in HCC patients, but usually in association with HCV, indicating that both agents share common routes of infection. HGV was the only hepatitis virus detected in 12% of HCC patients, but its possible role in the pathogenesis of HCC remains unclear.

Adult

[Normograms of spirometric values for the city of Buenos Aires].

There is a large variability between the different normograms of spirometric values, so that we designed our normogram for Buenos Aires and Gran Buenos Aires. We performed forced spirometry, under American Thoracic Society standardization, in 237 normal subjects (105 females) between 18 to 86 years old, and 144 to 194 cm. We measured Forced Vital Capacity (FVC), forced Expiratory Volume in one second (FEV1), and forced expiratory flow during the middle half of the Forced vital capacity (FEF25-75), in previously calibrated by the explosive decompressor spirometers. Linear regression using height and age was used for each measured value for each sex. The values obtained were in normal distribution, so that we determined the Low Limit of Normality calculating the 95% confidence interval to one tail, and this should replace the common method of the fixed percent of each value to determine the lower limit of normality for a predicted value.

Adolescent

Serological markers of hepatitis A, B and C in first year student nurses.

OBJECTIVE: To know the prevalence of serological markers of hepatitis A, B and C virus in first year student nurses. SETTING: A transversal study of prevalence. SUBJECTS AND METHODS: 81 first year student nurses, mean age 20.6 years (18-37, S.D. 3.8), with demographic, epidemiologic and clinical variables, performing liver enzymes, anti-HAV IgG, anti-HBcore and anti-HCV. RESULTS: The anti-HAV IgG was positive in 9 students (11.1%), with a prevalence of 6.7% between 17 and 19 years (C.I.95% 1.7 to 19.3%), 8.7% between 20 and 22 years (C.I.95% 1.5 to 29.5%), 20% between 23 and 25 years (C.I.95% 10.5 to 70.1%), and 37.5% (C.I.95% 10.2 to 74.1) in those over 25 years (p < 0.001). No other significative variables existed according to age-group. Regarding hepatitis B virus, of the 65 not previously vaccinated, only 1 (1.5%, C.I.95% 0.08 to 9.4%) was immunized, and there were no cases of HBsAg positive. The anti-VHC was positive in one case (1.2%, C.I.95% 0.06 to 7.6%), RIBA indeterminate and with normal ALT. Only one student (1.2%) showed increased transaminase values, attributed to liver steatosis. None of the students had suffered any episode of acute clinic hepatitis. CONCLUSIONS: The anti-HAV IgG prevalence in first year student nurses in our area is very low, and it is not necessary to carry out prevacunal screening. The low prevalence of anti-Hbcore also rejects a similar screening with respect to HBV. There were no HBsAg or anti-HCV positive cases, but it should not be the cause of forgetting to take the universal precautions or giving a false sensation of security.

Biomarkers

[Body mass index influence in the insulin action mechanisms].

OBJECTIVE: Improve the knowledge of the "in vitro" insulin action in healthy subjects with different body mass index (BMI), in order to know the role of obesity in the diabetes mellitus. MATERIAL: In 12 healthy subjects with different BMI and normal oral glucose test we made a gluteal biopsy to obtain adipose tissue. In the isolated adipocytes we studied the interaction of insulin with its receptor and the glucose transport. RESULTS: BMI was not correlated with the maximal specific 125I-insulin binding but was negative when correlated with the glucose transport in basal situation (r = -0.63, p < 0.05) as well as when stimulated with insulin (r = -0.67, p < 0.05), when the results were expressed as number of cells. When the data were expressed as surface, BMI was negative correlated with the percentage of maximal specific 125I-insulin binding (r = -0.81, p < 0.05), and also with the basal glucose transport (r = -0.69, p < 0.05) and stimulated with insulin (r = -0.77, p < 0.01). CONCLUSION: The increase of BMI is an important diabetogenic agent, acting at receptor as well as at postreceptor level, and the data should be expressed according to the cellular diameter rather than to the number of cells in subjects with different BMI. A cutting point was established at the 30 BMI level after which the described alterations could be observed.

Adult

Requirement of a second signal via protein kinase C or protein kinase A for maximal expression of CD40 ligand. Involvement of transcriptional and posttranscriptional mechanisms.

High levels of CD40 ligand (CD40L) protein expression are induced on native T cells by increasing the intracellular Ca2+ concentration. In the present study we have shown that ionomycin induces CD40L gene transcription leading to mRNA accumulation which translates to high levels of protein expression. Conversely, agents which increase the intracellular levels of cyclic AMP (cAMP), such as prostaglandin E2 (PGE2) or dibutyryl cyclic AMP (dbcAMP), were unable to induce CD40L expression on T lymphocytes. Cell activation by phorbol 12-myristate 13-acetate (PMA) treatment had a slight effect on increasing CD40L mRNA and protein levels. However, PMA and dbcAMP synergized with ionomycin to significantly increase and to prolong the CD40L expression. Nuclear run-on assays revealed that PMA, but not dbcAMP, increased threefold the CD40L gene transcription rate induced by ionomycin. This effect was independent of de novo protein synthesis. In addition, at a posttranscriptional level, both reagents synergized with the Ca2+ ionophore to prolong the CD40L mRNA half-life by a mechanism which was also independent of de novo protein synthesis. Moreover, when transcription was blocked with actinomycin D, an increment of the CD40L transcript levels induced by PMA or dbcAMP on ionomycin-treated cells was observed in the presence of cycloheximide. This probably means that newly synthesized protein may contribute to the CD40L mRNA destabilization. In summary, these data show that PMA and dbcAMP synergized with ionomycin to increase the CD40L mRNA and protein levels. The up-regulatory effect of PMA was accomplished at a transcriptional and posttranscriptional level, whereas dbcAMP exerted its synergistic effect exclusively at a posttranscriptional level.

Bucladesine

Cardiovascular effects of ethanolic and aqueous extracts of Pimenta dioica in Sprague-Dawley rats.

The hypotensive activity of ethanolic and aqueous extracts of Pimenta dioica and several fractions of the aqueous extract was observed in anaesthetized normotensive rats. General effects of the extracts and fractions were assessed through Hippocratic screening showing a central nervous system (CNS) depressant effect. The intravenous (i.v.) administration of the aqueous extract of Pimenta dioica (30, 70, 100 mg/kg) produced a dose-related significant fall in mean arterial blood pressure (MAP). The ED50 was 53.94 mg/kg. The hypotensive effect of identical doses (100 mg/kg) of the aqueous extract (95% decrease) was significantly greater (P < 0.05) than the effect of the ethanolic extract (67% decrease). The final aqueous fraction produced the greatest hypotensive activity compared to the other fractions of the total aqueous extract. There were no significant changes in the heart rate and no abnormalities were observed in the EKG. The mechanisms of action of the extracts have not been determined. Structural elucidation of the compounds responsible for this activity is under investigation.

Analysis of Variance

Generation of polyclonal antibodies against a chemically synthesized N-terminal fragment of the bacteriocin pediocin PA-1.

Six mice were immunized intraperitoneally (i.p.) with a chemically synthesized 9-mer fragment (PH1) designed from the N-terminal part of the bacteriocin pediocin PA-1 and conjugated to keyhole limpet haemocyanin (KLH). After three doses of the immunogen had been administered, serum-specific antibodies were detected by a competitive direct ELISA. Myeloma cells were injected i.p. into mice in order to obtain ascites polyclonal antibodies. Although four mice developed ascites, only mouse 2 had detectable specific antibodies in the ascites fluid. The serum and ascites antibodies were specific for PH1 but they did not recognize the whole pediocin PA-1 molecule. This is the first attempt to generate antibodies against bacteriocins with a chemically synthesized oligopeptide as immunogen. This approach still remains attractive for detection, quantification, mode of action studies and purification of bacteriocins, especially those for which the purification process is difficult or inefficient at present.

Amino Acid Sequence

[The prevalence of markers for the hepatitis A and B viruses in the population of Gijón between 6 and 25 years old].

BACKGROUND: The aim of this study was to know the prevalence of previous infection markers for hepatitis A and B viruses in a pediatric-juvenile population from Gijón, Spain. PATIENTS AND METHODS: A representative (according to the census) transversal randomized sample of a population from 6 to 25 years in age from Gijón, Spain, was included in the study analyzing demographic, epidemiologic and clinical variables, liver tests, anti-HAV IgG and anti-HBc. RESULTS: Of the 630 individuals selected a demographic error was detected in 28 (4.4%) and 453 subjects were studied (71.9%) in whom the anti-HAV IgG was positive in 37 cases (8.75% of prevalence adjusted for age), with 4.4% (12/271) (CI 95% 2.3%-7.6%) for the younger cases and 13.7% (25/182) (CI 95% 9.1%-19.6%) in the group ranging from 18 to 25 years in age (p < 0.001). No anti-HAV IgG positive case was detected in the population under the age of 10 years. Among the young adults the prevalence of anti-HAV IgG positive cases was higher in those born in the south of Spain (2/6, 33.3%) (CI 95% 4.3%-77.7%) with respect to those from the northern regions of Spain (9/259, 3.5%) (CI 95% 1.6%-6.4%). (p = 0.02). With respect to HBV markers, of the 433 unvaccinated cases, 6 (1.4%) presented markers of past infection and 2 (0.46%) HBsAg positivity. Both had normal serum ALT without viral replication. Six cases of hypertransaminasemia levels (1.3%) were detected all being related with obesity or alcoholism. All the cases with previous acute clinical hepatitis were found to be anti-HAV IgG positive and anti-HBc negative. CONCLUSIONS: The current prevalence of anti-HAV IgG in the population from 6 to 25 years from Gijón, Spain is very low and given the high degree of susceptibility (86%) for HAV infection in the young adult population (18-25 years) the implementation of vaccination programs is recommended even without previous serologic screening. The low prevalence of anti-Hbc would also undervalue its use as prevaccination screening against HB in this geographical area.

Adolescent

Sulphonylurea stimulates glucose uptake in rats through an ATP-sensitive K+ channel dependent mechanism.

We studied the effect of gliclazide, a second-generation sulphonylurea, on rat skeletal muscle glucose uptake using perfused hindquarter muscle preparations. Gliclazide at concentrations of 10 to 1000 microgram/ml increased (p < 0.05) the basal glucose uptake. The effect of gliclazide on glucose uptake was immediate and dose-dependent, reaching a plateau at a concentration of 300 micrograms/ml; the half-maximal effect was obtained between 25 and 50 micrograms/ml. The glucose uptake stimulated by gliclazide (300-1000 micrograms/ml) did not differ from that achieved by 10(-9) mol/l insulin, and was lower (p < 0.05) than that obtained with 10(-7) mol/l insulin. The combination of gliclazide (300 micrograms/ml) and 10(-9) mol/l insulin produced an increase in glucose uptake (7.7 +/- 0.6 mumol.g-1.h-1, n = 8, mean +/- SEM) which was higher (p < 0.05) than that achieved with 10(-9) mol/l insulin (5.6 +/- 0.7 mumol.g-1.h-1, n = 11) and not different from that obtained with 10(-7) mol/l insulin (9.8 +/- 1.0 mumol.g-1.h-1, n = 11). Diazoxide (100 mumol/l), an ATP-sensitive K+ channel opener, reversed the stimulatory effect of gliclazide (100 microgram/ml) on muscle glucose uptake from 3.1 +/- 0.4 to 0.5 +/- 0.2 mumol.g-1.h-1, (n = 7, p < 0.001). The addition of diazoxide prior to gliclazide into the perfusion medium blocked the gliclazide-induced glucose uptake by the hindquarter muscle preparations. In conclusion, gliclazide alone has an immediate stimulatory effect on glucose uptake by skeletal muscle and together with insulin has an additive effect on muscle glucose uptake. The effect of gliclazide on muscle glucose uptake seems to be due to the inhibition of ATP-sensitive K+ channels.

Adenosine Triphosphate

Dietary long-chain polyunsaturated fatty acids modify heart, kidney, and lung fatty acid composition in weanling rats.

The fatty acid composition of heart, kidney, and lung was studied in weanling rats fed three diets differing in their polyunsaturated fatty acid content for 0, 2, and 4 wk. The first group had a 10% w/w fat semipurified diet which consisted of a mixture of olive oil (62.5%), soybean oil (11.1%), and refined coconut oil (26.4%) and provided 18:1n-9, 18:2n-6, and 18:3n-3 in similar amounts to a maternal human milk (diet HO). The second group received 7% of HO fat and 3% fish oil (0.4% 20:4n-6 and 5% 22:6n-3 of total fatty acids) (diet FO), and the third group was fed 7% HO fat, 1.5% of the same fish oil, and 1.5% of a purified pig brain phospholipid concentrate (0.6% 20:4n-6 and 3.5% 22:6n-3 of total fatty acids) (diet FO + BPL). The experimental diets increased tissue monounsaturated fatty acids in comparison with rats at weaning. Tissue lipid content of 20:4n-6 was increased and 22:6n-3 decreased in Group HO compared with weanling rats, whereas opposite changes were observed in Group FO. Feeding diet FO + BPL increased 22:6n:3 in tissue lipids compared with diet HO, and increased 20:4n-6 content in relation to diet FO. Our results indicate that rat heart, kidney, and lung are highly responsive to dietary n-3 and n-6 long-chain polyunsaturated fatty acids during postnatal life.

Animals

Dietary long-chain polyunsaturated fatty acids influence tissue fatty acid composition in rats at weaning.

We studied the fatty acid composition of plasma, plasma phospholipids, erythrocyte membrane lipids, liver microsomal phospholipids and brain lipids in rats fed three different diets varying in their (n-3) and (n-6) long-chain polyunsaturated fatty acid (LCP) concentrations for 0, 2 and 4 wk after weaning. The three diets contained 10% fat; diet HO had a high-oleic acid proportion; diet FO was enriched in n-3 LCP provided by fish oil; and diet FO + BPL contained n-3 and n-6 LCP supplied by fish oil and a brain phospholipid concentrate. At 2 and 4 wk after weaning the proportions of oleic acid in all tissues, except in liver microsomes of the FO + BPL group, were significantly higher than in weanling rats. The absence of (n-3) LCP intake resulted in significantly lower levels of docosapentaenoic [20:5(n-3)] and 22:6(n-3) acids in plasma, plasma phospholipids, erythrocyte membrane lipids and liver microsomal phospholipids but not in brain lipids compared with rats at weaning. Dietary supplementation with (n-3) LCP (FO and FO + BPL groups) for 4 wk led to higher levels of 22:6(n-3) in all tissues compared with rats fed the HO fat. The proportions of 20:4(n-6) and total (n-6) LCP were significantly lower in all tissues from rats fed the FO diet than in rats at weaning and rats fed the HO diet. After 2 and 4 wk, rats fed the FO + BPL diet had significantly higher levels of 20:4(n-6) and total (n-6) LCP in plasma, plasma phospholipids, erythrocyte lipids and liver microsomal phospholipids; the brain also showed a higher content of those fatty acids after 4 wk. Our results suggest that dietary supplementation with 20:4(n-6) and 22:6(n-3) influences the concentration of 20:4-(n-6) and 22:6(n-3) in body tissues of rats after weaning.

Animals