Search PubMed⌕ Search

Biomedical subjects

F Vargas

Publications and source records attributed to F Vargas.

At least 145 records · Page 8Linked to original sources
PubMed1993

Chronic insulin treatment in rats: evidence against a role for insulin as a pressor agent.

1. The present study was undertaken to test whether insulin acts as a pressor agent and causes hypertension in rats. 2. Insulin at doses of 10 or 100 units day-1 kg-1 was administered daily by subcutaneous injection to normal rats for 6 weeks. As it has been suggested that sodium retention plays a major role in the putative hypertensive activity of this hormone, insulin was also administered to saline- (1% NaCl) drinking rats according to the same protocol. Water- and saline-drinking rats served as controls. 3. After 6 weeks of insulin treatment, the mean arterial blood pressure did not increase in any of the insulin-treated or the insulin-salt-treated groups. However, in both insulin-salt-treated groups, absolute and relative ventricular and renal hypertrophy with increased ventricular water content as well as increased urine output with reduced osmolality were observed. 4. All insulin-treated groups showed increased plasma levels of glucose, insulin and antidiuretic hormone when compared with their respective controls. 5. These results demonstrate that chronic insulin treatment did not increase blood pressure in rats, even when drinking water was supplemented with NaCl, and suggest that a polyuria-polydipsia syndrome was present in both insulin-salt-treated groups. Moreover, increased plasma levels of antidiuretic hormone were observed in all insulin-treated groups.

Animals↗
PubMed1993

Gamma delta lymphocytes in endocrine autoimmunity: evidence of expansion in Graves' disease but not in type 1 diabetes.

Endocrine autoimmune disorders are mediated by T cell-dependent responses to organ-specific antigens, but the mechanisms initiating the process remain unknown. Lymphocytes which use the gamma delta heterodimer as T cell receptor (TCR) for antigen constitute a distinct subset of T cells whose function remains elusive. In order to investigate their possible involvement in endocrine autoimmunity we have determined the proportion of gamma delta T cells in the peripheral blood of 23 patients with type 1 (insulin-dependent) diabetes mellitus (type-1 DM) and 30 patients with autoimmune thyrotoxicosis (Graves' disease). T lymphocyte TCR expression was assessed by fluorescence-activated flow cytometry on peripheral blood mononuclear cells using MoAbs UCHT1 (CD3), TCR delta 1 (gamma delta TCR), WT31 and beta F1 (alpha beta TCR) and both the percentage of T cells expressing gamma delta and the ratio gamma delta/alpha beta were calculated. In the diabetic patients gamma delta cells were not significantly different from the control group (7.7 +/- 54% versus 8.0 +/- 5.5% of T cells, P NS). There was no relation between the proportion of gamma delta lymphocytes and the presence of islet cell antibodies (ICA) in the sera. The Graves' patients showed a tendency towards a higher proportion of gamma delta T lymphocytes than the controls (gamma delta/alpha beta ratios: 0.095 +/- 0.047 versus 0.063 +/- 0.022, P = 0.03). In 14 Graves' patients the number of gamma delta were measured in paired samples of peripheral and intrathyroidal lymphocytes, demonstrating an expansion of gamma delta within the thyroid glands (0.21 +/- 0.3 versus 0.095 +/- 0.047, P = 0.032). Immunohistochemical studies showed that gamma delta cells were scattered among the predominant alpha beta lymphocytes infiltrating the thyroid gland and that they account for 10% of intraepithelial lymphocytes. No relation was found between the increase of gamma delta lymphocytes and any clinical features.

Adolescent↗
PubMed1993

Expression of glutamic acid decarboxylase (GAD) in the alpha, beta and delta cells of normal and diabetic pancreas: implications for the pathogenesis of type I diabetes.

One of the paradoxes of insulin-dependent diabetes mellitus is that the destruction of the pancreatic islets' endocrine cells is restricted to the insulin-producing beta cells, whereas the main autoantibodies, islet cell antibodies (ICA), are directed against all endocrine islet cells. GAD has recently been proposed as the main target of the humoral and cellular autoimmune attack to the islets, and since in rat pancreas this enzyme was expressed only in the beta cells, this provided an explanation for the cell specificity of the destructive process. The finding of GAD-positive cells in the islets of two diabetic patients, one of whom had completely lost the beta cells, led us to study in detail the distribution of GAD in normal human islet cells using a panel of GAD antisera and the double indirect immunofluorescence technique on cryostat sections, monolayer cultures and cytosmears. The results showed that GAD is present not only in the cytoplasm of beta cells but also in 69% of the alpha and 27% of the delta cells. GAD was not present, however, on the surface of the islet cells. These results suggest that the cellular distribution of GAD can not by itself explain the selectivity of beta cell destruction in insulin-dependent diabetes mellitus.

Adult↗
PubMed1993

Photodegradation and in vitro phototoxicity of fenofibrate, a photosensitizing anti-hyperlipoproteinemic drug.

The phototoxic anti-hyperlipoproteinemic drug fenofibrate was found to be photolabile under aerobic and anaerobic conditions. Irradiation under argon of a methanol solution of this drug produced the photoproducts isopropyl 4-(1-[4-chlorophenyl]-1,2-dihydroxy)ethylphenoxyisobutyrate, 1,2-bis(4-chlorophenyl)-1,2bis (4-[isopropoxycarbonylisopropoxy]phenyl)ethane-1,2-diol and 4-(4-chlorobenzoyl)phenol, while under oxygen the photoproducts were 4-chloroperbenzoic acid, methyl 4-chlorobenzoate, 4-chlorobenzoic acid and singlet oxygen, as evidenced by trapping with 2,5-dimethylfuran. These results can be rationalized through hydrogen abstraction by excited fenofibrate, to afford a free radical as key intermediate. Biologically active antioxidants such as glutathione and cysteine efficiently reduced 4-chloroperbenzoic acid to 4-chlorobenzoic acid. The involvement of an electron transfer mechanism is suggested by detection (UV-vis spectrophotometry) of the radical cation TMP+. during the oxidation of tetramethylphenylenediamine (TMP) with 4-chloroperbenzoic acid. Fenofibrate was phototoxic in vitro when examined by the photohemolysis test, both under oxygen and argon atmosphere, although the photohemolysis rate was markedly lower under anaerobic conditions. The photoproducts 4-(1-[4-chlorophenyl]-1,2-dihydroxy)ethylphenoxyisobutyrate and 4-chloroperbenzoic acid induced hemolysis in the dark; however, this effect was quantitatively less important than photohemolysis by fenofibrate. On the other hand, fenofibrate photosensitized peroxidation of linoleic acid, monitored by the UV detection of dienic hydroperoxides. Based on the inhibition of this process upon addition of butylated hydroxyanisole, a radical chain (type I) mechanism appears to operate. In summary, fenofibrate is phototoxic in vitro. This behavior can be explained through the involvement of free radicals, singlet oxygen and stable photoproducts.

Erythrocytes↗
PubMed1993

Regulation of apolipoprotein A-1 and E gene expression in liver and intestine of nephrotic and pair-fed rats.

Rats treated with puromycin aminonucleoside (PAN) developed characteristics of the nephrotic syndrome, including albuminuria, hypoalbuminemia and hyperlipidemia. To study the regulation of apolipoprotein (apo) A-1 and apo E gene expression in nephrotic rats, we analyzed the steady-state levels (SSLs) of hepatic and intestinal apo A-1 and apo E mRNA using the Northern technique, and the plasma levels of high-density lipoprotein (HDL) by biochemical methods. Male Wistar rats were treated with PAN and compared with pair-fed and untreated control rats at different stages of disease. Nephrotic rats presented with marked hypoalbuminemia and albuminuria at between 6 and 11 days after PAN treatment. During this stage of disease, plasma levels of HDL were elevated in correlation with an increase of both hepatic and intestinal apo A-1 mRNA. In liver of nephrotic rats, high levels of apo A-1 mRNA together with low levels of apo E mRNA caused an increase in the ratio of apo A-1/apo E mRNA, reaching a maximum 6 days after treatment. Apo E mRNA was barely detected in small intestine of pair-fed controls and PAN-treated rats. However, contrary to nephrotic rats, the ratio apo A-1/apo E mRNA was inverted in liver of pair-fed rats due to an increase in apo E mRNA. In conclusion, in nephrotic rats, the SSL of apo A-1 mRNA is increased in liver and small intestine and appears to regulate the plasma levels of apo A-1. These results also suggest a coordinated regulation of the apo A-1 and apo E gene expression in liver of nephrotic and pair-fed rats.

Animals↗
PubMed1993

Photolability and photohemolytic studies of fibrates.

Fenofibrate (1), gemfibrozil (2), clofibric acid (3), benzafibrate (4) and clofibrate (5) were found to be photolabile by UV-B (290-320 nm) light under aerobic conditions. The drugs 1, 2, 3 and 4 were phototoxic in vitro when examined by the photohemolysis test both under oxygen and argon atmosphere, although the photohemolysis rate was markedly lower under anaerobic conditions. Based on the inhibition of this process upon addition of butylated hydroxyanisole (BHA) and reduced glutathione (GSH), a radical chain (type I) mechanism appears to operate. Inhibition was seen in the presence of sodium azide (NaN3) and 1,4-diazabicyclo[2.2.2]octane (DABCO) as also in D2O induced-photohemolysis. No photohemolysis was evident for clofibrate (5) under these conditions. In summary, fenofibrate, gemfibrozil, clofibric acid and bezafribrate are phototoxic in vitro. This behavior can be explained through the involvement of free radicals, singlet oxygen and stable photoproducts.

Aerobiosis↗
PubMed1992

Methimazole treatment reduces cardiac hypertrophy and mortality without a concomitant reduction in blood pressure in established Goldblatt two-kidney one clip hypertension.

The effects of methimazole, an antithyroid drug, on blood pressure and other parameters were evaluated in the established phase of Goldblatt two-kidney one clip (G2K-1C) hypertension. Methimazole was administered via drinking water for five weeks, starting five weeks after hypertension had been induced. After this period of treatment, similarly high blood pressures were observed in methimazole-treated and non-treated G2K-1 C rats, despite the fact that a hypothyroid state had been achieved in methimazole-treated rats. Methimazole-treated G2K-1 C rats showed reductions in heart rate, ventricular weight, ventricular/body weight ratio and mortality in comparison with rats not treated with methimazole. These results clearly demonstrate that hypothyroidism induced by methimazole: a) does not reverse G2K-1 C hypertension, but b) improves the rate of survival and c) reduces relative cardiac hypertrophy, possibly by the reduction in cardiac work observed in Goldblatt hypothyroid rats.

Animals↗
PubMed1992

Views of problem drinking among Native American, Hispanic, and Anglo children.

Native American, Hispanic, and Anglo sixth graders reacting to an example of teenage problem drinking expressed similar beliefs and attitudes in many respects. However, Native American children viewed the problem as less serious, subscribed more to a disease theory of alcoholism, attributed less causal responsibility to the individual, and adopted a less aggressive approach toward treatment than did Hispanic, and especially Anglo, children. Their less conventional value orientations accounted for all these differences except their stronger endorsement of a disease theory of problem drinking.

Age Factors↗
PubMed1992

Renal beta-adrenoceptors in thyroxine-treated rats.

The number of beta-adrenoceptors was measured in cardiac and renal cortex membranes from controls and thyroxine-treated rats. Two methods of membrane preparation (sucrose- and KCl-extraction) were compared. KCl-extraction yielded a higher number of beta-adrenoceptors, accompanied by increased activity of the plasma membrane enzyme marker 5'-nucleotidase. Thyroxine increased the number of beta-adrenoceptors in both cardiac and renal cortex membranes prepared with both methods. These results suggest that: i) Enrichment of the membrane fraction may explain the higher number of beta-adrenoceptors found with KCl, ii) Thyroid hormone plays a role in the regulation of beta-adrenoceptors in the renal cortex.

5'-Nucleotidase↗
PubMed1992

Evaluation of serum levels of tumour necrosis factor-alpha (TNF-alpha) and soluble IL-2 receptor (sIL-2R) and CD4, CD8 and natural killer (NK) populations during infrared pulsed laser device (IPLD) treatment.

The purpose of this study was to evaluate serum levels of TNF-alpha, sIL-2R and distribution of peripheral leucocyte subsets in patients with advanced neoplastic disease undergoing IPLD treatment. Fifteen cancer patients with evidence of persistent disease were further divided in two groups according to outcome at the end of the period of clinical evaluation: group 1 patients were still alive and group 2 patients had died. Our results show: (i) an increase in the initial level of TNF-alpha in both groups; (ii) a decrease in TNF-alpha levels during the follow up of group 1 patients; (iii) a significant increase in serum levels of sIL-2R in patients in group 2 compared with those in group 1; (iv) a progressive and constant increase in TNF-alpha levels in group 2; (v) a decrease in CD4+CD45RA+ subpopulation in both groups; (vi) an increase in CD25+ cells; (vii) an increase in CD4+, CD4+CD45RA+ and CD25+ cells during the follow up of group 2 patients. The data generated here form the basis for further investigations on the use of IPLD as a single agent and in combination with other biological response modifiers in cancer patients.

Antigens, CD↗
PubMed1992

Effects of methimazole on low-renal-mass hypertension: changes in blood pressure and pressor responsiveness to vasoconstrictors.

The administration of the antithyroid drug methimazole to rats via drinking water prevented the development of hypertension that usually accompanies subtotal nephrectomy and saline drinking (1% NaCl). In methimazole-treated rats, elevated blood pressure induced 5 weeks previously returned to normotensive levels. Pressor responsiveness to angiotensin, vasopressin and norepinephrine in unanesthetized rats was studied after prevention of hypertension in control, low-renal-mass hypertensive (LRM) and low-renal-mass methimazole-treated (LRM-M) rats, and in the reversion study in LRM and LRM-M rats. In LRM rats, responsiveness to vasoconstrictors was increased, whereas responsiveness to vasoconstriction was clearly reduced in LRM-M rats after prevention and reversion studies. These results suggest that (a) thyroid hormones are required in the early and established phases of LRM hypertension, and (b) the decreased pressor responsiveness to vasoconstrictors may play a role in the prevention and reversion of this type of hypertension following methimazole administration. However, the changes in pressor responsiveness may also be secondary to the reduction in blood pressure.

Administration, Oral↗
PubMed1992

Specificity analysis of antibodies formed in rabbits to a mannosyl trisaccharide: similarity with lectin binding activity. Para-aminophenyl O-alpha-D-mannopyranosyl-(1-->2)-alpha-D-mannopyranosyl- (1-->6)-alpha-D-mannopyranoside linked to bovine serum albumin as an antigen.

The para-aminophenyl derivative of Man alpha 1-->2Man alpha 1-->6Man alpha 1-->was coupled via a diazotization reaction to bovine serum albumin, and the resulting glycoconjugate was used to immunize two rabbits. The resultant antisera were tested for reactivity with a number of related mono, di- and trisaccharides to determine the immunodominant portion of this trisaccharide. Two populations of antibody resulted, one of which required the reducing end mannose, and could react with either an N-acetylglucosamine or a mannose as the penultimate sugar. The other population reacted with the Man alpha 1-->2Man alpha 1-->6Man alpha 1-->. The aglycone moiety and its configurations play an important role in determining the specificity of antibodies to this synthetic antigen. The similarity of this reactivity to the reactivity of mannose binding lectins is discussed.

Animals↗
PubMed1992

Effects on renal function and digoxin-like immunoreactivity produced by methimazole in low-renal mass hypertension.

This study evaluates the effects of methimazole, an antithyroid drug, on blood pressure, digoxin-like immunoreactive factor (DLIF) production and other variables related to salt and water metabolism in low-renal mass (LRM) hypertension. Drinking administration of methimazole (0.025%) from replacement of water by the 1% NaCl solution maintained the blood pressure of low-renal mass rats at normal levels during four weeks after hypertension induction. Serum and urinary excretion of DLIF were significantly increased in LRM rats with respect to controls; in all tests, the highest values of DLIF were found in LRM-methimazole treated (LRM-M) rats. Urinary excretion of DLIF showed positive correlations with diuresis and natriuresis in all three groups (control, LRM and LRM-M rats). However, the correlation between DLIF and sodium disappeared when both factors were expressed as a function of their concentrations. These results indicate that methimazole prevents LRM hypertension and suggest that DLIF might not represent the putative natriuretic hormone. Other findings were that methimazole-treatment reduced renal compensatory hypertrophy subsequent to subtotal nephrectomy, and did not modify the characteristic polyuria-polydypsia in this type of hypertension.

Animals↗
PubMed1991

Cholecystokinin activation: evidence for an ordered reaction mechanism for the tyrosyl protein sulfotransferase responsible for the peptide sulfation.

The kinetics of the forward tyrosyl protein sulfotransferase (TPS) reaction were examined using an assay based on the 35SO4 transfer from 3'-phosphoadenosine 5'-phospho(35S)sulfate [( 35S]PAPS) to tyrosyl residues of the non-sulfated cholecystokinin derivative, BocCCK-8(ns). TPS present in the microsomal membranes from rat cerebral cortex was used for these studies. Initial velocity measurements performed over a wide range of PAPS, BocCCK-8(ns), 3'-PAP and BocCCK-8(s) concentrations, indicated that the reaction follows an ordered mechanistic pathway. The KM value determined for BocCCK-8(ns) was 160 +/- 18 microM, and that for [35S]PAPS was 0.15 +/- 0.03 microM. 3'-Phosphoadenosine 5'-phosphate (3'-PAP) was found to be a product inhibitor with a Ki = 0.30 +/- 0.02 microM. BocCCK-8(s) produced an uncompetitive inhibition pattern on the TPS reaction. Adenosine 5'-phosphosulfate (APS) behaved as a competitive inhibitor versus PAPS with a Ki = 3.0 +/- 0.3 microM. ATP inhibited competitively the reaction when PAPS was the varied substrate with a Ki = 3.6 +/- 0.5 microM. The results of product and substrate inhibition studies and the patterns of dead end inhibition obtained with APS are best fit by an ordered Bi-Bi reaction mechanism where PAPS is the first substrate to bind and 3'-PAP is the last product to be released.

Animals↗
PubMed1991

Urinary excretion of digoxin-like immunoreactive factor and arginine-vasopressin in rats after several osmotic loads.

Urinary digoxin-like immunoreactive factor (DLIF), arginine-vasopressin (AVP) and other urinary parameters were investigated under normal conditions and after the i.p. injection of the following solutions: distilled water, isotonic and hypertonic NaCl, NaHCO3, KCl and urea, at a rate of 3 ml/100 g body weight. The measurement of digoxin-like immunoreactivity by two different radioimmunoassays showed that DLIF was stimulated by all volume loads regardless of the presence or absence of osmolar compounds. This dissociation between DLIF and urinary sodium excretion suggests that DLIF may not constitute the natriuretic hormone. Moreover, a dissociation between DLIF and AVP excretion also were found, which speaks against the hypothesis of a common mechanism of stimulation for both substances.

Animals↗