PubMed Health⌕ Search

Biomedical subjects

M Palacios

Publications and source records attributed to M Palacios.

28 records · Page 2Linked to original sources

Enhancers of nonspecific immunity induce nitric oxide synthase: induction does not correlate with toxicity or adjuvancy.

A range of bacterial products and related synthetic compounds, either alone or in combination, enhance nonspecific resistance to infection and tumors. These compounds, which vary in their other properties such as pyrogenicity, toxicity and adjuvancy, were used to assess the hypothesis that nonspecific resistance is mediated by induction of the L-arginine: nitric oxide (NO) pathway. The results obtained show that agents which stimulate nonspecific immunity, such as endotoxin, muramyl dipeptide (MDP) and combinations of monophosphoryl lipid A (MPL) with either trehalose dimycolate (TDM) or MDP cause a substantial induction of Ca(2+)-independent NO synthase in murine lung. In contrast, agents which do not stimulate nonspecific resistance, such as either MPL or TDM alone or threonyl MDP (ThrMDP), do not induce NO synthase. This difference in the ability of MDP and ThrMDP to induce NO synthase in the lung in vivo was also manifest in peritoneal macrophages in vivo as well as being evident in the greater than 100-fold greater potency of MDP in inducing the enzyme in vitro in lung slices. In contrast to the good correlation between induction of NO synthase and induction of nonspecific resistance, no correlation was observed with either the toxic effects of these agents or their adjuvancy.

Acetylmuramyl-Alanyl-Isoglutamine↗

Kinetic characteristics of nitric oxide synthase from rat brain.

The relationship between the rate of synthesis of nitric oxide (NO) and guanylate cyclase stimulation was used to characterize the kinetics of the NO synthase from rat forebrain and of some inhibitors of this enzyme. The NO synthase had an absolute requirement for L-arginine and NADPH and did not require any other cofactors. The enzyme had a Vmax. of 42 pmol of NO formed.min-1.mg of protein-1 and a Km for L-arginine of 8.4 microM. Three analogues of L-arginine, namely NG-monomethyl-L-arginine, NG-nitro-L-arginine and NG-iminoethyl-L-ornithine inhibited the brain NO synthase. All three compounds were competitive inhibitors of the enzyme with Ki values of 0.7, 0.4 and 1.2 microM respectively.

Amino Acid Oxidoreductases↗

Nitric oxide from L-arginine stimulates the soluble guanylate cyclase in adrenal glands.

The formation of nitric oxide (NO) by an L-arginine:NO synthase and its stimulation of the soluble guanylate cyclase was studied in rat whole adrenal and bovine cortex and medulla cytosol. In the presence of L-arginine, the stimulation of soluble guanylate cyclase was accompanied by the formation of citrulline and NO2-, formed from NO. The NO synthase was NADPH- and Ca(2+)-dependent and was inhibited by several L-arginine analogues. These results indicate that rat and bovine adrenal cytosol contains an L-arginine:NO synthase.

Adrenal Cortex↗

Proximal small intestinal mucosal injury. Maintenance of glucose and glucose polymer absorption, attenuation of disaccharide absorption.

The effect of chronic intragastric infusion of hypertonic mannitol on small intestinal mucosal structure and function was studied in adult rats. Animals were gavage-fed 20% mannitol (1300 mosm) at a dose of 5 ml/100 g body weight daily for seven days. Control animals were gavage-fed tap water on the same schedule. On day 8, the animals were anesthetized, the duodenum cannulated, and a test sugar (glucose, glucose polymer, lactose, sucrose, or maltose) was infused at a dose of 0.5 g/kg body weight in 2.5 ml distilled water over less than 1 min. Portal vein glucose was measured at 30-min intervals from 0 to 120 min. Mannitol treatment resulted in histologic and biochemical alterations (reduced lactase, sucrase, maltase) limited to the proximal small intestine compared to the control group. The absorption of glucose and glucose polymers was similar in mannitol-treated and control animals. In contrast, digestion and absorption of lactose, sucrose, and maltose was significantly diminished in mannitol-treated animals when compared to controls. No changes in permeability to polyethylene glycol 4000 or Na+-coupled glucose transport were observed in mannitol-treated animals compared to controls. These data suggest that when the intestinal mucosa is exposed to hyperosmolar loads that the digestive capacity for disaccharides is suppressed more than its glucose absorptive capacities. Furthermore, glucose oligomers may be more readily digested and absorbed than disaccharides, in this setting, due, in part, to the proximal injury and less pronounced proximal-distal gradient for glucoamylase than other brush-border carbohydrases.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Formation of nitric oxide from L-arginine in the central nervous system: a transduction mechanism for stimulation of the soluble guanylate cyclase.

A soluble enzyme obtained from rat forebrain catalyzes the NADPH-dependent formation of nitric oxide (NO) and citrulline from L-arginine. The NO formed stimulates the soluble guanylate cyclase and this stimulation is abolished by low concentrations of hemoglobin. The synthesis of NO and citrulline is dependent on the presence of physiological concentrations of free Ca2+ and is inhibited by NG-monomethyl-L-arginine, but not by its enantiomer NG-monomethyl-D-arginine or by L-canavanine. L-Homoarginine, L-arginyl-L-aspartate, or L-arginine methyl ester can replace L-arginine as substrates for the enzyme. These results indicate that NO is formed from L-arginine in the brain through an enzymic reaction similar to that in vascular endothelial cells, neutrophils, and macrophages, adding support to our hypothesis that the formation of NO from L-arginine is a widespread transduction mechanism for the stimulation of the soluble guanylate cyclase.

Animals↗

[Program for the early detection of hyperphenylalaninemia: 11 years on].

In 1980 the Neonatal Screening Program was set in motion in Navarra. One of its aims is the early detection of hyperphenylalaninemias. In 1987 the quantification of phenylalanine came to be carried out in the Clinical Chemistry Department of the Hospital of Navarra. From then until December 1997, 51,815 newborn babies have been studied, which represents 99.24% of the infants born in Navarra. The quantification of phenylalanine in dried blood spots during 1989 enabled us to obtain the reference interval for this amino acid that is contained between 69.5 +/- 0.01 micromol/L and 139.9 +/- 0.03 micromol/L. During these 11 years we detected 2 cases of phenylketonuric hyperphenylalaninemia and one case of transitory hyperphenylalaninemia. From the clinical point of view, the children are well at present, following prescription of adequate treatment, which is based on a diet with a low phenylalanine content.

English Abstract↗

[Lipidic changes in subclinical hypothyroidism. Evolution according to whether or not corrections are made of TSH levels].

INTRODUCTION: The repercussion of subclinical hypothyroidism and its treatment on the levels of circulating lipids has received scarce definition. With the aim of obtaining our own data for evaluating the need of treatment in this pathology, we designed a study protocol in two phases. MATERIAL AND METHODS: In the first phase we determined the plasma values of total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides, Apo A-I, Apo B-100 and Lp(a) in two groups of patients: a control group formed by 123 healthy women from a Pamplona Health Area and a second group formed by 29 women affected by subclinical hypothyroidism who were attending our surgeries. In the second phase we included 42 women with subclinical hypothyroidism, on whom we carried out a comparative longitudinal study for three months, dividing them into two groups. One that was formed by 30 women, who were treated until their levels of TSH were normalised, and another in which the women were left in subclinical hypothyroidism. In both groups we have evaluated the lipidic profile and Apo A-I, Apo B100 and Lp (a). RESULTS: 1st phase: The total cholesterol and the LD-cholesterol were significantly higher in the group with SH than in the control group. There were no differences in the HDL-cholesterol nor in the triglycerides. 2nd phase: Group 1: The figures of total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides and Lp (a) were not modified on normalisation of the levels of TSH. The Apo A-I increased significantly and the Apo B-100 showed a tendency to diminish although without significant differences. Group 2: None of the parameters changed significantly as they remained in subclinical hypothyroidism. On comparing the final parameters between groups 1 and 2 (after 3 months), only the Apo A-I and the Lp (a) increased significantly on correction of SH. CONCLUSIONS: Subclinical hypothyroidism is accompanied by a modification of the lipidic profile of an atherogenic character although its treatment, according to our data, does not achieve significant variations.

English Abstract↗

[Coronary angioplasty in the treatment of symptomatic myocardial ischemia with one vessel disease].

Our group initiated a program of coronary angioplasty (CA) in patients with symptomatic one vessel disease, or multivascular lesions with a critical "culprit" stenosis. In a 16 month period we have performed CA of 28 lesions in 25 patients (20 men) with a mean age of 54 +/- 10 years. Stable angina was diagnosed in 14 patients, unstable angina in 7, and post-myocardial infarction residual angina or stenosis in 4 patients treated with streptokinase. Successful dilatation was obtained in 23 (82.1%) of 28 stenotic segments, reducing the stenosis from 90 +/- 8% (range 70-100) to 9 +/- 12% (range 0-30; p less than 0.00001). In 4 cases with total occlusion, dilatation was not obtained, and in one case the procedure was complicated by fatal brain embolism. There were 4 complications due to coronary occlusion or spasm, all of them resolved during CA without sequelae. The 20 cases with primary success have been followed during an average of 8.6 months. In three cases (15%) restenosis was detected; two of them underwent surgery, and CA was repeated successfully in the other. Disappearance of myocardial ischemia was confirmed in 14 patients, and functional improvement in the other three. In conclusion, CA is an effective and relatively safe therapeutic alternative in different clinical forms of coronary heart disease with a single vessel stenosis, or in selected cases of multivascular lesions with a critical stenosis.

Adult↗