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Biomedical subjects

M Puig

Publications and source records attributed to M Puig.

70 records · Page 4Linked to original sources
PubMed1975

The stereoisomers of 3,4-dihydroxyphenylserine as precursors of norepinephrine.

The action of the four stereoisomers of 3,4-dihydroxyphenylserine (DOPS) on the monoamine content of brain and heart was investigated with biochemical and histochemical methods. The (+)-erythro-DOPS (50-250 mg/kg i.p.), due to its alphaS configuration, was readily decarboxylated in vivo leading to an accumulation of norepinephrine (NE) in brain and heart. The amino probably corresponded to the unnatural (+) form since the amino acid shows betaS configuration. The NE was located in brain regions rich in noradrenergic (hypothalamus, locus ceruleus), dopaminergic (neostriatum, substantia nigra) and 5-hydroxytryptaminergic (raph'e nuclei) neurons. In addition, (+)-erythro-DOPS decreased the level of endogenous 5-hydroxytryptamine and dopamine and increased that of 5-hydroxyindoleacetic and homovanillic acid in the brain indicating a displacement of 5-hydroxytryptamine and dopamine, respectively, from their storage sites. Inhibitors of extracerebral decarboxylase (benserazid and carbidopa) diminished the (+)-erythro-DOPS-induced increase in cerebral NE by inhibiting the decarboxylation of the amino acid in the walls of the brain capillaries. The (-)-threo-DOPS, which also show alphaS configuration, was decarboxylated too, leading to a rise in cardiac NE. The amine was likely to correspond to the natural(-)-isomer since (-)-threo-DOPS has betaR configuration. This increase in NE lasted much longer than that caused by (+)-erythro-DOPS. In the brain, the accumulation of NE was negligible after i.p. administration of (-)-threo-DOPS but marked after injection of the isomer into a cerebral ventricle indicating a poor penetration of (-)-threo-DOPS through the blood-brain barrier. High doses (500 and 1000 mg/kg i.p.) of (-)-erythro- and (+)-threo-DOPS caused only a slight increase in cerebral and cardiac NE since, due to their alphaR configuration, they were probably not decarboxylated to a major extent. In conclusion, (+)-NE formed from (+)-erythro-DOPS probably accumulates in the storage sites of the endogenous monoamines where it might function as a false neurotransmitter.

Animals↗
PubMed1972

Modification of the evoked release of noradrenaline from the perfused cat spleen by various ions and agents.

1. Cat spleens were perfused with Krebs-bicarbonate solution at a rate of about 7 ml./min at 33-35 degrees C. Noradrenaline release after splenic nerve stimulation at 10 or 30 Hz was measured. Effects of various ions and drugs on noradrenaline release were determined.2. Perfusion of phenoxybenzamine- and [(3)H]noradrenaline-treated spleens with 1, 2.5 and 5 mM cobalt or nickel-2 Krebs solution markedly reduced the release of noradrenaline by nerve stimulation. Lanthanum was the most potent inhibitor of noradrenaline release. Increasing the calcium concentration or adding tetraethylammonium chloride (TEA) partially counteracted the inhibitory effects of cobalt on release. Cobalt did not inhibit release induced by tyramine.3. Calcium did not cause spontaneous release of noradrenaline either when high concentrations were injected directly into the spleen or after first perfusing the spleen with calcium-free medium.4. Carbachol, protoveratrine and high potassium inhibit, whereas TEA, barium and rubidium enhance, the evoked release of noradrenaline.5. The relation of noradrenaline release to influx of calcium ions and its modification by various agents has been discussed.

Animals↗
PubMed1971

Effect of flow-stop on noradrenaline release from normal spleens and spleens treated with cocaine, phentolamine or phenoxybenzamine.

1. Cat spleens were perfused with Krebs-bicarbonate solution, using a constant-flow pump at a rate of about 7 ml/min at 33-35 degrees C. Noradrenaline (NA) overflow by nerve stimulation at 10 Hz for 20 s was determined with or without flow-stop before and after treatment with cocaine, phentolamine or phenoxybenzamine. In order to determine the effect of flow-stop on overflow, the arterial and the venous flows were occluded by clamping the inflow and outflow tubes during the period of stimulation plus 30, 60 or 120 seconds.2. Without flow-stop, NA output was 0.93+/-0.25 ng/stimulus, which was significantly increased after cocaine (123+/-6.6%), phentolamine (415+/-93%) and phenoxybenzamine (578+/-107%). Phentolamine and phenoxybenzamine were much more effective than cocaine in enhancing overflow.3. Before treatment with drugs, flow-stops of 30, 60 and 120 s reduced NA outputs to 70+/-6.6, 27.5+/-2 and 7%, respectively, of the control outputs without flow-stop. None of the drugs significantly influenced the percentage reductions in NA outputs during a 30 s flow-stop. However, the percentage outputs after cocaine or phenoxybenzamine treatment during a 60 s flow-stop significantly increased to 45+/-2.5% and 57+/-6%, respectively, as compared to the percentage output of 27.5+/-2% from untreated spleens during a corresponding flow-stop period. During flow-stop, there was no appreciable metabolism of the released transmitter.4. Diffusion of the released transmitter from the site of liberation plays only a minor role in the removal of the released NA.5. It is suggested that the NA released by nerve stimulation acts on the presynaptic alpha sites to inhibit its own release by a negative feedback mechanism. Adrenoceptor blocking agents enhance the NA overflow from spleen because they remove this autoinhibition by blocking the presynaptic alpha sites.

Animals↗
PubMedDate not supplied

Burden of myocardial damage in cardiac allograft rejection: scintigraphic evidence of myocardial injury and histologic evidence of myocyte necrosis and apoptosis.

BACKGROUND: Because myocardial damage determines morbidity and outcomes in heart transplant rejection, assessment of total burden of myocardial damage is highly desirable. In addition to myocyte necrosis, programmed cell death, or apoptosis, has recently been shown to contribute to cardiac allograft rejection. In the present study, we noninvasively determined myocardial damage by antimyosin scintigraphy and compared it with necrotic and apoptotic myocardial damage in endomyocardial biopsy (EMB) specimens. METHODS AND RESULTS: Forty scintigraphic and histologic studies were simultaneously performed. Of these, 19 patients had no EMB evidence of allograft rejection (group I, International Society of Heart and Lung Transplantation [ISHLT] grade 0/4), 12 had mild rejection (group II, ISHLT grades 1A and 1B), and 9 had evidence of moderate allograft rejection (group III, ISHLT grades 2, 3A, and 3B). None of the biopsies demonstrated severe allograft rejection (ISHLT grade 4/4). The severity of global myocyte damage in 40 patients was assessed by antimyosin scintigraphy. Endomyocardial biopsies were performed in these patients within 48 hours of imaging study; biopsy specimens were characterized for presence of myocyte necrosis and apoptosis. Evidence of myocyte necrosis was observed in 9 (23%) of 40 EMB specimens. Nineteen EMB specimens of group I had no inflammation and no myocyte necrosis, 12 of group II specimens showed interstitial mononuclear cell infiltration (only) but no myocyte necrosis, and all 9 of group III specimens had evidence of cellular infiltration and myocyte damage. Myocyte necrosis was assessed by hematoxylin-eosin and trichrome staining of EMB specimens. On the other hand, apoptosis of myocytes, as assessed by TUNEL staining of DNA fragments, was seen in 22 (55%) of the 40 biopsy specimens: 47%, 58%, and 67% in groups I, II and III, respectively. Abnormal antimyosin scan findings, indicating presence of myocardial damage, were observed in 9 of the 19 patients in group I and in all patients in groups II and III. Although positive antimyosin scan results in group III patients are concordant with the presence of histologic myocardial necrosis, myocardial uptake of antimyosin antibodies in groups I and II (no apparent myocyte damage at light microscopic examination) could reflect either sampling error of the biopsy or ongoing apoptotic myocyte damage. CONCLUSIONS: Apoptosis of myocytes is frequently observed during cardiac allograft rejection. The presence of apoptotic myocytes in the absence of histologic rejection activity in patients with antimyosin uptake suggests that apoptosis could be an additional mechanism of transplant-associated myocardial damage.

Adult↗
PubMedDate not supplied

Plasma immunoreactive somatostatin is elevated in diabetic ketoacidosis and correlates with plasma non-esterified fatty acid concentration.

In experimental diabetes and after the administration of beta-hydroxybutyrate and non-esterified fatty acids (NEFA), an increase in circulating immunoreactive somatostatin (IRS) has been described. Both ketones and NEFA are raised in diabetic ketoacidosis. Therefore, we decided to investigate 10 patients in diabetic ketoacidosis by measuring, on admission and throughout the initial 24 hours of therapy, circulating levels of IRS, beta-hydroxybutyrate, acetoacetate, triglycerides, blood glucose, pH and NEFA. Fluids and insulin were administered IV following a previously established protocol. Nine patients showed abnormally high levels of circulating IRS. When compared with a group of controlled insulin-dependent diabetic patients, basal IRS was high (111 +/- 15 vs 28 +/- 3 pmol/l), and remained elevated for at least 24 h despite clear improvement of metabolic status. On admission we also found elevated levels of NEFA (1.04 +/- 0.2 mmol/l), triglycerides (4.7 +/- 1.1 mmol/l), beta-hydroxybutyrate (22.1 +/- 4mmol/l), and acetoacetate (4.8 +/- 1.1 mmol/l). A significant correlation was found initially between IRS and NEFA (p less than 0.01). We conclude that circulating IRS is high in most cases of diabetic ketoacidosis. The mechanism behind this hypersomatostatinaemia could be related to the abnormalities of lipid metabolism which occur in diabetic ketoacidosis.

3-Hydroxybutyric Acid↗
PubMedDate not supplied

Gastric mucosal energy metabolism in stress ulcer.

In this work we have studied the gastric mucosal energy metabolism in the restraint-rat experimental model. Gastric mucosal concentrations of glucose, AMP, ADP and ATP were determined, as well as free fatty acids and cholesterol, in order to evaluate alterations in the phospholipid composition of the cell membrane. We have observed a progressive decrease of glucose levels and an increase of ATP and Atkinson's index following 24 h of restraint; this finding refers to ATP not being used in HCl synthesis, and to activation of protein-kinase in the parietal cells due to an increase of histamine in the gastric mucosa. The increase in free fatty acids and a marked decrease of cholesterol in glandular mucosa suggest an alteration in the membrane phospholipid composition as a result of local phospholipases activated by histamine.

Adenosine Diphosphate↗