Biomedical subjects

M Rodriguez

Publications and source records attributed to M Rodriguez.

At least 91 records · Page 5Linked to original sources

PubMed1990

Electrochemical studies of the interaction of metal chelates with DNA. 4. Voltammetric and electrogenerated chemiluminescent studies of the interaction of tris(2,2'-bipyridine)osmium(II) with DNA.

Cyclic voltammetric and electrogenerated chemiluminescent data were used to study the binding of tris(2,2'-bipyridine)-osmium(II), Os(bpy)3(2+), an electrostatic binder, to calf thymus DNA. The oxidized form of the osmium complex, Os(bpy)3(3+), has a stronger association to DNA than the reduced form, Os(bpy)3(2+), as indicated by the negative shift of E0' of the CV waves (K3+/K2+ = 3.35). The calculated binding constant, K2+, and binding site size, s, for the Os(byp)3(2+)-DNA system depended slightly on whether a mobile or a static equilibrium was assumed. In 10 mM NaCl, 10 mM Tris pH 7, K2+ = (7.3 +/- 0.4) x 10(3) M-1 and s = 3 base pairs (mobile) and K2+ = (5.0 +/- 0.2) x 10(3) M-1 and s = 3 base pairs (static). Electrogenerated chemiluminescence (ECL) was produced upon oxidation of Os(bpy)3(2+) at a Pt electrode in a solution containing 10 mM C2O4(2-) and 10 mM phosphate at pH 5. Addition of DNA caused a decrease in the emission intensity (I); a plot of I vs relative DNA concentration yielded K2+ = (6.5 +/- 0.5) x 10(3) M-1 and s = 3 base pairs. The osmium complex produced ECL when bound to the DNA molecule with an efficiency of 30% that of the unbound chelate.

2,2'-Dipyridyl↗

PubMed1990

Changes in hypothalamic neuropeptide Y concentrations induced by cholecystokinin analogues.

Neuropeptide Y (NPY) and cholecystokinin (CCK) are two peptides involved in opposite ways in the control of food intake. A possible interaction between NPY and CCK has not yet been well defined. Two CCK derivatives with agonistic and antagonistic properties were studied with regard to their effects on brain and plasma NPY levels. The CCK agonist decreased NPY levels in plasma and in the hypothalamus but not in the other brain areas assayed. The CCK antagonist reversed the agonist-induced decrease in both plasma and hypothalamus. These results suggest a negative relation between NPY and CCK peptides, which is not surprising given their opposite role in feeding regulation. The hypothalamus, a preferential site of this regulation, appears to be the brain area most involved in the NPY-CCK interaction. The plasma NPY level variations closely reflect the hypothalamic profile, suggesting a direct release of NPY by a mechanism that remains to be investigated.

Animals↗

PubMed1990

Pharmacological activity of cholecystokinin analogues modified in the Met28-Gly29 region.

Analogues of the C-terminal octapeptide of cholecystokinin (CCK) modified in the Met28-Gly29 region, were tested for their ability to interact with peripheral cholecystokinin receptors on rat pancreatic acini and to stimulate amylase secretion. These analogues were further evaluated for their ability to recognize central CCK receptors on guinea pig brain membranes. The behavioral effect of these analogues was also tested after intrastriatal injection into mice. It appeared that these analogues were full CCK agonists in the peripheral system. Although some induced dopaminomimetic effects after intrastriatal injection into mice, being as potent as the C-terminal octapeptide of cholecystokinin (CCK-8), others did not have any effect and were able to antagonize CCK-8 actions in the striatum. The results of this study confirm that one can obtain very potent CCK analogues by modifying the peptide bond between Met28 and Gly29, and that this modification can produce either CCK agonists or antagonists of CCK-induced dopamine transmission in the striatum.

Amino Acid Sequence↗

PubMed1990

ACE-like hydrolysis of gastrin analogs and CCK-8 by fundic mucosal cells of different species with release of the amidated C-terminal dipeptide.

Various gastrin analogues and CCK-8 (Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2) are hydrolyzed in vitro by angiotensin-converting enzyme (ACE), the main and initial cleavage occurring at the Met-Asp (or Leu-Asp) bond, releasing the C-terminal dipeptide amide Asp-Phe-NH2. Tetragastrin analogues (e.g., Boc-Trp-Leu-Asp-Phe-NH2) are degraded by a vesicular membrane fraction from rat gastric mucosa, yielding the C-terminal dipeptide Asp-Phe-NH2. We report here on the degradation of gastrin analogues and CCK-8 by a gastric mucosal cell preparation containing specific gastrin receptors. We have shown that gastrin analogues were specifically degraded by gastric mucosal cells from different species (e.g., rabbit and dog) at 37 degrees C (pH 7.4), releasing the C-terminal dipeptide Asp-Phe-NH2, similarly to ACE. This cleavage was found to be temperature and pH sensitive, and was inhibited by metalloproteinase inhibitors and by captopril, strongly suggesting that this enzymatic system closely resembles ACE. We have also demonstrated that a close correlation seems to exist between the apparent affinity of the gastrin analogues for gastrin receptors on gastric mucosal cells, and their ability of being hydrolyzed by this cell preparation. Moreover, all gastrin analogues which have been demonstrated to act as gastrin antagonists remained unaffected in the incubation conditions.

Amides↗

PubMed1990

Determination of monoamines and indoles in amniotic fluid by high-performance liquid chromatography-electrochemical detection.

A technique is presented for the separation and detection in amniotic fluid of various substances associated with catecholamine metabolism. Monoamines and their metabolites were separated using reversed-phase ion-pair high-performance liquid chromatography. Detection and quantification were performed electrochemically. The retention times of 28 standards associated with the monoamines and their precursors and metabolites were evaluated with 14 different eluents. On the basis of the retention times of each standard and the modification of the retention times of the various peaks detected in amniotic fluid, the following substances were identified in this biological fluid: 4-hydroxy-3-methoxyphenylacetic acid, 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid, 4-hydroxy-3-methoxyphenylglycol, epinephrine, 4-hydroxy-3-methoxymandelic acid, octopamine, tyrosine and tryptophan.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1990

Two functionally distinct cholecystokinin receptors show different modes of action on Ca2+ mobilization and phospholipid hydrolysis in isolated rat pancreatic acini. Studies using a new cholecystokinin analog, JMV-180.

A new hepatapeptide cholecystokinin (CCK) analog, JMV-180 (Boc-Tyr(SO3-)-Nle-Gly-Trp-Nle-Asp-2-phenylethylester), acts as an agonist at high affinity CCK receptors on rat pancreatic acini to stimulate amylase release but unlike cholecystokinin octapeptide (CCK8) does not act on low affinity CCK receptors to inhibit amylase release (Galas, M. D., Lignon, M. F., Rodriguez, M., Mendre, C., Fulcrand, P., Laur, J., and Martinez, J. (1988) Am. J. Physiol. 254, G176-G188). To investigate the biochemical mechanisms initiated by CCK acting on each class of CCK receptor, the effects of JMV-180 and CCK8 on amylase release, Ca2+ mobilization, and phospholipid hydrolysis were studied in isolated rat pancreatic acini. When acini were loaded with the intracellular Ca2+ chelator BAPTA, amylase release stimulated by both JMV-180 and CCK8 was reduced. Measurement of 45Ca2+ efflux and cytosolic free calcium concentration ([Ca2+]i) by the fluorescence of fura-2-loaded acini in a stirred cuvette showed that JMV-180 induced a concentration-dependent increase but with a maximal response only two-thirds that induced by CCK8. When [Ca2+]i of individual fura-2-loaded acinar cells was measured by microspectrofluorometry, all concentrations of JMV-180 (1 nM-10 microM) induced repetitive transient [Ca2+]i spikes (Ca2+ oscillations). By contrast, stimulation with a high concentration of CCK8 (1 nM) caused a large increase in [CA2+]i followed by a small sustained elevation of [Ca2+]i. The measurement of inositol trisphosphate (IP3) production by both [3H]inositol labeling and 1,4,5-IP3 radioreceptor assay showed that JMV-180 had only minimal effects at 10 microM in contrast to the large increase induced by high concentrations of CCK8 (more than 1 nM). JMV-180 blocked the effect of a high concentration of CCK8 on both [Ca2+]i and 1,4,5-IP3 productions but did not affect the response to carbamylcholine. JMV-180 caused a delayed monophasic stimulation of 1,2-diacylglycerol (DAG) sustained to 60 min without the early increase in DAG observed in response to CCK8. Furthermore, JMV-180 stimulated the release of [3H]choline metabolites, primarily phosphorylated choline, from [3H]choline-labeled acini at low concentrations and to the same extent as CCK8. Since JMV-180 interacts not only with high affinity CCK receptors as an agonist but also with low affinity CCK receptors as a functional antagonist, the present results indicate that the occupancy of high affinity state receptors by CCK induces Ca2+ oscillations, DAG formation from phosphatidylcholine hydrolysis, and amylase release with minimal phosphatidylinositol 4,5-bisphosphate hydrolysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Amylases↗

PubMed1990

Immunoglobulins promote remyelination in the central nervous system.

Remyelination of central nervous system axons was promoted by systemic injection of serum immunoglobulin G (IgG) from donor mice hyperimmunized with homogenized spinal cord. In SJL/J mice infected with Theiler's virus, primary demyelination and inflammation in the spinal cord were extensive. Following treatment with IgG to spinal cord homogenate, new myelin synthesis as measured by quantitative morphometry increased sixfold. Cells in areas of remyelination that incorporated [3H]thymidine did not express differentiation markers of macrophages, oligodendrocytes, or astrocytes but were identified by electron microscopic autoradiography as progenitor glial cells. These findings raise the possibility that IgG secreted in demyelinating lesions might have the potential to promote myelin repair.

Animals↗

PubMed1990

Aluminum administration in the rat separately affects the osteoblast and bone mineralization.

Aluminum administration in the experimental animal results in osteomalacia as characterized by osteoid accumulation and decreased mineralization. Previous in vivo and in vitro studies have indicated that either aluminum directly inhibits mineralization or is toxic to the osteoblast. In the present study, PTH was continuously infused in rats with aluminum-induced osteomalacia to evaluate whether aluminum administration decreased mineralization without a concomitant decrease in osteoblasts. Four groups of rats were studied: chronic renal failure (CRF); CRF + aluminum (AL); CRF + PTH; and CRF + PTH + AL. Rats were sacrificed 5 and 12 days after aluminum or diluent administration; in the PTH groups, bovine PTH (1-34) was administered at 2 units/h via a subcutaneously implanted Alzet pump. Aluminum administration decreased osteoblast surface, increased osteoid accumulation, and produced a cessation of bone formation. The infusion of PTH alone increased osteoblast surface and bone formation. The simultaneous administration of aluminum and PTH resulted in an osteoblast surface intermediate between aluminum and PTH alone; however, despite a PTH-induced restoration of osteoblast surface, bone formation did not increase. These findings indicate (1) aluminum is toxic to osteoblasts and also directly inhibits mineralization even when osteoblasts are not decreased; (2) PTH is capable of increasing osteoblasts even in the presence of aluminum; and (3) despite a PTH-induced increase in osteoblast surface, mineralization of osteoid was not improved.

Aluminum↗

PubMed1990

Effect of parathyroidectomy on aluminum toxicity and azotemic bone disease in the rat.

In maintenance dialysis patients, low-turnover osteomalacia and aplastic bone disease are generally attributed to aluminum toxicity. Both groups of patients have a relative deficiency of PTH. The reason for the development of osteomalacia versus aplastic bone disease is unclear. The present study was performed to evaluate whether parathyroidectomy (PTX) modifies the effect of aluminum administration on bone histology in renal failure. Seven groups of pair-fed rats were studied: normals (N); renal failure (RF); RF + PTX; PTX; RF + aluminum (AL); RF + PTX + AL; and PTX + AL. Aluminum was administered intraperitoneally 5 days/week for 6 weeks. All groups were sacrificed at 6 weeks. Renal failure increased the serum calcium in both the parathyroid intact (RF versus N, 11 +/- 0.1 versus 10 +/- 0.3 mg/dl, X +/- SEM, P less than 0.05) and calcium-supplemented PTX groups (PTX + RF versus PTX, 9.7 +/- 0.2 versus 9.2 +/- 0.2 mg/dl, P less than 0.05). After PTX, aluminum administration increased the serum calcium (PTX + AL versus PTX, 9.8 +/- 0.3 versus 9.2 +/- 0.2, P less than 0.05, and PTX + RF + AL versus PTX + RF, 10.8 +/- 0.1 versus 9.7 +/- 0.2 mg/dl, P less than 0.05). In rats with renal failure receiving aluminum, PTX decreased osteoid volume and surface but not osteoid thickness. Rats receiving aluminum did not mineralize bone. Additionally, in PTX rats receiving aluminum, renal failure per se increased osteoblast surface, osteoid surface, osteoid volume, and osteoclast number.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗

PubMed1990

Successful diaphragmatic pacing for idiopathic alveolar hypoventilation.

We describe the case of a 17-year-old woman noted to have idiopathic alveolar hypoventilation, with multiple Intensive Care Unit (ICU) admissions because of acute respiratory failure (ARF) due to respiratory infections. After two years of diaphragmatic pacing arterial blood gases have substantially improved, without obstructive apnoea. Signs of right ventricular enlargement and pulmonary hypertension have decreased. Morning headache and diurnal somnolence have disappeared, and she is also able to perform more physical and mental activity, allowing her to enjoy a better quality of life.

Adolescent↗

PubMed1990

Diagnostic and therapeutic curettage in gestational trophoblastic disease.

From June 1976 through June 1989, 37 nonconsecutive patients underwent uterine curettage during the course of their gestational trophoblastic disease. In 22 patients (59%) trophoblastic tissue was obtained. Three (8.1%) patients sustained a uterine perforation during the procedure. In six patients curettage was performed for bleeding. There were six patients curetted during assessment for metastatic trophoblastic disease. Twenty-eight patients underwent curettage for the presumed diagnosis of nonmetastatic gestational trophoblastic disease. In retrospect, four of these women (14.3%) had insufficient criteria for the diagnosis of gestational trophoblastic disease. Of the remaining 23 patients, four (17.4%) went into clinical remission without further treatment. Ten patients (43.5%) had a transitory decline in serum beta-human chorionic gonadotropin levels that subsequently rose or plateaued. Six patients (26.1%) showed no effect from the curettage on their serum beta-human chorionic gonadotropin trend during a short period of observation. Three patients (13.0%) with nonmetastatic gestational trophoblastic disease were not observed for a possible therapeutic effect after curettage. Thus, in only 4/20 (20%) women with nonmetastatic trophoblastic disease was a therapeutic effect from curettage shown.

Chorionic Gonadotropin↗

PubMed1990

Interhemispheric regulation of dopaminergic ascending systems.

There are previous evidences of biochemical and functional interhemispheric asymmetry for central dopaminergic systems. The purpose of the current study was to establish an evidence of the existence of mechanisms for interhemispheric regulation of dopaminergic systems. The initial hypothesis was that to compensate the spontaneous interhemispheric asymmetry, the brain side with lower dopamine (DA) concentration show a higher DA turnover. The ratio of metabolite/neurotransmitter was computed as an index of presynaptic turnover rate. Both striatum and hippocampus showed a DOPAC/DA index higher in the brain side with a lower DA concentration. In addition, we found an inverse relation between the interhemispheric index of DA and interhemispheric index of DA turnover. Taken together the present data provide evidence of an interhemispheric regulation for the DA-innervation of both striatum and hippocampus in normal unlesioned rats.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1990

A cholecystokinin agonist/antagonist according to dose and time of action: effect on food intake.

A new CCK pseudopeptide (Boc-Tyr (SO3)-Nle-psi-(COCH2) Gly-Trp-Nle-Asp-Phe-NH2) has been described in a previous study as a potent CCK agonist in the peripheral system and as an antagonist in the central nervous system. When administered alone by a peripheral route, this pseudopeptide was found to decrease food intake in free/feeding rats, and thus behaved as a CCK agonist. However, it reversed the decreased feeding effect induced by a full potent agonist (Boc(Nle 28-Nle 31)-CCK26-33). This antagonistic action occurred 3-4 h after treatment, at a time when the agonistic properties of the pseudopeptide alone had disappeared, but when the effect of the full potent agonist remained. The dose-response curve of the antagonistic action was bell-shaped. These results suggest that this new pseudopeptide is not only agonistic in the periphery and antagonistic in the central nervous system as shown in the previous study, but is also both agonistic and antagonistic on the same paradigm according to the dose and time of action.

Amino Acid Sequence↗

PubMed1990

Changes in brain neuropeptide Y induced by cholecystokinin peptides.

Cholecystokinin (CCK) and neuropeptide Y (NPY) are two peptides with opposite effects on the regulation of feeding behaviour. The possible interaction between these two systems has always been controversial. In this study, rat brain NPY levels were assayed after treatment with CCK 8 S and with a potent CCK agonist (Boc-(Nle 28-Nle 31)-CCK 26-33). CCK 8 S and its agonist analogue (50 micrograms/kg i.p.) both decreased hypothalamic and hippocampal NPY levels. This result suggests a negative relationship between NPY and CCK-peptides which is not surprising given their opposite role in the control of feeding. The hypothalamus and secondarily the hippocampus appear to be the site of this interaction; no change in NPY levels was observed in other brain areas (striatum and cortex). The same pattern of variation was found in the plasma, suggesting a direct release from the brain via a mechanism which remains to be investigated. The effect appeared later with the CCK analogue than with CCK 8 S itself; this is not surprising with regard to other behavioural and biochemical effects of the analogue and provides further characterization of its action.

Animals↗

PubMed1990

Effects of a new cholecystokinin analogue (JMV 236) on food intake and brain monoamines in the rat.

JMV 236, a new cholecystokinin-octapeptide-sulfate (CCK 8 S) derivative (Boc-Tyr (SO3)-Nle-Gly-Trp-Nle-Asp-Phe-NH2) has been synthesized in the Centre de Pharmacologie-Endocrinologie (Montpellier). This peptide has been shown to present the same activity as CCK 8 S on pancreatic amylase secretion and has the advantage of a better chemical stability. With a view to further characterization, the effect of JMV 236 on food intake and brain monoamine and metabolite variations was assayed in the rat after intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administrations. JMV 236 decreased food intake 2 and 3 hours after i.p. administration of 12.5 and 50 micrograms/kg but was inactive after i.c.v. injection. Its global action was similar to that of CCK 8 S, but was less marked with delayed onset of response. As in our previous work with CCK 8 S, JMV 236 was more potent in inducing monoaminergic variations after i.p. than after i.c.v. administration. The main effects were decreases in striatal dopamine metabolite levels and increases in hypothalamic and striatal serotonin metabolite (5-HIAA) levels. These effects are classically observed with CCK 8 S and are described in our previous reports. The interesting peptide will require further characterization and may serve as a possible reference compound for studies on CCK derivatives.

Animals↗

PubMed1990

Abrogation of resistance to Theiler's virus-induced demyelination in C57BL mice by total body irradiation.

Theiler's murine encephalitis virus (TMEV) produces an unusual biphasic disease in susceptible mice characterized by poliomyelitis with early viral replication in neurons, followed by chronic demyelination with viral antigen expression in spinal cord white matter. In addition, infectious virus persists in the central nervous system (CNS) throughout the chronic phase of disease. Previous studies have indicated an important role for major histocompatibility complex (MHC)-gene products in determining resistance/susceptibility to disease. In particular, certain class I gene products of the D region of the H-2 gene complex render mice of the C57BL lineage resistant to induction of demyelination. Intracerebral infection of B10.S(DS) mice results in demyelination in the spinal cord while infection of C57BL/10(Db) or B10.S(9R)(Dd) fails to produce white matter destruction. In this study we showed that immunosuppression with gamma irradiation renders normally resistant B10.S(9R) and C57BL/10 mice susceptible to TMEV-induced demyelination and allowed for increased viral replication. In addition, the majority of irradiated C57BL/10 mice infected with virus showed extensive areas of CNS remyelination by oligodendrocytes beginning at 63 days post-infection. In contrast, immunosuppression of normally susceptible B10.S mice resulted in acute disease and high mortality accompanied by overwhelming destruction of neurons. The study supports the hypothesis that MHC-conferred resistance in C57BL mice is associated with MHC D region products and indicate an important active role for the immune system early in infection in limiting vital infection during disease induction in nonimmunosuppressed mice.

Animals↗

PubMed1990

Intrathecal somatostatin, somatostatin analogs, substance P analog and dynorphin A cause comparable neurotoxicity in rats.

Rats chronically implanted with intrathecal catheters received intrathecal injections (10 microliters followed by 10 microliters saline flush) of either saline (n = 5), somatostatin (100 micrograms, n = 10), the somatostatin analog BIM 23003 (100 micrograms, n = 5), the somatostatin analog SMS 201-995 (100 micrograms, n = 5), the substance P analog [D-Pro2, D-Trp7,9] SP (10 micrograms, n = 10), or dynorphin A (1-17) (20 nmol, n = 8). These doses (somatostatin, substance P and dynorphin A) were selected based on previous studies in which they caused significant motor deficits. Effects on thermal cutaneous nociception, behavior, motor function and spinal cord histopathology were evaluated. All peptides caused severe neurotoxicity, evidenced by flaccid hind leg paralysis and lumbar spinal neuronal degeneration, which was accompanied by an inflammatory reaction in meninges and spinal gray matter. Histopathological changes had developed within 24 h after injection of somatostatin, substance P analog and dynorphin A, showing mild to severe neuronal degeneration and mild inflammatory responses in spinal cord and meninges. Significant antinociceptive effects, due to severe neurotoxic effects, were only observed following intrathecal injection of SMS 201-995 and the substance P analog. Potential neurotoxic mechanisms of the different peptides are discussed.

Animals↗

PubMed1990

Theiler's virus-induced demyelination in mice immunosuppressed with anti-IgM and in mice expressing the xid gene.

Intracerebral infection with Theiler's murine encephalomyelitis virus produces chronic immune-mediated demyelination in susceptible strains of mice. We examined the role of Ig in the pathogenesis of demyelination. In susceptible SJL/J mice (H-2s), suppression of B cell responses with IgG fraction of goat anti-mu (anti-mu IgG) from birth resulted in increased numbers and severity of demyelinating lesions in the spinal cord 35 days after infection. In contrast, treatment of resistant C57BL/10 (H-2b), C57BL/6 (H-2b), or B10.D2 (H-2d) mice with anti-mu IgG had no apparent effect since these mice did not develop demyelination or inflammation in the spinal cord following infection. Similar results were obtained with certain strains of B-cell deficient mice that exhibit the xid gene mutation. Male CBA/NJ (xid) showed increased meningeal inflammation and demyelination compared to male CBA/J mice. However, B6.CBAN, C3.CBAN, or C.CBAn mice showed no or minimal evidence of demyelination despite the presence of the xid mutation. In the SJL/J mouse, the majority of the humoral immune response to virus antigen was restricted to the IgG2b and IgM isotypes. These data indirectly support the hypothesis that immunoglobulins protect partially against development of virus-induced demyelination in susceptible but not resistant animals. In addition, the data argue strongly against the hypothesis that TMEV-induced demyelination is mediated predominantly by humoral autoimmune or humoral viral immune mechanisms.

Animals↗