Biomedical subjects

M Rodriguez

Publications and source records attributed to M Rodriguez.

At least 523 records · Page 29Linked to original sources

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↗

PubMed1990

Correlation between phospholipid breakdown, intracellular calcium mobilization and enzyme secretion in rat pancreatic acini treated with Boc-[Nle28, Nle31]-CCK-7 and JMV180, two cholecystokinin analogues.

In this work in vitro pharmacological profiles of two analogues of the C-terminal heptapeptide of cholecystokinin (CCK) were evaluated. The analogue Boc-[Nle28, Nle31]-CCK-7, a stable analogue of CCK-8, has the same activity profile as CCK-8, and was found to be very potent in stimulating amylase secretion, phospholipid breakdown and [Ca2+]i mobilization from rat pancreatic acini. It can be used as a probe for studying CCK-actions. The CCK-analogue Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-2-phenylethylester, (JMV180), which stimulates amylase secretion without inhibition at supramaximal concentrations, has different effects on phospholipid hydrolysis and [Ca2+]i mobilization, compared to CCK-8 and Boc-[Nle28, Nle31]-CCK-7. Compound JMV180 was unable to significantly promote phospholipid breakdown, and was only 50%-60% as efficacious as Boc-[Nle28, Nle31]-CCK-7 in promoting [Ca2+]i mobilization. These findings suggest that low affinity CCK-receptors might be responsible for the supra-maximal inhibition of amylase secretion, and are correlated with phospholipid breakdown and maximal [Ca2+]i mobilization.

Amylases↗

PubMed1990

Insulin in the acute renal adaptation to dietary phosphate restriction in the rat.

Dietary phosphate restriction produces a rapid increase in tubular reabsorption of phosphate. To evaluate whether insulin is important in the acute renal adaptation following a low phosphate meal, four groups of conscious rats were studied by renal clearance methods, following a single meal by gavage. Group A received a normal (0.8%) phosphate meal, followed by saline infusion; Group B, a low (0.03%) phosphate meal, followed by saline infusion; Group C, a low phosphate meal, followed by infusion of somatostatin to suppress endogenous insulin secretion; and Group D, a low phosphate meal, followed by infusion of somatostatin plus insulin. Baseline plasma phosphate, insulin, glomerular filtration rate, and fractional excretion of phosphate were similar in all four groups. Following a low phosphate meal in Groups B, C, and D, there was a decrease in plasma phosphate, as compared with Group A. Whereas fractional excretion of phosphate decreased when plasma phosphate fell in Group B, administration of somatostatin (Group C) prevented the drop in fractional excretion of phosphate, despite a lower plasma phosphate. The addition of exogenous insulin (Group D) restored the antiphosphaturic effect of the low phosphate meal. These results suggest that insulin contributes to the acute decrease in phosphate excretion following a low phosphate meal.

Adaptation, Physiological↗

PubMed1990

Sodium and water excretion in nephrotic patients: effects of changes in renal haemodynamics.

1. Eight nephrotic patients were studied in order to evaluate the effects of acute changes in renal plasma flow and glomerular filtration rate on renal solute and water handling, in the absence of plasma volume expansion. 2. The subjects were studied first after the administration of captopril, a manoeuvre that increased renal plasma flow without a significant change in glomerular filtration rate, and a second time after receiving combined therapy with captopril and ibuprofen, a manoeuvre that decreased glomerular filtration rate without a significant change in renal plasma flow. 3. After captopril therapy, despite the increase in renal plasma flow, there was no significant change in proximal sodium reabsorption (as estimated from fractional lithium reabsorption), urine volume or urine osmolality. 4. The decrease in glomerular filtration rate observed after the administration of captopril plus ibuprofen was associated with decreases in fractional excretion of sodium and urine volume, and an increase in urine osmolality. The changes in these parameters of tubular function were proportionate to the changes in glomerular filtration rate. Fractional proximal sodium reabsorption increased substantially. 5. These observations suggest that, in the absence of plasma volume expansion, an increase in renal plasma flow does not increase sodium or water excretion by the nephrotic kidney. Moreover, during acute decreases in glomerular filtration rate, glomerulotubular balance appears to be disrupted, resulting in disproportionately high rates of proximal tubule sodium reabsorption.

Adult↗

PubMed1990

Inhibition of Theiler's virus-induced demyelination in vivo by tumor necrosis factor alpha.

Employing a murine model of multiple sclerosis which utilizes intracranial injection of Theiler's virus murine encephalomyelitis (TMEV) into SJL/J mice, we tested the potential role of tumor necrosis factor alpha (TNF-alpha) in ameliorating CNS demyelination. Infection with TMEV caused early grey matter inflammation (7 days post-infection) in the brain and spinal cord followed by chronic demyelination (35 days post-infection) in the spinal cord. Administration of recombinant human or mouse TNF-alpha starting 12 h prior to infection and then three times weekly had minimal effect on development of grey matter inflammation in the spinal cord. In contrast, TNF-alpha dramatically reduced demyelination present in spinal cord on days 14 and 35 after TMEV infection (P less than 0.01) when compared to controls. CNS virus titers of TMEV were not modified by TNF-alpha administration as measured on days 7, 14, and 35 following infection. In vivo administration of TNF-alpha inhibits TMEV-induced demyelination in susceptible SJL/J mice without affecting virus replication in the CNS.

Animals↗

PubMed1990

Persistent infection of a glioma cell line generates a Theiler's virus variant which fails to induce demyelinating disease in SJL/J mice.

Theiler's murine encephalomyelitis virus (TMEV) induces demyelinating disease which is associated with persistent virus infection of the central nervous system. To study the interaction between TMEV and host cells, we infected the G26-20 glioma cell line in vitro, and this resulted in a lytic infection in which most, but not all, cells were killed. Surviving cells divided and formed a viable monolayer in which a small proportion of cells displayed viral cytopathic effects. Levels of virus produced by these cultures over a 6 month period fluctuated between 6 and 8 log10 p.f.u./ml as measured by viral plaque assay. Similarly, the percentage of cells producing both viral antigen and viral RNA, as measured by a simultaneous immunoperoxidase/in situ hybridization technique, varied between 5 and 30%. Although persistently infected cultures were susceptible to challenge by both vesicular stomatitis virus and herpes simplex virus, they were resistant to infection by homologous viruses. Interferon activity was not identified. TMEV isolated from passage 12 produced smaller plaques than wild-type Daniels strain virus (wt-DAV) on L-2 cell monolayers. In contrast to demyelination induced in SJL/J mice after intracerebral inoculation with wt-DAV, mice infected with the small plaque variant virus failed to develop viral persistence or chronic demyelination. However, following immunosuppression by total body irradiation, SJL/J mice infected with the small plaque variant developed viral persistence but no demyelination. Characterization of the biochemical and molecular determinants of the variant will lead to a better understanding of determinants important in viral persistence.

Animals↗