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R Andrade

Publications and source records attributed to R Andrade.

At least 37 records · Page 2Linked to original sources
PubMed1999

Muscarinic receptors regulate two different calcium-dependent non-selective cation currents in rat prefrontal cortex.

Pyramidal neurons of layer V in rat prefrontal cortex display a prominent fast afterdepolarization (fADP) and a muscarinic-induced slow afterdepolarization (sADP). We have shown previously that both of these ADPs are produced by the activation of calcium-dependent non-selective cation currents. In the present report we examine whether they represent two distinct currents. In most pyramidal neurons recorded with caesium gluconate-based intracellular solution, a calcium spike is followed by a fast decaying inward aftercurrent (IfADP). The decay of IfADP is monoexponential with a time constant (t) of approximately 35 ms. Administration of carbachol (10-30 microm) increases the time constant of this decay by approximately 80% and induces the appearance of a much slower inward aftercurrent (IsADP). IfADP recorded in control conditions and in the presence of carbachol increases linearly with membrane hyperpolarization. In contrast, the carbachol-induced IsADP decreases with membrane hyperpolarization. When the sodium driving force across the cell membrane was reduced, IfADP was found to reverse at around -40 mV whereas IsADP remain inward over the same voltage range tested. Finally, bath administration of flufenamic acid (100 microm-1 mm) selectively blocks the carbachol-induced IsADP without a significant effect on the amplitude of IfADP. These differences in the electrical and pharmacological properties of IfADP and IsADP suggest that they were mediated by two distinct non-selective cation currents.

Animals↗
PubMed1998

Regulation of membrane excitability in the central nervous system by serotonin receptor subtypes.

Serotonin exerts multiple electrophysiological effects on neurons of the central nervous system. It is now known that this diversity reflects at least in part the existence of multiple serotonin receptor subtypes. An example of this occurs in the CA1 region of the hippocampus where as many as ten different serotonin receptor subtypes appear to be expressed. Recent electrophysiological studies have been able to assign specific functional roles to at least 5 of these receptors. These receptors are differentially expressed in the two different cell types present in this region, pyramidal cells and GABAergic interneurons, and mediate different effects on membrane excitability. This distribution is consistent with the different functional roles played by these cells in hippocampus. Thus the differential expression of serotonin receptor subtypes in the CA1 region allows serotonin to modify the function of hippocampal neuronal networks in a manner that is both selective and precise.

Animals↗
PubMed1998

The nuclear basket of the nuclear pore complex is part of a higher-order filamentous network that is related to chromatin.

We have achieved well-preserved nuclear basket structures in amphibian nuclear envelope spreads dried by the critical point method after tannic acid fixation, and we have compared these images with those obtained from conventional sections of amphibian oocyte nuclei. In cross sections, bundles of filaments from adjacent nuclear pore complexes were interconnected at regular distances, building up a higher-order network. Sometimes these bundles were observed to extend inward to amplified nucleoli located near the nuclear envelope. Furthermore, immunoelectron analysis indicated that DNA and histones were localized at these intranuclear filaments, suggesting a close relationship between chromatin and nuclear pore complexes. A model is proposed by which the intranuclear filaments associated with adjacent nuclear pore complexes create a regular higher-order network, which extends into the nucleus.

Animals↗
PubMed1998

Ionic mechanism of the slow afterdepolarization induced by muscarinic receptor activation in rat prefrontal cortex.

The mammalian prefrontal cortex receives a dense cholinergic innervation from subcortical regions. We previously have shown that cholinergic stimulation of layer V pyramidal neurons of the rat prefrontal cortex results in a depolarization and the appearance of a slow afterdepolarization (sADP). In the current report we examine the mechanism underlying the sADP with the use of sharp microelectrode and whole cell recording techniques in in vitro brain slices. The ability of acetylcholine (ACh) and carbachol to induce the appearance of an sADP in pyramidal cells of layer V of prefrontal cortex is antagonized in a surmountable manner by atropine and is mimicked by application of muscarine or oxotremorine. These results indicate that ACh acts on muscarinic receptors to induce the sADP. In many cell types afterpotentials are triggered by calcium influx into the cell. Therefore we examined the possibility that calcium influx might be the trigger for the generation of the sADP. Consistent with this possibility, buffering intracellular calcium reduced or abolished the sADP but had little effect on the direct muscarinic receptor-induced depolarization also seen in these cells. These results, coupled to the previous observation that calcium channel blockers inhibit the sADP, indicated that the sADP results from a rise in intracellular calcium secondary to calcium influx into the cell. The ionic basis for the current underlying the sADP (IsADP) was examined with the use of ion substitution experiments. The amplitude of IsADP was found to be reduced in a graded fashion by replacement of extracellular sodium with N-methyl-D-glucamine (NMDG). In contrast no clear evidence for the involvement of potassium or chloride channels in the generation of the sADP or IsADP could be found. This result indicated that IsADP is carried by sodium ions flowing into the cell. However, the dependence of IsADP on extracellular sodium was less pronounced than expected for a pure sodium current. We interpret these results to indicate that the sADP is most likely mediated by nonselective cation channels. Examination of the current underlying the sADP at different voltages indicated that this current was also voltage dependent, turning off with hyperpolarization. We conclude that the sADP elicited by muscarinic receptor activation in rat cortex is mediated predominantly by a calcium- and voltage-sensitive nonselective cation current. This current could represent an important mechanism through which ACh can regulate neuronal excitability in prefrontal cortex.

Acetylcholine↗
PubMed1998

Outcome of 337 intracranial aneurysms patients operated in a public hospital.

Many recent series of surgery for intracranial aneurysms have been based on experience of developed countries with great resources and a state of art health care. The purpose of the current study is to correlate the outcome of patients operated for intracranial aneurysms, reported from intensive high technology neurosurgical centers with the results of low technology, environment, where we practice. Between January 1986 and December 1996, 337 patients with intracranial aneurysms were operated on at the Servidores do Estado Hospital. We retrospectively reviewed the medical and radiologic records and compared the outcome of this group with other series derived from developed countries. The overall mortality of this series was 6.9%. Of the 313 good grades surgical patients, the mortality was 4.7% and the successful results were obtained in 88.8% individuals. We conclude that patients harboring intracranial aneurysms can be satisfactory handled in less developed nations, if a meticulous intraoperative technique is employed, even though sophisticated technology and equipment are not available.

Adolescent↗
PubMed1998

5-Hydroxytryptamine2 receptor facilitates GABAergic neurotransmission in rat hippocampus.

5-Hydroxytryptamine (5-HT; serotonin) administration enhances GABAergic synaptic activity recorded in pyramidal neurons of the CA1 region of hippocampus. Previous studies have attributed this effect to the activation of HT-5(3) receptors located on GABAergic interneurons. During unrelated experiments, we noticed that under our recording conditions, 5-HT can still increase GABAergic synaptic activity after the complete blockade of 5-HT3 receptors. This indicated the involvement of an additional 5-HT receptor subtype. Therefore, we reinvestigated the effects of 5-HT on GABAergic synaptic activity recorded in pyramidal cells of the CA1 region. The ability of 5-HT to increase GABAergic synaptic activity in the presence of 5-HT3 receptor blockade was mimicked by the selective 5-HT2 agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane and blocked by the selective 5-HT2 antagonist ketanserin. This indicated that the additional 5-HT receptor belongs to 5-HT2 receptor family. 5-HT2 receptor activation resulted in an increase in the frequency of spontaneous inhibitory postsynaptic currents as well as a shift in their amplitude distribution toward larger sizes. These effects were absent in the presence of tetrodotoxin. We interpret these results to indicate that 5-HT2 receptors activate GABAergic interneurons in the slice, leading to an increase in GABAergic synaptic activity onto pyramidal cells of the CA1 region.

Animals↗
PubMed1998

[Use of interferon in hepatic necrosis produced by paraquat and yellow phosphorus: experimental evaluation].

Paraquat and Yellow Phosphorus are toxic substances that ingested, accidentally or for suicidal intentions, produce a high morbimortality usually associated to the resultant hepatic necrosis. We performed an experimental study to evaluate the protector effect of Interferon in intoxicated rats with these two substances. Rats were divided in groups that only received the toxic (Paraquat or Yellow Phosphorus) and other groups that receive both the toxic and Interferon. The results showed a higher survival rate in the groups treated with Interferon, which was more than 20%. Also, the histopathologic findings showed a hepatic protector effect that was more than 90% in the rats that received Interferon. Clinically, Paraquat was more toxic than Yellow Phosphorus. These favorable experimental results obtained with the use of Interferon will need more research in the future to evaluate its usefulness in the treatment of these intoxications.

Animals↗
PubMed1998

Molecular characterization of human and rat RGS 9L, a novel splice variant enriched in dopamine target regions, and chromosomal localization of the RGS 9 gene.

A novel splice variant of RGS 9 was isolated from a rat hypothalamus, human retina, and a human kidney (Wilm's) tumor. This variant, termed RGS 9L, differs from the retinal form (termed RGS 9S) identified previously in that it contains a 211- (rat) or 205- (human) amino acid proline-rich domain on the carboxyl terminus. The pattern of RGS 9 mRNA splicing was tissue specific, with striatum, hypothalamus- and nucleus accumbens expressing RGS 9L, whereas retina and pineal expressed RGS 9S almost exclusively. This pattern of mRNA splicing seemed to be highly conserved between human and rodents, suggesting cell-specific differences in the function of these variants. Transient expression of RGS 9L augmented basal and beta-adrenergic receptor-stimulated adenylyl cyclase activity while suppressing dopamine D2 receptor-mediated inhibition. Furthermore, RGS 9L expression greatly accelerated the decay of dopamine D2 receptor-induced GIRK current. These results indicate RGS 9L inhibits heterotrimeric Gi function in vivo, probably by acting as a GTPase-activating protein. The human RGS 9 gene was localized to chromosome 17 q23-24 by radiation hybrid and fluorescent in situ hybridization analyses. The RGS 9 gene is within a previously defined locus for retinitis pigmentosa (RP 17), a disease that has been linked to genes in the rhodopsin/transducin/cGMP signaling pathway.

Alternative Splicing↗
PubMed1997

The clinical, neuroradiographic, and endocrinologic profile of patients with bilateral optic nerve hypoplasia.

PURPOSE: The purpose of the study was to expand on ophthalmologic and endocrinologic data and report the neuroimaging findings of 35 patients with bilateral optic nerve hypoplasia (BONH). METHODS: A retrospective chart review of 35 children with BONH was conducted. Data on visual acuity, refractive error, and presence of nystagmus and strabismus were collected. Twenty-six children underwent full-endocrinologic evaluation and magnetic resonance imaging or computed tomography scanning. RESULTS: The male:female ratio was 2:1. Ten percent of eyes had visual acuity of 20/60 or better, whereas 34% had no light perception. Eighty-six percent of eyes had acuity less than 20/200, and 80% of patients were legally blind. Most patients (86%) had nystagmus or strabismus or both. Forty-six percent had absence of the septum pellucidum and corpus callosum on neuroimaging. Twenty-seven percent of patients had endocrinologic abnormalities, with growth hormone deficiency being the most common. Panhypopituitarism occurred in 11.5% of children. CONCLUSIONS: Although the visual prognosis of children with BONH generally is poor, 10% of such patients have excellent acuity. In contrast to previous reports, endocrine abnormalities were seen in only one quarter of patients, and the full-blown deMorsier syndrome (septo-optic dysplasia with panhypopituitarism) was seen in only 11.5% of patients with BONH.

Abnormalities, Multiple↗
PubMed1997

Calcium-activated cation nonselective current contributes to the fast afterdepolarization in rat prefrontal cortex neurons.

Pyramidal cells of layer V in rat prefrontal cortex display a prominent fast afterdepolarization (fADP) following an action potential. This ADP is blocked by replacing extracellular calcium with magnesium, by the application of the calcium-channel blocker cadmium, and by buffering intracellular calcium at near physiological levels. Thus this fast ADP appears mediated by a calcium-activated current. A prominent ADP is also observed following a calcium spike recorded in the presence of tetrodotoxin. The current underlying this ADP was recorded using a hybrid current-voltage protocol. A strong ADP could be observed in the presence of potassium channel blockers as well as at ECl. Furthermore, the current underlying the ADP increased with hyperpolarization in the subthreshold range and displayed an extrapolated reversal potential near +30 mV. Reducing the ratio of extracellular to intracellular sodium inhibited the current underlying the ADP and caused a hyperpolarizing shift in its reversal potential. We conclude that these cells express a calcium-activated cation nonselective current whose activation contributes to the generation of the fADP. This current could play an important role in determining the firing properties of pyramidal cells in cortex.

Action Potentials↗
PubMed1997

Acute renal failure in open heart surgery.

A case-control study was performed to establish possible risk factors for acute renal failure (ARF) and mortality in patients undergoing cardiac surgery. A consecutive series of 704 patients were included in the study. A randomized sample of 255 patients was taken to analyze risk factors for ARF and mortality. Incidence of acute renal failure was 3.8% (27/704). Low cardiac output (LCO) was observed in all patients who developed ARF and in 72/255 without ARF (p < 0.0005). When LCO was isolated, no difference was found between groups. Association to prolonged perfusion time and sepsis increased the probability of developing ARF: 5/27 versus 0/255, p < 0.001; and 9/27 versus 0/255, p < 0.001, respectively. Overall mortality was 7.2% (51/704). Significant difference was found between ARF (55.6%, 15/27) and non-ARF patients (5.4%, 36/704), p < 0.005. Neither age nor sex was associated to outcome. Nonsurvivor patients were more oliguric (11/15 vs. 0/12, p < 0.005), required dialysis more frequently (7/15 vs. 0/12, p < 0.005), and were complicated with sepsis more often (9/15 vs. 0/12, p < 0.005), compared to survivors. We concluded that ARF was an uncommon complication in this group of patients, but mortality rate was dramatically high. This study identified LCO associated to prolonged perfusion time and sepsis as risk factors for ARF. Severity of ARF (oliguric forms and dialysis requirement) and postoperative events (sepsis) were associated with mortality.

Acute Kidney Injury↗
PubMed1997

[Intestinal perforation caused by chicken bone mimicking perforated colonic diverticulitis].

Intestinal Perforation can occur in less than 1% of cases of ingestion of foreign bodies. Clinical suspicion is very important to make the diagnosis since many medical conditions can simulate this pathology. We present a case of a 63 years old man who swallowed a chicken bone that perforated the sigmoid colon and produced a clinical picture mimicking a perforated colonic diverticulitis. At surgery, the bone was removed without any evidence of abscess formation. A Hartmann procedure was performed and we reanastomosed it 3 month later. The patient followed an uneventful postoperative course. We demonstrated that early detection and opportune surgical treatment decrease the risk of developing complications such as abscess formation, intestinal fistula or obstruction.

Animals↗
PubMed1996

[Retrospective multicenter study of the efficacy of interferon alpha in chronic hepatitis C].

BACKGROUND: Until very recently, interferon (INF) in Spain was authorized in chronic hepatitis C (C-HCV) at a dosis of 3 megaunits (mu) for 6 months. Nonetheless, the rate of maintained complete response is lower than that obtained with more prolonged treatments. The first aim of this study was to retrospectively know the effectiveness of alpha INF in patients treated for 6 or 12 months with a dosis of 3 or 5-6 MU. The second was to analyze the characteristics of the patients who achieved a maintained complete response. PATIENTS AND METHODS: Patients with C-HCV treated in 9 hospitals in Andalucía, Spain who fulfilled the following conditions were retrospectively analyzed: liver biopsy prior to treatment, positive test for anti HCV and a follow up of at least 6 months after alpha INF treatment. A total of 344 patients were studied: 267 treated with alpha INF-2b, 51 with alpha INF-2a and 26 with lymphoblastoid INF. One hundred ninety-five patients were treated for 6 months and 149 for 12 months. RESULTS: Seventy-seven (22%) of the patients presented maintained complete response, 170 (50%) did not respond and 97 (28%) relapsed. On comparing the three types of interferon used over 6 months, no significant differences were observed. Neither were differences found on comparing the dosis of 3 mu versus 5 or 6 mu. On analyzing the treatments of 6 and 12 months, the following was observed, respectively: maintained complete response 15% vs 32%, relapse 29% vs 30% and non responders 57% vs 38% (p < 0.001). Multivariate analysis demonstrated that the patients who responded the best to INF were those who presented the following characteristics: female sex, age under 40 years last, history of transfusion or IVDA, basal GPT level higher than 145 IU/I, GGT less than 55 IU/I, less evolved histologic lesions and duration of treatment over 12 months. CONCLUSIONS: Of the different treatments analyzed with alpha interferon in chronic hepatitis C, the best was found to be that with 3 mu during 12 months.

Adult↗
PubMed1996

Muscarinic activation of a voltage-dependent cation nonselective current in rat association cortex.

The ionic mechanism underlying the acetylcholine-induced depolarization of layer V pyramidal neurons of rat prefrontal cortex was examined using whole-cell recording in in vitro rat brain slices. Consistent with previous results, pressure application of acetylcholine to layer V pyramidal neurons elicited a strong depolarization. Pharmacological analysis of this response indicated that it was mediated by the stimulation of muscarinic receptors as it was mimicked by muscarinic agonists, but not by nicotine, and was blocked by atropine. The inward current responsible for the depolarization resulted from the activation of a voltage-dependent, cation nonselective current. Thus, the amplitude of the current was critically dependent on extracellular sodium concentration but not on extracellular potassium or chloride concentration. Examination of the I-V relationship for the muscarinic current using voltage clamp revealed that the current reversed near -15 mV and exhibited a strong voltage dependence, turning off rapidly in the subthreshold range. The voltage dependence of the current led to the appearance of a current associated with a conductance decrease when examined using steady-state voltage- or current-clamp measurements. This might have led to earlier misidentification of this response as mediated by a decrease in potassium conductance. These results question the traditional interpretation that muscarinic depolarization in cortex is mediated by a decrease in potassium conductance. They indicate that the fundamental mechanism responsible for muscarinic depolarization in prefrontal cortex involves the activation of a voltage-dependent, cation nonselective current. This current might represent a previously unsuspected mechanism capable of mediating slow depolarization in the central nervous system.

Acetylcholine↗
PubMed1996

5-Hydroxytryptamine4 receptors reduce afterhyperpolarization in hippocampus by inhibiting calcium-induced calcium release.

Serotonin acting on 5-hydroxytryptamine4 receptors increases membrane excitability in CA1 hippocampal pyramidal cells by reducing the slow calcium-activated afterhyperpolarization. This effect is mediated through an increase in cAMP and activation of protein kinase A, although subsequent steps have not been elucidated. We now report that a significant portion of the calcium responsible for the generation of the afterhyperpolarization originates from the release of intracellular calcium through a calcium-induced calcium-release mechanism. Thus, the afterhyperpolarization is enhanced by caffeine, whereas it is inhibited by dantrolene and ruthenium red, two blockers of calcium-induced calcium release. The afterhyperpolarization is also inhibited by thapsigargin, which depletes intracellular calcium stores. These observations raised the possibility that serotonin might reduce the afterhyperpolarization by regulating calcium-induced calcium release. Consistent with this possibility, administration of calcium-induced calcium-release blockers, as well as of thapsigargin, occluded the ability of serotonin to inhibit the afterhyperpolarization. Similarly, administration of caffeine, which enhances the contribution of calcium-induced calcium release to the afterhyperpolarization, enhanced the effect of serotonin. These results indicate that serotonin inhibits the afterhyperpolarization in the CA1 region of hippocampus by reducing the ability of extracellular calcium to trigger calcium release from intracellular stores. As such, they identify a physiological role for the calcium-induced calcium release in hippocampus and provide evidence for its regulation by G protein-coupled receptors and, more specifically, 5-hydroxytryptamine4 receptors.

Action Potentials↗
PubMed1995

Cyclic AMP and protein kinase A mediate 5-hydroxytryptamine type 4 receptor regulation of calcium-activated potassium current in adult hippocampal neurons.

In the CA1 region of the hippocampus, activation of serotonin receptors of the 5-hydroxytryptamine (5-HT)4 subtype increases membrane excitability by reducing the calcium-activated potassium current responsible for the slow afterhyperpolarization observed in these cells. In the present study, the signaling mechanism by which 5-HT4 receptors reduce the afterhyperpolarization in the CA1 region was examined using intracellular recording in brain slices. Administration of the membrane-permeable cAMP analog 8-bromo-cAMP mimicked the effect of serotonin on the afterhyperpolarization, whereas administration of the protein kinase inhibitor staurosporine inhibited the effects of serotonin. These observations suggested a role for protein kinase A in this response. This was confirmed by intracellular injection of the selective protein kinase A inhibitor Rp-adenosine 3',5'-cyclic monophosphothioate ((Rp)-cAMPS), which noncompetitively inhibited the ability of serotonin to reduce the after-hyperpolarization. Additional evidence for the involvement of cAMP in the signaling by 5-HT4 receptors was obtained using the general phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. When this compound was bath administered at concentrations sufficient to enhance a known cAMP-mediated response, a significant enhancement of the ability of 5-HT4 receptors to reduce the afterhyperpolarization was observed. Together, these results indicate that serotonin reduces the afterhyperpolarization in the CA1 region by acting on 5-HT4 receptors that increase intracellular cAMP levels and activate protein kinase A.

Alkaloids↗