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Biomedical subjects

M Velasco

Publications and source records attributed to M Velasco.

At least 73 records · Page 4Linked to original sources

Metoclopramide enhances labetalol-induced antihypertensive effect during handgrip in hypertensive patients.

The effects of metoclopramide, labetalol, and metoclopramide plus labetalol treatments on baseline cardiovascular parameters and isometric handgrip-induced changes were evaluated in 11 hypertensive subjects. Although all treatments were effective in reducing resting systolic (SBP) and diastolic (DBP) blood pressures, the combination of metoclopramide and labetalol appeared to provide a greater decrease (changes in SBP/DBP: 15/11 mm Hg, P < 0.05; from 149 +/- 4/95 +/- 4 mm Hg to 134 +/- 5/84 +/- 3 mm Hg) than did labetalol alone (changes in SBP/DBP: 10/9 mm Hg, P < 0.05; from 149 +/- 4/95 +/- 4 to 139 +/- 4/86 +/- 3 mm Hg). At 2 minutes, handgrip increased blood pressure on placebo (changes in SBP/DBP: 34/7 mm Hg, P < 0. 001). In the presence of metoclopramide and metoclopramide plus labetalol, however, handgrip induced lesser increases in blood pressure (changes in SBP/DBP: 23/7 mm Hg, P < 0.01, and 18/4 mm Hg, P < 0.01, for metoclopramide and metoclopramide plus labetalol treatments). We conclude that (1) metoclopramide lowers blood pressure in hypertensive patients; (2) metoclopramide attenuates blood pressure response to isometric handgrip; and (3) both compounds, labetalol and metoclopramide, seem to have a pharmacologic interaction concerning blood pressure decrease. A clinical significance is suggested for the metoclopramide effect.

Antihypertensive Agents↗

Attenuated metoclopramide-induced vascular hyperreactivity to cold stress in athletic subjects.

We have previously reported a metoclopramide-induced vascular hyperreactivity to the cold pressor test (CPT) in normotensive and hypertensive subjects. The present study was designed to determine whether the state of physical training influences the cardiovascular responses to the CPT in normotensive subjects under metoclopramide (MTC) treatment. In 20 untrained subjects and 32 athletes (football players and runners), the blood pressure and heart rate responses to the CPT were studied after a 30-minute infusion of MTC (7.5 microg/kg per minute) and two placebo periods, before and after MTC, with 5% glucose solution. Under placebo conditions, the CPT produced significant increases of systolic blood pressure (SBP) in the untrained subjects and the runners, but not in the football players (17.2, 17.8, and 6.5 mm Hg for untrained subjects, runners, and football players, respectively). The runners responded with a lesser increase in diastolic blood pressure (DBP) during the CPT than did the others (15.8, 17.9, and 18.2 mm Hg for runners, untrained subjects, and football players, respectively). In the presence of MTC, the CPT induced a larger increase in blood pressure (SBP/DBP) in the untrained subjects (21.4/24.1 mm Hg) than in the football players (10/18.7 mm Hg) and runners (18.7/13.9 mm Hg). MTC diminished the hyperreactivity responses to the CPT in the trained subjects (41 and 56% for football players and runners, respectively). Our conclusions are as follows: (1) Vascular responses to cold stress are attenuated in athletic subjects compared with untrained subjects. (2) The metoclopramide-induced vascular hyperreactivity, formerly reported for normotensive and hypertensive subjects, seems to be absent in trained subjects. (3) It is suggested that a probable dopaminergic system adaptation occurs during exercise.

Adult↗

Effect of fentanyl and naloxone on a thalamic induced painful response in intractable epileptic patients.

Acute high-frequency (60/s) high-intensity (2,100-2,300 microA) stimulation of the mesial, caudal and inferior portion of the centromedian thalamic region within or close to the parafascicular nucleus produced a sharp, intense, cramp-like painful response localized to the face and shoulder (medial stimulation) or arm and hand (lateral stimulation) contralateral to the stimulation site in 4 intractable epileptic patients in whom depth electrodes had been implanted as a part of a neuroaugmentive procedure for seizure control. This thalamic induced painful response was always accompanied by objective clinical signs (facial gesticulation and contraction of the corresponding muscles) during thalamic stimulation and significant increments in EEG, EKG and respiratory frequencies and EMG muscular tonus from 10 s before to 10 s after thalamic stimulation. Opioid agonists (fentanyl 5.0 microg/kg) and antagonists (naloxone 3.5 microg/kg) were administered to induce and regulate a state of neuroleptanalgesia used for the subcutaneous internalization of the chronic stimulation systems. Under these conditions, we observed that fentanyl greatly attenuated and naloxone increased the intensity of the painful response, as well as the EEG, somatic and vegetative parameters evaluating such a painful response. Differences were significant when one compares the changes in response to electrical stimulation in EEG, EKG, respiration and EMG after the administration of fentanyl (decrease p = 0.001) and naloxone (increase p = 0.01) compared to those obtained after the administration of saline or no drugs during baseline recordings. These data suggest that this thalamic induced painful response is mediated by inhibition or activation of the morphine receptors of the thalamic cells primarily related to the pain process.

Adult↗

Adenoid cystic carcinoma of the breast: mammographic appearance and pathologic correlation.

OBJECTIVE: The objective of our study was to describe the mammographic features of adenoid cystic carcinoma of the breast and to correlate mammography findings with histopathologic findings. CONCLUSION: Adenoid cystic carcinoma is a rare type of breast neoplasm that usually appears as a slowly enlarging nodule. In spite of its low incidence, recognition is important because early detection ensures good prognosis. On mammography, these tumors often appear as moderately circumscribed, lobulated nodules that are similar to other types of benign and malignant tumors. Therefore, cytologic and histologic evaluations are needed for accurate diagnosis.

Adult↗

Dopamine: pharmacologic and therapeutic aspects.

Dopamine is a biogenic amine synthesized in the hypothalamus, in the arcuate nucleus, the caudad, and various areas of the central and peripheral nervous system. It has been widely established that dopamine and its agonists play an important role in cardiovascular, renal, hormonal, and central nervous system regulation through stimulation of alpha and beta adrenergic and dopaminergic receptors. There are several agonists of dopamine-2 (DA 2 ) dopaminergic receptors, such as bromocriptine, pergolide, lisuride, quinpirole, and carmoxirole, which inhibit norepinephrine release and produce a decrease in arterial blood pressure; in some cases, bromocriptine and pergolide also reduce heart rate. From a therapeutic point of view, the above-mentioned agonists are used for treating Parkinson's disease, acting over DA 2 dopaminergic receptors of the nigrostriatal system. Bromocriptine and the other dopaminergic agonists mentioned act over DA 2 receptors of the tuberoinfundibular system, inhibiting prolactin release and decreasing hyperprolactinemia and tumor size. Among DA 1 receptor agonists, we can mention fenoldopam, piribedil, ibopamine, SKF 3893, and apomorphine (nonspecific). Activation of these receptors decreases peripheral resistance, inducing lowering of arterial blood pressure and increases in heart rate, sympathetic tone, and activity of the renin aldosterone system. Among DA 2 receptor antagonists, we can mention metoclopramide, domperidone, sulpiride, and haloperidol. From a therapeutic point of view, metoclopramide and domperidone are used in gastric motility disorders, and haloperidol is used in psychotic alterations. Antagonists of DA 1 receptors are SCH23390 and clozapine. Clozapine is used for treating schizophrenia.

Brain Ischemia↗

[Primary MALT-type lymphoma of the breast].

A 47 year old woman with a MALT lymphoma affecting the breast exclusively is reported. Complete response was achieved after CHOP chemotherapy but three years later a relapse was observed. Second-line chemotherapy (CNOP) and local radiotherapy were administered, and a second remission was obtained lasting for 1 year at last follow-up. A bibliographic search of MALT lymphomas of the breast showed that most such cases correspond to localized forms (stage I-II) and that from the radiologic point of view nodular lesions are almost the rule, although in the present case diffuse involvement was observed. MALT lymphomas of the breast tend to remain localized, and to relapse locally, and these facts appear as independent of the treatment applied (surgery, radiotherapy, chemotherapy or any combination).

Antineoplastic Combined Chemotherapy Protocols↗

[Prevalence and genotypes of hepatitis C virus in blood donors and in patients with chronic liver disease and hepatocarcinoma in a Chilean population].

BACKGROUND: The impact of hepatitis C virus infection in Chile has not been well established. AIM: To assess hepatitis C virus infection in normal Chileans and in patients with liver disease. SUBJECTS AND METHODS: Antibodies against hepatitis C virus were investigated in 21,000 blood donors, 133 patients with non alcoholic chronic liver disease and in 50 patients with hepatocarcinoma. Viral RNA was studied by polymerase chain reaction in all positive blood donors, in 51 patients with chronic liver disease and in all patients with hepatocarcinoma. Hepatitis C virus genotype was established using restriction fragment length polymorphism in 118 RNA positive samples. RESULTS: In blood donors, a 0.3% prevalence of positive antibodies was found. The figure for chronic liver disease was 53% and for hepatocarcinoma, 48%. Viral RNA was detected in 100% of patients with chronic liver disease and hepatocarcinoma and in 68% of blood donors with positive antibodies. Genotype 1b was identified in all infected patients with hepatocarcinoma, in 86% of patients with chronic liver disease and in 46% of blood donors. CONCLUSIONS: Hepatitis C virus infection is an important etiologic agent for chronic liver disease in Chile. The predominance of genotype 1b among patients with the most severe form of liver disease is in agreement with observations made abroad.

Adult↗

The prevalence of hypertension and the state of cardiovascular health in Venezuela and surrounding nations.

This review summarizes the prevalence of hypertension and the state of cardiovascular health in Venezuela and surrounding nations. First, the review discusses the fact that cardiovascular disease (CVD) is the main cause of death in Venezuela, Colombia, Brazil, and Trinidad and Tobago, accounting for 20% to 35% of all deaths. These data are similar to data from the developed world. Second, prevalence of hypertension in this region varies from 8% to 40% in the adult population, and, on average, 22% of the adult population of this region has an elevated blood pressure. However, prevalence rates vary considerably from country to country and within regions of the same country. Although mortality from hypertension as the main cause of death accounts for 1% to 4% of all deaths, mortality from stroke, mainly caused by hypertension, accounts for 10% of all deaths, indicating a failure in the treatment of hypertension. In most Latin American countries, the degree of awareness, treatment and control of hypertension is low, necessitating the establishment of programs to prevent, detect and effectively treat hypertension and decrease CVD risk factors.

Adolescent↗

Nuclear factor kappaB is required for the transcriptional control of type II NO synthase in regenerating liver.

A concerted activation of transcription factors involved in the transactivation of type II NO synthase (iNOS) gene occurred after partial hepatectomy (PH), resulting in the transient expression of iNOS. The corresponding mRNA and protein levels of iNOS reached a maximum at 4 h and 8 h post-PH respectively. This induction was preceded by an early and transient activation of nuclear factor kappaB (NF-kappaB). Analysis of the kappaB inhibitory (I) proteins showed an important role for IkappaBalpha in the process of NF-kappaB activation, whereas the contribution of IkappaBbeta was less evident. Interferon regulatory factor 1, which has been described as an important activator of iNOS expression, was up-regulated after PH but failed to bind to the corresponding DNA binding sequences of the iNOS promoter. The transcriptional control of iNOS after PH, was compared with the events associated with the hepatic expression of this enzyme in animals challenged with lipopolysaccharide, showing a differential pattern of transcription-factor activation and IkappaB degradation between both models. Transfection of hepatoma cell lines with iNOS promoter constructs, followed by stimulation with post-PH sera, revealed the requirement of NF-kappaB activation for iNOS expression. These data suggest that there is an important role for the restricted NF-kappaB activation in the temporal pattern of iNOS expression in regenerating liver.

Animals↗

Rapid Up-regulation of IkappaBbeta and abrogation of NF-kappaB activity in peritoneal macrophages stimulated with lipopolysaccharide.

Lipopolysaccharide (LPS) administration to mice elicited the activation of nuclear factor kappaB (NF-kappaB) in several tissues including liver and macrophages. Maximal activation was observed 1 h after treatment but declined at 3 and 6 h. The levels of IkappaBalpha and IkappaBbeta were analyzed during this period in an attempt to correlate NF-kappaB activity with IkappaB resynthesis. Degradation of IkappaBalpha was very rapid and was followed by recovery 1 h after LPS administration. IkappaBbeta degradation, which has been associated with persistent NF-kappaB activation, was complete at 1 h. However, a rapid recovery of IkappaBbeta in these tissues was observed at 3 h in parallel with the abrogation of NF-kappaB activity. Immunolocalization of newly synthesized IkappaBbeta by confocal microscopy revealed its preferential accumulation in the cytosol. Analysis of IkappaBbeta by Western blot using high resolution polyacrylamide gel electrophoresis showed the presence of two bands in cytosolic extracts of LPS-treated macrophages at 3 h, but only one band with the same mobility as the control was detected at 6 h. Moreover, treatment of extracts of resynthesized IkappaBbeta with alkaline phosphatase resulted in the accumulation of the protein of slightly higher electrophoretic mobility, indicating the prevalence of a rapid phosphorylation of the newly synthesized IkappaBbeta. At the mRNA level, up-regulation of IkappaBbeta was observed in macrophages stimulated for 1 h with LPS. When the effect of pro-inflammatory cytokines was investigated, tumor necrosis factor alpha, but not interleukin-1 or interferon-gamma, promoted an important degradation of IkappaBbeta followed by an increase in the mRNA at 1 h. These results suggest the existence of LPS- and tumor necrosis factor alpha- specific pathways involved in a rapid IkappaBbeta degradation and resynthesis and might explain the transient period of activation of NF-kappaB in these tissues upon stimulation with these factors. This rapid control of NF-kappaB function may contribute to the attenuation of the inflammatory response of these cells.

Acute-Phase Reaction↗

Macrophage triggering with cecropin A and melittin-derived peptides induces type II nitric oxide synthase expression.

Triggering of RAW 264.7 cells with a cecropin A-melittin hybrid peptide (CA(1-8)M(1-18)) promoted a rapid rise in the intracellular calcium concentration that was followed, after a lag period of 6 h, by nitric oxide synthesis through the expression of the cytokine-inducible form of nitric oxide synthase (type II NOS or iNOS). The maximal effect was obtained at peptide concentrations in the 2 to 5-microM range. Simultaneous incubation with the peptide and LPS abrogated the nitric oxide synthesis elicited after LPS treatment of the cells. CA(1-8)M(1-18) induced a rapid activation of nuclear factor kappaB as evidenced by the presence of p50/p65 heterodimers of the nuclear factor kappaB/c-Rel family in the nuclei of activated cells. This peptide also activated the reporter activity of cells transfected with a plasmid harboring a 1-kb fragment corresponding to the 5'-flanking region of the murine iNOS gene. CA(1-8)M(1-18) promoted apoptotic cell death at concentrations below 1 to 2 microM, whereas higher concentrations altered the plasma membrane integrity. These results suggest the involvement of multiple intracellular signaling pathways in the mechanism by which this peptide elicits macrophage triggering.

Animals↗

Absence of NO synthase type II expression in fetal liver from pregnant rats under septic shock conditions.

Treatment of rats at 21 days' gestation with lipopolysaccharide (LPS) induced type II NO synthase (iNOS) expression in maternal liver but completely failed to elicit this response in the corresponding fetal tissue. The impaired response of fetal liver cannot be attributed to alterations in the sensitivity of this organ to LPS or to proinflammatory cytokines involved in iNOS expression (tumor necrosis factor alpha [TNF-alpha], interferon gamma [IFN-gamma]), because cultured fetal and adult hepatocytes similarly responded to these factors. Measurement of TNF-alpha and IFN-gamma levels in maternal and fetal serum showed a restricted permeability of placenta to these cytokines, results that were in agreement with the absence of iNOS expression in fetal liver. Moreover, analysis of nuclear factor kappaB, which is required for iNOS expression, showed an activation in nuclear extracts from livers of mothers under septic shock conditions but not in the corresponding fetal livers. However, cultured fetal hepatocytes prepared from mothers in septic shock displayed an anomalous pattern of iNOS expression, including a decreased response to LPS as well as a shift in sensitivity to TNF-alpha. These hepatocytes from LPS-treated mothers showed significant expression of iNOS in the absence of added stimuli. These results suggest that there is a priming of the fetal hepatocytes from mothers with septic shock. The characterization of the factors causing this priming process might provide additional clues understanding the control of iNOS expression in liver.

Animals↗

Electrocortical and behavioral responses produced by acute electrical stimulation of the human centromedian thalamic nucleus.

Incremental, desynchronizing and spike-wave electrocortical responses and concomitant symptoms to acute electrical stimulation of the centromedian thalamic nucleus (CM) were studied in 12 patients with intractable complex partial and tonic-clonic generalized seizures. Low-frequency (6/s), 320-800 microA stimulation of the caudal-basal and central portions of CM elicited incremental recruiting and augmenting-like responses with a bilateral regional scalp distribution, with emphasis at the ipsilateral frontal (recruiting) and central (augmenting) regions, while ventral-basal CM stimulation elicited primary-like responses with a focal distribution at the ipsilateral parietal region. High-frequency (60/s), 320-800 microA stimulation of caudal-basal and central, but not ventral-basal CM, elicited EEG desynchronization and a slow negative shift of the EEG baseline with scalp distribution similar to that showed by recruiting- and augmenting-like responses. Neither incremental nor desynchronization EEG responses were accompanied by evident patient sensory or motor responses. Low-frequency (3/s), high-intensity (30 V = 2400 microA) combined stimulation of the right CM and left non-specific mesencephalic ascending pathways elicited a response similar to the typical absence attack with all EEG and clinical ingredients: S1, S2, P1 and W components of the individual spike-wave complex and generalized spike-wave discharges followed by sleep spindle EEG afterdischarges, accompanied by motionless stare, 3/s eye blinking, lip smacking and total failure to respond to visual stimuli in patients under a simple responding task.

Behavior↗

Dopaminergic influence on cardiovascular responses to exercise stress in hypertensive subjects.

Ten hypertensive subjects were studied at the Vargas Medical School in Caracas, Venezuela. They were submitted to submaximal treadmill exercises according to Bruce's protocol under treatment with dopaminergic drugs (metoclopramide, bromocriptine). Before and during submaximal exercises, metoclopramide caused a hypotensive effect accompanied by an increased heart rate, which was blocked by the administration of bromocriptine. We conclude that a probable dopaminergic modulatory influence takes place during exercise.

Blood Pressure↗

The cold pressor test: pharmacological and therapeutic aspects.

In this review article we discuss several aspects of the physiology, diagnosis, and pharmacology of the cold pressor test. The cold pressor test has been used for the diagnosis of cardiovascular reactivity in normotensive and hypertensive subjects. Some authors have stated that the cold pressor test will identify normotensive candidates at future risk of suffering from hypertensive disease. Interestingly, not all antihypertensive drugs block the exaggerated pressor response induced by cold stress. The most beneficial compounds belong to the alpha- and beta-blocker groups. Furthermore, several neurohormones such as norepinephrine, endothelins, prostaglandins, and angiotensin II have been reported to be released during cold exposure. The neurophysiology of cold pressor test indicates that after stress a great sympathetic discharge is induced at the spinal cord and terminal endings of the sympathetic nervous system. The release of norepinephrine is the cause of arteriolar vasoconstriction and elevation of blood pressure.

Antihypertensive Agents↗

Temporo-spacial correlations between cortical and subcortical EEG spike-wave complexes of the Idiopathic Lennox-Gastaut syndrome.

All-night EEG recordings of the interictal 2/s spike-wave complexes (SKW) from different cortical and subcortical regions were performed in 5 patients with atypical absences of the Idiopathic Lennox-Gastaut syndrome (ILGS), in whom multicontact depth electrodes were implanted in the centromedian thalamic region as a part of a neuroaugmentive procedure for seizure control. Since during slow wave sleep III cortical spike (S2) and subcortical negative spike (NSK) consisting of simple monophasic negative potentials appeared together with a ratio of almost 1:1 and with fixed temporal relations, it was possible to determine visually the differences in peak-to-peak intervals of S2 and NSK, as well as their amplitude distribution in different cortical and subcortical structures. It was found that the peak of subcortical NSK preceded by 35 ms that of cortical S2. In addition, subcortical NSK and cortical S2 potentials attained maximal amplitude at the mesencephalic-thalamic reticular and frontal cortical regions, respectively, from which amplitude of NSK and S2 decreased with distance to other subcortical and cortical regions. These data suggest that interictal 2/s SKW of the ILGS result from ascending reticular impulses impinging upon the frontal cortical neurons.

Brain↗