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Biomedical subjects

M Ibarra

Publications and source records attributed to M Ibarra.

At least 37 records · Page 2Linked to original sources

HPV prevalence among Mexican women with neoplastic and normal cervixes.

Genital human papillomavirus (HPV) infection is causally linked to cervical cancer, yet little is known regarding HPV prevalence in cancerous and normal women in Mexico, a country with a high cervical cancer incidence. We studied 185 Mexican women among the patients attending gynecological outpatient clinics in four hospitals in Mexico City. Each woman had a Pap smear, a colposcopy, and, when necessary, a biopsy. HPVs were identified by a consensus-primer-based polymerase chain reaction (PCR) assay. HPV was detected in 87% of 69 cancers, 83% of 24 high-grade squamous intraepithelial lesions (HGSILs), 33% of 21 low-grade squamous intraepithelial lesions (LGSILs), and 17% of 71 normals. Twenty-one of the 32 HPV types tested were detected at least once. The ratio of high-risk:low-risk types was 87:6 in HGSILs and cancers, compared to 11:8 for LGSILs and normals. In invasive cancers, HPV types found at the highest frequency were, in descending order: HPV-16, -18, and -45, followed by -39, -59, and -58 with the same frequency. HPV-16 and related types were present in 52% of the cancer cases, as well as in 79% of HGSILs, and HPV-18 and related types were present in 36% of the cancers but in only 12.5% of the HGSILs. HPV-16 was predominant in squamous carcinomas, and HPV-18 and related types were predominant in adenosquamous carcinoma. Both biopsies and scrapes were tested for HPVs in 63 women, all of them with cervical neoplasia. Identical HPV results were obtained in 89% of the samples, but additional types were often identified in scrapes. HPV prevalence and type distribution in cervical cancer in Mexico was similar to the reported worldwide, as well as in other Latin American countries.

Carcinoma, Adenosquamous↗

Evidence for an age-dependent functional expression of alpha 1D-adrenoceptors in the rat vasculature.

The role of the alpha 1-adrenoceptor subtypes, and their possible change with maturation, in alpha 1-adrenoceptor-induced pressor responses in the rat has not been established. Thus, the effects of the alpha 1D-, alpha 1A/1D- and alpha 1B/1D-adrenoceptor antagonists, BMY 7378 (8-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl) 8-azaspiro (4.5) decane-7,9-dione 2HCl), 5-methyl-urapidil and chloroethylclonidine, respectively, on the pressor responses induced by phenylephrine in 1- and 5-month-old pithed rats were investigated. The pressor responses induced by phenylephrine were competitively antagonized by both BMY 7378 and chloroethylclonidine in 5-month-old, but not in young immature animals; in marked contrast, 5-methylurapidil antagonized with similar potency the phenylephrine-induced pressor responses in animals of both ages. The present pharmacological data suggest that functional expression of alpha 1D-adrenoceptors in the rat resistance vessels increases with age; alpha 1A-, but not alpha 1B- or alpha 1D-adrenoceptors, seem to predominate in immature animals. These findings represent the first evidence that age-related changes in functional alpha 1-adrenoceptor subtypes occur in the systemic vasculature in vivo.

Adrenergic alpha-Antagonists↗

Alpha 1D- and alpha 1A-adrenoceptors mediate contraction in rat renal artery.

To investigate the alpha 1-adrenoceptor subtype(s) mediating contraction in rat renal artery, we have compared the effect of the alpha 1-adrenoceptor antagonists, 5-methylurapidil, BMY 7378 (8-(2-(4-(2-methoxyphenyl)-1-piperazinyl) ethyl) 8-azaspiro (4.5) decane-7,9-dione 2HCl) and chloroethylclonidine on functional responses to noradrenaline. A clear blockade by chloroethylclonidine (10(-4) M) of noradrenaline-induced contraction was observed and, along with this effect. pKB values of 9.12 and 8.40 for BMY 7378 and 9.75 and 10.06 for 5-methylurapidil were obtained, indicating that the renal artery expresses the alpha 1D-adrenoceptor subtype as the one involved in contraction and not only the alpha 1A subtype as has been reported.

Animals↗

Effects of nimodipine on learning in normotensive and spontaneously hypertensive rats.

It is well known that the calcium channel blocker, nimodipine, has beneficial effects on learning in either aged or hypertensive animals and humans. However, no attempts have been made to investigate if nimodipine can reverse the synergistic deleterious effects of aging and hypertension in the same subject. Therefore, this study investigated the effects of stable infusions of nimodipine in the autoshaping learning task using middle-aged normotensive (WKY) and hypertensive (SHR) rats. WKY and SHR of 12 months of age were implanted with osmotic minipumps releasing either vehicle or nimodipine (0.4 mg/kg/day). After 3 weeks of treatment, the animals received autoshaping training sessions during 4 consecutive days. The WKY animals treated with nimodipine exhibited the highest levels of learning during the last session, the rank order being WKY-nimodipine > SHR-nimodipine > WKY-vehicle > SHR-vehicle. These results confirm that nimodipine can reverse the impairing effects of either aging or hypertension on learning; the presence of both conditions, however, might produce more severe dysfunctional changes that cannot be totally reversed by nimodipine.

Aging↗

Alpha 1-adrenoceptors mediating contraction in arteries of normotensive and spontaneously hypertensive rats are of the alpha 1D or alpha 1A subtypes.

Alpha 1-Adrenoceptor subtypes mediating contraction in carotid, aorta, mesenteric and caudal arteries from both Wistar Kyoto (WKY) normotensive and spontaneously hypertensive (SHR) rats were investigated by using the alpha 1A-adrenoceptor agonist methoxamine and antagonized with selective, competitive antagonists WB-4101, 5-methyl urapidil or BMY 7378 (8-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-8-azaspiro(4,5)decane -7,9-dione dihydrochloride). Isometric tension changes were recorded after methoxamine addition to the arterial rings, and the effects of the antagonists determined. All the antagonists shifted to the right the concentration-response curve to methoxamine. pA2 values indicate that all arteries but caudal express the alpha 1D-adrenoceptor subtype, since BMY 7378 values were high in these arteries. Due to the high pA2 values for 5-methyl urapidil and WB-4101 and the low values for BMY 7378 we conclude that the tail artery expresses the alpha 1A and not the alpha 1B subtype. No differences were found between both strains of rats, suggesting that hypertension does not modify the alpha 1-adrenoceptors in conductance arteries.

Adrenergic alpha-1 Receptor Agonists↗

Immediate and long-term results of balloon mitral commissurotomy for rheumatic mitral stenosis: comparison between Inoue and double-balloon techniques.

We examined the immediate results and 2-year follow-up of percutaneous transvenous mitral commissurotomy (PTMC) using the Inoue balloon (IB) and double-balloon (DB) techniques. Short-term comparisons have been described, but long-term comparisons have not been available. PTMC was performed in 208 adult patients with symptomatic mitral stenosis (MS) and mitral valve area (MVA) of 0.94 +/- 0.2 cm2, by use of the IB in 157 (73.4%) and the DB technique in 56 (26.3%). Procedures were performed successfully and without complications in 198 (93%) cases. Adequate mitral dilatation (MVA = 1.6 cm2) without significant regurgitation was obtained in 179 (86%) of 192 patients. The final MVA was 2.0 +/- 0.43 cm2 after IB and 2.06 +/- 0.51 cm2 after DB (not significant). Technical difficulties and complications were more frequent with DB (16% vs 3.8%; p<0.001). Severe mitral regurgitation (grade III to IV) occurred in 4.6% of IB and 4.1% of DB (not significant), whereas grade 1 mitral regurgitation was greater with IB (21% vs 10.2%; p=0.01). A total of 172 patients were monitored an average of 23.8 +/- 10.6 months, with 83% in New York Heart Association functional class 1, echocardiographic MVA of 1.84 +/- 0.44 cm2, and restenosis rate of 22% at 36 months. PTMC is a safe, effective treatment for symptomatic MS. Results of both IB and DB techniques are similar, but the IB is simpler and safer, Long-term clinical improvement is maintained, although the restenosis rate seems to be progressive and related to inadequate immediate results.

Adolescent↗

Effects of aging and hypertension on learning, memory, and activity in rats.

A comparison between behavioral alterations induced by hypertension and aging was made in spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY) of different ages (3-24 months old), trained to perform autoshaping learning and activity tasks. Food-deprived rats received autoshaping training sessions during 6 days; the animals were retrained 1 month later. Two weeks after autoshaping training, the animals were evaluated in the spontaneous activity task during 2 consecutive days. The results show an age-related decrease in learning, memory, and spontaneous activity. Independently of the age group compared, WKY, though showing lower activity, learned and retrieved more than SHR. Accordingly, the reductions in learning and memory were correlated with both aging and hypertension. The combined influence of these two factors had synergistic detrimental effects on cognitive functions.

Aging↗

The 5-HT2 receptor antagonist, pelanserin, inhibits alpha 1-adrenoceptor-mediated vasoconstriction in vitro.

The antagonism by pelanserin (2,4(1H,3H)-quinazolinedione,3-[3-(4-phenyl-1- piperazinyl)-propyl]-HCl), a potent 5-HT2 receptor antagonist, of alpha 1-adrenoceptor-mediated contractions of endothelium-denuded carotid, aorta, mesenteric and caudal arteries of both normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats was investigated. The selective alpha 1-adrenoceptor agonist methoxamine elicited concentration-dependent contractions in all four arterial rings, an effect which was competitively antagonized by pelanserin. pA2 values for pelanserin were in the 7.67-8.11 range when evaluated against the alpha 1-adrenoceptor agonist in arteries from normotensive or hypertensive rats. These data support the conclusion that pelanserin displays alpha 1-adrenoceptor blocking properties. The ability of the 5-HT2 receptor antagonist pelanserin to additionally block alpha 1-adrenoceptor-mediated constriction in different vessels of WKY and SHR may potentially contribute to its blood pressure lowering effects.

Animals↗

A comparative study of the effects of some 5-HT1A receptor agonists on the blood pressure of pithed rats.

The intention of this study was to supply additional information about direct effects of the 5-HT1A receptor agonist indorenate on the arterial blood pressure. The effects of indorenate were compared with those of buspirone and ipsapirone (all selective 5-HT1A agonists) on the blood pressure of pithed rats. These compounds increased the blood pressure in a dose-dependent fashion. The effects of either ipsapirone or buspirone were clearly inhibited with 100 micrograms/kg of prazosin (selective alpha 1-adrenoceptor antagonist), whereas 1 mg/kg of this blocker elicited only a mild inhibition of the pressor effect of indorenate. Pindolol (100 micrograms/kg; a beta-adrenoceptor and 5-HT1 receptor blocker) was unable to modify the effects of all the 5-HT1A agonists tested. In addition, the 5-HT2 receptor and weak alpha 1-adrenoceptor blocker ketanserin (10-100 micrograms/kg) antagonized the pressor effect of indorenate. Nevertheless, only a mild inhibition was observed in the case of both ipsapirone and buspirone. On the other hand, the latter drugs diminished the blood pressure of pithed rats intravenously infused with norepinephrine, but indorenate was inactive. However, in rats infused with quipazine, all the 5-HT1A agonists failed to reduce blood pressure. These results indicate that buspirone and ipsapirone behaved as partial alpha 1-adrenoceptor agonists. Furthermore, the results show that indorenate-elicited pressor effects are probably due to stimulation of 5-HT2 receptors. Thus, unlike ipsapirone and buspirone, indorenate did not show conclusively activity related with alpha 1-adrenoceptors.

5-Methoxytryptamine↗

Changes in endothelium-dependent vascular responses associated with spontaneous hypertension and age in rats.

The aim of this study was to investigate if the endothelium-dependent relaxation and the inhibitory effect of endothelium against vasoconstrictor stimuli are reduced by aging and hypertension in rat aorta. Both relaxation and isometric contraction of intact and denuded aortic rings from spontaneously hypertensive rats (SHR) of 7-9, 12-18, 28-36 and more than 70 weeks old and from age-matched Wistar-Kyoto rats (WKY) were measured in parallel. An age-related decrease of endothelium-dependent relaxation to acetylcholine was found, which was greater in arteries from SHR (p < 0.05). Indomethacin normalized the endothelium-dependent relaxations in aortic rings from either old or hypertensive rats. Relaxations elicited by nitroglycerin were slightly enhanced with age in both WKY and SHR (p < 0.05). Moreover, endothelium removal increased responsiveness to indanidine and to 5-hydroxytryptamine (5-HT). Endothelium-dependent inhibition on the contraction decreased with aging (to a greater extent in SHR). These results indicate that aging and hypertension are associated with a decrease in the endothelium-dependent responses. Endothelium-dependent relaxations of aortae from old normotensive and hypertensive rats were impaired by the production of a cyclooxygenase-derived contractile factor. However, the higher response to nitroglycerin suggests a lesser production of endogenous nitric oxide by endothelial cells.

Aging↗

Control of rapid ventricular response by radiofrequency catheter modification of the atrioventricular node in patients with medically refractory atrial fibrillation.

BACKGROUND: Pharmacological control of rapid ventricular response to atrial fibrillation may be difficult in some patients. Alternative treatments, including curative surgery or atrioventricular (AV) node ablation with pacemaker implantation, have significant potential morbidity. In view of evidence that dual AV nodal physiology may exist in a significant percentage of the population, even in those without AV nodal reentrant tachycardia, we postulated that control of ventricular response might be achieved by radiofrequency (RF) catheter ablation in the region of the AV nodal slow pathway with its short refractory period. METHODS AND RESULTS: Ten patients underwent attempted AV node modification using a 4-mm-tipped electrode catheter positioned in the middle or posterior septum, between the His bundle and coronary sinus ostium on the tricuspid valve annulus. RF energy was applied at 16 to 30 W for up to 60 seconds, until average ventricular response fell below 100 beats per minute. Reduction of maximal ventricular response below 120 beats per minute was confirmed with atropine 1 mg IV. If required, additional ablations were performed progressively more posteriorly up to the coronary sinus ostium. Patients with successful AV node modification were discharged off AV node-blocking drugs and followed in the clinic at regular intervals. Twenty-four-hour ambulatory ECG recordings and/or treadmill stress tests were obtained before and after ablation for statistical comparison of maximum ventricular rate. Resting average ventricular rate was determined during electrophysiology study before and after ablation. In 7 of 10 patients (70%), maximum ventricular rate was reduced from a mean of 164 +/- 12 to 123 +/- 16 beats per minute (P < .01) and average ventricular rate from a mean of 128 +/- 11 to 83 +/- 10 beats per minute after ablation. Mean minimum ventricular rate was 54 +/- 11 beats per minute after ablation. These 7 patients have remained symptom free from rapid ventricular response for a mean of 14 +/- 8 months (range, 1 to 22). Three remain off all AV node-blocking drugs, 3 remain on digoxin alone, which was previously ineffective, and 1 remains on a beta-blocker for angina. In the 3 patients who did not respond to AV node modification, complete AV node ablation and permanent pacemaker implantation was performed in 2 and DC cardioversion after amiodarone loading was performed in 1. CONCLUSIONS: RF catheter modification of AV node conduction is effective in controlling rapid ventricular response to atrial fibrillation in a significant percentage of medically refractory patients. A possible mechanism of RF modification of AV node conduction is AV nodal slow pathway ablation. Large-scale clinical trials will be needed to determine the overall efficacy and safety of this technique.

Adult↗

Pharmacological evidence for interactions between 5-HT1A receptor agonists and subtypes of alpha 1-adrenoceptors on rabbit aorta.

This study was designed to determine if alpha 1-adrenoceptors are involved in the vascular responses to 5-HT1A receptor agonists. Buspirone (3.1 x 10(-7)-3.1 x 10(-5) M) and 8-hydroxy-2(di-N-propylamino)tetralin (8-OH-DPAT; 3.1 x 10(-6)-10(-4) M) elicited contractions of rabbit aorta rings which were blocked by prazosin (10(-9)-5.6 x 10(-9) M), but which were unaffected by reserpine pretreatment (1 mg/kg i.p.). 5-Methylurapidil (10(-7) and 10(-6) M) blocked contractions elicited by 8-OH-DPAT and by buspirone, whereas chloroethylchonidine (10(-5) and 10(-4) M) inhibited only the effect of buspirone. In addition, these 5-HT1A receptor agonists relaxed arteries precontracted with alpha-adrenoceptor agonists in a similar range of concentrations in which they elicited contraction. Moreover, 8-OH-DPAT and buspirone protected the alpha-adrenoceptors from the irreversible blockade provoked by phenoxybenzamine (10(-7) M), as judged by the norepinephrine contraction and stimulated phosphatidylinositol labeling. According to these results the contractile and relaxant effects elicited by 5-HT1A receptor agonists are a consequence of a direct interaction with alpha 1-adrenoceptors. The contraction elicited by 8-OH-DPAT may be mediated by alpha 1A-adrenoceptors, whereas both alpha 1A- and alpha 1B-adrenoceptors may mediate the effect of buspirone in rabbit aorta.

Adrenergic alpha-Agonists↗

Vascular effects of ipsapirone are related with subtypes of alpha 1-adrenergic receptors.

The aim of this study was to provide further evidence about the participation of alpha 1-adrenoceptors in the vascular responses elicited by ipsapirone. This 5-HT1A agonist displayed vasodilator activity only when aortic rings were precontracted by alpha-adrenergic compounds. The relaxant effect was particularly evident when rings were precontracted with methoxamine (selective alpha 1A-adrenergic agonist). On the other hand, ipsapirone but not chloroethylclonidine (selective alpha 1B-adrenergic antagonist), clearly displaced norepinephrine and methoxamine vasocontractile concentration-response curves to the right. Finally, ipsapirone protected the alpha-adrenoceptors form the irreversible blockade provoked by phenoxybenzamine, as judged by the norepinephrine contraction and stimulated phosphatidylinositil labeling. Accordingly the relaxant effect elicited by ipsapirone in aortic rings precontracted with alpha-adrenergic agonists and the protective action against blockade by phenoxybenzamine shown by this agent are proof of its ability to occupy alpha 1-adrenoceptors. Specifically, alpha 1A-adrenergic receptors seem to be involved in ipsapirone vascular effects, since this agent selectively relaxed aortic preparation precontracted with methoxamine and unlike chloroethylclonidine, clearly inhibited the contractile effect of this agonist. In summary, the present findings can be explained by accepting that ipsapirone may act as an antagonist at alpha 1A-adrenoceptors.

Adrenergic alpha-1 Receptor Antagonists↗

Alpha 1-adrenoceptor blocking properties of spiroxatrine in rat aorta.

This preliminary study has analyzed the potential ability of the 5-HT1A ligand spiroxatrine to interact with vascular alpha 1-adrenoceptors. Norepinephrine and the selective alpha 1-adrenoceptor agonist, methoxamine, elicited concentration-dependent contractions of rat aortic rings. In contrast, (+/-)-spiroxatrine (from 10(-8) to 3.1X10(-7) M) was devoid of any effect on vascular tone per se, but shifted the concentration-response curves of norepinephrine and methoxamine to the right in a concentration-dependent manner with pA2 values of 8.48 +/- 0.22 and 8.93 +/- 0.33, respectively. Endothelium removal did not significantly affect the above pA2 values of (+/-)-spiroxatrine. These data, taken in concert, support the contention that (+/-)-spiroxatrine displays alpha 1-adrenoceptor blocking properties in rat aortic rings.

Adrenergic alpha-Antagonists↗

Radiofrequency catheter ablation for the treatment of human type 1 atrial flutter. Identification of a critical zone in the reentrant circuit by endocardial mapping techniques.

BACKGROUND: Recent studies of human type 1 atrial flutter demonstrated reentry in the right atrium and an area of slow conduction in the low posteroseptal right atrium. Direct-current catheter ablation of this area has been only moderately successful in preventing recurrence. Therefore, we performed endocardial activation mapping and entrainment pace mapping during atrial flutter to determine the critical site for radiofrequency ablation of this arrhythmia. METHODS AND RESULTS: Twelve consecutive patients (seven men and five women; age, 21-73 years) with type 1 atrial flutter (mean cycle length, 253 +/- 39 msec) underwent right atrial endocardial activation and entrainment pace mapping using standard transvenous catheter techniques to localize the atrial flutter reentrant circuit, the area of slow conduction, and the exit site from the area of slow conduction. Upon identifying appropriate sites, radiofrequency energy (16-29 W) was applied via a 4-mm tipped catheter. Activation mapping of atrial flutter revealed a counterclockwise reentrant wave front originating just inferior or posterior to the coronary sinus ostium, proceeding superiorly in the atrial septum to the right atrial free wall, then inferiorly toward the tricuspid annulus and finally medially between the inferior vena cava and the tricuspid annulus, where low-amplitude fragmented electrical activity was noted. Entrainment pace mapping from this area produced an exact P wave match to atrial flutter on 12-lead ECG with a long (greater than 40 msec) stimulus-to-P interval indicating slow conduction, whereas pacing just inferior or posterior to the coronary sinus ostium produced an exact P wave match with a short stimulus-to-P interval (less than 40 msec), presumably identifying the exit site from the area of slow conduction. Radiofrequency energy (one to 14 applications) was effective in terminating and preventing reinduction of atrial flutter in 10 patients. In two patients, atrial flutter was not terminated during radiofrequency energy application but during subsequent pacing attempts. Sites where ablation was successful, located just inferior or posterior to the coronary sinus ostium, were characterized by discrete electrograms with activation times of -20 to -50 msec before P wave onset and exact entrainment pace maps with a stimulus-to-P interval of 20 to 40 msec, consistent with the exit site from the area of slow conduction. Follow-up (mean, 16 +/- 9 weeks; range, 2-31 weeks) revealed recurrence of the original atrial flutter in two patients, one of whom underwent repeat ablation without further recurrence, self-limited infrequent recurrence of a new atrial flutter or atrial fibrillation in three suppressed by beta-blocker or digoxin, and no recurrence in seven. CONCLUSIONS: 1) Radiofrequency energy applied to a critical area in the atrial flutter reentrant circuit, inferior or posterior to the coronary sinus ostium, will terminate and prevent arrhythmia reinduction. 2) Long-term follow-up in a larger series of patients will be required to confirm efficacy of this technique, although short-term results look promising.

Adult↗