Biomedical subjects

L Rivera

Publications and source records attributed to L Rivera.

At least 19 recordsLinked to original sources

PubMed2006

Combination of Ca2+ -activated K+ channel blockers inhibits acetylcholine-evoked nitric oxide release in rat superior mesenteric artery.

BACKGROUND AND PURPOSE: The present study investigated whether calcium-activated K+ channels are involved in acetylcholine-evoked nitric oxide (NO) release and relaxation. EXPERIMENTAL APPROACH: Simultaneous measurements of NO concentration and relaxation were performed in rat superior mesenteric artery and endothelial cell membrane potential and intracellular calcium ([Ca2+]i) were measured. KEY RESULTS: A combination of apamin plus charybotoxin, which are, respectively, blockers of small-conductance and of intermediate- and large-conductance Ca2+ -activated K channels abolished acetylcholine (10 microM)-evoked hyperpolarization of endothelial cell membrane potential. Acetylcholine-evoked NO release was reduced by 68% in high K+ (80 mM) and by 85% in the presence of apamin plus charybdotoxin. In noradrenaline-contracted arteries, asymmetric dimethylarginine (ADMA), an inhibitor of NO synthase inhibited acetylcholine-evoked NO release and relaxation. However, only further addition of oxyhaemoglobin or apamin plus charybdotoxin eliminated the residual acetylcholine-evoked NO release and relaxation. Removal of extracellular calcium or an inhibitor of calcium influx channels, SKF96365, abolished acetylcholine-evoked increase in NO concentration and [Ca2+]i. Cyclopiazonic acid (CPA, 30 microM), an inhibitor of sarcoplasmic Ca2+ -ATPase, caused a sustained NO release in the presence, but only a transient increase in the absence, of extracellular calcium. Incubation with apamin and charybdotoxin did not change acetylcholine or CPA-induced increases in [Ca2+]i, but inhibited the sustained NO release induced by CPA. CONCLUSIONS AND IMPLICATIONS: Acetylcholine increases endothelial cell [Ca2+]i by release of stored calcium and calcium influx resulting in activation of apamin and charybdotoxin-sensitive K channels, hyperpolarization and release of NO in the rat superior mesenteric artery.

Acetylcholine↗

PubMed2006

Neuronal and smooth muscle receptors involved in the PACAP- and VIP-induced relaxations of the pig urinary bladder neck.

BACKGROUND AND PURPOSE: As pituitary adenylate cyclase-activating polypeptide 38 (PACAP 38)- and vasoactive intestinal peptide (VIP) are widely distributed in the urinary tract, the current study investigated the receptors and mechanisms involved in relaxations induced by these peptides in the pig bladder neck. EXPERIMENTAL APPROACH: Urothelium-denuded strips were suspended in organ baths for isometric force recordings and the relaxations to VIP and PACAP analogues were investigated. KEY RESULTS: VIP, PACAP 38, PACAP 27 and [Ala(11,22,28)]-VIP produced similar relaxations. Inhibition of neuronal voltage-gated Ca(2+) channels reduced relaxations to PACAP 38 and increased those induced by VIP. Blockade of capsaicin-sensitive primary afferents (CSPA), nitric oxide (NO)-synthase or guanylate cyclase reduced the PACAP 38 relaxations but failed to modify the VIP responses. Inhibition of VIP/PACAP receptors and of voltage-gated K(+) channels reduced PACAP 38 and VIP relaxations, which were not modified by the K(+) channel blockers iberiotoxin, charybdotoxin, apamin or glibenclamide. The phosphodiesterase 4 inhibitor rolipram and the adenylate cyclase activator forskolin produced potent relaxations. Blockade of protein kinase A (PKA) reduced PACAP 38- and VIP-induced relaxations. CONCLUSIONS AND IMPLICATIONS: PACAP 38 and VIP relax the pig urinary bladder neck through muscle VPAC(2) receptors linked to the cAMP-PKA pathway and involve activation of voltage-gated K(+) channels. Facilitatory PAC(1) receptors located at CSPA and coupled to NO release, and inhibitory VPAC receptors at motor endings are also involved in the relaxations to PACAP 38 and VIP, respectively. VIP/PACAP receptor antagonists could be useful in the therapy of urinary incontinence produced by intrinsic sphincter deficiency.

Adenylyl Cyclases↗

PubMed2005

Development of an HPLC method for determination of diphenidol in plasma and its application in an oral multi-dose bioequivalence study in a healthy female Mexican population.

Diphenidol was determined by an HPLC method developed in our laboratory. It was validated and proved to be linear in the 40-400 ng/ml range. Accuracy for quality-control samples for intra and inter day assays ranged from 96.1-98.9% and 98.8-101.4%, respectively. This method was applied to a multi-dose bioequivalence study. No serious side effects were observed in the multi-dose design. Pharmacokinetic parameters (mean+/-standard error [S.E.]) of Cavg (ng/ml) and AUCtau (ngh/ml) for reference and test products were 139.54+/-12.66 versus 148.60+/-16.51 and 551.07+/-53.53 versus 588.78+/-69.02, respectively. Log-transformed values were compared by analysis of variance (ANOVA) followed by the classical 90% confidence interval (CI 90%) test and Schuirmann's test. Confidence limits ranged from 91.48-116.18% for Cmax and from 91.24-117.65% for AUCtau. These results suggest that the analytical method was linear, precise, and accurate for our purpose, and that both assayed formulations were bioequivalent.

Adult↗

PubMed2005

Bioequivalence evaluation of two brands of meloxicam tablets (Promotion and Mobicox): pharmacokinetics in a healthy female Mexican population.

We conducted a randomized, crossover study in 23 healthy young female volunteers to compare the bioavailability of two brands of meloxicam (7.5 mg) tablets and to obtain pharmacokinetic parameters of this molecule in Mexican population not reported previously. Two tablets (15 mg) were administered as a single dose on 2 treatment days separated by a 1-week washout period. After dosing, serial blood samples were collected for a period of 72 h. Plasma harvested was analyzed for meloxicam by a modified and validated high-performance liquid chromatography (HPLC) method previously reported. Pharmacokinetic parameters AUC(0-t), AUC(0-alpha), C(max), T(max), k(e), MRT and t(1/2) were determined from plasma concentrations of both formulations, resulting in a C(max) 120% larger than and a T(max) 65% faster than those reported in other populations. AUC(0-t), AUC(0-alpha), and C(max) were statistically tested for bioequivalence after log transformation data in a non-balanced design, and no significant differences were found either in 90% classical confidence interval (90% CI) or in Schuirmann test (p < 0.05); thus, we concluded that bioequivalence existed between both formulations.

Administration, Oral↗

PubMed2004

Bioequivalence evaluation of two brands of ketoconazole tablets (Onofin-K and Nizoral) in a healthy female Mexican population.

A randomized, crossover study was conducted in 24 healthy female volunteers to compare the bioavailability of two brands of ketoconazole (200 mg) tablets; Onofin-K (Farmacéuticos Rayere S.A., Mexico) as the test and Nizoral (Janssen-Cilag, Mexico) as the reference products. The study was performed at the Clinical Pharmacology Research Center of the Hospital General de Mexico in Mexico City. Two tablets (400 mg) were administered as a single dose with 250 ml of water after a 12 h overnight fast on two treatment days separated by a 1 week washout period. After dosing, serial blood samples were collected for a period of 12 h. Plasma harvested was analysed for ketoconazole by a modified and validated HPLC method with UV detection in the range 400-14000 ng/ml, using 200 microl of plasma in a full-run time of 2.5 min. The pharmacokinetic parameters AUC(0-t), AUC(0-alpha), Cmax, Tmax and t(1/2) were determined from plasma concentrations of both formulations and the results discussed. AUC(0-t), AUC(0-alpha) and Cmax were tested for bioequivalence after log transformation of data, and no significant differences were found either in 90% classic confidence interval or in the Anderson and Hauck test (p < 0.05). Based on statistical analysis, it is concluded that Onofin-K is bioequivalent to Nizoral.

Adolescent↗

PubMed2004

Immunohistochemical and functional evidence for a noradrenergic regulation in the horse penile deep dorsal vein.

Our aim was to study the presence of noradrenergic nerves and to characterize the alpha-adrenergic receptors involved in the contractions to electrical field stimulation and to alpha-adrenergic agonists of the horse penile deep dorsal vein. Noradrenergic fibres were visualized by immunohistochemistry using an antibody against dopamine-beta-hydroxylase (DBH). For functional studies, the responses of the venous rings to electrical field stimulation and to alpha-adrenergic agonists (noradrenaline, phenylephrine and BHT 920) were studied in the absence and the presence of noradrenergic transmission- and neuronal sodium channel-blockers (guanethidine and tetrodotoxin, respectively) and of alpha1- and alpha2-adrenergic antagonists (prazosin and rauwolscine, respectively). DBH-immunoreactive fibres were present in the adventitia and in the media layer of the venous rings. Electrical field stimulation (0.5-32 Hz) caused frequency-dependent contractions that were abolished by guanethidine (10(-6) M) and tetrodotoxin (10(-6) M) and reduced by prazosin (10(-9)-10(-7) M) and rauwolscine (3 x 10(-8)-3 x 10(-7) M). Noradrenaline, phenylephrine and BHT 920 induced equipotent contractions of the rings. Prazosin and rauwolscine competitively antagonized the contractions to phenylephrine and BHT 920, respectively. In conclusion, DBH-immunoreactive nerve fibres are present in the horse penile dorsal vein. Both transmural nerve stimulation and alpha-adrenergic agonists induce contraction of the venous rings through a heterogeneous population of alpha1- and alpha2-adrenoceptors.

Adrenergic alpha-Agonists↗

PubMed2004

Preterm birth and maternal country of birth in a French district with a multiethnic population.

OBJECTIVES: This analysis explores the association between preterm birth and maternal country of birth in a French district with a multiethnic population. DESIGN: Prospective observational study. SETTING: District of Seine-Saint-Denis in France POPULATION: 48,746 singleton live births from a population-based birth register between October 1998 and December 2000. METHODS: We compare preterm birth rates by mother's country of birth controlling for demographic and obstetric factors as well as insurance coverage and timing of initiation of antenatal care. MAIN OUTCOME MEASURES: Overall preterm birth rates and preterm birth rates by timing of delivery (<33 weeks versus 33-36 weeks of gestation), mode of onset (spontaneous or indicated preterm birth) and the presence of hypertension in pregnancy. RESULTS: Women born in Northern Africa, Southern Europe and South/East Asia did not have higher preterm birth rates than women born in continental France. Rates were significantly higher for women born in the overseas French districts in the Caribbean and Indian Ocean and Sub-Saharan Africa. Excess risk was greatest for early preterm births, medically indicated births and preterm births associated with hypertension. CONCLUSIONS: Patterns of preterm birth with relation to timing, mode of onset and medical complications among of Afro-Caribbean origin should be confirmed in future research.

Adult↗

PubMed2003

Retrospective analysis of the treatment of psoriasis of the palms and soles.

In this retrospective analysis, the effect of currently used treatments in 26 patients with psoriasis of the palms and soles were analyzed. In general, patients are treated initially with topical medications including superpotent topical corticosteroids in combination with calcipotriene ointment or tazarotene gel or both. If satisfactory improvement is not achieved in 4-8 weeks, systemic retinoids are added, formerly etretinate and currently acitretin, except in women of childbearing potential. If the latter regimen is not effective within two months, soak PUVA is added to the regimen of oral retinoids and topical medications. If improvement is inadequate, or if the treatment regimen is not tolerated, methotrexate or cyclosporine have been added in the past. The availability of the excimer laser has recently modified our approach so that this therapy is used in combination with acitretin before soak PUVA. With the availability of biologic agents, methotrexate is avoided because of its hepatotoxicity and bone marrow toxicity and cyclosporine is avoided because of its nephrotoxicity. If oral acitretin plus topical therapy is not adequate to control the disease and the excimer laser is not an option because of its limited availability, alefacept, etanercept and infliximab are added when possible. Other biologic agents are likely to be added to this list in the future.

Adult↗

PubMed2003

A phase II study of multimodality treatment for locally advanced cervical cancer: neoadjuvant carboplatin and paclitaxel followed by radical hysterectomy and adjuvant cisplatin chemoradiation.

BACKGROUND: Our aim was to evaluate the efficacy and safety of neoadjuvant chemotherapy followed by radical hysterectomy and adjuvant radiation concurrent with weekly cisplatin for locally advanced cervical carcinoma. PATIENTS AND METHODS: Forty-three patients staged as IB2-IIIB were treated with three 21-day courses of carboplatin (area under the time-concentration curve 6 mg.min/ml) and paclitaxel at 175 mg/m(2) by 3-h infusion both on day 1 followed by radical type III hysterectomy and adjuvant radiation concurrent with 6-weekly doses of cisplatin at 40 mg/m(2). Response rate, resectability, toxicity and survival were evaluated. RESULTS: From December 2000 to June 2001, 43 patients were recruited. All were evaluated for response and toxicity to neoadjuvant chemotherapy. A total of 129 courses were administered. Clinical responses were seen in 41 patients (95%) [95% confidence interval (CI) 89.2% to 100%] with four (9%) complete and 37 (86%) partial. Forty-one patients underwent surgery (resectability 95%); pathologically complete or near-complete responses were seen in seven (17%) and eight (20%), respectively, positive surgical margins in five (12%), and positive pelvic lymph nodes in eight (20%). Twenty-six patients were scheduled for adjuvant chemoradiation. External radiation was delivered for 42.8 days (range 33-61), with a mean dose of 49.3 Gy (range 46-56), and a median of five cisplatin courses (two to six). The mean dose of brachytherapy was 32 Gy (range 25.5-35.6). Neoadjuvant therapy was well-tolerated with neutropenia grade 3 and 4 in 12% and 3% of the courses, respectively. Toxicity to adjuvant chemoradiation was mainly hematological and gastrointestinal, mostly grades 1/2. A total of 39 patients completed all scheduled treatment. At a median follow-up of 21 months (range 3-26), the projected overall survival in the intention-to-treat analysis was 79% (95% CI 62% to 88%). CONCLUSIONS: The triple modality of neoadjuvant chemotherapy followed by radical hysterectomy and adjuvant radiation concurrent with cisplatin is a highly active treatment for locally advanced cervical carcinoma with acceptable toxicity.

Adult↗

PubMed2003

Preterm birth in a French population: the importance of births by medical decision.

This analysis describes the prevalence of preterm birth by medical decision among 50,307 live births from the district of Seine-Saint-Denis in France, using a classification that distinguishes between medically decided preterm births associated with premature rupture of membranes and those for other reasons. Thirty-seven percent of singleton and 28% of twin preterm births result from labour induction or a caesarean section in the absence of labour. One-quarter of singleton indicated preterm births are associated with premature rupture of membranes. Between 28 and 31 weeks of gestation, 40% of all singleton preterm births result from a medical decision not associated with premature rupture of membranes. The high levels of indicated preterm birth must be taken into account in evaluations of preterm birth rates and trends in developed countries.

Cohort Studies↗

PubMed2002

Concomitant chemoradiation versus neoadjuvant chemotherapy in locally advanced cervical carcinoma: results from two consecutive phase II studies.

BACKGROUND: Randomized studies comparing induction chemotherapy followed by surgical resection with radiation alone found that the neoadjuvant approach produces better results. So far, this latter modality has not been compared with standard concomitant chemoradiation. The objective of this report was to compare the results of two consecutive phase II studies: neoadjuvant chemotherapy followed by surgery or chemoradiation for the unresectable cases versus standard cisplatin-based chemoradiation. PATIENTS AND METHODS: From February 1999 to July 1999, 41 patients with cervical carcinoma, stages IB2-IIIB, were treated with neoadjuvant chemotherapy. Treatment consisted of three 21-day courses of cisplatin 100 mg/m(2) on day 1 and gemcitabine 1000 mg/m(2) on days 1 and 8, followed by either surgery or concomitant chemoradiation for the non-operable cases. From August 1999 to December 1999, an equal number of patients having comparable clinicopathological characteristics were treated with six weekly courses of cisplatin 40 mg/m(2) during standard pelvic radiation. RESULTS: A total of 82 patients were analyzed. Both groups were similar with regard to age, histology, International Federation of Gynecology and Obstetrics (FIGO) stage, tumor size, pretreatment hemoglobin levels, parametrial infiltration and performance status. In the neoadjuvant arm the overall response rate to induction chemotherapy was 95% (95% confidence interval 88% to 100%). Twenty-three patients had surgery and 14 underwent chemoradiation. In the definitive chemoradiation study, 38 patients completed treatment, the median number of cisplatin courses was six for a dose intensity of 33 mg/m(2)/week. Doses to points A and B were 85 Gy (range 68-95) and 55 Gy (range 51-65), respectively. Chemoradiation was delivered in 44.6 (range 28-113) days. Complete response rates after all treatment were similar: 97% and 87% in the neoadjuvant and chemoradiation groups, respectively. At a median follow-up of 28 (range 2-33) and 24 (range 3-30) months, respectively, there were no differences in overall survival. To date, 15 and 13 patients in the neoadjuvant and chemoradiation groups, respectively, have died of disease (P = 0.8567). CONCLUSIONS: The results of this non-randomized comparison suggest that induction chemotherapy followed by surgery or chemoradiation is at least as effective in terms of response and survival as standard cisplatin-based chemoradiation. A randomized study is needed to confirm these findings.

Adenocarcinoma↗

PubMed2002

Correlation of tumor growth index with early treatment response in cervical carcinoma.

Despite the recent progress in the management of cervical carcinoma, treatment failure is quite common and therefore it is necessary to identify predicting factors for tumor response. It is known that both cell proliferation and apoptosis determine the tumor growth index (TGI) which reflects the overall contribution of gene defects. Here we explored whether the TGI index could be a better predictor of response in comparison to cell proliferation or apoptosis as separate phenomena. Twenty-five patients with cervical carcinoma treated with radiation alone or neoadjuvant chemotherapy plus surgery were analyzed. Cell proliferation and apoptosis determined by PCNA immunohistochemical expression and tumor nucleosomes by ELISA, respectively, were used to calculate the TGI, which was analyzed with regard to early tumor response. Our results show that most patients with a negative TGI had early response suggesting increased tumor sensitivity(p = 0.0186). On the other hand, patients with a positive TGI were more resistant to treatment. TGI was not related to age, clinical stage or tumor size. In conclusion, the results of this study show that the determination of the TGI, but no cell proliferation or apoptosis, as separate events, is able to predict an early treatment response to either radiation or chemotherapy in cervical carcinoma.

Adenocarcinoma↗

PubMed2001

Contribution of age and gender to outcome of blunt splenic injury in adults: multicenter study of the eastern association for the surgery of trauma.

BACKGROUND: The purpose of this study was to examine the contribution of age and gender to outcome after treatment of blunt splenic injury in adults. METHODS: Through the Multi-Institutional Trials Committee of the Eastern Association for the Surgery of Trauma (EAST), 1488 adult patients from 27 trauma centers who suffered blunt splenic injury in 1997 were examined retrospectively. RESULTS: Fifteen percent of patients were 55 years of age or older. A similar proportion of patients > or = 55 went directly to the operating room compared with patients < 55 (41% vs. 38%) but the mortality for patients > or = 55 was significantly greater than patients < 55 (43% vs. 23%). Patients > or = 55 failed nonoperative management (NOM) more frequently than patients < 55 (19% vs. 10%) and had increased mortality for both successful NOM (8% vs. 4%, p < 0.05) and failed NOM (29% vs. 12%, p = 0.054). There were no differences in immediate operative treatment, successful NOM, and failed NOM between men and women. However, women > or = 55 failed NOM more frequently than women < 55 (20% vs. 7%) and this was associated with increased mortality (36% vs. 5%) (both p < 0.05). CONCLUSION: Patients > or = 55 had a greater mortality for all forms of treatment of their blunt splenic injury and failed NOM more frequently than patients < 55. Women > or = 55 had significantly greater mortality and failure of NOM than women < 55.

Adult↗

PubMed2001

Glycaemic and insulinaemic indices of Mexican foods high in complex carbohydrates in Type 2 diabetic subjects.

The glycaemic (GI) and insulinaemic indices (InIn) of 3 indigenous single foods and 3 indigenous realistic high complex carbohydrate meals (bread=100) were determined in 7 Mexican type 2 diabetic subjects. Observed GI (mean+/-SEM) were: beans (B) 39.9+/-7.3, wheat tortilla (WT) 53.2+6.4, corn tortilla (CT) 84.8+/-6.0, wheat tortilla beans taco (BWT) 71.2+/-9.5, corn tortilla beans taco (BCT) 73.5+/-4.3 and corn tortilla potato taco (PT) 121.5+/-12.8. The GI of white bread (WB) was higher than B (p<0.01), WT (p<0.01), BWT (p<0.05) and BCT (p<0.05) and did not differ from CT and PT. Observed InIn were: B 36.2+/-7.0, WT 49+/-5.6, CT 83.4+/-17.6, BWT 66.1+/-5.9, BCT 80.3+/-7.9 and PT 164.2+/-26.5. InIn of B, WT and BWT were lower than WB (p<0.01), whereas PT was higher (p<0.05) and CT and BCT did not differ. Diabetic subjects do not have to eliminate WT, B or beans tacos, as suggested by some physicians. Nevertheless, they could lower the consumption of CT and PT. This information presents an alternative to diabetic subjects to live and eat more freely, by preventing the alteration of familiar and dining cultural habits.

Adult↗

PubMed2000

Responses of nerve fibres of the rat saphenous nerve neuroma to mechanical and chemical stimulation: an in vitro study.

The response of neuroma nerve endings to different stimuli was studied in a saphenous nerve neuroma preparation in vitro. Electrical activity was recorded from 141 single fibres dissected of saphenous nerve. One-third (27 %) displayed spontaneous activity. Based on their response to mechanical and chemical stimuli, neuroma nerve fibres were classified as mechanosensory fibres (47.5 %), mechanically insensitive chemosensory fibres (17.0 %), polymodal nociceptor fibres (28.4 %) and unresponsive fibres (7.1 %). Mechanosensory and polymodal neuroma endings responded to von Frey hair stimulation either with a few impulses (phasic units) or a sustained discharge (tonic units). Polymodal units were additionally activated by at least one of the following stimuli: acidic solutions; a combination of bradykinin, prostaglandin E2, serotonin, substance P and histamine (all at 1 microM) plus 7 mM KCl (inflammatory soup); 600 mM NaCl and capsaicin. Low pH solutions increased the firing discharge of polymodal endings proportionally to the proton concentration. The 'inflammatory soup' evoked a firing response characterized by the absence of tachyphylaxis, which appeared when its components were applied separately. Both stimuli sensitized polymodal fibres to mechanical stimulation. Hypertonic NaCl (600 mM) and capsaicin (3.3 mM) induced a prolonged discharge that outlasted the stimulus duration. Mechanically insensitive chemosensory neuroma fibres exhibited responses to chemical stimuli analogous to polymodal fibres. They became mechanically sensitive after chemical stimulation. These findings show that neuroma nerve endings in the rat saphenous nerve neuroma in vitro are functionally heterogeneous and exhibit properties reminiscent of those in intact mechanosensory, polymodal and 'silent' nociceptor sensory afferents, including their sensitization by algesic chemicals.

Animals↗

PubMed2000

Evidence of histamine receptor function in isolated horse penile dorsal arteries.

The effect of histamine (10(-9)-10(-3) M) on horse penile dorsal artery was evaluated. Precontracted vessels showed a biphasic response (relaxation-contraction) to histamine, while at basal tone, histamine only induced a contractile effect. The H1 receptor agonist, 2-pyridylethylamine (PEA) (10(-9)-10(-3) M), induced concentration-dependent relaxation in precontracted rings and provoked vasoconstriction at basal tone. Mepyramine (10(-9)-10(8) M), an H1 receptor antagonist, competitively antagonized the relaxant response to histamine (pA2 = 9.7) and PEA (pA2 = 9.2). At basal tone, mepyramine (10(-10)-10(-8) M) also caused a rightward shift in the histamine contraction curve (pA2 = 10.1). Mepyramine (10(-9)-10(-8) M)/PEA Schild plots for resting vessels yielded a pA2 value of 9.4. A regulatory role for H2 and H3 receptors was precluded since there was no response to their agonists (dimaprit (10(-9)-10(-3) M), (R)-alpha-methylhistamine (10(-10)- 3 x 10(-4) M)), and antagonists (cimetidine (10(-5) M), thioperamide (10(-6) M)) did not affect control curves. Removal of the endothelium abolished the relaxant component causing a leftward shift in the contractile component in precontracted rings, with no effect on maximum contraction. Inhibitors of nitric oxide (NO) synthesis, L-NAME (3 x 10(-4) M) and L-NOARG (3 x 10(-4) M), modified the relaxant response while contraction was unaffected. L-Arginine (3 x 10(-4) M) potentiated maximum relaxation but did not affect contraction in precontracted rings. Effects of a prostanoid and K+ channels were ruled out. The biphasic response of precontracted vessels persisted in the presence of indomethacin (3 x 10(-6) M), tetraethylammonium (10(-3) M) and gliblenclamide (10(-5) M). L-NAME plus indomethacin, or this combination plus TEA or glibenclamide produced similar effects as isolated treatments. In resting vessels, histamine contraction was also unaffected by the lack of endothelium, or L-NAME, L-arginine or indomethacin pretreatment. The biphasic response to histamine is probably mediated by H1 receptors with a partial role for NO in the relaxant response in precontracted vessels. In the absence of tone, the contractile effect may be mediated by direct action on smooth muscle.

Animals↗

PubMed2000

Hepatitis E virus in Cuba.

The hepatitis E virus (HEV) has a global distribution and is known to have caused large waterborne epidemics of icteric hepatitis. The transmission is primarily fecal-oral. Some reports have suggested parenteral transmission of HEV from its association to hepatitis B or hepatitis C infection, or due to the development of hepatitis E after blood transfusion. Though most of the developing countries in Asia and Africa have been shown to be endemic for HEV infection, studies in the Latin American countries have been limited to Mexico, Brazil and Venezuela. We have developed an enzyme immunoassay (EIA) for IgM and IgG antibodies to a recombinant protein containing antigenic epitopes of the ORF3 region of the HEV. This system, as well as a commercial kit that includes ORF2 and ORF3 antigenic epitopes, were used to study the prevalence of anti-HEV antibodies in a sample of Cuban blood donors, acute hepatitis cases and individuals subjected to plasmapheresis. The incidence of anti-HEV IgM was compared with other viral hepatitis markers. Our findings suggest that infections due to HEV are an important viral cause of sporadic hepatitis in Cuba, and that HEV is endemic to this region of the world.

Adult↗

PubMed2000

Biphasic response to histamine in rabbit penile dorsal artery.

The effects of specific histamine agonists and antagonists on isolated rabbit penile dorsal artery segments were explored using in vitro isometric techniques. Histamine caused the constriction of both precontracted and resting segments. In precontracted arterial rings treated with the H1 receptor antagonist mepyramine, histamine evoked a vasodilatation, followed by contraction at higher concentrations. The vasoconstrictor effect of histamine and the H1 receptor agonist, 2-pyridylethylamine (PEA) on preparations under conditions of basal tone, was competitively antagonized by mepyramine (10(-9)-10(-8) M). The relaxant effect of histamine, unmasked by mepyramine, was abolished by cimetidine. Dimaprit, the H2 receptor agonist, provoked a relaxation of precontracted segments that was also competitively inhibited by cimetidine (10(-6)-10(-5) M). Selective H3 receptor activation with the agonist (R)alpha-methylhistamine (10(-10)-10(-4) M) produced no effect in penile dorsal artery. The biphasic response to histamine was unaffected by endothelium removal or the nitric oxide inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (3 x 10(-4) M) and its precursor, L-arginine (3 x 10(-4) M). Similarly, the cyclooxygenase inhibitor, indomethacin (3 x 10(-6) M) and a combination of Ca2+-activated K+ channel blockers apamin (5 x 10(-7) M) and charybdotoxin (10(-7) M) showed no effect on the histamine-induced relaxation or contraction. In conclusion, contraction, the predominant effect of histamine, is mediated by the activation of H1 receptors that mask the relaxant effect brought about by H2 receptors. Both these effects appear to be mediated by direct action on the smooth muscle, with no participation of nitric oxide or cyclooxygenase products or Ca2+-activated K+ channels.

Animals↗