Effects of beta-adrenoceptor drug stimulation on various models of gastric ulcer in rats.

1. Experiments were designed to evaluate the effect of the pharmacological activation of beta-adrenoceptors on various models of gastric ulcer in the rat. 2. Pretreatment with the beta-adrenoceptor stimulant drugs, isoprenaline or salbutamol, significantly inhibited stress-induced gastric ulcers. This anti-ulcer effect was abolished by propranolol but not by atenolol, suggesting that beta 2-adrenoceptors mediate this response. 3. In the pylorus-ligation model, salbutamol inhibited lesion formation and reduced the intragastric content of hydrogen ions, histamine and pepsin although the latter was only affected with the higher dose of salbutamol. 4. Salbutamol also prevented the ulcerogenic action on the gastric mucosa of an exogenously perfused artificial gastric juice, showing that the anti-ulcer effect is not necessarily dependent on acid inhibition. 5. Salbutamol also reduced the formation of acute ulcers induced by various iatrogenic means (histamine, polymyxin B, reserpine and indomethacin). 6. Long-term treatment with salbutamol accelerated the healing of experimental chronic gastric ulcer. 7. In anaesthetized rats, salbutamol produced a dose-related increase in mucosal blood flow which may contribute to its mode of action. 8. It is concluded that beta-adrenoceptor agonists exert preventive and curative effects on gastric damage induced in the rat. This effect seems specific and mediated through beta-adrenoceptor activation.

Effects of cimetidine, atropine and prostaglandin E2 on rat mucosal erosions produced by intragastric distension.

The effects of three typical antisecretory agents: cimetidine, atropine and prostaglandin E2 were compared on an acute rat gastric ulcer model which consisted of perfusing the stomach continuously, at a high intraluminal pressure (120 mm H2O), with a simulated gastric juice (0.1 M HCl plus 600 mg pepsin/l). As the acid and pepsin are given exogenously the inhibitory action of the antisecretory drugs is obviated in this model. Cimetidine and atropine failed to reduce gastric erosions, whereas prostaglandin E2 markedly reduced the severity of the mucosal lesions with respect to control values. Long-term treatment with cimetidine also failed to increase the resistance of the gastric mucosa to the digestive action of the artificial gastric juice. These findings indicate that only prostaglandin E2 is cytoprotective and do not support the view that anticholinergics or histamine H2-receptor antagonists have a cytoprotective role on the cells of the gastric mucosa.

Effects of Ca2+ channel antagonists in guinea-pig normal and skinned gall bladder.

CaCl2 (0.01-50 mM, in K(+)-depolarized tissues), KCl (0.1-100 mM) and acetylcholine (1 nM-10 mM) produced concentration-dependent contractions of guinea-pig isolated gall bladder. Nifedipine (1-100 microM), verapamil (1-100 microM), diltiazem (1-100 microM), cinnarizine (1-100 microM), and flunarizine (1-100 microM) each produced a concentration-related inhibition of the log concentration-effect curve for CaCl2. The rank order of potencies of these antagonists, measured as the IC50 against Ca2+ (50 mM)-induced contraction of depolarized gall bladder, was diltiazem (0.25 microM) > or = verapamil (0.8 microM) approximately nifedipine (1.2 microM) >> cinnarizine (25 microM) approximately flunarizine (80 microM). Verapamil and diltiazem depressed KCl-induced contraction with an effectiveness and potency similar to those displayed against CaCl2 but nifedipine, cinnarizine and flunarizine were less effective against contractions in response to KCl compared to CaCl2. Verapamil and diltiazem, but not the other Ca2+ channel antagonists tested, had a specific inhibitory effect on the contractions due to KCl when compared to acetylcholine-induced contractions. Cinnarizine (10-100 microM) and flunarizine (10-100 microM), but not the other antagonists tested, depressed Ca2+ (20 microM)-evoked contraction of skinned guinea-pig gall bladder preparations. It is concluded that distinct differences exist between the Ca2+ channel antagonists examined. The action of nifedipine, verapamil and diltiazem is restricted to the plasmalemma whereas cinnarizine and flunarizine also act on the intracellular contractile apparatus.

Effects of zinc sulphate on gastric mucosal blood flow and gastric emptying of the rat.

Zinc sulphate (50 mg kg-1 p.o.) did not modify basal gastric mucosal blood flow, as measured by [3H]aniline clearance, but inhibited its reduction by noradrenaline (3.5 micrograms kg-1 min-1). Zinc sulphate also influenced gastric emptying of phenol red but its effects depended upon the dose; 30 mg kg-1 caused no variation whereas 80 mg kg-1 induced a significant delay. The nature of both actions is discussed and their implications in the development and prevention of gastric ulceration have been analysed.

[Effect of LHRH agonists on testicular microcirculation with Doppler laser flowmetry]. / Acción de los agonistas LHRH sobre la microcirculación testicular medida mediante flujometria laser doppler.

The purpose of this paper is to present the changes that take place in testicular microcirculation measured by DLF during systemic administration of LHRH agonists. The essay includes a comparison with the variations registered in the volume of testicular interstitial fluid, the anatomopathological changes and the associated leucocyte demyeloperoxidase levels. We also examine the relationship between testicular microcirculation changes and plasma testosterone levels. To do this, 50 male Wistar rats were randomly divided into 5 groups, using 10 as control group and the remaining 40 distributed in 4 groups. Measurements were done at 2, 4, 8 and 24 hours after administration of Tryptorelin 0.4 mg i.v. We found that acute administration of an LHRH agonist causes a series of significant changes on testicular microcirculation. Testicular rhythmic microcirculatory flow, i.e., vasomotion, disappears. In turn, accumulation of PMN leucocytes associated to increased venular permeability takes places. Such pre- and postcapillary vascular changes lead to increased vascular permeability which results in increased volume of testicular interstitial fluid. This increased capillary permeability is responsible for the extensive interstitial oedema that would explain the serious histological changes seen on the seminiferous tubule with these drugs.

[Testicular microcirculation in rats measured with laser-Doppler flowmetry]. / Microcirculación testicular en la rata medida mediante flujometría laser doppler.

Study carried out in 50 male Wistar rats distributed into 5 groups: baseline and at 2, 4, 8 and 24 hours after subcutaneous injection of Human Chorionic Gonadotropin, 100 IU. It was observed that testicular microcirculatory flow shows a rhythmical fluctuating pattern (5-10 fluctuations per minute), which becomes continuous at 4 hours but recovers at 24 hours. At the same time, there is an increased volume of testicular interstitial fluid that peaks at 8 hours, and returns to baseline levels at 24 hours. Serum testosterone values increase with HCG injection, reaching a peak at 4 hours (25.9 mg/ml), to return to nearly baseline levels at 24 hours (5.04 mg/ml). Disappearance of the rhythmical microcirculatory pattern, and the increase of interstitial fluid volume do not appear to be mediated by testosterone, since the raise in hormone levels, occurred after HCG administration, preceded the observed microcirculatory changes.

[Anatomopathologic changes in the testis following prolonged treatment with LHRH agonists. Experimental study in rats]. / Cambios anatomopatológicos en el testículo tras un tratamiento prolongado con agonistas LHRH. Estudio experimental en ratas.

Presentation of a study conducted on 20 male Wistar rats treated for 3 months with Leuprolide (LHRH agonist). Analysis of pathophysiological testicular changes resulting from the treatment and extent of recovery at 3 months of therapy discontinuation, relating those changes to testosterone plasma levels in peripheral blood. Serum testosterone fell to 1.17 +/- 0.30 ng/ml in the treated group, shifting to figures overlapping with normal values within 3 months of discontinuing treatment. Such decreased testosterone levels translate into significant testicular histological damage. Three months after interruption of treatment there is nearly complete recovery of such damage, with just around 10% tubules without spermatozoa, with unchanged germinal line. We conclude that the marked suppression in testosterone levels caused by LHRH agonists translates into a significant degeneration of the seminiferous tubule, which appears to be reversible 3 months after treatment discontinuation.

[Treatment of gastroesophageal reflux by pexis to the round ligament. Report of 100 operated patients followed-up for 16 to 23 years]. / Le traitement du reflux gastro-oesophagien par pexie avec le ligament rond. A propos de 100 opérés suivis entre 16 et 23 années.

In a study of 1,491 patients operated with ligament cardiopexy from 1,694 onwards, which we published in 1986, we reviewed 100 consecutive cases operated 15 years earlier or more. The review was based on a radioclinical (100), fiberscopic (53) and manometric (71) study, as well as on a measurement of the pH in doubtful cases (22). The results were distributed into categories A (normal), B (occasional disorders), C (functional disorders without recurrence) and R (recurrence), as follows: A + B 81%, C 12% and R 6%. This recent study confirms the conclusions we drew in 1981: a 15-minute operation that cures 94% of the patients without recurrence after 15 years and more is an appropriate procedure.

Gastric juice and analysis of basal and stimulated secretion following treatment with rice-bran oil.

In determining whether rice-bran oil (RBO) has antisecretory activity, we induced stress ulcers in 20 Wistar rats (10 controls; 10 animals given 0.2 ml/day RBO orally for 4 days prior to ulcer induction). In turn, we analyzed gastric juice for histamine, pepsin, H+ concentration ([H+]) and output volume. A second, complementary study was made of basal and stimulated gastric secretion through continuous "in vivo" recording of output. Secretion was stimulated with increasing doses of histamine, betanechol and pentagastrin. Ninety-four rats were used (47 controls and 47 rats given 0.2 ml/day RBO orally for 4 days prior to gastric output evaluation). The results were evaluated by the Student t-test. Ulcer index in the RBO-treated rats was significantly lower than among the controls (p less than 0.01), as also reflected by a significantly greater decrease in [H+] among the RBO-treated rats (p less than 0.05). However, no significant differences were observed for the remaining parameters. Continuous recording of basal gastric output showed a significant decrease in [H+] among the RBO-treated rats (p less than 0.01). Following histamine stimulation, [H+] was likewise significantly lower among the RBO-treated rats than in the controls. However, no significant differences were observed following stimulation with either betanechol or pentagastrin. RBO contains a high percentage of unsaturated fats; the latter act as precursors in the synthesis of arachidonic acid, which in turn is the essential precursor of prostaglandins--established inhibitors of gastric secretion. RBO also contains antioxidants such as alpha-tocopherol, which may likewise stimulate the synthesis of prostaglandins. RBO likely acts by increasing prostaglandin output, thus interfering with gastric HCl production.

Ferrocene-cyclam: a redox-active macrocycle for the complexation of transition metal ions and a study on the influence of the relative permittivity on the coulombic interaction between metal cations.

The reaction of 1,1'-ferrocene-bis(methylenepyridinium) salt with 1,4,8,11-tetraazacyclotetradecane-5,12-dione, followed by LiAlH4 reduction results in the formation of FcCyclam. Metal complexes of FcCyclam with M2+ = Co2+, Ni2+, Cu2+, and Zn2+ were synthesized from FcCyclam and the respective metal triflates. The complexation of Cu2+ and FcCyclam in CH3CN is preceeded by a rapid electron transfer, followed by a slower complex formation reaction and a reverse electron transfer. The protonation constants of FcCyclam and the stability constants for the Cu2+ complex of FcCyclam (logK = 9.26(4) for the formation of the [Cu(FcCyclam)]2+ complex) were determined in 1,4-dioxane/water 70:30 v/v, 0.1 moldm(-3), KNO3, 25 degrees C. By using FcCyclam one can selectively sense the presence of Cu2+ ions in the presence of Ni2+, Zn2+, Cd2+, Hg2+, and Pb2+ with a very large deltaE approximately 200 mV, depending on pH. The X-ray crystal structures of FcCyclam and of complexes with Co2+, Ni2+, Cu2+, and Zn2+ were determined and Fe-M2+ distances obtained: Fe-Co2+ 395.9, Fe-Ni2+ 385.4, Fe-Cu2+ 377.7, and Fe-Zn2+ 369.0 pm. The redox potential of FcCyclam is influenced in a characteristic manner by the complexation of M2+. A linear correlation of 1/r approximately/= deltaE [r = distance Fe-M2+ from crystal data, deltaE=-E1/2([M(FcCyclam)]2+) - E1/2(FcCyclam)] was found; this is indicative of a mainly Coulomb type interaction between the two metal centers. The nature of the Fe...M2+ interaction was also investigated by determining deltaE in several solvents (mixtures) of different dielectric constants epsilon. The expected relation of deltaE approximately/= 1/epsilon was only found at very high values of epsilon. At epsilon < 40 increased ion-pairing appears to reduce the effective positive charge at M2+ leading to progessively smaller values of deltaE with lowered epsilon. The dependence of deltaE and epsilon can be calculated semiquantitatively by combining the Fuoss ion-pairing theory with the Coulomb model.

[Role of testosterone in the testicular microcirculatory changes produced in the rat by the administration of high doses of human chorionic gonadotrophin]. / Papel de la testosterona en las variaciones microcirculatorias testiculares producidas en la rata por la administración de altas dosis de gonadotrofina corionica humana.

A study was performed in 20 male Wistar rats weighing 250-300 gm; 10 comprised the control group and the other 10 were treated with 5 mg/day of cyproterone acetate which was given with the meal for 2 months. The rat testicular microcirculation was studied by laser Doppler flowmetry. Similarly, the testicular interstitial fluid volume and plasma testosterone in peripheral blood were determined. Within each of the two groups, 5 were studied without any pharmacologic stimulation and 5 at 4 hours following the administration of 100 IU subcutaneous HCG. The rats treated with cyproterone acetate had very low levels of serum testosterone (1.254 +/- 0.667) versus the control group (3.686 +/- 0.705), the difference being statistically significant (p < 0.05). Following administration of HCG, the microcirculation changes and the interstitial fluid were the same as those of the control group despite the blockade of the androgenic receptors by cyproterone acetate. The increase in testosterone levels therefore does not appear to mediate the testicular microcirculation changes produced by HCG.