Structure, absolute configuration, and antidiarrheal activity of a thymol derivative from Ageratina cylindrica.

The leaves of Ageratina cylindrica afforded a thymol derivative that was characterized by physical and spectroscopical methods as (8S)-8,9-epoxy-6-hydroxy-l0-benzoyloxy-7-oxothymol isobutyrate (1). The absolute configuration of 1 was established as 8S by vibrational circular dichroism spectroscopy in combination with density functional theory calculations and by evaluation of the Flack and Hooft X-ray parameters. Compound 1 showed weak antiprotozoal activity against Entamoeba histolytica and Giardia lamblia trophozoites and a high inhibitory effect on hyperpropulsive movement of the small intestine in rats.

Effect of plants used in Mexico to treat gastrointestinal disorders on charcoal-gum acacia-induced hyperperistalsis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: A total of 28 plant extracts, belonging to 26 different plant species are commonly used in Traditional Mexican Medicine for the treatment of gastrointestinal disorders such as diarrhea. AIM OF THE STUDY: To evaluate the effect of medicinal plant extracts on induced hyperperistalsis in rats. MATERIALS AND METHODS: Charcoal meal test was used in this study. Extracts were tested at a dose of 300mg/kg. RESULTS: From all the plant extracts tested, only Geranium mexicanum (roots) showed 100% of inhibition. The extracts of Artemisia absinthium, Matricaria recutita, Caesalpinia pulcherrima, Lygodium venustum, Chenopodium ambrosoides (green variety), Aloysia triphylla, Artemisia ludoviciana, Chiranthodendron pentadactylon, and Cocos nucifera showed moderate inhibitory activity with values ranging from 30 to 57%. Their activities were greater than that of or equal to loperamide (34% of inhibition at doses of 10mg/kg) drug used as control. The remaining plants exhibited marginal or null inhibitory effect on hyperpropulsive movement of the small intestine. CONCLUSIONS: The results obtained in this study give some scientific support to the popular use of 23 of the plants tested for the treatment of gastrointestinal disorders such as diarrhea in Mexican traditional medicine. However, roots of Geranium mexicanum should be used in herbal medicine with care to avoid toxicity.

Iridoids from the aerial parts of Verbena littoralis (Verbenaceae).

The iridoids, 6S-hydroxy-8S-methyl-4-methylene-hexahydro-cyclopenta[c]pyran-3-one and 6S,9S-dihydroxy-8S-methyl-4-methylene-hexahydro-cyclopenta[c]pyran-3-one, were isolated from the aerial parts of Verbena littoralis. Their structures and stereochemistry were elucidated by means of NMR spectral data analysis. Both compounds showed moderate in vitro activity against gram positive and negative bacteria as well as moderate in vivo intestinal peristaltic action in mouse. The iridoids also showed moderate free radical scavenging activity against l,l-diphenyl-2-picrylhydrazyl (DPPH) as well as antioxidant activity, the latter being evidenced by redox properties measured using E1CD-HPLC.

Shaker-type Kv1 channel blockers increase the peristaltic activity of guinea-pig ileum by stimulating acetylcholine and tachykinins release by the enteric nervous system.

1 A constant intraluminal pressure system was used to evaluate the effects of Kv1 channel blockers on the peristaltic activity of guinea-pig ileum. 2 The nortriterpene correolide, a non-selective inhibitor of all Kv1 sub-types, causes progressive and sustained reduction of the pressure threshold for eliciting peristaltic contractions. 3 Margatoxin (MgTX), alpha-dendrotoxin (alpha-DTX) and dendrotoxin-K (DTX-K), highly selective peptidyl inhibitors of certain Kv1 sub-types, cause immediate reduction of the pressure threshold. This effect subsides with time, irrespective of the peptides' concentration in the bath. In preparations pretreated with saturating concentrations of MgTX, correolide further stimulates the peristaltic activity. 4 Iberiotoxin (IbTX), a selective inhibitor of the high-conductance Ca(2+)-activated K(+) (BK) channels, and charybdotoxin (ChTX), which inhibits Kv1.2 and Kv1.3 as well as BK channels, fail to stimulate the peristaltic activity. 5 Blockade of muscarinic receptors by atropine reduces, and occasionally suppresses the peristaltic activity of guinea-pig ileum. In atropine-treated preparations, correolide and MgTX retain their abilities to reduce the pressure threshold and are able to restore the peristaltic reflex in the preparations where this reflex was suppressed by atropine. 6 The stimulatory effect of correolide and MgTX in atropine-treated preparations is abolished by subsequent addition of selective antagonists of both NK1 and NK2 receptors. 7 In conclusion, blockade of Kv1, particularly Kv1.1 channels, increases the peristaltic activity of guinea-pig ileum by enhancing the release of neurotransmitters at the enteric nervous system. In contrast, stimulation of the myogenic motility by blockade of BK channels does not affect the threshold for the peristaltic reflex.

Intracellular calcium mobilization by muscarinic receptors is regulated by micromolar concentrations of external Ca2+.

Carbachol-induced contractions of rat stomach fundus strips, obtained in a nutrient solution containing 1.8 mM Ca2+, were resistant to Ca2+ withdrawal, even after 1 h of bathing the tissues in a nominal 0 Ca2+ solution. This was not observed when K+ was used to evoke contractions, which were rapidly inhibited after Ca2+ removal (t1/2=2 min). The effect of carbachol in 0 Ca2+ solution was reduced by using drugs that reduce intracellular pools of Ca2+, such as caffeine (1-3 mM), ryanodine (30 microM) or thapsigargin (1 microM), corroborating the involvement of intracellular Ca2+ stores. On the other hand, when the 0 Ca2+ solution contained EGTA, a complete decline of carbachol effects was observed within about 8 min, indicating the involvement of extracellular Ca2+. Atomic absorption spectrometry showed that our 0 Ca2+ solution still contained 45 microM Ca2+, which was drastically reduced to 5.9 nM in the presence of EGTA. Taken together, our results indicate that the effects of carbachol are due to the mobilization of caffeine-, ryanodine- and thapsigargin-sensitive intracellular Ca2+ stores, and that these stores are not inactivated or depleted if micromolar concentrations (45 microM), but not nanomolar concentrations (5.9 nM) of Ca2+ are maintained in the extracellular milieu.

Esophageal motility in patients with esophageal caustic injury.

OBJECTIVE: There are few studies of esophageal function subsequent to the ingestion of lye. We investigated the esophageal motility of patients who had ingested liquid sodium hydroxide. METHODS: Esophageal manometry was performed on 21 patients who [1-53 yr before the manometric examination (median: 13 yr)] had drunk 10-30 g of sodium hydroxide diluted in water. The results were compared with those obtained for a control group of 22 healthy volunteers. RESULTS: The lower esophageal sphincter (LES) pressure of the caustic group (14.9 +/- 1.7 mm Hg, mean +/- SE) did not differ (p > 0.05) from that of the control group (17.4 +/- 1.1 mm Hg). LES pressure in eight patients was below 10 mm Hg. The amplitude of contraction was lower (p < 0.01) in the caustic group than in the control group. In the proximal part of the esophageal body, the duration of contraction was longer (p < 0.01) in the caustic group (2.3 +/- 0.1 s) than in controls (1.8 +/- 0.1 s). Nonperistaltic contraction was a finding in 14 patients, repetitive in five of them. The velocity of peristaltic contractions was higher (p < 0.05) in the caustic group (distal: 3.2 +/- 0.2 cm/s) than in the control group (2.2 +/- 0.2 cm/s). Although there was some impairment of esophageal motor function in 71% of the patients, they were asymptomatic when we performed esophageal manometry. CONCLUSIONS: Esophageal motility impairment was present in most of the patients who ingested sodium hydroxide. Nonperistaltic contractions of low amplitude were found most frequently.

Effects of nifedipine on esophageal tone and perception of esophageal distension.

The effects of nifedipine (20 mg orally) on esophageal body resting tone and perception of esophageal distension were compared with those of placebo in 10 healthy volunteers, using a double-blind crossover design. A 3-cm silicon balloon positioned 10 cm above the lower esophageal sphincter was inflated with 2-20 ml of air, in 2-ml increments. The subjects scored their chest sensations, while pressure in the balloon was continuously recorded. In each experiment three series of measurements were made, at baseline and 15 and 30 min after administration of nifedipine or placebo. Bench tests were run to determine pressure-to-volume relationships for each of the balloons used in the study. Thirty minutes after nifedipine ingestion, a significant decrease in systolic blood pressure (from 112.6 +/- 2.3 to 99.0 +/- 2.0 mm Hg) was observed. Amplitude and duration of esophageal peristaltic contractions were significantly decreased by nifedipine (from 128.1 +/- 16.7 to 98.7 +/- 10.6 mm Hg and from 3.9 +/- 0.3 to 3.3 +/- 0.2 sec, respectively). With balloon volumes of 8 ml and higher, balloon pressures were higher with the balloon in the esophagus than on the bench, the difference being determined by the compliance of the esophagus. This difference rose from 18.5 +/- 6.8 to 40.2 +/- 7.2 mm Hg (8-20 ml) with placebo and from 23.1 +/- 3.7 to 35.9 +/- 5.8 mm Hg with nifedipine. No significant differences between nifedipine and placebo were found. The esophageal sensation scores increased linearly with increasing balloon volume from 6 ml onwards. Nifedipine had no significant effect on the perception of esophageal balloon distension.

[Effect produced by the alkaloid fraction of Mimosa tenuiflora (tepescohuite) on the peristaltic reflex of the guinea pig ileum]. / Efecto producido por la fracción de alcaloides de Mimosa tenuiflora (tepescohuite) sobre el reflejo peristáltico del íleón del cobayo.

An alkaloidal fraction was obtained from Mimosa tenuiflora (Willd.) Poir (tepescohuite) trunk bark. The product contained mainly an indolealkylamine and three minor alkaloids. This fraction inhibited the peristaltic reflex in the guinea-pig isolated ileum in vitro.

[Model of intraluminal perfusion of the guinea pig ileum in vitro in the study of the antidiarrheal properties of the guava (Psidium guajava)]. / Modelo de perfusión intraluminal del ileon del cobayo in vitro en el estudio de las propiedades antidiarréicas de la guayaba (Psidium guajava).

An experimental in vitro model was developed for the study of plant extracts reported by traditional medicines in the treatment of diarrhea. The guinea-pig isolated ileum is perfused with the plant extract using an intraluminal approach. The peristaltic reflex is induced by electrical stimulation while the plant extract is perfused. The spasmolytic effects of Psidium guajava leaf methanol, hexane and water extracts were demonstrated suggesting the existence of two different types of active components. The results obtained allow to propose this in vitro method as a useful model to reproduce some of the characteristics of the oral way of administration of plant extracts.

Efecto del clebopride y metaclopramida en la presión del esfínter esófagico inferior y actividad peristáltica esofagica / The effect of clebopride and metoclopramide on lower esophageal sphincter pressure, and on esophageal peristaltic activity

Se investiga en 73 pacientes adultos el efecto de dos Ortopramidas (metoclorpramida y Clebopride) administradas por vía endovenosa, en dos poblaciones de pacientes; un grupo con reflujo Gastro Esofágico Patológico (56 pacientes) y otro grupo sin reflujo Gastro Esofágico Patológico (17 pacientes), en un estudio prospectivo y doble ciego. Se analiza el efecto de ambas drogas sobre el tono del Esfínter Esofágico Inferior (EEI), Intensidad de las Ondas Peristálticas (OP) y Fracción de las Ondas Peristálticas Eficaces (OPE), comparando estos parámetros en condiciones basales y después de la administración de 2 mgs. de Clebopride o 10 mgs de Metoclopramida, con registro a los 5-15 minutos post-inyección. No hubo reacciones adversas con ninguna de las dos drogas. Sólo encontramos pequeñas diferencias en algunos parámetros, que no permiten atribuir a éstos efectos importantes, por lo menos en las dosis usadas en esta experimentación. Nos parece necesario ampliar los estudios al respecto, con casuísticas mayores y dosis más altas

Effects of domperidone therapy on symptoms and upper gastrointestinal motility in infants with gastroesophageal reflux.

We evaluated the effect of domperidone, a novel prokinetic agent, on symptoms and esophageal and gastric motility in 15 infants (six boys), mean age 7.9 months, with moderate to severe gastroesophageal reflux (GER) and upper gastrointestinal motility disturbances. Patients received domperidone orally for 6 weeks and underwent weekly assessment of five GER-associated symptoms, weight change, and side effects. Mean total symptom scores significantly improved after treatment (P less than 0.01). Vomiting, "spitting," and coughing each improved significantly. Postprandial reflux time (defined as esophageal pH less than 4.0) and percent peristaltic esophageal contractions improved significantly (p less than 0.05). Gastric fundic contractions, present in only four infants before treatment, occurred in nine after domperidone administration. Although mean gastric emptying of isotope-labeled formula was not improved, it improved greater than or equal to 10% over baseline in nine patients. Peristaltic amplitude, lower esophageal sphincter pressure, and esophageal acid clearance time were unchanged. Side effects were minimal. We conclude that domperidone is a useful and safe agent for treatment of gastroesophageal reflex in infants because it addresses the motility abnormalities inherent in the pathophysiology of the disorder.

[Diltiazem in esophageal motility disorders]. / Diltiazem en los trastornos de la motilidad esofágica.

The effects of the calcium blocking agent diltiazem upon esophageal motility was studied with electromanometric technique in 23 patients. In 10 achalasic patients lower esophageal sphincter pressure was reduced in 40.1%, in the remaining 13 in only 19.15%. Other parameters showed only minor changes such as reduction in the pressure of contractile waves in the body of the esophagus.

Efeitos respiratórios e cardiovasculares agudos de mascagnea rigida (tingui) no cäo / Acute respiratory and cardiovascular effects of Mascagnea regida (tingui) in dogs

Estudaram-se os efeitos cardiovasculares, respiratórios e peristálticos intestinais de princípio tóxicos de Mascagnea rigida, em cäes e ratos. Foi observado intensa e permanente queda da pressäo arterial média, broncoconstriçäo e exacerbaçäo da propulsäo peristáltica intestinal com reduçäo na freqüência cardíaca. Esses efeitos näo säo revertidos por agentes anticolinérgicos, nem säo bloqueados pelo propranolol, nem por agentes antihistamínicos, sugerindo um efeito por princípio ativo de natureza desconhecida

[Action of metoclopramide bromide and metoclopramide chloride on the lower esophagogastric junction and the peristalsis of the lower 3d of the esophagus]. / Acción del bromuro de metoclopramida y del chlorhidrato de metoclopramida sobre el esfínter esofágico inferior y la peristalsis del tercio inferior del esófago.

In 10 patients with esophageal hiatus hernia the effect of metoclopramide bromide and metoclopramide chloride compared with placebo, was studied by the double blind method. Both drugs produced an increase of the lower esophageal sphincter pressure and of the peristalsis of the lower third of the esophagus, only being statistically significative the action of metoclopramide chloride on the perstalsis. No significative side-effects were noted.

The effect of glucagon on cholinomimetic responses of the recto-sigmoid.

Motor activity of the lower bowel was induced by the parenteral administration of prostigmine or bethanechol in 7 subjects. Intraluminal pressure recordings from the sigmoid colon and rectum revealed that the augmented responses of motor activity to these cholinomimetic drugs were similar both in duration and in motility indexes. The intravenous administration of glucagon inhibited the motor responses to both cholinomimetic stimuli employed. A possible mechanism for the inhibitory action of glucagon is suggested and the clinical application of these observations is discussed.