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PubMed1999

New phenanthrene derivatives from maxillaria densa(1)

Two new phenanthrene derivatives, 2,5-dihydroxy-3, 4-dimethoxyphenanthrene (1) and 9,10-dihydro-2,5-dihydroxy-3, 4-dimethoxyphenanthrene (2), were isolated from an extract prepared from the whole plant of the orchid Maxillaria densa with spasmolytic activity. In addition, four known compounds, namely 2,7-dihydroxy-3, 4-dimethoxyphenanthrene, 9,10-dihydro-2,7-dihydroxy-3, 4-dimethoxyphenanthrene (3), 2,5-dihydroxy-3,4, 9-trimethoxyphe-nanthrene, and 2,7-dihydroxy-3,4, 9-trimethoxyphenanthrene, were obtained. The structures of the isolated compounds were elucidated by spectroscopic methods. In the case of phenanthrene derivatives 1 and 3, the structures were unambiguously assigned by X-ray analysis.

Journal Article↗
PubMed1994

Menthol-beta-D-glucuronide: a potential prodrug for treatment of the irritable bowel syndrome.

Menthol-beta-D-glucuronide is a potential prodrug for colonic delivery of the spasmolytic agent menthol. Menthol is the primary constituent of peppermint oil, which is used to treat the irritable bowel syndrome. The chemical stability of menthol-beta-D-glucuronide was assessed at various pHs (1.5, 4.5, 6.0 and 7.4) over a 4 to 24 h period at 37 degrees C. The prodrug was stable, i.e., there was less than 0.1% hydrolysis of the prodrug, at pHs of 4.5, 6.0 and 7.4. At pH 1.5, the prodrug was about 20% hydrolyzed over a 4 h period suggesting the need for an enteric coating to prevent premature hydrolysis in the stomach. The stability of the prodrug was also assessed in luminal contents of the laboratory rat and in human stool samples. These studies were performed at concentrations designed to assess relative velocities of hydrolysis (i.e., substrate concentrations in excess of the Km). The prodrug was stable in luminal contents of the rat stomach, proximal small intestine, and the distal small intestine. The rate of hydrolysis of menthol-beta-D-glucuronide was 6.26 +/- 2.88 nmol min-1 mg-1 and 2.34 +/- 1.22 nmol min-1 mg-1 in luminal contents of the rat cecum and colon, respectively. The hydrolysis rate of menthol-beta-D-glucuronide was lower in human stool samples (0.52 +/- 0.46 nmol min-1 mg-1). The prodrug had a measured log octanol/buffer partition coefficient of -1.61 suggesting it should be poorly absorbed from the lumen of the gastrointestinal tract. The data support the hypothesis that menthol-beta-D-glucuronide is a candidate for the delivery of menthol to the large intestine under in vivo conditions.

Animals↗
PubMed2003

[Gallstones--natural history and conservative management].

Gallstones have a very high prevalence affecting 9.5 and 19.5% of men and women, respectively. The pathophysiology and risk factors for cholesterol gallstones are considered. Modern imaging techniques, in particular ultrasound, are very sensitive to detect cholecystolithiasis, while ERCP remains the gold standard to detect choledocholithiasis. ERCP could be supplanted soon by endosonography and MRCP. Biliary scintigraphy is useful to detect a 'vésicule exclue' and to document gallbladder/sphincter Oddi dysfunction. The different conservative management strategies including litholytic treatment with ursodeoxycholate and lithotripsy have been largely abandoned in favor of laparoscopic cholecystectomy. Litholytic treatment has still a role to play in the prevention of gallstone formation in patients with rapid weight loss and in the newly detected MDR3 defect associated with sludge formation. Biliary colic is treated with non-steroidal analgesic drugs, analgesics and/or spasmolytic agents.

Cholecystectomy↗
PubMed2001

Augmented intestinal trefoil factor (TFF3) and loss of pS2 (TFF1) expression precedes metaplastic differentiation of gastric epithelium.

The trefoil peptides spasmolytic polypeptide (SP), intestinal trefoil factor (ITF), and pS2 show lineage-specific expression in the normal gut and are strongly induced after mucosal injury. We assessed the relationship between this induction and the development of the regenerative epithelial lineage over time in the rat stomach and verified these observations in the metaplastic and dysplastic human stomach. Antral or colonic ulcers were induced in Wistar rats by application of serosal acetic acid and tissues harvested 2 hours to 125 days later. Human endoscopic biopsies or gastric resection specimens were also assessed. Tissues were examined by radioimmunoassay, immunoblotting, or immunohistochemistry for ITF, SP, and transforming growth factor alpha (rat) or ITF and pS2 (human) expression. ITF and SP mRNA in antral ulcer margins was localized by in situ hybridization. ITF and SP peptide expression rose steadily in ulcer margins after 4 days, with the rise in ITF being more pronounced. By 40 days, several hundred-fold elevations in ITF levels were present, with a field effect in uninvolved mucosa. Hyperproliferative, elongated glands of undifferentiated cells expressing abundant trefoil peptides and acid sulfomucins were present after day 12 and persisted after ulcer healing. ITF mRNA was aberrantly expressed in basal and mid-regions of these regenerative glands. In contrast, transforming growth factor alpha peptide expression rose promptly after injury then fell to baseline levels with healing. Seven months after injury, gastric atrophy, intestinal metaplasia, and severe dysplasia with conserved ITF expression were seen. ITF was also induced in human intestinal metaplasia and conserved in all gastric cancers, whereas expression of the gastric peptide pS2 was progressively reduced in the progression from metaplasia to dysplasia. Persistent, selective overexpression of ITF, possibly acting in an autocrine fashion, is a feature of regeneration after antral ulceration, and may provide insight into the nature of metaplastic phenotypes arising from chronic gastric injury. The loss of pS2 expression in metaplasia and cancer supports a role for this protein in gastric tumor suppression.

Adenocarcinoma↗
PubMed1986

Early clinical experience with clonidine in spinal spasticity.

The centrally active, alpha-2 adrenergic receptor agonist clonidine was given to 12 spinal cord injury patients with problematic spasticity not adequately controlled by recognized spasmolytic drug therapy. Five patients had an excellent reduction and 2 patients had some reduction in clinical spasticity (average dose 0.39 mg daily). Four of the 7 responders discontinued clonidine because of adverse reactions after an average of ten weeks of therapy. Three responders have continued to tolerate the drug well with excellent control of spasticity for 18 to 34 months. Five patients had no change in clinical spasticity (average dose of 0.24 mg daily). Three of the non-responders discontinued clonidine because of adverse reactions after an average of three weeks of therapy. Significant associated adverse reactions included syncopal seizures (3), cerebrovascular accident (1), deep vein thrombosis (1), autonomic hyperreflexia (3), lethargy/drowsiness (3), and nausea/vomiting (1). Possible mechanisms of action for clonidine to affect spasticity and the unstable cardiovascular system of quadriplegics is discussed. While spinal cord injured patients with severe spasticity may benefit from clonidine, great caution is recommended during its use until further study establishes safe parameters of administration and efficacy is confirmed on controlled studies.

Adult↗
PubMed2001

Role of PGE(2) in protease-activated receptor-1, -2 and -4 mediated relaxation in the mouse isolated trachea.

1. The potential mediator role of the prostanoid PGE(2) in airway smooth muscle relaxations induced by peptidic and proteolytic activators of PAR-1, PAR-2, PAR-3 and PAR-4 was investigated in carbachol-precontracted mouse isolated tracheal segments. 2. The tethered ligand domain sequences of murine PAR-1 (SFFLRN-NH(2)), PAR-2 (SLIGRL-NH(2)) and PAR-4 (GYPGKF-NH(2)), but not PAR-3 (SFNGGP-NH(2)), induced smooth muscle relaxation that was abolished by the non-selective cyclo-oxygenase (COX) inhibitor, indomethacin. The relative order for mean peak relaxation was SLIGRL-NH(2)>GYPGKF-NH(2) approximately amp; SFFLRN-NH(2)>SFNGGP-NH(2). 3. SFFLRN-NH(2), SLIGRL-NH(2) and GYPGKF-NH(2), but not SFNGGP-NH(2), induced significant PGE(2) release that was abolished by indomethacin. Like that for relaxation, the relative order for mean PGE(2) release was SLIGRL-NH(2)>GYPGKF-NH(2)>SFFLRN-NH(2)>SFNGGP-NH(2). 4. In dose-response studies, SLIGRL-NH(2) induced concentration-dependent increases in PGE(2) release (EC(50)=20.4 microM) and smooth muscle relaxation (EC(50)=15.8 microM). 5. The selective COX-2 inhibitor, nimesulide, but not the COX-1 inhibitor valeryl salicylate, significantly attenuated SLIGRL-NH(2)-induced smooth muscle relaxation and PGE(2) release. 6. Exogenously applied PGE(2) induced potent smooth muscle relaxation (EC(50)=60.3 nM) that was inhibited by the mixed DP/EP(1)/EP(2) prostanoid receptor antagonist, AH6809. SLIGRL-NH(2)-induced relaxation was also significantly inhibited by AH6809. 7. In summary, the results of this study strongly suggest that PAR-mediated relaxation in murine tracheal smooth muscle is dependent on the generation of the spasmolytic prostanoid, PGE(2). PAR-stimulated PGE(2) release appears to be generated preferentially by COX-2 rather than COX-1, and induces relaxation via activation of the EP(2) receptor.

Animals↗
PubMed2001

Evidence that the anti-spasmogenic effect of the beta-adrenoceptor agonist, isoprenaline, on guinea-pig trachealis is not mediated by cyclic AMP-dependent protein kinase.

1. The spasmolytic and anti-spasmogenic activity of beta-adrenoceptor agonists on airways smooth muscle is thought to involve activation of the cyclic AMP/cyclic AMP-dependent protein kinase (PKA) cascade. Here we have tested the hypothesis that PKA mediates the anti-spasmogenic activity of isoprenaline and other cyclic AMP-elevating agents in guinea-pig isolated trachea by utilizing a number of cell permeant cyclic AMP analogues that act as competitive 'antagonists' of PKA. 2. Anion-exchange chromatography of guinea-pig tracheae resolved two peaks of PKA activity that corresponded to the type I ( approximately 5%) and type II ( approximately 93%) isoenzymes. 3. Pre-treatment of tracheae with zardaverine (30 microM), vasoactive intestinal peptide (VIP) (1 microM) and the non-selective activator of PKA, Sp-8-CPT-cAMPS (10 microM), produced a non-parallel rightwards shift in the concentration-response curves that described acetylcholine (ACh)-induced tension generation. The type II-selective PKA inhibitor, Rp-8-CPT-cAMPS (300 microM), abolished this effect. 4. Pre-treatment of tracheae with Sp-8-Br-PET-cGMPS (30 microM) produced a non-parallel rightwards shift of the concentration-response curves that described ACh-induced tension generation. The selective cyclic GMP-dependent protein kinase (PKG) inhibitor, Rp-8-pCPT-cGMPS (300 microM), abolished this effect. 5. Pre-treatment of tracheae with isoprenaline (1 microM) produced a 10 fold shift to the right of the ACh concentration-response curve by a mechanism that was unaffected by Rp-8-Br-cAMPS (300 microM, selective inhibitor of type I PKA), Rp-8-CPT-cAMPS (300 microM) and Rp-8-pCPT-cGMPS (300 microM). 6. We conclude that the anti-spasmogenic activity of Sp-8-CPT-cAMPS, zardaverine and VIP in guinea-pig trachea is attributable to activation of the cyclic AMP/PKA cascade whereas isoprenaline suppresses ACh-induced contractions by a mechanism(s) that is independent of PKA and PKG.

Acetylcholine↗
PubMed1976

Effects of calcium-antagonistic drugs on the stimulation by carbamoylcholine and histamine of phosphatidylinositol turnover in longitudinal smooth muscle of guinea-pig ileum.

A number of drugs classed as calcium antagonists, spasmolytics, non-specific receptor antagonists or receptor antagonists with multiple sites of action were tested to determine whether they prevent the stimulation of phosphatidylinositol turnover caused in various tissues by the activation of receptors which increase cell-surface Ca2+ permeability. The experiments were done with fragments of longitudinal smooth muscle from guinea-pig ileum; these were incubated in vitro with 32Pi and either 100 muM-carbamoylcholine or 100 muM-histamine, in the presence of antagonistic drugs at concentrations at least sufficient to cause complete blockade of smooth-muscle contraction. The phosphatidylinositol response to carbamoylcholine was not changed by cinchocaine, papaverine, nifedipine, dibenamine, amethocaine, cinnarizine, lidoflazine, methoxyverapamil, prenylamine or two antimuscarinic alkane-bis-ammonium compounds, and the response to histamine was unaffected by the first four drugs. In contrast, phenoxybenzamine prevented the increase in phosphatidylinositol labelling caused by either carbamoylcholine or histamine. The insensitivity of the phosphatidylinositol response to most of the drugs provides further experimental support for the conclusion that the receptor-stimulated phosphatidylinositol breakdown which initiates the increase in phosphatidylinositol turnover is not caused by an increase in intracellular Ca2+. The simplest interpretation of the available information appears to be that phosphatidylinositol breakdown plays a role in the coupling between the receptor-agonist interaction and the opening of cell-surface Ca2+ gates [Michell, R. H. (1975) Biochim. Biophys. Acta 415, 81-147]. If this is correct, then phenoxybenzamine must exert its inhibitory effects on phosphatidylinositol breakdown early in this sequence of events, but the drugs must act at a stage later than phosphatidylinositol breakdown. The unexpected difference in the effects of dibenamine and phenoxybenzamine, which are chemically very similar, may provide a useful experimental tool with which to explore the way in which activated receptors provoke the opening of cell-surface Ca2+ gates.

Anesthetics, Local↗
PubMed1996

cDNA cloning of rat pS2 peptide and expression of trefoil peptides in acetic acid-induced colitis.

By using a combination of the methods of reverse transcription-PCR and rapid amplification of cDNA ends, a cDNA for rat pS2 peptide (rpS2) was successfully cloned and sequenced from rat stomach. By RNA blot analysis, the gene was shown to be expressed abundantly in the stomach and only faintly in the duodenum, but not in other tissues including the distal small and large intestines. rpS2 expression was also examined in the rectum during the course of acetic acid-induced colitis; rpS2 mRNA was detected during the acute phase of colitis but not in normal controls or during the recovery phase. On the other hand, expression of rat intestinal trefoil factor (rITF) was down-regulated during the acute phase of colitis and then up-regulated during the recovery phase, whereas rat spasmolytic peptide was not detectable throughout the course of the induced colitis. These results indicate that the patterns and timing of the expression of these trefoil peptides are different from each other. rpS2 may play an important role in the proliferation of intestinal epithelial cells during the acute phase of mucosal ulceration, whereas rITF may be involved in differentiation of the cells, particularly to form goblet cells, during the recovery phase.

Acetic Acid↗
PubMed1984

Bile salts, hypotension and obstructive jaundice.

We have examined the effects of bile duct ligation on vascular and extravascular smooth muscle responsiveness to noradrenaline and tyramine using isolated rat hindlimb perfusion, and portal vein and vas deferens preparations. Bile duct ligation reduced the contractile responses to noradrenaline of vascular and extravascular smooth muscle. Exposure of smooth muscle to some bile salts caused a reduction in contractility. This effect was dependent upon bile salt type and concentration. These studies in vitro suggest that the reduced total peripheral resistance and hypotension seen in obstructive jaundice cannot be explained by a spasmolytic effect of some of the bile salts on smooth muscle.

Animals↗
PubMed1996

Review article: beta 3-adrenoceptor agonists--future anti-inflammatory drugs for the gastrointestinal tract?

The beta 3-adrenoceptor is now a recognized sub-type of beta-adrenoceptor and is the principle adrenoceptor responsible for lipolysis in rat adipocytes. The receptor is also found in the gastrointestinal tract where beta 3-adrenoceptor agonists are both spasmolytic and potent inhibitors of experimental non-steroidal anti-inflammatory drug (NSAID)-induced gastric and small intestinal ulcers. There is evidence to suggest that the underlying mechanism of protection involves enhancement of mucosal blood flow, possibly as a result of relaxation of vascular and non-vascular smooth muscle. This review examines some possible therapeutic applications for beta 3-adrenoceptor agonists in ulcero-inflammatory disorders of the gastrointestinal tract where an altered blood flow state is a component of the underlying pathogenic process.

Adrenergic beta-Agonists↗
PubMed1998

Otilonium bromide in irritable bowel syndrome: a double-blind, placebo-controlled, 15-week study.

AIM: To evaluate the efficacy of otilonium bromide, a spasmolytic agent, in the treatment of irritable bowel syndrome using modern and validated diagnostic criteria. METHODS: Three hundred and seventy-eight patients with irritable bowel syndrome were enrolled in the study. At entry, endoscopy/barium enema, clinical examination and laboratory tests were used to rule out organic diseases. After a 2-week placebo run-in, 325 patients were randomly assigned to receive either otilonium bromide 40 mg t.d.s. or placebo for 15 weeks. Abdominal pain, abdominal distension and disturbed defecation were scored at the beginning of the study and every 5 weeks. A global determination of well-being by visual analogue scale and the tenderness of the sigmoid colon were also scored. RESULTS: The reduction in the number of abdominal pain episodes was significantly higher (P < 0.01) in otilonium bromide patients (55.3%) than in those taking placebo (39.9%) as was the severity of abdominal distension (42.0%, vs. 30.2%; P < 0.05). Bowel disturbance improved in both groups. but without any statistically significant difference. The visual analogue scale of well-being revealed a significant improvement (P < 0.05) in patients taking otilonium bromide. The investigators' global positive assessment was in favour of otilonium bromide (65.2%) compared with placebo (49.6%) (P < 0.01). CONCLUSIONS: Otilonium bromide may represent an effective treatment for irritable bowel syndrome because it reduces its predominant symptom (abdominal pain/ discomfort) more than placebo does.

Colonic Diseases, Functional↗
PubMed1999

Interactions of new and conventional H3-antagonists with non-histaminergic receptors involved in neurogenic and myogenic contractile responses of guinea-pig ileum.

1. Possible effects of new and conventional H3-receptor antagonists towards various non-histaminergic receptors (alpha2-adrenergic, 5-HT3-serotonin, mu-opiate, A1-adenosine, M1-and M3-muscarinic) involved in neurogenic and myogenic contractile responses of guinea-pig ileum are investigated. 2. When the isolated ileum was contracted by the 5-HT3 receptor agonist, 2-methyl-5-HT (5 x 10(-7)-8 x 10(-6) M), acetylcholine (1 x 10(-9)-1 x 10(-7) M), KCl (3 x 10(-2) M) or electrical stimulation some of the drugs, included thioperamide and clobenpropit, reduced the contractile response when tested at micromolar concentrations (1-3 x 10(-5) M) (only compound IV exhibited an M3 competitive antagonism with a pK(B) = 5.49 +/- 0.18). 3. Ileal twitch responses to electrical stimulation were dose-dependently inhibited by the selective agonists clonidine (3 x 10(-10)-1 x 10(-7) M), dermorphin (1 x 10(-11)-1 x 10(-8) M), R-N6-(2-phenylisopropyl)-adenosine (1 x 10(-9)-3 x 10(-8) M) and McN-A-343 (1 x 10(-7)-1 x 10(-5) M) with different potencies and comparable efficacy (spike amplitude reduction > 85%). All the H3 antagonists under study (up to 1 x 10(-5) M) showed no or minor interactions at the neuronal sites except the compound V which behaved as a weak competitive antagonist at alpha2-adrenoreceptors (pK(B) = 5.96 +/- 0.06). 4. In conclusion, both new and conventional H3-blockers interacted at the enteric neuronal sites here studied with a 1000-30,000 fold lower antagonistic potency than that previously reported for the ileal H3 histamine receptors. Their spasmolytic activity precludes firm conclusions about the non-competitive interaction with 5-HT3 ileal receptor which requires further investigations.

Animals↗
PubMed2002

Involvement of the signal transduction pathway mediated by epidermal growth factor receptor in the differentiation of chicken glandular stomach.

During the development of the chicken proventriculus (glandular stomach), the initially undifferentiated epithelium differentiates into two distinct cell populations: the glandular epithelium, cells of which secrete embryonic chicken pepsinogen (ECPg), and luminal epithelial cells, which express the chicken spasmolytic polypeptide gene (cSP). Based on knowledge of the adult mouse stomach, the ligands of epidermal growth factor (EGF) receptor (EGFR) were expected to affect differentiation of the proventricular epithelium. When EGF was added to the medium in which proventriculi were cultured in vitro, gland formation was suppressed in a dose-dependent manner and the amount of ECPg mRNA decreased, whereas morphological differentiation of luminal epithelium was stimulated. Simultaneous treatment of the proventriculus with EGF and tyrphostin 47 resulted in the attenuation of the effect of EGF, suggesting that EGF, or other ligands of EGFR, may actually be involved in the normal course of development of the proventricular epithelium.

Animals↗
PubMed2003

The effect of drotaverine hydrochloride in acute colicky pain caused by renal and ureteric stones.

OBJECTIVE: To assess the spasmolytic effect of drotaverine hydrochloride in colicky pain caused by renal and ureteric stones. PATIENTS AND METHODS: In a placebo-controlled, multicentre, multinational, randomized, double-blind study changes in the intensity of pain were recorded using a visual analogue scale (VAS), a four-grade (five points) pain intensity (PI) scale and a pain-relief scale. The primary endpoint was the evaluation of the antispasmodic effect of drotaverine during a 3-h study period, to confirm that drotaverine abolished or significantly decreased the intensity of pain in renal colic. The painkilling effect was defined as a decrease by at least half in the PI scale, and/or a >or= 40% decrease in the VAS 40 min after either the first or the second injection of 80 mg drotaverine or placebo (if necessary the dose could be repeated once). In all, 140 patients were enrolled but 38 withdrew, leaving 102 patients for analysis (48 drotaverine, 54 placebo; mean age 42.5 years, sd 11.25, and 41.7, sd 10.79). RESULTS: Drotaverine was effective in 79% of patients and placebo in only 46% (P < 0.001). There were no serious adverse effects. There were 20 minor side-effects in the drotaverine and four in the placebo group; none of the patients required treatment. The most frequent side-effects were a transitory decrease in blood pressure, vertigo, nausea or vomiting. CONCLUSION: Intravenous drotaverine provides effective pain relief in more than two-thirds of patients with renal colic, with no serious side-effects.

Acute Disease↗
PubMed1996

Intracolonic injection of glycerol: a model for abdominal pain in irritable bowel syndrome?

BACKGROUND & AIMS: Abdominal pain is the main symptom in patients with irritable bowel syndrome (IBS). Glycerol is an irritant of colonic mucosa. The aim of this study was to evaluate the effects of an intraluminal injection of glycerol on colonic motility and tone in patients with IBS and their modulation by drugs. METHODS: Colonic motility was evaluated using electromyography, and colonic tone was assessed using a barostat. Glycerol was injected in the right colon or the rectum. RESULTS: After intracolonic injection of glycerol, a strong abdominal colic occurred and was associated with an increase in long spike burst activity (+280%), which was eliminated by previous administration of lidocaine and was not observed after paraffin oil. When glycerol was injected intrarectally, abdominal pain occurred and long spike burst activity was increased (+240%) in the left colon. Simultaneously, colonic tone decreased (-70%) and high-amplitude phasic contractions occurred (10 +/- 1/patient). This rectocolonic reflex was reproducible in the same patient. Drugs acting on visceral afferent pathways (octreotide and granisetron) did not modify this reflex, whereas the spasmolytic drug phloroglucinol inhibited phasic contractions without affecting tone. CONCLUSIONS: Intraluminal injection of glycerol triggers viscerovisceral reflexes, resulting in abdominal pain in patients with IBS. It could be used as a model for the study of effects of drugs on pain in these patients.

Abdominal Pain↗
PubMed1996

Oral trefoil peptides protect against ethanol- and indomethacin-induced gastric injury in rats.

BACKGROUND & AIMS: The trefoil factors, a family of proteins abundantly expressed in gastrointestinal mucous cells, protect the epithelium in vitro. This study determines the effects of exogenously administered trefoil peptides on experimental injury in rats in vivo. METHODS: Gastric injury was induced by either intragastric absolute ethanol (1.0 mL) or subcutaneous indomethacin (20 mg/kg). Recombinant human spasmolytic polypeptide (rHSP) or rat intestinal trefoil factor (ITF) were administered at different doses and time points before or after injury. Vehicle or bovine serum albumin was used as control. The pH of the stomach contents was assessed when the rats were killed. Gastric injury was blindly evaluated macroscopically and histologically. Serum levels of rHSP and ITF were determined by an enzyme-linked immunosorbent assay. RESULTS: Oral rHSP and ITF markedly protected against both ethanol- and indomethacin-induced gastric injury (P < 0.005 at doses of 1-15 mg/rat) when given up to 2 hours before injury; no protection was noted by intraperitoneal rHSP against ethanol injury. Intraperitoneal rHSP protected against indomethacin-induced injury only at the maximal dose given (15 mg). Neither rHSP nor ITF altered gastric pH. Protection was not associated with systemic absorption of trefoil peptides. CONCLUSIONS: Topical trefoil peptides protect the gastric mucosa against ethanol- and indomethacin-induced gastric injuries. These peptides contribute to surface mucosal defense.

Administration, Oral↗
PubMed2002

Resolution of cerebral vasospasm with trapidil; an animal model.

Cerebral vasospasm and rebleeding are important clinical phenomena associated with a high mortality rate. Therefore, any promising finding in the laboratory deserves assessment in clinical practice. The present study was designed to examine the possible effects of trapidil on the basilar artery of the rabbit through a cerebral vasospasm model. This experimental study was carried out on 26 adult New Zealand albino rabbits of both sexes weighing 2.5-3.0 kg. A transclival exposure was performed. Vasospasm was produced by an intracisternal injection of autologous blood. After observation of the vasospasm, trapidil was locally applied in increasing concentrations (10(-5)-10(-4) M). The effect of each concentration was measured independently after 10 minutes for each application and was extended to three hours. Trapidil was shown to have a clear spasmolytic effect on the rabbit's basilar artery. These data suggest that trapidil can have a potential use in the treatment of patients suffering from cerebral vasospasm.

Animals↗