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At least 1,297 records · Page 72Linked to original sources
PubMed2000

Renal infarction: an uncommon mimic presenting with flank pain.

A 39-year-old woman arrived to the emergency department complaining of a constant, progressive, left flank pain, with no beneficial effect from spasmolytic and nonsteroidal antiinflammatory drugs. Two years before, she suffered another episode of right flank pain and stranguria, but instrumental examinations (ultrasonography, urography) remained negative. Besides a mild tenderness in the left flank, physical examination was normal. Blood chemistry panel showed leukocytosis (17.2 x 10(3) mL, neutrophils 82.8%) and a slight increase of serum lactate dehydrogenase (LDH) (543 U/L versus 230 to 460 U/L). Urinanalysis showed a slight hemoglobinuria (0.5 mg/dL), and sediment contained some red cells and leukocytes. Diagnostic examinations (ultrasonography, computed tomography) showed a left renal nonhomogeneous space-occupying lesion, orientative for renal malignancy. She was transferred to the urology department and operated. Both intraoperatory and histological diagnosis was ischemic infarction and, after exclusion of all possible underlying causes, final diagnosis was idiopathic renal infarction. Diagnostic procedures and literature reports are discussed.

Adult↗
PubMed2004

Treatment of spastic esophageal motility disorders.

Treatment of spastic motility disorders continues to be challenging. Therapeutic options remain limited due in part to our lack of understanding of the pathophysiology and significance of these disorders. Furthermore, most of therapeutic trials to date are hampered by the poorly designed nature of the study, including the small size of the trials and the lack of placebo arm. Most of the available information suggests that there seems to be an important dissociation between symptoms (chest pain/dysphagia) and esophageal dysmotility. Drug treatment aimed at visceral sensitivity seems more effective in relieving symptoms than spasmolytic medications. Recent trials with Botox, nitric oxide derivatives, and SSRIs offer promising results. Rigorous study design that includes large placebo-controlled trials is needed in this area.

Chest Pain↗
PubMed1998

Growth factors and the gastrointestinal tract.

This paper reviews areas of interest in gut mucosal growth factor physiology. Several epidermal growth factor (EGF)-like peptides (EGF, transforming growth factor [TGF]-alpha, heparin-binding EGF-like peptide, amphiregulin, and betacellulin) have been identified in the gut, EGF is produced by the salivary glands and is present in milk. It may act on the mucosa from the lumen as a surveillance peptide promoting mucosal repair. A stem-cell-derived "ulcer-associated cell lineage" develops adjacent to ulcers and produces EGF, which may play a role in ulcer healing. TGF-alpha is expressed by villus enterocytes and may have an important role in mucosal healing. The Trefoil peptides (pS2, spasmolytic polypeptide, intestinal trefoil factor) are protease resistant molecules secreted by mucin cells throughout the gut, with a role in mucosal healing. The TGF-beta family inhibit cell proliferation, and promote cell differentiation. TGF-beta has a gradient of expression along the crypt villus axis, with maximum production at the villus tip. It is suspected that it may prevent cell proliferation and support differentiation of villus enterocytes. Hepatocyte growth factor is a multifunctional growth factor expressed in many tissues, including the gastrointestinal tract. It has a role in organogenesis. Intestinal adaptation is highly dependent on enteral nutrition, and it is likely that growth factors are involved in adaptation. Little is known, however, about interactions between nutrients and growth factors. Milk contains a range of potentially important growth factors. Their biological significance is uncertain, and this is an area of active research.

Animals↗
PubMed2003

Pharmacokinetics and bioavailability of denaverine hydrochloride in healthy subjects following intravenous, oral and rectal single doses.

The neurotropic-musculotropic spasmolytic agent denaverine hydrochloride is used mainly in the treatment of smooth muscle spasms of the gastrointestinal and urogenital tract. Despite its commercial availability as a solution for intravenous or intramuscular administration (ampoule) and as a suppository formulation, no pharmacokinetic data in man was available to date. Therefore, the objectives of this clinical trial were to determine the basic pharmacokinetic parameters of denaverine after intravenous administration, to assess the feasibility of using the oral route of administration and to characterise the bioavailability of the suppository formulation. To achieve this, healthy subjects received 50 mg denaverine hydrochloride intravenously, orally and rectally in aqueous solutions and rectally as suppository in an open, randomised crossover design. Total body clearance, volume of distribution at steady-state and half-life of denaverine are 5.7 ml/min per kg, 7.1 l/kg and 33.8 h, respectively. The absolute bioavailability after oral administration of an aqueous solution is 37%. First-pass metabolism leading to the formation of N-monodemethyl denaverine was found to be one reason for the incomplete bioavailability after oral administration. Rectal administration of an aqueous solution of denaverine hydrochloride resulted in a decreased rate (median of C(max) ratios: 26%, difference in median t(max) values: 1.9 h) and extent (31%) of bioavailability compared to oral administration. Using the suppository formulation led to a further reduction in rate (median of C(max) ratios: 30%, difference in median t(max) values: 3 h) and extent (42%) of bioavailability compared to the rectal solution.

Administration, Oral↗
PubMed2000

Pharmacodynamic study of Hypericum perforatum L.

The effects of Hypericum perforatum L. (Hypericaceae) crude ethanol extract (A), ethyl acetate extract (B), aqueous extract (C) and infusion (I), on pentobarbital induced sleeping time, intestinal motility, and their analgesic activity, have been investigated. Extracts A and B exhibited significant stimulatory and antidepressant effects on the CNS. Both extracts prolonged sleep, increasing time up to more than 25 min. The antidepressive activity of extract A was also achieved by significant reduction of the myorelaxant activity of diazepam. Extract B exhibited strong analgesic activity reducing abdominal stretching induced by acetic acid by nearly 50 %. Extracts A, B and C exhibited spasmolytic activity, significantly reducing intestine motility.

Acetic Acid↗
PubMed2002

New insights into the pharmacological properties of potent antiplatelet 2-amino-benzo[d]isothiazol-3-one derivatives.

A series of 2-amino-benzo[d]isothiazol-3-one derivatives (1-8), previously described as in vitro potent antiaggregatory agents endowed with spasmolytic properties, was evaluated for in vitro antiplatelet activity in guinea-pig platelet rich plasma and for in vivo effects on experimental thrombosis and bleeding time in mice. All the 2-amino-benzo[d]isothiazol-3-one derivatives 1-8 were more potent antiplatelets against collagen than acetylsalicylic acid and, unlike this drug, strongly inhibited thromboxane agonist U46619-induced aggregation. Subacutely administered (5mgkg(-1) day i.p. for 5 days), compounds 6 and 7 protected mice from collagen/epinephrine induced pulmonary thromboembolism at about 20-fold lower doses than acetylsalicylic acid and they prolonged bleeding time like the most part of the other derivatives. The potent antithrombotic activity was coupled with the absence of any lethal and ulcerogenic effect up to 200mgkg(-1) os.

Administration, Oral↗
PubMed2004

Complementary and alternative medicine in gastroenterology: the good, the bad, and the ugly.

A large proportion of the American population avails itself of a variety of complementary and alternative medicine (CAM) interventions. Allopathic practitioners often dismiss CAM because of distrust or a belief that there is no sound scientific evidence that has established its utility. However, although not widely appreciated, there are thousands of randomized controlled trials (RCTs) that have addressed the efficacy of CAM. We reviewed the RCTs of herbal and other natural products, acupuncture, and homeopathy as examples of typical CAM modalities, focusing on conditions of interest to gastroenterologists. Peppermint (alone or in combination) has supportive evidence for use in patients with dyspepsia, irritable bowel syndrome, and as an intraluminal spasmolytic agent during barium enemas or endoscopy. Ginger appeared to be effective in relieving nausea and vomiting due to motion sickness or pregnancy. Probiotics were useful in childhood diarrhea or in diarrhea due to antibiotics; one particular formulation (VSL#3) prevented pouchitis. Acupuncture appeared to ameliorate postoperative nausea and vomiting and might be useful elsewhere. There is even a suggestion that homeopathy has efficacy in treatment of gastrointestinal problems or symptoms. The major problem in interpreting these CAM data is the generally low quality of the RCTs, although that quality might not be different compared to RCTs in the general medical literature. Gastroenterologists should become familiar with these techniques; it is likely that their patients already are.

Acupuncture Therapy↗
PubMed1975

Decorticate spasticity: a re-examination using quantitative assessment in the primate.

Decorticate spasticity in the squirrel monkey was chosen as a convenient laboratory model of spasticity capable of quantitative assessment upon which to evaluate various currently popular clinical spasmolytic measures. The effects of a wide variety of cortical lesions were studied involving primary and supplementary motor, premotor and parietal cortex unilaterally and bilaterally, measuring muscle tone with the evoked integrated E.M.G. technique. Measurable spasticity resulted only if primary motor cortex was ablated bilaterally usually but not always preferentially involving biceps brachii and quadriceps. Resulting postures were variable offering no justification for the term "decorticate posture". The integrated evoked E.M.G. was proportional to rate of stretch and chiefly phasic in type as in hemiplegic man. Stereotactic dentatectomy resulted in profound ipsilateral reduction in this spasticity, but was without effect in intercollicular or anemic decerebrate cats. The mechanism of the spasticity and of the cerebellar effects are discussed.

Animals↗
PubMed1984

Reversal of acute experimental cerebral vasospasm by calcium antagonism with verapamil.

Acute vasospasm of the transclivally exposed basilar artery of anesthetised cats was produced by the subarachnoid injection of platelet-rich plasma (PRP) treated with enough adenosine diphosphate (ADP) to induce platelet aggregation and secretion. Vasorelaxation was produced by the topical application of the calcium antagonist verapamil. Changes in the internal diameter of the basilar artery were determined by measuring the blood column diameter from photomicrographs taken sequentially, at 5 minute intervals, through the operating microscope. Changes in blood vessel diameter are expressed as a plus or minus percentage of the pretreatment diameter. Arterial blood pressure and blood gas values were kept in the physiological range for the cat. The subarachnoid injection of PRP-ADP produced severe constriction of the basilar artery (mean constriction at 5 minutes after injection: -40.7% +/- 2.8 SEM). Platelet-free plasma, ADP alone and Elliott's A solution had no spasmogenic effect when injected into the subarachnoid space. The topical application of the calcium channel blocker verapamil (0.1 mg per kg) 30 minutes after the injection of PRP-ADP, with the basilar artery still in spasm (mean constriction: -23% +/- 3.5 SEM), produced prompt and dramatic vasodilation (mean dilation at 5 minutes after application: +52.7% +/- 18.1 SEM). This spasmolytic effect persisted in a decremental fashion for the 60 minute period of observation, by which time the previously constricted vessel had returned to its normal size. These observations indicate that the platelet fraction of whole blood may be involved in the genesis of acute vasospasm following subarachnoid hemmorrhage and that this phenomenon can be readily reversed by calcium antagonism.

Acute Disease↗
PubMed1993

Intrathecal baclofen--the importance of catheter position.

In a patient receiving intrathecal baclofen injections for intractable trunk and leg spasms, positioning the subarachnoid catheter tip just caudal to the spinal segments innervating the spastic muscles enhanced the spasmolytic effect of bolus injections of intrathecal baclofen on the affected muscles. Such selective positioning of subarachnoid catheters may facilitate segmental spasmolysis with lower intrathecal doses of baclofen and provide an important alternative to relying only on ascending CSF concentration gradients of baclofen from chronic lumbar intrathecal infusion.

Adult↗
PubMed2001

High-resolution solution structure of human intestinal trefoil factor and functional insights from detailed structural comparisons with the other members of the trefoil family of mammalian cell motility factors.

The secreted proteins intestinal trefoil factor (ITF, 59 residues), pS2 (60 residues), and spasmolytic polypeptide (SP, 106 residues) form a small family of trefoil domain-containing mammalian cell motility factors, which are essential for the maintenance of all mucous-coated epithelial surfaces. We have used 1H NMR spectroscopy to determine the high-resolution structure of human ITF, which has allowed detailed structural comparisons with the other trefoil cell motility factors. The conformation of residues 10-53 of hITF is determined to high precision, but the structure of the N- and C-terrminal residues is poorly defined by the NMR data, which is probably indicative of significant mobility. The core of the trefoil domain in hITF consists of a two-stranded antiparallel beta-sheet (Cys 36 to Asp 39 and Trp 47 to Lys 50), which is capped by an irregular loop and forms a central hairpin (loop 3). The beta-sheet is preceded by a short alpha-helix (Lys 29 to Arg 34), with the majority of the remainder of the domain contained in two loops formed from His 25 to Pro 28 (loop 2) and Ala 12 to Arg 18 (loop 1), which lie on either side of the central hairpin. The region formed by the surface of loop 2, the cleft between loop 2 and loop 3, and the adjacent face of loop 3 has previously been proposed to form the functional site of trefoil domains. Detailed comparisons of the backbone conformations and surface features of the family of trefoil cell motility factors (porcine SP, pS2, and hITF) have identified significant structural and electrostatic differences in the loop 2/loop 3 regions, which suggest that each trefoil protein has a specific target or group of target molecules.

Amino Acid Sequence↗
PubMed1994

Novel 1-phenylcycloalkanecarboxylic acid derivatives are potent and selective sigma 1 ligands.

Carbetapentane (1, 2-[2-(diethylamino)ethoxy]ethyl 1-phenyl-1-cyclopentanecarboxylate) binds with high affinity to sigma sites and is a potent antitussive, anticonvulsant, and spasmolytic agent. However, carbetapentane interacts at muscarinic binding sites as well, and it is not clear whether either of these receptor systems is involved in the mechanism(s) of action(s) of this drug. In an attempt to determine whether these psychoactivities can be attributed to interaction at sigma sites, a series of carbetapentane analogs were prepared. Phenyl ring substitution; contraction, expansion, and replacement with a methyl group of the cyclopentyl ring; replacement of the carboxylate function with an amide, methyl ether, and methylamine; and replacement of the N,N-diethyl substituent with a morpholino or piperidino moiety were investigated. All of these novel analogs were evaluated for binding to sigma 1 and sigma 2 sites, and comparison of binding at muscarinic m1 and m2 and PCP (1-(1-phenylcyclohexyl)piperidine) receptors was performed. All of the compounds were selective for sigma 1 over sigma 2 sites, with the three most selective analogs being compounds 34 (65-fold), 35 (78-fold), and 39 (51-fold). None of the compounds were active at PCP sites, and chemical modification including (1) replacing the ester function, (2) replacing the cyclopentyl ring with a smaller ring system (cyclopropyl) or a methyl group, and (3) replacing the diethylamino moiety with a morpholino group resulted in > 220-fold selectivity over muscarinic receptor binding. Therefore, several of these novel compounds are potent, sigma 1-selective ligands which can now be investigated as potential antitussive, anticonvulsant, and antiischemic agents. These studies may reveal whether sigma 1 sites play a role in the pharmacological actions of these drugs.

Animals↗
PubMed1978

Pharmacology on rat ileum of certain 2-substituted 3-(dimethylamino)-5,6-dimethoxyindenes related to 5,6-(methylenedioxy)indene calcium antagonists.

Whereas the 2-propyl- and 2-butyl-5,6-(methylenedioxy)indene calcium antagonists reversed the spasmogenic action of several agonists including PGF2alpha and acetylcholine at 5 X 10(-5) to 10(-4) M on the rat ileum, the corresponding 5,6-dimethoxy analogues exhibited spasmogenic activity at higher concentration (10(-4)-10(-3) M) and exhibited neither spasmogenic nor spasmolytic activity at lower (10(-6)-10(-5) M) concentration. The results are compared to the methyl and 2-ethyl analogues. At 10(-4) M only the butyl analogue was capable of moderate antagonism of acetylcholine and at 10(-3) M all four analogues were capable of moderately antagonizing the actions of acetylcholine.

Acetylcholine↗
PubMed1975

Synthesis and pharmacological properties of 4-piperazino-5-methylthiopyrimidines. Selection of new antiemetic agents.

We have synthetized a series of 22 new 4-piperazinopyrimidines bearing a methylthio substituent in the 5 position of the pyrimidine ring. These compounds have been obtained by separation of the isomers formed during nucleophilic attack of the corresponding 2,4,6-trichloropyrimidine by amines. Pharmacological screening has shown that this chemical series displays a very interesting profile, which includes antiemetic, tranquilizing, analgesic, antiserotonin, and musculotropic-spasmolytic properties. We have particularly selected for clinical investigations two compounds with powerful antiemetic activity: 2-methylamino-4-(N-methylpiperazino)-5-methylthio-6-chloropyrimidine and 2-isopropylamino-4-(H-methylpiperazino)-5-methylthio-6-chloropyrimidine.

Animals↗
PubMed2006

Anxiolytic effect of natural galphimines from Galphimia glauca and their chemical derivatives.

The anxiolytic effects of galphimine B (1), galphimine A (2), and galphimine E (3), natural nor-secofriedelanes isolated from Galphimia glauca, as well as derivatives obtained by acetylation (4), hydrogenation of the C-1/C-2 double bond (5), basic hydrolysis followed by hydrogenation of the C-1/C-2 double bond (6), and deacetylation (7) of galphimine E (3), were evaluated on ICR mice exposed to the elevated plus-maze test. This study also included the evaluation of a galphimines-rich fraction (GRF) with a known concentration of 1-3, obtained from the dry leaves of G. glauca. Intraperitoneal administration of 15 mg/kg of 1, 2, 6, and GRF (1 h before testing) caused an anxiolytic-like effect in the animals, increasing significantly (p <0.001) the percentage of time of permanence and the number of crossings toward the open arms of the plus-maze. No activity was detected after administration of compounds 3, 4, 5, and 7. These results showed that GRF had activity similar to the most active pure galphimines (1 and 2) and that, like for the spasmolytic activity previously reported, the main determining factor responsible for the anxiolytic activity of the compounds was the presence of free hydroxyl groups at C-4, C-6, and C-7 and the presence of the double bond in the A ring.

Animals↗
PubMed2006

Qualitative and quantitative analysis of the active components of the essential oil from Brickellia veronicaefolia by nuclear magnetic resonance spectroscopy.

The composition of the spasmolytic essential oil of the medicinal species Brickellia veronicaefolia was established by NMR spectroscopy in addition to GC-MS analysis and HPLC studies. Seven major compounds, representing ca. 86% of the oil, were identified as benzyl 2,6-dimethoxybenzoate (1), 2-hydroxybenzyl 2'-methoxybenzoate (2), chamazulene (3), beta-caryophyllene (4), germacrene D (5), bicyclogermacrene (6), and beta-eudesmol (7). A sensitive and accurate analytical 1H NMR method has been developed for the quantification of the major compounds in the essential oil of B. veronicaefolia. The method was validated using benzyl 2,6-dimethoxybenzoate (1) and beta-caryophyllene (4), two of the active principles in the oil, and successfully applied to the determination of these pharmacologically active compounds in three different batches of the oil collected in different geographical regions and/or seasons.

Asteraceae↗
PubMedDate not supplied

The alkaloids of Corydalis meifolia.

Six tetrahydroprotoberberines, (+)-sinactine, apocavidine, stylopine, (+)-cavidine, cheilanthifoline, and dehydrocavidine; two spirobenzylisoquinolines, yenhusomine and yenhusomidine; one phthalideisoquinoline, corlumine; one benzophenanthridine, dihydrosanguinarine and protopine, have been isolated from the leaves and stems of Corydalis meifolia Wall. Of these alkaloids, dehydrocavidine was a new base. The remaining alkaloids, although known, were isolated for the first time for this plant. (+)-Cavidine, protopine, corlumine, yenhusomine, and dehydrocavidine exhibited spasmolytic activity.

Alkaloids↗
PubMedDate not supplied

The alkaloids of Corydalis meifolia.

Six tetrahydroprotoberberines, (+)-sinactine, apocavidine, stylopine, (+)-cavidine, cheilanthifoline, and dehydrocavidine; two spirobenzylisoquinolines, yenhusomine and yenhusomidine; one phthalideisoquinoline, corlumine; one benzophenanthridine, dihydrosanguinarine and protopine, have been isolated from the leaves and stems of Corydalis meifolia Wall. Of these alkaloids, dehydrocavidine was a new base. The remaining alkaloids, although known, were isolated for the first time for this plant. (+)-Cavidine, protopine, corlumine, yenhusomine, and dehydrocavidine exhibited spasmolytic activity.

Alkaloids↗