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PubMed1986

Modulation of smooth muscle responses by serine proteases and related enzymes.

Standard isolated smooth muscle tissue preparations were used to screen the musculotropic actions of serine proteases and other substances that are generated during hemostatic activation. Sera obtained from human, rabbit, and guinea pigs produced a dose-dependent contraction of these isolated tissue preparations. These sera also augmented the actions of epinephrine and other agonists on different tissue preparations. Both contractile and relaxant actions of proteases were observed with various serine proteases and their complexes. Thrombins (alpha, beta, and gamma) produced varying degrees of contractile actions of rabbit aortic strips; however, Factor Xa produced a marked relaxation of this preparation. Trypsin and kallikrein did not produce any action on the aortic strip and thrombin, however, produced contraction of the guinea pig ileum. Protease complexes produced varying musculotropic actions on the isolated tissue preparations, which may be related to their composition. The musculotropic actions of serum and thrombin were not blocked by conventional pharmacologic antagonists. However, protease inhibitors, such as hirudin, D-Phe-Pro-Arginal, and other derivatives, produced varying effects of the musculotropic actions of serum and thrombins. These results indicate that thrombin and related proteases generated during the activation of the hemostatic system are capable of producing direct musculotropic actions of various smooth muscles. Various serine proteases and serine protease complexes were found to produce strong hemodynamic effects in a rabbit model for the study of blood plasma. The smooth muscle modulant actions of serine proteases should be taken into account to clarify the vascular pathologic changes in relation to spasmogenic and spasmolytic syndromes observed during hemostasis disorders.

Animals↗

PubMed1997

Pancreatic carcinoma: applications for helical computed tomography.

Helical computed tomography (CT) represents a significant technical improvement over conventional (incremental) CT. This noninvasive imaging technique is now routinely used in the evaluation of patients with suspected pancreatic cancer. This paper focuses on the topics of CT technique (scanning parameters, use of intravenous contrast media, use of oral contrast media and spasmolytic agents, calculation of reformatted and projective images), as well as on the CT appearance of pancreatic carcinoma and the differential diagnosis and staging. A short comparison with other methods is included.

Adenocarcinoma↗

PubMed1987

Relief of blood-induced arterial vasospasm by pharmacologic solutions.

A partially amputated rat hind limb model was used to evaluate the potency of 1 percent, 2 percent, and 20 percent Xylocaine, 0.3 percent papaverine, and normal saline in both the treatment and prevention of blood-induced arterial spasm. Direct application of blood to the femoral artery was shown to produce a 60 percent reduction in limb perfusion. The 0.3 percent papaverine and 20 percent Xylocaine solutions were statistically superior to normal saline and the lower Xylocaine concentrations in their ability to relieve the blood-induced vasospasm and prevent further spasm. Normal saline, 1 percent Xylocaine, and 2 percent Xylocaine showed no preventive effect against blood-induced spasm. These findings emphasize the importance of good hemostasis in microsurgery, and simplify the choice of an effective spasmolytic agent.

Amputation, Surgical↗

PubMed1984

[Sonography of gallbladder kinetics during cholagogue therapy].

Sonography of gallbladder kinetics shows that a cholagogue exercising a spasmolytic action counteracts the periodic voiding of the gallbladder or even induces an increase in volume of the gallbladder in healthy persons and in patients with cholecystolithiasis. This effect cannot be seen in chronic cholecystitis.

Aged↗

PubMed1996

[Gastrointestinal imaging with hydrosonography and hydro-CT].

AIM: To determine the accuracy of hydrosonography (HUS) und hydro-CT (HCT) for staging colon carcinoma. MATERIAL AND METHODS: 74 patients in whom colorectal carcinoma was suspected were examined. At HUS the colonic wall ist distended by a methylcellulose/water suspension and the carcinoma is enlarged to perform staging of the tumour. HCT is a spiral-CT optimised for parenchymal and vessel contrast. Before the scan is started, up to two litres of fluid are given rectally and spasmolytics are administered to reduce peristalsis. Colorectal carcinomas were classified according to the TNM system and histopathologic correlation was achieved. RESULTS: Out of 43 (HUS) and 39 (HCT) colonic lesions 33 (77%) and 36 (92%), respectively, were diagnosed. T-stage accuracy was 88% (HUS) and 66% (HCT), N-stage accuracy 33% and 46% and M-stage accuracy 88% and 85%, respectively. CONCLUSION: The T-stage of sonographically visible tumours of the colon is determined precisely by HUS. In contrast to predicting lymph node involvement distant metastases are reliably detected by both methods. If performed together, HUS and HCT achieve high diagnostic accuracy for staging carcinoma of the colon.

Adult↗

PubMed1989

[Treatment of sudden deafness with the calcium antagonist nimodipine. Results of a comparative study].

In a prospective randomised clinical study on 80 patients with idiopathic sudden hearing loss the therapeutic value of nimodipine was evaluated. Nimodipine is a 4-5-dihydropyridine calcium antagonist with selective spasmolytic and vasodilatory properties on cerebral vessels. The mean improvement of hearing (250, 500, 1000, 2000, 4000 Hz) amounted to 16.5 +/- 11.3 dB as compared with 18.6 +/- 10.2 dB achieved by standard treatment with hydroxyethyl starch (HAES) and naftidrofuryl. The difference is not significant (p greater than 0.2). These results together with the low rate of side effects indicate nimodipine as a therapeutic alternative in cases of hypertension, cardiac failure and allergic predisposition. The possible role of spontaneous recovery on one side and of specific parameters such as rheologic abnormalities or type of audiogram are discussed. They are important for a more sophisticated therapeutic approach towards sudden hearing loss.

Adult↗

PubMed1988

[Impulse galvanization in postoperative urination disorders].

In this study we examined the therapeutic effect of impulse-galvanization in patients with voiding difficulties after anterior vaginal repair. Patients (n = 56/79) revealing residual urine until the sixth postoperative day were studied. Considering the onset of the first spontaneous micturition and the lack of residual urine no significant difference was found in the group undergoing impulse-galvanization (n = 19) compared to a group without therapy (n = 37). By adjuvant treatment with alpha-sympathicolytics, spasmolytics or tranquilizers patients with impulse-galvanization and the comparative group were found to be without residual urine 11.2 and 13 days after surgery, respectively (p less than 0.001).

Electric Stimulation Therapy↗

PubMed1980

[First experience with flavoxat in bladder - conditioned types of incontinence in gynaecology (author's transl)].

40 gynecological patients with motoric and sensoric urge incontinence were treated with the spasmolytic substance Flavoxat. Before treatment and after 4 weeks clinical and urodynamic evaluation were carried out. The results show that 65% of the patients improved under Flavoxat treatment. Incontinence was slightly improved in one third of the patients, in another third it was markedly improved or cured. An increased bladder capacity in the standing position and a decreased frequency of detrusor contractions was found in the urodynamic investigations. The residual urine remained constant.

Adult↗

PubMed2001

An easy method for the intraluminal administration of peppermint oil before colonoscopy and its effectiveness in reducing colonic spasm.

BACKGROUND: Systemic administration of a cholinergic blocking agent or glucagon is used to reduce spasms, but it is inconvenient and sometimes causes side effects. This study is an evaluation of the intracolonic administration of peppermint oil during colonoscopy for the control of colonic spasm. METHODS: Each patient in the treated group (n = 409) was given approximately 200 mL of the solution (a mixture of 8 mL of peppermint oil and 0.2 mL of Tween 80 per 1 L of water with 0.04% indigo carmine) by using a hand pump attached to the accessory channel of the colonoscope. Changes in patient posture were made to distribute the solution. The patients in the control group (n = 36) were given the solution without peppermint oil. RESULTS: A satisfactory spasmolytic effect was seen in 88.5% of the treated patients and in 33.3% of those in the control group (p<0.0001). No adverse effect was observed. The mean time to onset was 21.6 +/- 15.0 seconds, and the effect continued for at least 20 minutes. In patients with irritable bowel syndrome, efficacy was significantly lower (p < 0.0001). CONCLUSIONS: The intraluminal administration of peppermint oil by using a hand pump is a simple, safe, and convenient alternative to the systemic injection of a cholinergic blocking agent or glucagon during colonoscopy.

Adult↗

PubMed1993

hP1.B, a human P-domain peptide homologous with rat intestinal trefoil factor, is expressed also in the ulcer-associated cell lineage and the uterus.

The six-cysteine P-domain motif forms the basic repeat unit of a growing family of mucin-associated peptides. A precursor for a human secretory polypeptide has been discovered by molecular cloning and deduced to have a single P-domain, termed hP1.B. The pre-pro-peptide has 67% amino acid identity with rat intestinal trefoil factor. We find, using the techniques of RNA analysis and in situ hybridization, that this P-domain peptide is expressed in the human gastrointestinal tract, where a number of pathological conditions affect its expression, and surprisingly find it is expressed in the uterus also. In the intestine, hP1.B is expressed by goblet cells, but in Crohn disease this peptide is synthesized and secreted additionally by the ulcer-associated cell lineage that is known to secrete two other trefoil peptides, pS2 and spasmolytic polypeptide (hSP). In the stomach, hP1.B mRNA is relatively scarce but is more abundant in foci of intestinal metaplasia and near to ulceration. Mucin-rich epithelial cells in hyperplastic polyps of the colon also express this peptide. The discovery of this P-domain peptide and its expression in association with mucins support the hypothesis that P-domains with mucins may subserve related functions in the maintenance and repair of mucosal function.

Amino Acid Sequence↗

PubMed1999

Mutated epithelial cadherin is associated with increased tumorigenicity and loss of adhesion and of responsiveness to the motogenic trefoil factor 2 in colon carcinoma cells.

Epithelial (E)-cadherin and its associated cytoplasmic proteins (alpha-, beta-, and gamma-catenins) are important mediators of epithelial cell-cell adhesion and intracellular signaling. Much evidence exists suggesting a tumor/invasion suppressor role for E-cadherin, and loss of expression, as well as mutations, has been described in a number of epithelial cancers. To investigate whether E-cadherin gene (CDH1) mutations occur in colorectal cancer, we screened 49 human colon carcinoma cell lines from 43 patients by single-strand conformation polymorphism (SSCP) analysis and direct sequencing. In addition to silent changes, polymorphisms, and intronic variants in a number of the cell lines, we detected frameshift single-base deletions in repeat regions of exon 3 (codons 120 and 126) causing premature truncations at codon 216 in four replication-error-positive (RER+) cell lines (LS174T, HCT116, GP2d, and GP5d) derived from 3 patients. In LS174T such a mutation inevitably contributes to its lack of E-cadherin protein expression and function. Transfection of full-length E-cadherin cDNA into LS174T cells enhanced intercellular adhesion, induced differentiation, retarded proliferation, inhibited tumorigenicity, and restored responsiveness to the migratory effects induced by the motogenic trefoil factor 2 (human spasmolytic polypeptide). These results indicate that, although inactivating E-cadherin mutations occur relatively infrequently in colorectal cancer cell lines overall (3/43 = 7%), they are more common in cells with an RER+ phenotype (3/10 = 30%) and may contribute to the dysfunction of the E-cadherin-catenin-mediated adhesion/signaling system commonly seen in these tumors. These results also indicate that normal E-cadherin-mediated cell adhesion can restore the ability of colonic tumor cells to respond to trefoil factor 2.

Animals↗

PubMed2004

Characteristics, clinical effect profile and tolerability of a nasal spray preparation of Artemisia abrotanum L. for allergic rhinitis.

A nasal spray formulation containing an extract of Artemisia abrotanum L. was developed for therapeutic use in patients with allergic rhinitis and other upper airway disorders. The nasal spray preparation used contains a mixture of essential oils (4 mg/ml) and flavonols (2.5 microg/ml), of which some components have been shown to possess antiinflammatory, expectorant, spasmolytic as well as antiseptic and antimicrobial activities. The most important constituents in the essential oil fraction of the preparation are 1,8-cineole, linalool and davanone, while the flavonol fraction contains centauredin, casticin and quercetin dimethyl-ethers. No trace of thujon was observed in the essential oil of the Artemisia abrotanum L. genotype "Tycho" used for the manufacture of the nasal spray preparation. In 12 patients with diagnoses of allergic rhinitis, allergic conjunctivitis and/or bronchial obstructive disease, the nasal spray was given immediately after the appearance of characteristic allergic nasal symptoms. In 10 of the 12 patients, allergic rhinitis with nasal congestion, sneezing and rhinorrhea was dominant. After administration of the nasal spray, all patients experienced a rapid and significant symptom relief of nasal symptoms, comparable to the effect of antihistamine and chromoglicate preparations which several of the patients had used previously. The effect was present within 5 minutes after the administration and lasted for several hours. In 7 of the 10 rhinitis patients with concomitant symptoms of allergic conjunctivitis, a significant subjective relief of eye symptoms was also experienced. In 3 of the 6 patients who had a history of characteristic symptoms of endogenous, exogenous or exercise induced bronchial obstructive disease, there was a bronchial symptom relief by the nasal spray preparation which was experienced as rapid and clinically significant. It is concluded from the present proof of concept study, that a nasal spray formulation containing an extract characterised by a mixture of essential oils and flavonols from the Artemisia abrotanum L. genotype "Tycho", appears to be clinically useful and suitable for the prophylactic and therapeutic management of patients with allergic rhinitis and adjuvant symptoms.

Administration, Inhalation↗

PubMed1993

The mouse one P-domain (pS2) and two P-domain (mSP) genes exhibit distinct patterns of expression.

We have previously shown that the human pS2 gene, which codes for a secreted peptide of 60 amino acids, is expressed in a number of human carcinomas, including carcinomas of the breast, the pancreas, and the large bowel. Strong pS2 gene expression was also observed in the normal gastric mucosa and in the regenerative tissues surrounding ulcerous lesions of the gastrointestinal tract. A number of pS2 similar peptides, designated as P-domain peptides, have been described, notably the porcine (PSP), murine (mSP), and human (hSP) spasmolytic polypeptides, which correspond to duplicated pS2 proteins. We have now cloned a mouse homolog of the human pS2 cDNA to dispose of an animal model to study the pS2 protein function, which remains unknown at the present time. We show that the mouse putative pS2 protein sequence and the physiological pattern of expression of the mouse pS2 gene are well conserved. The mouse pS2 gene is highly expressed in the stomach mucosa cells, whereas no pS2 gene expression could be detected in the mouse mammary gland, even during postnatal development processes dependent on growth factors or hormones. Using in situ hybridization, we show that although coexpressed in the fundus, the antrum and the antrum-pyloric regions of the stomach, the mouse pS2 and mSP genes exhibit distinct and complementary cellular patterns of expression.

Aging↗

PubMed1999

Extracorporeal shockwave lithotripsy in the pediatric population.

BACKGROUND: Shockwave lithotripsy (SWL) is being used increasingly as a therapeutic modality for childhood urolithiasis. We reported our experience and results of SWL in the pediatric population. METHODS: The 59 renal units (RU) of 54 patients were retrospectively reviewed. The mean patient age was 10+/-3.5 years. All patients were treated with the Lithostar lithotripter in outpatient settings. Those with positive culture results were treated under appropriate antibiotic coverage. Seven patients were treated under general anesthesia and the rest under sedoanalgesia. Shielding of the lung fields or gonads was not used. For the upper pole stones, protection of the lungs was accomplished by elevating the upper half of the body with supportive pillows, thus moving the kidney away from the lung fields. Six RUs were catheterized via double-pigtail ureteral catheters or by percutaneous nephrostomy tube prior to treatment. The average stone load was 1.8+/-2.5 cm2. RESULTS: Patients were treated with an average of 2.5 sessions. A total of 1000 to 2500 shockwaves were delivered between 14.5 and 17.8 kV. Routine spasmolytic treatment was not initiated. The stone-free rate was 64%, and clinically insignificant residual fragments (CIRF) were present in 29% of RUs; thus, the success rate was 93%. Fever that necessitated hospitalization occurred in one patient. No other complications were seen except skin bruising and early hematuria. CONCLUSION: Shockwave lithotripsy is a safe and effective treatment modality for childhood stones of appropriate size and radiologic characteristics.

Child↗

PubMed2006

Use of tramadol drip in controlling renal colic pain.

BACKGROUND AND PURPOSE: Although the continuous perfusion of antispasmodic drugs has been the traditional mainstay in the treatment of renal colic, the results more often than not are unsatisfactory. Our hypothesis was that a continuous intravenous (IV) drip of tramadol would be an effective and safe alternative. PATIENTS AND METHODS: In this prospective study, 300 patients with renal colic were randomized into four treatment groups, single blind for the patients. At the start, all received an anti-inflammatory drug intramuscularly and an antiemetic and antispasmodic IV. Group A was given the classical IV antispasmodic perfusion combined with a sham drip. Group B received the classical antispasmodic perfusion in combination with a tramadol drip. Group C had a sham perfusion and drip. Group D received a sham perfusion and tramadol drip. There was no significant difference in the degree of pain between the groups on a visual analog scale (VAS) at the start. The pain was scored again on the VAS at 30 minutes, 1 hour, and 4 hours after the start of the treatment and at IV urography. Side effects, as well as the need for rescue medication, were registered. RESULTS: Both tramadol groups scored significantly better after 60 and 240 minutes and during IV urography (P < 0.005). There was a significant decrease in VAS in group B after 30 minutes. The tramadol groups needed significantly less rescue medication (P = 0.001). There was no significant difference in the reported side effects. The combination spasmolytic-tramadol drip scored the best, although the difference was not statistically significant. CONCLUSION: We consider our hypothesis proved that a continuous tramadol drip is a safe and valuable analgesic regimen in renal colic.

Colic↗

PubMed2001

Induction of scattering and cellular invasion by trefoil peptides in src- and RhoA-transformed kidney and colonic epithelial cells.

Trefoil factors (TFFs) are protease-resistant peptides that promote epithelial cell migration and mucosal restitution during inflammatory conditions and wound healing in the gastrointestinal tract. To date, the molecular mechanism of TFFs action and their possible role in tumor progression are unclear. In the present study, we observed that premalignant human colonic PC/AA/C1 and canine kidney MDCK epithelial cells are not competent to invade collagen gels in response to exogenously added TFFs (pS2, spasmolytic polypeptide, and intestinal trefoil factor). In contrast, activated src and RhoA exert permissive induction of invasion by the TFFs that produce similar parallel dose-response curves in src-transformed MDCKts.src and PCmsrc cells (EC50=20-40 nM). Cell scattering is also induced by TFFs in MDCKts.src cells. Stable expression of the pS2 cDNA promotes constitutive invasiveness in MDCKts.src-pS2 cells and human colonic HCT8/S11-pS2 cells established from a sporadic tumor. Furthermore, we found that TFF-mediated cellular invasion is dependent of several signaling pathways implicated in cell transformation and survival, including phosphoinositide PI3'-kinase, phospholipase C, protein kinase C, and the rapamycin target TOR. Constitutive and intense expression of pS2 was revealed by Western blot analyses and immunohistochemistry in human colorectal tumors and their adjacent control mucosa during the neoplastic progression, from the adenoma to the liver metastases. Our studies indicated that TFFs can be involved in cell scattering and tumor invasion via autocrine loops and may serve as potential targets in the control of colon cancer progression.

Animals↗

PubMed2003

Trefoil peptides as proangiogenic factors in vivo and in vitro: implication of cyclooxygenase-2 and EGF receptor signaling.

We previously established that the trefoil peptides (TFFs) pS2, spasmolytic polypeptide, and intestinal trefoil factor are involved in cellular scattering and invasion in kidney and colonic cancer cells. Using the chorioallantoic membrane (CAM) assay and the formation of tube-like structures by human umbilical vein endothelial cells (HUVEC) plated on the Matrigel matrix substratum, we report here that TFFs are proangiogenic factors. Angiogenic activity of TFFs is comparable to that induced by vascular endothelial growth factor, leptin, and transforming growth factor-alpha. Stimulation of angiogenesis by pS2 in the CAM assay is blocked by pharmacological inhibitors of cyclooxygenase COX-2 (NS-398) and epidermal growth factor receptor (EGF-R) tyrosine kinase (ZD1839), but is independent of KDR/Flk-1 and thromboxane A2 receptors. In contrast, the morphogenic switch induced by pS2 in HUVEC cells could be inhibited by the specific KDR heptapeptide antagonist ATWLPPR and by inhibitors of COX-2 and EGF-R signaling. These results implicate TFFs in the formation of new blood vessels during normal and pathophysiological processes linked to wound healing, inflammation, and cancer progression in the digestive mucosa and other human solid tumors associated with aberrant expression of TFFs.

Allantois↗

PubMed2000

Milrinone attenuates serotonin-induced pulmonary hypertension and bronchoconstriction in dogs.

UNLABELLED: We determined whether milrinone, a phosphodiesterase III inhibitor, attenuates serotonin-induced (5-hydroxytryptamine [5HT]) pulmonary hypertension (PH) and bronchoconstriction. Dogs were anesthetized with pentobarbital (30 mg/kg + 2 mg. kg(-1). h(-1)). Bronchoconstriction and PH were elicited by 5HT (10 microg/kg + 1.0 mg. kg(-1). h(-1)). Pulmonary vascular resistance was used to assess PH. Bronchoconstriction was also assessed by changes in bronchial cross-sectional area obtained from our bronchoscopic method. At 30 min after 5HT infusion started, seven dogs were given milrinone: 0 (saline), 5, 50, 500, and 5000 microg/kg at 10-min intervals. The other 12 dogs were given milrinone 5000 microg/kg 30 min after 5HT infusion, and 5 min later were given propranolol 0.2 mg/kg (n = 6) or saline (n = 6) IV. The 5HT significantly increased percentage of pulmonary vascular resistance to 208% +/- 27% and decreased percentage of bronchial cross-sectional area to 52% +/- 5% of the basal. Milrinone significantly attenuated both PH and bronchoconstriction in a dose-dependent manner. However, -log 50% effective concentration (mean ED(50) in microg/kg) of milrinone for bronchoconstriction: 4.32 +/- 0.13 (47.6) was significantly smaller than that for PH: 3.84 +/- 0.29 (144.9) (P < 0.01). In addition, the spasmolytic effects of milrinone (5000 microg/kg) were not antagonized by propranolol, although this dose significantly increased plasma catecholamines. In conclusion, milrinone attenuates 5HT-induced PH and bronchoconstriction; however, this drug may be more sensitive to phosphodiesterase III in the airway smooth muscle than in pulmonary vascular smooth muscle. In addition, the relaxant effects could not be caused by beta-adrenoceptor activation because beta-blocker did not antagonize. IMPLICATIONS: We studied the effects of milrinone on serotonin-induced pulmonary hypertension and bronchoconstriction in dogs. Milrinone produces pulmonary vasodilation and bronchodilation, whose effects may not be caused by beta-adrenoceptor activation. In addition, this drug may be more sensitive to phosphodiesterase III in the airway smooth muscle than that in pulmonary vascular smooth muscle.

Animals↗