Investigation of antinociceptive, antipyretic, antiasthmatic, and spasmolytic activities of Brazilian Cannabis sativa L. roots in rodents.

ETHNOPHARMACOLOGICAL RELEVANCE: Many studies are performed with the aerial parts of Cannabis sativa L. (Cannabaceae). However, roots remain poorly studied, despite citations in the scientific literature. The C. sativa roots are indicated for the treatment of pain, inflammation, fever, among other health problems. AIM OF THE STUDY: This study aimed to evaluate the antinociceptive, antipyretic, antiasthmatic, and spasmolytic activities of C. sativa roots in experimental models using mice and rats. MATERIAL AND METHODS: The chemical composition of the aqueous extract of C. sativa roots (AECsR) was evaluated by LC-MS. The antinociceptive activity was assessed in mice by the induction of writhing with acetic acid, paw licking with formalin, and reactivity in the hot plate test. Fever was induced by the administration of a suspension of Saccharomyces cerevisiae in young rats. The asthmatic activity was performed with ovalbumin (OVA)-immunized mice with cellular and histological analysis. Finally, the spasmolytic activity was performed using mice isolated trachea. For in vivo studies, the doses were 12.5, 25, or 50 mg/kg whereas for in vitro, the concentration of AECsR was 729 µg/mL. RESULTS: From the LC-MS data, we identified p-coumaroyltyramine, feruloyltyramine canabissativine in AECsR. The extract promoted a reduction of writhing in all tested doses (12.5, 25, or 50 mg/kg). Similarly, it reduced the pain in the formalin test at doses of 12.5 and 50 mg/kg (first phase) and 12.5 and 25 mg/kg (second phase). In the hot plate test, the doses of 12.5, 25, and 50 mg/kg promoted antinociceptive effect at different times, and the lowest dose maintained its action in the analyzes performed at 60, 90, and 120 min after administration. The anti-inflammatory activity of AECsR was observed in the mouse model of asthma, reducing the total leukocyte count in the bronchoalveolar fluid (BALF) at a dose of 25 mg/kg, as well as reducing eosinophilia in all tested doses (12.5, 25, and 50 mg/kg). Histological analysis of lungs stained with H&E and PAS showed a reduction in the number of inflammatory cells in the perivascular and peribronchial region, as well as reduced mucus production. CONCLUSION: The results suggest that AECsR promotes pain control, either by a central or inflammatory mechanism, and has antiasthmatic activity. However, there was no antipyretic or spasmolytic effect.

Cannabis roots: Pharmacological and toxicological studies in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: There are many studies and therapeutic properties attributed to the flowers and leaves of the Cannabis species, but even with few pharmacological studies, Cannabis sativa L. (Cannabaceae) roots presents several therapeutic indications in folk medicine. AIM OF THE STUDY: This study aimed to evaluate the anti-inflammatory and spasmolytic effects as well as the toxicological profile of the aqueous extract of Cannabis sativa roots (CsAqEx) in mice. MATERIALS AND METHODS: We assessed the anti-inflammatory effect with carrageenan-induced leukocyte migration assay, and carrageenan and histamine-induced paw edema methods; The spasmolytic effect was assessed through in vitro assays with isolated mice trachea. To assess motor coordination and mobility, mice went through the rotarod and open field tests, respectively. For the single-dose toxicity study, we administered CsAqEx at the dose of 1000 mg/kg by gavage. In a repeated dose toxicity study, animals received CsAqEx at doses of 25 mg or 100 mg/kg for 28 days. RESULTS: The CsAqEx inhibited the migration of leukocytes at the doses of 25, 50, and 100 mg/kg. The CsAqEx showed anti-inflammatory activity after the intraplantar injection of carrageenan, presenting a reduction in edema formation at all tested doses (12.5, 25, 50 and 100 mg/kg). The dose of 12.5 mg/kg of CsAqEx prevented edema formation after intraplantar injection of histamine. In an organ bath, 729 µg/mL of CsAqEx did not promote spasmolytic effect on isolated mice tracheal rings contracted by carbachol (CCh) or potassium chloride (KCl). We did not observe clinical signs of toxicity in the animals after acute treatment with CsAqEx, which suggested that the median lethal dose (LD50) is greater than 1000 mg/kg. Repeated dose exposure to the CsAqEx did not produce significant changes in hematological, biochemical, or organ histology parameters. CONCLUSIONS: The results suggest that the anti-inflammatory effect of CsAqEx is related to the reduction of vascular extravasation and migration of inflammatory cells, without effects on the central nervous system. Moreover, there was no spasmolytic effect on airway smooth muscle and no toxicity was observed on mice.

Oral IBGard™ Before Colonoscopy: A Single-Center Double-Blinded, Randomized, Placebo-Controlled Trial.

BACKGROUND: Peppermint oil is well known to inhibit smooth muscle contractions, and its topical administration during colonoscopy is reported to reduce colonic spasms. AIMS: We aimed to assess whether oral administration of IBGard™, a sustained-release peppermint oil formulation, before colonoscopy reduces spasms and improves adenoma detection rate (ADR).  METHODS: We performed a single-center randomized, double-blinded, placebo-controlled trial. Patients undergoing screening or surveillance colonoscopies were randomized to receive IBGard™ or placebo. The endoscopist graded spasms during insertion, inspection, and polypectomy. Bowel preparation, procedure time, and time of drug administration were documented. Statistical analysis was performed using the Student's t test and Wilcoxon rank-sum test. RESULTS: There was no significant difference in baseline characteristics or dose-timing distribution between IBGard™ and placebo groups. Similarly, there was no difference in ADR (IBGard™ = 47.8%, placebo = 43.1%, p = 0.51), intubation spasm score (1.23 vs 1.2, p = 0.9), withdrawal spasm score (1.3 vs 1.23, p = 0.72), or polypectomy spasm score (0.52 vs 0.46, p = 0.69). Limiting the analysis to patients who received the drug more than 60 min prior to the start of the procedure did not produce any significant differences in these endpoints. CONCLUSIONS: This randomized controlled trial failed to show benefit of orally administered IBGard™ prior to colonoscopy on the presence of colonic spasms or ADR. Because of its low barrier to widespread adoption, the use of appropriately formulated and timed oral peppermint oil warrants further study to determine its efficacy in reducing colonic spasms and improving colonoscopy quality.

MR enterocolonography in patients with Crohn's disease and healthy volunteers - Do we achieve diagnostic bowel distension?

PURPOSE: The aim of our prospective randomized study was to assess diagnostic quality and stability of bowel distension in patients with Crohn's disease (CD) and healthy volunteers subjected to synchronous magnetic resonance enterography and colonography (MREC), as well as to test the role of water enema and intravenous spasmolytics. The influence of gastric content, age, gender, and body mass on bowel distension was also evaluated. METHOD: Study groups included 164 CD patients and 53 healthy volunteers. After bowel preparation, randomized subgroups started ingestion ≥1000 mL of hyperosmolar solution within 30, 45, 60, 75, and 90 min before admission to MRI, respectively. Patients were examined in prone position and water enema was applied. Spasmolytics were administered prior to I.V. gadolinium. Distension of five bowel segments was independently assessed by two experienced radiologists. RESULTS: MREC yields diagnostic distension of the jejunum in 81.1 % and 79.2 % patients in the CD group and controls, respectively. For the terminal ileum it was >94 % in both groups. Good and excellent distension was achieved in other bowel segments. Distension was maintained up to 75 min from the start of oral ingestion. Water enema and spasmolytics significantly and independently improved distension of the small bowel. Distension of the cecum after spasmolytics was decreased. Gastric content, age, gender and body mass had no significant influence of bowel distension. CONCLUSIONS: MREC enables diagnostic distension of the colon and ileum (including terminal segment) in CD patients and healthy volunteers and diagnostically acceptable distension of the jejunum.

Evaluation of the Antispasmodic and Antisecretory Activities of the 80% Methanol Extracts of Verbena officinalis L: Evidence From In Vivo Antidiarrheal Study.

Verbena officinalis L. has a folkloric repute for the management of digestive disorders, including diarrhea. However, the safety and efficacy of the plant material has not been scientifically validated yet. This study was, therefore, aimed to evaluate the overall antidiarrheal activity of the 80% methanol extracts of V officinalis in mice. The antidiarrheal activity of the 80% methanol extracts of the roots (R-80ME) and the leaves (L-80ME) of V officinalis was tested in castor oil-induced diarrhea in mice. R-80ME was further evaluated using charcoal meal and entero-pooling. In each test, group I and group II (controls) received 10 mL/kg distilled water and standard drug (5 mg/kg loperamide), respectively, whereas groups III, IV, and V (test groups) received 100, 200, and 400 mg/kg of the 80ME, respectively. The R-80ME at 200 mg/kg (P < .01) and 400 mg/kg (P < .001) significantly delayed the onset of diarrhea compared with negative control. Both R-80ME and L-80ME at 200 and 400 mg/kg significantly decreased the frequency of wet fecal outputs (P < .01). Generally, 70.24% inhibition of the number of wet fecal output was recorded at R-80ME 400 mg/kg. Results from the charcoal meal test revealed that the R-80ME at 200 (P < .01) and 400 mg/kg (P < .001) produced a significant antimotility effect. In entero-pooling test, the R-80ME, at 200 and 400 mg/kg doses (P < .01), showed a significant decline in both the volume and weight of intestinal contents. The maximum in vivo antidiarrheal index was determined to be 95.25 at dose of 400 mg/kg R-80ME. This study demonstrated that the 80ME, mainly the root extract, produced promising antidiarrheal activity and hence provides a scientific support for acclaimed traditional use of the plant material for treatment of diarrheal diseases.

A Novel Ileocolonic Release Peppermint Oil Capsule for Treatment of Irritable Bowel Syndrome: A Phase I Study in Healthy Volunteers.

INTRODUCTION: Peppermint oil (PO) has been shown to reduce abdominal pain in patients with irritable bowel syndrome (IBS). PO is assumed to induce intestinal smooth muscle relaxation and desensitization of nociceptive nerve afferents. To increase colonic PO concentration, an ileocolonic release peppermint oil (IC-PO) capsule has been developed. The aim of this study was to compare pharmacokinetic parameters of the currently available small intestinal release PO (SI-PO) and the novel IC-PO. METHODS: In this randomized, double-blind, crossover study, subjects received 182 mg of either SI-PO or IC-PO in a crossover design with a washout period of more than 14 days. Blood samples were collected to determine menthol glucuronide concentrations. RESULTS: Eight healthy volunteers (50% female, median age 22) were included. The time to reach the maximum concentration (Tmax) of IC-PO was significantly longer compared to SI-PO with a median (IQR) of 360 (360-405) versus 180 (120-180) min. The lag time (Tlag) was significantly longer with a median (IQR) of 225 (204-284) for IC-PO compared to 37 (6-65) min for SI-PO. The areas under the menthol glucuronide plasma concentration-time curves were significantly smaller with a median (IQR) of 2331 µg h/L (2006-2510) for IC-PO compared to 2623 µg h/L (2471-2920) for SI-PO. No significant differences were found in peak concentrations and elimination half-lives. CONCLUSION: IC-PO has a significantly delayed peak menthol glucuronide concentration and Tlag, both pointing to the release of PO in the more distal part of the intestine. This may enhance therapeutic efficacy as it results in increased exposure of colonic mucosal afferents to the PO. A randomized controlled trial investigating the efficacy of SI and IC-PO in IBS is currently ongoing. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02291445, EudraCT database 2014-004195-32.

Broccoli sprouts produce abdominal antinociception but not spasmolytic effects like its bioactive metabolite sulforaphane.

Abdominal pain is a common health problem that requires efficacious and safe therapy. Broccoli is a rich source of health-promoting bioactive compounds with potential for pain therapy. However, there is a lack of scientific pharmacological evidence to support this. Our aim was to investigate the antinociceptive and spasmolytic activities of broccoli aqueous extracts from seeds, sprouts, and inflorescence, as well as some metabolites. Experiments were done using enteral and parenteral administration in an in vivo model of pain accompanied with an in vitro assay. Data established that sprouts (100 mg/kg, i.p. and 1000 mg/kg, p.o.) produced significant and major antinociceptive effect at similar or even lower doses in comparison to the seeds (125 mg/kg, i.p. and 1000 mg/kg, p.o.) and broccoli heads (250 mg/kg, i.p. and 1000 mg/kg, p.o.). These results resembled the analgesic response observed with the reference drug metamizole (80 mg/kg, i.p.). Chlorogenic acid (CA, 3, 10, 30, and 100 mg/kg, i.p.) and SFN (0.1, 1 and 10 mg/kg, i.p.) were partial responsible antinociceptive metabolites of broccoli. SFN effects involved participation of endogenous opioids, since they were inhibited in the presence of naltrexone (5 mg/kg, s.c.). In the in vitro assay, a significant 80% spasmolytic-like response was reached with SFN alone in comparison to 20% obtained with aqueous extracts of sprouts and seeds. Participation of calcium channels was a mechanism involved in the in vitro response of SFN. In conclusion, broccoli sprouts, SFN and CA are potential nutraceuticals for abdominal pain therapy.

Inhaled peppermint, rosemary and eucalyptus essential oils do not change spirometry in healthy individuals.

Essential oils of herbal origin are widely used in the treatment of diseases of the upper and lower respiratory tract primarily due to their antibacterial and antiviral effects. Menthol, the major component of the essential oil of mint (Mentha) species, exhibits antispasmodic activity, which might result in improved lung function. In a randomized experiment, 106 healthy participants received nebulized peppermint, eucalyptus, or rosemary essential oil for 15 min or no treatment (control). None of the essential oils had an impact on the measured spirometric variables (forced vital capacity, peak expiratory flow, the ratio of the volume of air forcibly blown out in the first second to forced vital capacity). Participants' expectations regarding the effects of essential oils did not affect their objective performance, however, they predicted perceived (subjective) changes. Perceived and measured changes were not connected with each other. In conclusion, inhaled rosemary, peppermint, and eucalyptus essential oils' subjective (perceived) effect on spirometry is mediated at least partly by expectations.

Antitussive, antispasmodic, bronchodilating and cardiac inotropic effects of the essential oil from Blepharocalyx salicifolius leaves.

ETHNOPHARMACOLOGY RELEVANCE: Blepharocalyx salicifolius (Kunth) O. Berg (Myrtaceae) is a tree native to Argentina and Uruguay that grows and is cultivated along the riverside of the Rio de la Plata. The leaves of this plant species, locally known as "anacahuita" are used in South America to prepare infusions for the empiric treatment of cough and bronchospasm, as well as diarrhoea and other intestinal disorders. Although previous phytochemical studies have been performed with the essential oil extracted from Blepharocalyx salicifolius, pharmacological evidence supporting its traditional use is still lacking. AIM OF THE STUDY: To experimentally evaluate the pharmacological properties of Blepharocalyx salicifolius based on its traditional use. The studies were performed with tincture (T-Bs) and essential oil (EO-Bs) prepared from its leaves, in isolated rat trachea, intestine and heart preparations. METHODS: The ex-vivo effects of T-Bs and EO-Bs were evaluated with the agonists carbachol (CCh) and calcium chloride (Ca2+) in the contractile concentration-response curves (CRC) of the isolated intestine. The muscle relaxant effect of EO-Bs was evaluated in the isolated trachea and compared with the effect achieved with papaverine as a positive control. The T-Bs and EO-Bs cardiac effects were analysed by perfusion of an isolated rat heart before a period of ischemia/reperfusion (stunning model). The antitussive effect of both T-Bs and EO-Bs was evaluated in mice exposed to ammonia using codeine as a positive control. RESULTS: Both T-Bs and EO-Bs induced a non-competitive inhibition of the CCh-CRC in the rat intestine, with IC50 values of 170.3 ± 48.5µg T-Bs/mL (n = 6) and 5.9 ± 1.6µg EO-Bs/mL (n = 6), respectively. EO-Bs also inhibited non-competitively the Ca2+-CRC, with IC50 value of 1.8 ± 0.3µg EO-Bs/mL (n = 8). A similar effect was obtained with the main active component of the EO-Bs 1,8-cineole. In isolated trachea, EO-Bs induced the relaxation of the CCh-contracted tissue (1.7 ± 0.2µg EO-Bs/mL, n = 11) up to a maximal relaxation that was 1.9 times higher than that of papaverine. In the isolated heart, EO-Bs induced a poor negative inotropic response, and did not improve the contractile and energetic recovery after ischemia and reperfusion. In the mouse cough model, EO-Bs (90mg/Kg) was as effective as codeine (30mg/Kg) in reducing cough frequency. CONCLUSIONS: The results indicate that the preparations from Blepharocalyx salicifolius leaves were effective as central antitussive, bronchodilating and antispasmodic agents, suggestive of a mechanism associated with the inhibition of Ca2+ influx into smooth muscle. The EO-Bs displayed only a poor ability to reduce cardiac inotropism, and was devoid of any cardioprotective properties. Thus, the present study validates the traditional use of this South American plant for asthma, cough and bronchospasm, shedding new light into its potency and putative mechanism of action.

Transcutaneous posterior tibial nerve electrostimulation with low dose trospium chloride: Could it be used as a second line treatment of overactive bladder in females.

AIM: To evaluate the effect of adding low dose trospium chloride with transcutaneous posterior tibial nerve stimulation (TPTNS) in the treatment of overactive bladder (OAB) in females after failure of behavioral therapy. METHODS: We randomized 30 women with OAB, in two groups: G I received 30 min TPTNS, three times a week; GII received TPTNS plus 20 mg trospium chloride daily. OAB Symptom Score questionnaire (OABSS), Incontinence Impact Questionnaire-short form 7 (IIQ-7), 3 day voiding diary and urodynamics at weeks 0 and 8 were evaluated. RESULTS: The groups were similar before treatment. Eight weeks after treatment, the mean OABSS decreased significantly to 8.53 ± 1.30 for group II vs 10.0 ± 2.0 for GI (P < 0.024). The mean IIQ-7 score decreased significantly to 51.86 ± 17.26 in group I vs 31.99 ± 9.26 in group II (P < 0.001). Before treatment, 11 (73.3%) and 4 (26.7%) patients in each group had moderate and poor quality of life (QoL), respectively. After treatment, 6 (40%) and 14 (93.3%) had good QoL, 7 (46.7%) and 1 (6.7%) had moderate QoL in GI and GII, respectively. Two (13.3%) patients in GI had poor QoL. The mean frequency was reduced to 8.60 ± 0.83 vs 10.60 ± 2.32 for GII and GI respectively (P = 0.006). The cystometric capacity increased from 263.40 ± 50.45 to 377.80 ± 112.92 mL (P = 0.001) for GII vs 250.13 ± 56.24 to 296.40 ± 99.0 mL (P = 0.026) for GI. CONCLUSION: TPTNS combined with low dose trospium chloride proved to be more effective than TPTNS alone in the treatment of OAB in females.

The effect of premedication with peppermint oil capsules (Colpermin) prior to colonoscopy: A double blind randomized placebo-controlled trial.

BACKGROUND AND STUDY AIMS: Colonoscopy is the cornerstone of diagnosing colonic diseases. Investigators have evaluated the effectiveness of antispasmodic agents in colonoscopy with conflicting evidence. The aim of this study is to determine the efficacy of enteric coated peppermint oil capsules (Colpermin®), an antispasmodic agent, on outcomes during colonoscopy. PATIENTS AND METHODS: A total of 80 patients undergoing elective colonoscopy were recruited and randomized in a double blinded fashion to receive either placebo or peppermint oil capsules administered 4 h prior to the procedure. RESULTS: Peppermint oil capsules did not affect caecal intubation time when compared with placebo. Patients' tolerance, endoscopist's satisfaction and demand on sedation were also not affected. CONCLUSION: This randomized controlled trial does not support the routine use of peppermint oil capsules prior to colonoscopy as a tool for procedure optimization, and patients' and endoscopist's satisfaction.

Spasmolytic Mechanism of Aqueous Licorice Extract on Oxytocin-Induced Uterine Contraction through Inhibiting the Phosphorylation of Heat Shock Protein 27.

Licorice derived from the roots and rhizomes of Glycyrrhiza uralensis Fisch. (Fabaceae), is one of the most widely-used traditional herbal medicines in China. It has been reported to possess significant analgesic activity for treating spastic pain. The aim of this study is to investigate the spasmolytic molecular mechanism of licorice on oxytocin-induced uterine contractions and predict the relevant bioactive constituents in the aqueous extract. The aqueous extraction from licorice inhibited the amplitude and frequency of uterine contraction in a concentration-dependent manner. A morphological examination showed that myometrial smooth muscle cells of oxytocin-stimulated group were oval-shaped and arranged irregularly, while those with a single centrally located nucleus of control and licorice-treated groups were fusiform and arranged orderly. The percentage of phosphorylation of HSP27 at Ser-15 residue increased up to 50.33% at 60 min after oxytocin stimulation. Furthermore, this increase was significantly suppressed by licorice treatment at the concentration of 0.2 and 0.4 mg/mL. Colocalization between HSP27 and α-SMA was observed in the myometrial tissues, especially along the actin bundles in the oxytocin-stimulated group. On the contrary, the colocalization was no longer shown after treatment with licorice. Additionally, employing ChemGPS-NP provided support for a preliminary assignment of liquiritigenin and isoliquiritigenin as protein kinase C (PKC) inhibitors in addition to liquiritigenin, isoliquiritigenin, liquiritin and isoliquiritin as MAPK-activated protein kinase 2 (MK2) inhibitors. These assigned compounds were docked with corresponding crystal structures of respective proteins with negative and low binding energy, which indicated a high affinity and tight binding capacity for the active site of the kinases. These results suggest that licorice exerts its spasmolytic effect through inhibiting the phosphorylation of HSP27 to alter the interaction between HSP27 and actin. Furthermore, our results provide support for the prediction that potential bioactive constituents from aqueous licorice extract inhibit the relevant up-stream kinases that phosphorylate HSP27.

When the low FODMAP diet does not work.

Irritable bowel syndrome (IBS) is heterogeneous. Patients need proper assessment and explanation of IBS pathophysiology and appropriate therapies. A low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) diet effectively reduces symptoms in 75% of patients. Best treatment for those nonresponsive will depend on the pathophysiological basis for symptom genesis, with the following possible abnormalities: (i) Visceral hypersensitivity and/or enhanced gut-brain communication: a low FODMAP diet is mainly targeted for this patient group. A dietitian may also recommend antispasmodic agents, including peppermint oil. Another dietary treatment is a low food chemical diet, although this diet is often extremely limited, and therefore, not suited for some populations. Psychological therapies are also clinically beneficial. (ii) Altered motility: in patients with fast transit, a dietitian may recommend a reduction in all FODMAPs or targeted monosaccharides and disaccharides, which are more osmotic in nature. If not effective, patients may benefit from psyllium, which has an exceptional water-holding capacity aimed to promote more formed stools. Patients with slow or uncoordinated transit are often more difficult to treat. Dietary interventions have some success and usually comprise a combination of adequate fiber and fluid, osmotic laxatives, and stimulating agents such as caffeine, senna, and exercise. (iii) Altered microbiome: supplementary probiotics and prebiotics have weak evidence of efficacy with some notable exceptions. A dietitian may trial supplementary Bifidobacterium infantis or oligosaccharides, usually as an adjunct therapy. Guidance from a dietitian will encompass dietary methods to treat IBS but additionally identify where dietary treatment is not indicated to ensure that diet is correctly used and patients are not nutritionally or psychologically compromised.

Abdominal pain, cramping or discomfort impairs quality of life in women: An internet-based observational pilot study focussing on impact of treatment.

Background Abdominal pain, cramping, and discomfort (APCD) are experienced by up to 30 % of adults in Europe. Objective To assess the impact of APCD on quality of life (QoL) and to investigate the effectiveness, tolerability, and impact on QoL of hyoscine butylbromide (HBB, Buscopan®) compared with STW 5 (Iberogast®) or analgesics in women with APCD. Methods An internet-based observational pilot study was conducted in Germany in women who had predominantly used HBB, STW 5, or analgesics (n = 240 per treatment) to treat APCD. This online survey included questions on QoL, effectiveness, and tolerability. Results A total of 720 completed questionnaires was evaluated. APCD had a major impact on QoL, with 96 % of women reporting that daily activities were disrupted at least sometimes, and 44 % at least often. Other aspects of QoL, such as quality of work, eating habits, and social activities, were also affected in most women. After taking their medication of choice, 91 % of women in the HBB group reported they could "very often" or "often" continue with their daily activities, compared with 84 % and 85 % in the STW 5 and analgesic groups, respectively (p < 0.05 for both comparisons). HBB was perceived to be the "best solution" to overcome APCD symptoms "very often" or "often" by more women (86 %) than STW 5 (75 %) and analgesics (74 %) (p < 0.05 for both comparisons). Conclusion Women with APCD have impaired QoL. All treatments were considered effective by the majority of participants. Compared with STW 5 or analgesics, HBB was reported to facilitate return to daily activities more frequently.

Preoperative Belladonna and Opium Suppository for Ureteral Stent Pain: A Randomized, Double-blinded, Placebo-controlled Study.

OBJECTIVE: To investigate whether the use of a belladonna and opium (B&O) rectal suppository administered immediately before ureteroscopy (URS) and stent placement could reduce stent-related discomfort. METHODS: A randomized, double-blinded, placebo-controlled study was performed from August 2013 to December 2014. Seventy-one subjects were enrolled and randomized to receive a B&O (15 mg/30 mg) or a placebo suppository after induction of general anesthesia immediately before URS and stent placement. Baseline urinary symptoms were assessed using the American Urological Association Symptom Score (AUASS). The Ureteral Stent Symptom Questionnaire and AUASS were completed on postoperative days (POD) 1, 3, and after stent removal. Analgesic use intraoperatively, in the recovery unit, and at home was recorded. RESULTS: Of the 71 subjects, 65 had treatment for ureteral (41%) and renal (61%) calculi, 4 for renal urothelial carcinoma, and 2 were excluded for no stent placed. By POD3, the B&O group reported a higher mean global quality of life (QOL) score (P = .04), a better mean quality of work score (P = .05), and less pain with urination (P = .03). The B&O group reported an improved AUASS QOL when comparing POD1 with post-stent removal (P = .04). There was no difference in analgesic use among groups (P = .67). There were no episodes of urinary retention. Age was associated with unplanned emergency visits (P <.00) and "high-pain" measure (P = .02) CONCLUSION: B&O suppository administered preoperatively improved QOL measures and reduced urinary-related pain after URS with stent. Younger age was associated with severe stent pain and unplanned hospital visits.

Pulmonary anti-inflammatory effects and spasmolytic properties of Costa Rican noni juice (Morinda citrifolia L.).

ETHNOPHARMACOLOGICAL RELEVANCE: Morinda citrifolia L. (Noni) is a medicinal plant used in Polynesia for many properties such as anti-inflammatory, anti-diabetic and antineoplastic effects. Recent studies showed that noni juice have anti-oxidant and acute anti-inflammatory activities likely due to polyphenols, iridoids and vitamin C content. The present study was undertaken to evaluate chronic anti-inflammatory and spasmolytic effects of noni juice. MATERIALS AND METHODS: Therefore, we evaluated the effect of oral or intraperitoneal administrations of noni juice in vivo on the lung inflammation in ovalbumin (OVA) sensitized Brown Norway rat (with prednisolone 10mg/kg intraperitoneously as reference compound) and the ex vivo effect of noni juice on BaCl2 (calcium signal) or methacholine (cholinergic signal) induced spasms in jejunum segments. RESULTS: We found that noni juice (intraperitoneously 2.17mL/kg and orally 4.55mL/kg) reduced the inflammation in OVA-sensitized Brown Norway rat with regard to the decreased number of inflammatory cells in lung (macrophages minus 20-26%, lymphocytes minus 58-34%, eosinophils minus 53-30%, neutrophils minus 70-28% respectively). Noni juice demonstrated a dose-dependent NO scavenging effect up to 8.1nmol of nitrites for 50µL of noni juice. In addition noni juice inhibited (up to 90%) calcium and cholinergic induced spasms on the jejunum segments model with a rightward shift of the concentration response curve. CONCLUSION: We describe for the first time that noni juice demonstrate (1) a chronic anti-inflammatory activity on sensitized lungs along with (2) a spasmolytic effect integrating a calcium channel blocker activity component.

Antispasmodic Effects and Action Mechanism of Essential Oil of Chrysactinia mexicana A. Gray on Rabbit Ileum.

The Chrysactinia mexicana A. Gray (C. mexicana) plant is used in folk medicine to treat fever and rheumatism; it is used as a diuretic, antispasmodic; and it is used for its aphrodisiac properties. This study investigates the effects of the essential oil of C. mexicana (EOCM) on the contractility of rabbit ileum and the mechanisms of action involved. Muscle contractility studies in vitro in an organ bath to evaluate the response to EOCM were performed in the rabbit ileum. EOCM (1-100 µg·mL(-1)) reduced the amplitude and area under the curve of spontaneous contractions of the ileum. The contractions induced by carbachol 1 µM, potassium chloride (KCl) 60 mM or Bay K8644 1 µM were reduced by EOCM (30 µg·mL(-1)). Apamin 1 µM and charybdotoxin 0.01 µM decreased the inhibition induced by EOCM. The d-cAMP 1 µM decreased the inhibition induced by EOCM. l-NNA 10 µM, Rp-8-Br-PET-cGMPS 1 µM, d,l-propargylglycine 2 mM, or aminooxyacetic acid hemihydrochloride 2 mM did not modify the EOCM effect. In conclusion, EOCM induces an antispasmodic effect and could be used in the treatment of intestinal spasms or diarrhea processes. This effect would be mediated by Ca(2+), Ca(2+)-activated K⁺ channels and cAMP.

Clinically Diagnosed Acute Diverticulitis in Outpatients: Misdiagnosis in Patients with Irritable Bowel Syndrome.

BACKGROUND: Physicians often diagnose diverticulitis and prescribe antibiotics in outpatients with abdominal pain and tenderness without other evidence. AIM: We investigated the misattribution of irritable bowel syndrome (IBS) symptoms to diverticulitis in outpatients. METHODS: In patients diagnosed with diverticulitis and dispensed antibiotics in an integrated healthcare system, we retrospectively compared 15,846 outpatients managed without computed tomography (CT) versus 3750 emergency department/inpatients who had CT. We assessed demographics and past history, including 17 symptom-based somatic and 11 mental disorders and three somatic-mental comorbidity pairs (dyads) coded over 3 years and seven drug classes dispensed over 1 year before diagnosis. RESULTS: Univariate analysis showed small intergroup demographic differences. Outpatients had increases in prior diverticulitis, including outpatient-managed episodes, total somatic diagnoses (p < .0001), eight somatic and three mental disorders (p ≤ .015), all three dyads (p ≤ .05), and dispensing of three drug classes (p ≤ .016). IBS had been diagnosed in 2399 (15.1 %) outpatients versus 361 (9.6 %) emergency department/inpatients (p < .0001), the greatest increase in any comorbidity. Emergency department/inpatients had no somatic comorbidity more often but more alcohol dependence, non-dependent drug abuse, and opioid dispensing (p ≤ .05). Regression analysis revealed outpatient care was independently positively associated with younger age, non-Hispanic white race/ethnicity, less Charlson comorbidity, diverticulitis history, IBS, chest pain, dyspepsia, fibromyalgia, low back pain, migraine, acute reaction to stress, and antispasmodic and anxiolytic dispensing and negatively associated with non-dependent drug abuse and opioid dispensing (p ≤ .0226). CONCLUSIONS: Multiple types of indirect and concordant evidence suggest misattribution of IBS pain to diverticulitis and unnecessary antibiotic therapy in outpatients.

A Novel Delivery System of Peppermint Oil Is an Effective Therapy for Irritable Bowel Syndrome Symptoms.

BACKGROUND: Peppermint oil (PO) has shown promise as an IBS therapy, but previous trials have demonstrated variable efficacy and tolerability results. AIMS: To evaluate the efficacy and tolerability of a novel formulation of PO designed for sustained release in the small intestine in patients with IBS-M and IBS-D. METHODS: This is a 4-week, randomized, double-blind, placebo-controlled clinical trial of PO or identical placebo 3 times daily in patients fulfilling Rome III criteria for IBS-M or IBS-D. The primary endpoint was the change from baseline in the Total IBS Symptom Score (TISS) after 4 weeks of treatment. RESULTS: Seventy-two patients (mean age 40.7 years, 75 % female, 77.8 % white) were randomized to PO (n = 35) or placebo (n = 37). At 4 weeks, PO was associated with a 40 % reduction in the TISS from baseline (mean change -1.16, SD ± 0.807), superior to the 24.3 % decrease (mean change -0.70, SD ± 0.737) observed with placebo (P = 0.0246). The decrease in the TISS of 19.6 % (mean change -0.55, SD ± 0.613) in the PO group at 24 h was also significantly larger than placebo (-10.3 %, mean change -0.27, SD ± 0.342) (P = 0.0092). At trial completion, patients in the PO group experienced greater improvement in multiple individual gastrointestinal symptoms as well as in severe or unbearable symptoms, compared to placebo. PO was well tolerated with few adverse events. CONCLUSIONS: A novel PO formulation designed for sustained release in the small intestine is a safe, effective treatment capable of providing rapid relief of IBS symptoms.

A stepwise approach to the induction of idiopathic fascicular ventricular tachycardia.

PURPOSE: Noninducibility of the clinical tachycardia is a major limitation while mapping and ablating idiopathic fascicular ventricular tachycardia (FVT). There is very little data on systematic induction protocols in this entity. Our aim was to study the role of systematic induction protocols in patients with clinically documented ventricular tachycardia (VT). METHODS: Programmed electrical stimulation was performed at baseline from high right atrium, right ventricular apex, right ventricular outflow tract and from left ventricle as per the protocol. Programmed ventricular stimulation was performed at two drive cycle lengths up to three extrastimuli and short-long-short sequence. If FVT remained non inducible at baseline, pharmacological provocation with isoprenaline/atropine/phenylephrine was used based on the baseline atrio-ventricular Wenckebach cycle length. RESULTS: This systematic induction protocol was studied in 68 patients with clinically documented FVT and sustained FVT was inducible in 64 patients (94 %). Of these 64 patients, pharmacological provocation was required in 18 patients (28 %) while in the remaining, sustained VT was induced at baseline. This high induction rate allowed ablation during tachycardia, which resulted in 100 % acute procedural success in the patients where sustained tachycardia could be induced. At a follow up of 29 ± 13 months, two patients (3 %) had recurrence. CONCLUSIONS: Systematic induction protocol along with the appropriate use of pharmacological agents results in a high induction rate of FVT. This may result in more defined and limited ablation during tachycardia with better success rates and lesser recurrence.