Pentoxifylline, a nonselective phosphodiesterase inhibitor, in adjunctive therapy in patients with irritable bowel syndrome treated with mebeverine.

BACKGROUND: Irritable bowel syndrome (IBS) is a functional gastrointestinal condition marked by chronic bowel pain or discomfort, as well as changes in abdominal motility. Despite its worldwide prevalence and clinical impact, the cause of IBS is unknown. Inflammation could play a fundamental role in the development of IBS. The aim of this study was to examine whether pentoxifylline, a competitive nonselective phosphodiesterase inhibitor, is useful in alleviating abdominal pain in IBS patients treated with mebeverine. METHODS: A randomized, controlled, and prospective clinical study that included 50 outpatients who met the inclusion criteria for IBS. Patients are allocated randomly into two groups (n = 25). Group 1 (mebeverine group) received mebeverine 135 mg three times daily (t.i.d) for three months. Group 2 (pentoxifylline group) received mebeverine 135 mg t.i.d and pentoxifylline 400 mg two times daily for three months. Patients were assessed by a gastroenterologist at baseline and three months after the medication had been started. The serum levels of interleukin-6, interleukin-8 and tumor necrosis factor-alpha, fecal Neutrophil Gelatinase Associated Lipocalin (NGAL), and fecal myeloperoxidase were measured at the start and after three months of therapy. The Numeric Pain Rating scale (NRS) was assessed at baseline and after therapy. RESULTS: the pentoxifylline group showed a significant decrease in the level of measured biomarkers and a significant decrease in NRS. CONCLUSION: Pentoxifylline could be a promising adjuvant anti-inflammatory drug in the treatment of abdominal pain in IBS patients treated with mebeverine.

Effect of hyoscine-N-butylbromide on labor duration among nullipara in a southwestern Nigerian teaching hospital: A randomized controlled trial.

OBJECTIVE: To assess the effectiveness of hyoscine-N-butylbromide on the duration of the first stage of labor among nulliparous women. METHODS: A randomized double-blind placebo-controlled study among 126 nulliparous women admitted in the active phase of labor to a teaching hospital in Sagamu, Nigeria, from January to August 2018. Based on the inclusion criteria, women were recruited and randomized to the study or control group, and given intravenous hyoscine-N-butylbromide 20 mg (1 mL) or sterile water (1 mL), respectively, during the active phase. Labor progress and outcomes were compared between the groups. RESULTS: The mean ± SD duration of active phase of first stage of labor was significantly shorter in the hyoscine-N-butylbromide group (324.9 ± 134.6 min) than in the control group (392.7 ± 119.6 min) (P = 0.004). The rate of cervical dilatation was 1.4 ± 0.8 cm/h in the hyoscine-N-butylbromide group and 1.0 ± 0.5 cm/h in the control group (P = 0.004). There were no significant differences in fetal heart rate, maternal vital signs, or Apgar scores between the two groups. CONCLUSION: Hyoscine-N-butylbromide was found to be effective in shortening the duration of the first stage of labor without adverse outcomes for mother or neonate. The trial was registered with the Pan African Clinical trials Registry (PACTR), protocol number: PACTR201808146688942 (https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=3532).

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.

Effect of Vemurafenib on the Pharmacokinetics of a Single Dose of Tizanidine (a CYP1A2 Substrate) in Patients With BRAFV600 Mutation-Positive Malignancies.

This phase 1 open-label, multicenter, 3-period, fixed-sequence study evaluated the effect of multiple doses of vemurafenib on the pharmacokinetics of 1 dose of tizanidine, a probe CYP1A2 substrate, in patients with BRAFV600 mutation-positive metastatic malignancy. Patients received 1 dose of tizanidine 2 mg on day 1 (period A), vemurafenib 960 mg twice daily on days 2-21 (period B), and 1 dose of tizanidine 2 mg and vemurafenib 960 mg twice daily on day 22 (period C). Log-transformed area under the concentration-time curve (AUC) and maximum plasma concentration (Cmax ) values for tizanidine in 16 patients were compared between periods A (tizanidine alone) and C (tizanidine plus vemurafenib) using an analysis of variance model. Multiple doses of vemurafenib increased plasma exposure of 1 dose of tizanidine, with geometric mean ratios (period C/period A) for Cmax , AUCinf , and AUClast of 2.15 (90%CI, 1.71-2.71), 4.22 (90%CI, 3.37-5.28), and 4.74 (90%CI, 3.55-6.33), respectively; 90%CIs were all outside predefined limits for lack of drug-drug interaction (0.82-1.22). This study confirmed vemurafenib as a moderate inhibitor of CYP1A2 in vivo, with a statistically significant drug-drug interaction with tizanidine. Caution should be exercised when dosing vemurafenib concurrently with CYP1A2 substrates.

Coronary stent embolism to the right posterior cerebral artery.

A 57-year-old male was admitted to the emergency room with chest pain that has been present for 3 hours. His blood pressure was 70/50 mmHg and heart rate was 48 bpm. 12-lead surface electrocardiography revealed inferior myocardial infarction and third-degree atrioventricular (AV) block. An emergency coronary angiography showed a 50% stenosis in the middle segment of the left anterior descending artery and 90% in the proximal circumflex (Cx) artery. The right coronary artery was totally occluded. After the predilatation with a 2.0x15 mm compliant balloon at 10 atm, a 3.5x24 mm bare metal stent was implanted. The third-degree AV block improved and a sinus rhythm of 124 bpm was achieved, but hemodynamic stability was not attained. Percutaneous coronary intervention for the Cx artery was performed. Without predilatation, a 3.5x12 mm low profile BMS was easily advanced over the lesion. Just before the stent implantation, asystole developed, followed by convulsions. Blood pressure and heart rate recovered after the administration of 1 mg of atropine. However, during the seizure, the guidewire and coronary stent device fell to the aortic root. Stent struts were not seen on the balloon catheter in a fluoroscopic examination. Fluoroscopic scanning of the vascular system showed that the coronary stent was in the right posterior cerebral artery. There were no symptoms or signs of neurological disorder. Consultant invasive neuroradiologist recommended medical follow-up. Clopidogrel and acetylsalicylic acid were prescribed indefinitely. Two months after the primary PCI, a successful coronary artery bypass graft operation was performed. After 4 years, the patient remained without any symptoms of neurological problems.

Effects of L-Menthol and Carbon Dioxide on the Adenoma Detection Rate during Colonoscopy: L-Menthol and Carbon Dioxide on Colonoscopy.

BACKGROUND AND AIMS: We examined the efficacy of the combined use of L-menthol spraying (L-mentholS) as an antispasmodic agent and carbon dioxide insufflation (CO2I) on the adenoma detection rate (ADR) in a prospective, single-center trial with a 2 × 2 factorial design. METHODS: We randomly assigned 611 patients scheduled to undergo colonoscopy to 4 groups: (1) the L-mentholS + CO2I (n = 153), (2) L-mentholS + air insufflation (AI; n = 156), (3) CO2I (n = 153), and (4) AI (n = 149) groups. We used 20 mL of 0.8%-L-menthol solution for the L-mentholS. The primary outcome was the difference in the ADR, and the secondary outcomes were the differences in colonic peristalsis and abdominal pain. -Results: The ADRs were not different among the groups: 1/2/3/4; 39.9%/43.6%/41.2%/51.0%. CO2I was associated with a significant decrease in the ADR (OR 0.57; 95% CI 0.35- 0.93) with a multiple logistic regression. The interaction between L-mentholS and CO2I was associated with a suppression of the decrease in the ADR. Both L-mentholS and CO2I were associated with a significant decrease in abdominal pain, and L-mentholS was associated with a significant improvement of peristalsis. CONCLUSIONS: The fact that CO2I was associated with significant decreases in the ADR was a problem. The combined use of L-mentholS and CO2I could help to suppress the decrease in the ADR.

A comparison of intravenous sugammadex and neostigmine + atropine reversal on time to consciousness during wake-up tests in spinal surgery.

OBJECTIVE: The effect of sugammadex on consciousness is not yet fully understood. This prospective, randomized, double-blind, multicenter study was performed to compare the effects of intravenous (IV) sugammadex and neostigmine + atropine reversals on time-to-consciousness during intraoperative wake-up tests in patients undergoing spinal surgery. SUBJECTS AND METHODS: A total of 66 American Society of Anesthesiologists I-II patients aged 10-25 years undergoing spinal surgery were recruited. In all patients, bispectral index (BIS), motor-evoked potential (MEP), somatosensory-evoked potentials (SSEP), and train-of-four (TOF) scores were monitored. Patients received the same total IV anesthesia protocol with a propofol-remifentanil mixture. Patients were randomly allocated into two groups. During wake-up test, when the TOF count reached 2 (T2), either sugammadex 2 mg.kg-1 in group S or neostigmine 0.04 mg.kg-1 + atropine 0.01 mg.kg-1 in group N were administered. BIS90, SSEP90, MEP90 was recorded when TOF ratio reached 90, whereas time-to-consciousness (Timecons) was recorded when the patient responded to verbal commands. RESULTS: BIS90 (77.4 ± 4.7, 74.8 ± 3.7), SSEP90(36 ± 9.9, 29.7 ± 8.5), and MEP90 (465.3 ± 34.8, 431.3 ± 28.2) values were significantly greater in group S than in group N (P < 0.05 for each variables). Timecons was significantly shorter with sugammadex than with the neostigmine + atropine combination (P < 0.05). CONCLUSION: Using IV sugammadex 2 mg.kg-1 reversal provides faster responses to verbal commands than neostigmine-atropine combination during the intraoperative wake-up test in patients undergoing spinal surgery because the time to consciousness was significantly shorter. This difference was thought to be related with faster return of neuromuscular transmission because the TOF ratio was >0.9 well before return of consciousness in both groups.

The Role of Muscle Relaxants ­ Spasmolytic (Thiocochlicoside) in Postoperative Pain Management after Mastectomy and Breast Reconstruction

Purpose: Post-operative pain after breast cancer surgery is a major problem and women undergoing mastectomy and breast reconstruction experience post-operative pain syndromes in approximately one-half of all cases. Patients who have undergone breast reconstruction after mastectomy can suffer from acute postoperative pain with moderate or strong tension. In some cases, chronic neuropathic pain syndromes may occur after surgery. Opioids are used to treat pain, with serious side effects. The systemic postoperative analgesic regimen as thiocochlicoside P.O. along with paracetamol and NSAIDs I.V., which may limit the administration of opioids without reducing pain relief, seems to be necessary. Materials and Methods: This study was a clinical trial randomizing 70 patients undergoing breast reconstruction. Two main protocols of systematic post-operative analgesia, one using thiocochlicoside (group A) and the other without them (group B), were used. Both groups received paracetamol X3 and lornoxicam X2 I.V. systematically. The pain measurement scale (NPS) used to measure post-operative pain. Likert scales were used to evaluate patient's satisfaction and the difficulty from the side effects . An anonymous questionnaire was used for the data collection. Results: Statistically significant difference was found between pain on the day of surgery (p = 0.017) as well as the three subsequent days (p = 0.000). In group A , pain was reduced directly to half (Χ2 surgery pain = 93.888, p = 0.000) especially on the first post-operative day. In group A the satisfaction with analgesic treatment was higher than in group B (p = 0.002). Conclusion: The use of thiocochlicoside in post-operative analgesia in breast reconstruction after mastectomy contributes to reduce the pain intensity experienced by patients and to reduce the side effects of opioid analgesics as a result of reduced demand for opioid analgesics. Patients who received the analgesia using muscle relaxants-spasmolytic reported greater satisfaction.

Optimising prostate mpMRI: prepare for success.

Multiparametric magnetic resonance imaging (MRI) now plays an essential role in prostate cancer diagnosis and management. The increasing use of MRI before biopsy makes obtaining images of the highest quality vital. The European Society of Urogenital Radiology (ESUR) 2012 guidelines and subsequent Prostate Imaging -Reporting Data System (PI-RADS) version 2 recommendations in 2015 address the technical considerations for optimising MRI acquisition; however, the quality of the multiparametric sequences employed depends not only on the hardware and software utilised and scanning parameters selected, but also on patient-related factors, for which current guidance is lacking. Patient preparation factors include bowel peristalsis, rectal distension, the presence of total hip replacement (THR), post-biopsy haemorrhage, and abstinence from ejaculation. New evidence has been accrued since the release of PI-RADS v2, and this review aims to explore the key issues of patient preparation and their potential to further optimise the image quality of mpMRI.

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.

Hyoscine Butylbromide for the Management of Death Rattle: Sooner Rather Than Later.

CONTEXT: Death rattle (DR) is a dramatic sign in the dying patient. Existing studies with anticholinergic agents are controversial, as this class of drugs has been commonly administered without considering the rationale of the mechanism of action. A meaningful use of these drugs may provide a better outcome. OBJECTIVES: The aim of this study was to assess the efficacy of hyoscine butylbromide (HB), given prophylactically in comparison with HB administered once DR occurs. METHODS: Dying patients having a score of ≥3 in the Richmond Agitation-Sedation Scale-palliative version were included in the study. HB (60 mg/day) was given when DR occurred (Group 1) or as pre-emptive treatment (Group 2). The onset of DR (death rattle free time) and intensity of DR were recorded at intervals until death. RESULTS: Eighty-one and 51 patients were randomized to Group 1 and 2, respectively. Patients in Group 2 survived longer than those in Group 1 (P < 0.05). DR occurred in 49 (60.5%) and three patients (5.9%) in Group 1 and 2, respectively (P = 0.001). A significant difference in the number of patients reporting DR was found at intervals examined (30 minutes, one hour, and then every six hours until death [P = 0.001]). In Group 1 and 2, DR free time was 20.4 (20.5) and 27.3 hours (25.2), respectively (P = 0.001). In Group 1, the treatment was considered effective in 10 patients (20.4%) only, after a mean of 14.4 hours (SD 8.57). CONCLUSION: The prophylactic use of HB is an efficient method to prevent DR, whereas the late administration produces a limited response, confirming data from traditional studies performed with anticholinergics. This could be considered a new paradigm to manage a difficult and dramatic sign, such as DR.

Cimetropium bromide does not improve polyp and adenoma detection during colonoscope withdrawal: A randomized, double-blind, placebo-controlled study.

BACKGROUND: Endoscopic inspection of colonic mucosa is disturbed by colonic folds and peristalsis, which may result in missed polyps. Cimetropium bromide, an antispasmodic agent, inhibits peristalsis and colonic spasms, which may improve polyp detection. The purpose of this randomized, double-blind, placebo-controlled study was to investigate whether cimetropium bromide could improve polyp and adenoma detection in the colorectum and right colon. METHODS: Patients undergoing screening or diagnostic colonoscopy were randomized to receive intravenous cimetropium bromide (5 mg) or placebo after cecal intubation. The primary outcomes were the number of polyps per patient (PPP) and adenomas per patient (APP); secondary outcomes were the polyp detection rate (PDR), adenoma detection rate (ADR), and advanced neoplasm detection rate (ANDR). RESULTS: A total of 181 patients were analyzed; 91 patients received cimetropium bromide and 90 patients received placebo. Cimetropium bromide and placebo groups did not significantly differ in the PPP and APP for the colorectum (1.38 ±â€Š1.58 vs 1.69 ±â€Š2.28, P = .298; 0.96 ±â€Š1.27 vs 1.11 ±â€Š1.89, P = .517, respectively) and right colon (0.70 ±â€Š0.95 vs 0.78 ±â€Š1.21, P = .645; 0.47 ±â€Š0.81 vs 0.51 ±â€Š0.81, P = .757, respectively). Two groups also did not significantly differ in the PDR, ADR, and ANDR for the colorectum and right colon. Furthermore, there were no difference between groups in the PPP, APP, PDR, ADR, and ADNR in a sub-analysis of expert and non-expert endoscopists. CONCLUSIONS: Cimetropium bromide did not improve polyp and adenoma detection in the colorectum and right colon during colonoscope withdrawal, regardless of the expertness of the endoscopist. However, its use may be helpful in patients with active peristalsis or for beginning endoscopists during standard colonoscopy without a transparent cap.

Hyoscine N-Butylbromide for Preventing Propofol Injection Pain: A Randomized, Placebo-Controlled and Double-Blind Study.

OBJECTIVE: In this study, the aim was to investigate the effect of hyoscine N-butylbromide (HnBB) pretreatment on pain during propofol injection. SUBJECTS AND METHODS: In this prospective, randomized, placebo-controlled and double-blind trial, 60 patients scheduled to undergo routine outpatient surgery under general anesthesia were randomly allocated to 2 groups, the HnBB (n = 30) and sodium chloride (n = 30) groups. Twenty seconds after the injection of 20 mg HnBB or 0.9 % sodium chloride, a 50-mg dose of propofol was injected in 2-3 s. Ten seconds later, the pain intensity was assessed using a 4-point scale: no pain (0), mild (1), moderate (2), and severe (3) pain. The Student t test was used for the analysis of parametric data and the Pearson χ2 test for categorical data. RESULTS: The occurrence of pain in the HnBB group (43.3%) was significantly lower than the control group (73.3%) (p < 0.018). Of the 30 patients in each group, 10 in the control group and 3 in the HnBB group experienced severe pain (p = 0.001). CONCLUSIONS: Pretreatment with 20 mg HnBB significantly reduced propofol injection pain compared to placebo.

Hyoscine butylbromide significantly decreases motion artefacts and allows better delineation of anatomic structures in mp-MRI of the prostate.

OBJECTIVES: To prospectively evaluate the effect of hyoscine butylbromide (HBB) on visualisation of anatomical details and motion-related artefacts in mp-MRI of the prostate at 3.0 Tesla. METHODS: One hundred and three consecutive patients (65 ± 10 years) were included in this trial, powered to demonstrate an improvement of image quality after HBB administration, assessed on a 5-point scale by two blinded readers. All patients received high-spatial resolution axial T2-weighted TSE sequences at 3.0 T without spasmolytic agent, repeated after application of 40 mg HBB and followed by routine mp-MRI. Secondary endpoints were (1) susceptibility to side effects, (2) dependence of spasmolytic effect on patients´ weight, and (3) prostate volume. RESULTS: In 68% of patients, HBB significantly improved the anatomic score (mean 3.4 ± 0.9 before and 4.4 ± 0.7 after HBB for both readers, p = <0.001). In 67%, HBB significantly enhanced the artefact score (mean 3.2 ± 1 before and 4.2 ± 0.8 after HBB for reader 1, p = <0.001; 3.2 ± 1 and 4.1 ± 0.8 for reader 2, p = <0.001). Subgroup analysis revealed no statistically significant difference between patients with different bodyweight or prostate volume. Inter-reader agreement was excellent (k = 0.95-0.98). CONCLUSIONS: Hyoscine butylbromide significantly improves image quality and reduces motion-related artefacts in mp-MRI of the prostate independent of bodyweight or prostate volume. No side effects were reported. KEY POINTS: • Hyoscine butylbromide (HBB) improved image quality in over 2/3 of patients. • Severe artefacts were reduced after HBB in more than 20%. • The number of non-diagnostic MRI was reduced to <1% after HBB. • HBB effect was independent of bodyweight and prostate volume. • No side effects of HBB were reported in this study population.

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.

Effect of hyoscine butyl-bromide on the duration of active phase of labor: A randomized-controlled trial.

OBJECTIVE: Hyoscine butyl bromide (HBB) is known for its antispasmodic action and has been in use for over five decades, there is however no consensus on its effectiveness in the labor process. The aim of this study was to determine the effect of HBB on the duration of the active phase of labor. MATERIALS AND METHODS: A randomized double-blind placebo-controlled clinical trial involving 160 parturient who received either intravenous Hyoscine butyl-bromide (20 mg in 1 ml; n = 80) or intravenous normal saline (1 ml, n = 80). The mean duration of active phase of labor was compared between the two groups. RESULTS: The observed mean duration of the active phase of labor was significantly shorter (P = 0.001) in the Hyoscine butyl-bromide group (365.11 ± 37.32 min, range = 280-490) than in the Placebo group (388.46 ± 51.65 min, range = 280-525). There was no significant difference between the two groups in the mean duration of the second and third stages of labor (20.46 ± 10.46 vs. 23.38 ± 18.95 min, P = 0.43 and 8.96 ± 4.34 vs. 9.23 ± 5.92 min, P = 0.75, respectively). The mean 1-min APGAR scores were also comparable (8.08 ± 1.54 vs. 7.64 ± 1.60, P = 0.08). The mean postpartum blood loss was significantly less in the Hyoscine butyl-bromide group (303 ± 96.52 vs. 368 ± 264.19 ml, P = 0.04). CONCLUSION: Hyoscine butyl-bromide was effective in shortening the duration of the active phase of labor. It was also associated with significantly less postpartum blood loss.

Effect of a single exacerbation on decline in lung function in COPD.

BACKGROUND: COPD exacerbations are associated with accelerated lung function decline, but whether they are causal is unknown. We evaluated the effect of a single exacerbation on rate of lung function change using data from the 4-year Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT®) trial. METHODS: Retrospective analysis of annual rates of decline in FEV1 and FVC before and after a single (and the only) moderate-to-severe exacerbation in patients during UPLIFT® (exacerbator subgroup), compared with changes between the first and second half of the study in a non-exacerbator subgroup. A sensitivity analysis examined annual rates of decline in matched pairs of exacerbators and non-exacerbators. RESULTS: Following the single moderate-to-severe exacerbation, mean annual decline in post-bronchodilator lung function increased compared with the rate of decline before the exacerbation (FEV1 76.5 vs. 39.1 mL/year, p = 0.003; FVC 106.5 vs. 34.7 mL/year, p = 0.011). In non-exacerbators, there were no differences in rates of decline between the first and second halves of the study (post-bronchodilator FEV1 38.2 vs. 41.8 mL/year, FVC 45.3 vs. 43.9 mL/year. Before the single (moderate-to-severe) exacerbation in the exacerbator subgroup, declines in post-bronchodilator FEV1 or FVC were similar to non-exacerbators in the first half of the study; after the single exacerbation they were significantly higher than for non-exacerbators in the second half of the study. The sensitivity analysis showed similar results. CONCLUSION: A single COPD exacerbation may result in significant increase in the rate of decline in lung function.