The Effect of Acupuncture and Electro-acupuncture at ST41 on Intestinal Hypomotility Induced with Loperamide in Rats

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Lee Sang-mi

2009-12-01

Full Text Available Objectives : The purpose of this study was to compare the effect of acpuncture and electro-acupuncture of low(EA(L and high(EA(H frequency at Haegye(ST41 on intestinal hypomotility induced with loperamide in rats. Methods : We made suppressed state of intestinal motility with loperamide in rats and carried out needle retention acupuncture, low frequency electro-acupuncture and high frequency electro-acupuncture at ST41 in rats devided into pre-treatment group and post-treatment group. We fed charcoal to them after the treatment and measured the travel rate of charcoal in the gastrointestinal track to analyze which treatment is more effective in state of intestinal hypomotility. Results : None of acupuncture, EA(L and EA(H at ST41 had significant influences on intestinal motility of rat in normal state. Needle retention at ST41 did not significantly increase intestinal motility suppressed with loperamide in rats. Pre-treatment of EA(L and EA(H at ST41 significantly increased intestinal motility suppressed with loperamide in rats. Post-treatment of EA(L and EA(H at ST41 did not have significant influences on intestinal motility of rat in normal state. Conclusions : These results suggest that treatment of EA(L and EA(H at ST41 may be effective on gastric disorders such as intestinal hypomotility and its effect had more prevention than cure. Further study is necessary to know more effects of ST41 and electro-acupuncture of low and high frequency.

Effects of Fermented Milk with Mixed Strains as a Probiotic on the Inhibition of Loperamide-Induced Constipation.

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Kim, Byoung-Kook; Choi, In Suk; Kim, Jihee; Han, Sung Hee; Suh, Hyung Joo; Hwang, Jae-Kwan

2017-01-01

To investigate the effects of a single bacterium and a mixture of bacteria as probiotics in loperamide-treated animal models, loperamide (3 mg/kg) was administered to SD rats to induce constipation. The individual lactic acid bacterial doses, Enterococcus faecium (EF), Lactobacillus acidophilus (LA), Streptococcus thermophilus (ST), Bifidobacterium bifidum (BB), Bifidobacterium lactis (BL), Pediococcus pentosaceus (PP), and a mixture of the bacteria were orally administered to loperamide-induced constipated rats at a concentration of 10 8 CFU/kg for 14 days. The weights and water contents of their stools were found to be significantly higher in PP, CKDB (mixture of 5 strains except PP), and CKDBP (CKDB+PP) groups than in the normal (constipation not induced) and the control (constipation-induced) groups ( p mucus secretion were significantly improved in all probiotic-treated-groups, as compared to that in the control group, and the CKDBP group was found to be the most effective according to immunohistochemistry (IHC) staining and total short chain fatty acid content analysis ( p <0.05). Lastly, PP, CKDB, and CKDBP showed relatively higher Lactobacillus sp. ratios of 61.94%, 60.31% and 51.94%, respectively, compared to the other groups, based on metagenomic analysis.

Topical Loperamide-Encapsulated Liposomal Gel Increases the Severity of Inflammation and Accelerates Disease Progression in the Adjuvant-Induced Model of Experimental Rheumatoid Arthritis

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Susan Hua

2017-08-01

Full Text Available This study evaluates the prophylactic effect of the peripherally-selective mu-opioid receptor agonist, loperamide, administered topically in a liposomal gel formulation on pain, inflammation, and disease progression in the adjuvant-induced model of experimental rheumatoid arthritis in female Lewis rats. In a randomized, blinded and controlled animal trial, AIA rats were divided into six groups consisting of eleven rats per group based on the following treatments: loperamide liposomal gel, free loperamide gel, empty liposomal gel, diclofenac gel (Voltaren®, no treatment, and naive control. Topical formulations were applied daily for a maximum of 17 days—starting from day 0 at the same time as immunization. The time course of the effect of the treatments on antinocieption and inflammation was assessed using a paw pressure analgesiometer and plethysmometer, respectively. Arthritis progression was scored daily using an established scoring protocol. At the end of the study, hind paws were processed for histological analysis. Administration of loperamide liposomal gel daily across the duration of the study produced significant peripheral antinociception as expected; however, increased the severity of inflammation and accelerated arthritis progression. This was indicated by an increase in paw volume, behavioral and observational scoring, and histological analysis compared to the control groups. In particular, histology results showed an increase in pannus formation and synovial inflammation, as well as an upregulation of markers of inflammation and angiogenesis. These findings may have implications for the use of loperamide and other opioids in arthritis and potentially other chronic inflammatory diseases.

Behavior of printable formulations of loperamide and caffeine on different substrates--effect of print density in inkjet printing

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Genina, Natalja; Fors, Daniela; Palo, Mirja

2013-01-01

The primary goal of the current work was to study the applicability of precision inkjet printing in fabrication of personalized doses of active pharmaceutical ingredients (APIs). Loperamide hydrochloride (LOP) and caffeine (CAF) were used as model compounds. Different doses of the drugs in a single...

Validation of 13C-acetic acid breath test by measuring effects of loperamide, morphine, mosapride, and itopride on gastric emptying in mice.

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Matsumoto, Kenjiro; Kimura, Hiroshi; Tashima, Kimihito; Uchida, Masayuki; Horie, Syunji

2008-10-01

Several methods are used to evaluate gastric motility in rodents, but they all have technical limitations. Recent technical developments enable a convenient method to evaluate gastric motility. The (13)C-acetic acid breath test in rodents is a non-invasive and repeatable method that can be used without physical restraints. The present study aimed to validate the (13)C-acetic acid breath test by measuring the effects of loperamide, morphine, mosapride, and itopride on gastric emptying in mice. Loperamide (1-10 mg/kg) and morphine (1.25-10 mg/kg) slowed gastric emptying and decreased the maximum concentration (C(max)) and area under the curve (AUC(90 min)) value in a dose-dependent manner. Mosapride (0.2-5 mg/kg) accelerated gastric emptying and increased C(max) value. Mosapride (20 mg/kg) did not accelerate gastric emptying on the (13)C-breath test. Itopride (30 mg/kg, per os) significantly accelerated gastric emptying compared with the vehicle group. In a comparison with the conventional phenol red test, there was a correlation between the C(max) value of breath test and gastric emptying (%) of phenol red tests in treatment with loperamide or mosapride. These results indicate that the (13)C-acetic acid breath test is an accurate, noninvasive, and simple method for monitoring gastric emptying in mice. This method is useful to assess the effect of drugs and gut function pharmacologically.

Development of orodispersible polymer films with focus on the solid state characterization of crystalline loperamide.

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Woertz, Christina; Kleinebudde, Peter

2015-08-01

The formulation of active pharmaceutical ingredients (API) as orodispersible films is gaining interest among novel oral drug delivery systems due to their small size, enhanced flexibility and improved patient compliance. The aim of this work was the preparation and characterization of orodispersible films containing loperamide hydrochloride (LPH) as model drug. As loperamide hydrochloride is poorly soluble in water it was used in crystalline form with a loading of 2mg/6cm(2) film. Hydroxypropyl methylcellulose (HPMC) and different types of hydroxypropyl cellulose (HPC) in different concentrations were used as film forming polymers whereas arabic gum, xanthan gum and tragacanth served as thickening agents. Films were characterized with respect to the content uniformity, morphology, thermal behavior and crystallinity. Suspensions were investigated regarding their viscosity using a rotational rheometer and the crystal structure of the Active Pharmaceutical Ingredient (API) was analyzed using polarized light microscopy. The development of flexible, non-brittle and homogeneous films of LPH was feasible. Two polymorphic forms of LPH appeared in the film formulations dependent on the utilized polymer. While in presence of HPMC the original polymorphic form I remained stable in suspension and films, the polymorphic form II occurred in presence of HPC. Both polymorphic forms were prepared separately and a solid state characterization was performed. Polymorph I showed isometric crystals whereas polymorph II showed needle shaped crystals. Tragacanth was able to prevent the transformation to polymorph II, if it was dissolved first before HPC. When HPC was added first to the suspension, the conversion to form II occurred irreversibly also after further addition of tragacanth. Copyright © 2015 Elsevier B.V. All rights reserved.

Co-precipitation of loperamide hydrochloride and polyethylene glycol using aerosol solvent extraction system

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Widjojokusumo, Edward; Youn, Yong-Suk; Lee, Youn-Woo; Veriansyah, Bambang; Tjandrawinata, Raymond Rubianto

2013-01-01

The co-precipitation of loperamide hydrochloride (LPM) and polyethylene glycol (PEG) using aerosol solvent extraction system (ASES) was examined. Scanning electron microscopy - energy dispersive X-ray spectroscopy (SEM-EDS) analysis showed that the co-precipitation was achieved in various LPM-PEG mass ratios with changes in its morphology. In 10-50% PEG mass ratios, angular-shaped particles were formed, whereas in 65-90% PEG mass ratios, irregular-shaped particles were formed. X-ray diffraction (XRD) analysis of the co-precipitates revealed that the LPM retained amorphous structure, while, on the other hand, the PEG retained crystalline structure. Fourier transform infrared (FT-IR) spectra indicated carbonyl function group of LPM and ether function group of PEG appeared in the co-precipitates. Results of a dissolution test showed that the co-precipitates of LPM-PEG had higher dissolution rate compared to that of the raw material and processed LPM with ASES. Taken together, the co-precipitation of LPMPEG was achieved using ASES and higher in its dissolution rate

Acetylcholine serves as a derepressor in Loperamide-induced Opioid-Induced Bowel Dysfunction (OIBD) in zebrafish.

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Shi, Yanyan; Zhang, Yu; Zhao, Fangying; Ruan, Hua; Huang, Honghui; Luo, Lingfei; Li, Li

2014-07-07

The mechanisms underlying gut development, especially peristalsis, are widely studied topics. However, the causes of gut peristalsis-related diseases, especially Opioid-Induced Bowel Dysfunction (OIBD) disorder, have not been well defined. Therefore, our study used zebrafish, a popular model for studying both gut development and peristalsis, and DCFH-DA, a dye that clearly labels the live fish gut lumen, to characterize the formation process of gut lumen as well as the gut movement style in vivo. By applying Loperamide Hydrochloride (LH), the μ-opioid receptor-specific agonist, we established an OIBD-like zebrafish model. Our study found that acetylcholine (ACh) was a key transmitter that derepressed the phenotype induced by LH. Overall, the study showed that the antagonistic role of ACh in the LH-mediated opioid pathway was evolutionarily conserved; moreover, the OIBD-like zebrafish model will be helpful in the future dissection of the molecular pathways involved in gut lumen development and pathology.

Genes and Gut Bacteria Involved in Luminal Butyrate Reduction Caused by Diet and Loperamide.

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Hwang, Nakwon; Eom, Taekil; Gupta, Sachin K; Jeong, Seong-Yeop; Jeong, Do-Youn; Kim, Yong Sung; Lee, Ji-Hoon; Sadowsky, Michael J; Unno, Tatsuya

2017-11-28

Unbalanced dietary habits and gut dysmotility are causative factors in metabolic and functional gut disorders, including obesity, diabetes, and constipation. Reduction in luminal butyrate synthesis is known to be associated with gut dysbioses, and studies have suggested that restoring butyrate formation in the colon may improve gut health. In contrast, shifts in different types of gut microbiota may inhibit luminal butyrate synthesis, requiring different treatments to restore colonic bacterial butyrate synthesis. We investigated the influence of high-fat diets (HFD) and low-fiber diets (LFD), and loperamide (LPM) administration, on key bacteria and genes involved in reduction of butyrate synthesis in mice. MiSeq-based microbiota analysis and HiSeq-based differential gene analysis indicated that different types of bacteria and genes were involved in butyrate metabolism in each treatment. Dietary modulation depleted butyrate kinase and phosphate butyryl transferase by decreasing members of the Bacteroidales and Parabacteroides . The HFD also depleted genes involved in succinate synthesis by decreasing Lactobacillus . The LFD and LPM treatments depleted genes involved in crotonoyl-CoA synthesis by decreasing Roseburia and Oscilllibacter . Taken together, our results suggest that different types of bacteria and genes were involved in gut dysbiosis, and that selected treatments may be needed depending on the cause of gut dysfunction.

Bifidobacterium adolescentis Exerts Strain-Specific Effects on Constipation Induced by Loperamide in BALB/c Mice

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Linlin Wang

2017-02-01

Full Text Available Constipation is one of the most common gastrointestinal complaints worldwide. This study was performed to determine whether Bifidobacterium adolescentis exerts inter-strain differences in alleviating constipation induced by loperamide in BALB/c mice and to analyze the main reasons for these differences. BALB/c mice underwent gavage with B. adolescentis (CCFM 626, 667, and 669 once per day for 17 days. The primary outcome measures included related constipation indicators, and the secondary outcome measures were the basic biological characteristics of the strains, the concentration changes of short-chain fatty acids in feces, and the changes in the fecal flora. B. adolescentis CCFM 669 and 667 relieved constipation symptoms by adhering to intestinal epithelial cells, growing quickly in vitro and increasing the concentrations of propionic and butyric acids. The effect of B. adolescentis on the gut microbiota in mice with constipation was investigated via 16S rRNA metagenomic analysis. The results revealed that the relative abundance of Lactobacillus increased and the amount of Clostridium decreased in the B. adolescentis CCFM 669 and 667 treatment groups. In conclusion, B. adolescentis exhibits strain-specific effects in the alleviation of constipation, mostly due to the strains’ growth rates, adhesive capacity and effects on the gut microbiome and microenvironment.

Combination therapy with biofeedback, loperamide, and stool-bulking agents is effective for the treatment of fecal incontinence in women - a randomized controlled trial.

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Sjödahl, Jenny; Walter, Susanna A; Johansson, Elin; Ingemansson, Anna; Ryn, Ann-Katrine; Hallböök, Olof

2015-08-01

Biofeedback and medical treatments have been extensively used for moderate fecal incontinence (FI). There is limited data comparing and combining these two treatments. The objective of this study was to evaluate the effect of biofeedback and medical treatments, separately and in combination. Sixty-four consecutive female patients, referred to a tertiary centre for FI, were included. The patients were randomized to start with either biofeedback (4-6 months) or medical treatment with loperamide and stool-bulking agents (2 months). Both groups continued with a combination of treatments, i.e. medical treatment was added to biofeedback and vice versa. A two-week prospective bowel symptom diary and anorectal physiology were evaluated at baseline, after single- and combination treatments. Fifty-seven patients completed the study. Median number of leakage episodes during two weeks decreased from 6 to 3 (p biofeedback and medical treatment is effective for symptom relief in FI. The symptom improvement was associated with improved fecal consistency, reduced urgency, and increased rectal sensory thresholds.

Electroacupuncture for patients with diarrhea-predominant irritable bowel syndrome or functional diarrhea: A randomized controlled trial.

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Zheng, Hui; Li, Ying; Zhang, Wei; Zeng, Fang; Zhou, Si-Yuan; Zheng, Hua-Bin; Zhu, Wen-Zeng; Jing, Xiang-Hong; Rong, Pei-Jing; Tang, Chun-Zhi; Wang, Fu-Chun; Liu, Zhi-Bin; Wang, Shi-Jun; Zhou, Mei-Qi; Liu, Zhi-Shun; Zhu, Bing

2016-06-01

Diarrhea-predominant irritable bowel syndrome (IBS-D) and functional diarrhea (FD) are highly prevalent, and the effectiveness of acupuncture for managing IBS-D and FD is still unknown.The aim of this study was to compare the effectiveness of electroacupuncture with loperamide.It was a prospective, randomized, parallel group controlled trial.A total of 448 participants were randomly assigned to He electroacupuncture group (n = 113), Shu-Mu electroacupuncture group (n = 111), He-Shu-Mu electroacupuncture group (n = 112), or loperamide group (n = 112). Participants in the 3 acupuncture groups received 16 sessions of electroacupuncture during a 4-week treatment phase, whereas participants in the loperamide group received oral loperamide 2 mg thrice daily. The primary outcome was the change from baseline in stool frequency at the end of the 4-weeks treatment. The secondary outcomes were the Bristol scale, the MOS 36-item short form health survey (SF-36), the weekly average number of days with normal defecations and the proportion of adverse events.Stool frequency was significantly reduced at the end of the 4-week treatment in the 4 groups (mean change from baseline, 5.35 times/week). No significant difference was found between the 3 electroacupuncture groups and the loperamide group in the primary outcome (He vs. loperamide group [mean difference 0.6, 95% CI, -1.2 to 2.4]; Shu-Mu vs. loperamide group [0.4, 95% CI, -1.4 to 2.3]; He-Shu-Mu vs. loperamide group [0.0, 95% CI, -1.8 to 1.8]). Both electroacupuncture and loperamide significantly improved the mean score of Bristol scale and increased the weekly average number of days with normal defecations and the mean scores of SF-36; they were equivalent in these outcomes. However, the participants in electroacupuncture groups did not report fewer adverse events than those in the loperamide group. Similar results were found in a subgroup analysis of separating patients with IBS-D and FD patients.Electroacupuncture is

Establishment of a protocol for determining gastrointestinal transit time in mice using barium and radiopaque markers

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Myagmarjaibuu, Bilomaa; Moon, Myeong Ju; Heo, Suk Hee; Jeong, Seo In; Jeong, Yong Yeon; Kang, Heoung Keun [Dept. of Radiology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun (Korea, Republic of); Park, Jong Seong [Dept. of Physiology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Jun, Jae Yeoul [Dept. of Physiology, College of Medicine, Chosun University, Gwangju (Korea, Republic of)

2013-01-15

The purpose of this study was to establish a minimally invasive and reproducible protocol for estimating the gastrointestinal (GI) transit time in mice using barium and radiopaque markers. Twenty 5- to 6-week-old Balb/C female mice weighing 19-21 g were used. The animals were divided into three groups: two groups that received loperamide and a control group. The control group (n = 10) animals were administered physiological saline (1.5 mL/kg) orally. The loperamide group I (n = 10) and group II (n = 10) animals were administered 5 mg/kg and 10 mg/kg loperamide orally, respectively. Thirty minutes after receiving the saline or loperamide, the mice was administered 80 μL of barium solution and six iron balls (0.5 mm) via the mouth and the upper esophagus by gavage, respectively. Afterwards, the mice were continuously monitored with fluoroscopic imaging in order to evaluate the swallowing of the barium solution and markers. Serial fluoroscopic images were obtained at 5- or 10-min intervals until all markers had been excreted from the anal canal. For analysis, the GI transit times were subdivided into intestinal transit times (ITTs) and colon transit times (CTTs). The mean ITT was significantly longer in the loperamide groups than in the control group (p < 0.05). The mean ITT in loperamide group II (174.5 ± 32.3) was significantly longer than in loperamide group I (133.2 ± 24.2 minute) (p < 0.05). The mean CTT was significantly longer in loperamide group II than in the control group (p < 0.05). Also, no animal succumbed to death after the experimental procedure. The protocol for our study using radiopaque markers and barium is reproducible and minimally invasive in determining the GI transit time of the mouse model.

Ameliorative Effect of Lecaniodiscus cupanioides (Sapindaceae ...

African Journals Online (AJOL)

Purpose: To evaluate the efficacy of aqueous root extract of Lecaniodiscus cupanioidies Planch. (Sapindaceae) against loperamide-induced constipation in Wistar rats. Methods: Constipation was induced by oral administration of loperamide (3 mg/kg body weight). The constipated rats were orally treated daily either with 50 ...

Targeted nanoparticles that mimic immune cells in pain control inducing analgesic and anti-inflammatory actions: a potential novel treatment of acute and chronic pain condition.

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Hua, Susan; Cabot, Peter J

2013-01-01

The peripheral immune-derived opioid analgesic pathway has been well established as a novel target in the clinical pain management of a number of painful pathologies, including acute inflammatory pain, neuropathic pain, and rheumatoid arthritis. Our objective was to engineer targeted nanoparticles that mimic immune cells in peripheral pain control to deliver opioids, in particular loperamide HCl, specifically to peripheral opioid receptors to induce analgesic and anti-inflammatory actions for use in painful inflammatory conditions. This peripheral analgesic system is devoid of central opioid mediated side effects (e.g., respiratory depression, sedation, dependence, tolerance). A randomized, double blind, controlled animal trial. Thirty-six adult male Wistar rats (200 - 250 g) were randomly divided into 6 groups: loperamide HCl-encapsulated anti-ICAM-1 immunoliposomes, naloxone methiodide + loperamide HCl-encapsulated anti-ICAM-1 immunoliposomes, loperamide HCl-encapsulated liposomes, empty anti-ICAM-1 immunoliposomes, empty liposomes, and loperamide solution. Animals received an intraplantar injection of 150 μL Complete Freund's Adjuvant (CFA) into the right hindpaw and experiments were performed 5 days post-CFA injection, which corresponded to the peak inflammatory response. All formulations were administered intravenously via tail vein injection. The dose administered was 200 μL, which equated to 0.8 mg of loperamide HCl for the loperamide HCl treatment groups (sub-therapeutic dose). Naloxone methiodide (1 mg/kg) was administered via intraplantar injection, 15 minutes prior to loperamide-encapsulated anti-ICAM-1 immunoliposomes. An investigator blinded to the treatment administered assessed the time course of the antinociceptive and anti-inflammatory effects using a paw pressure analgesiometer and plethysmometer, respectively. Biodistribution studies were performed 5 days post-CFA injection with anti-ICAM-1 immunoliposomes and control liposomes via tail vein

Characterization of Changes in Global Genes Expression in the Distal Colon of Loperamide-Induced Constipation SD Rats in Response to the Laxative Effects of Liriope platyphylla.

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Ji Eun Kim

Full Text Available To characterize the changes in global gene expression in the distal colon of constipated SD rats in response to the laxative effects of aqueous extracts of Liriope platyphylla (AEtLP, including isoflavone, saponin, oligosaccharide, succinic acid and hydroxyproline, the total RNA extracted from the distal colon of AEtLP-treated constipation rats was hybridized to oligonucleotide microarrays. The AEtLP treated rats showed an increase in the number of stools, mucosa thickness, flat luminal surface thickness, mucin secretion, and crypt number. Overall, compared to the controls, 581 genes were up-regulated and 216 genes were down-regulated by the constipation induced by loperamide in the constipated rats. After the AEtLP treatment, 67 genes were up-regulated and 421 genes were down-regulated. Among the transcripts up-regulated by constipation, 89 were significantly down-regulated and 22 were recovered to the normal levels by the AEtLP treatment. The major genes in the down-regulated categories included Slc9a5, klk10, Fgf15, and Alpi, whereas the major genes in the recovered categories were Cyp2b2, Ace, G6pc, and Setbp1. On the other hand, after the AEtLP treatment, ten of these genes down-regulated by constipation were up-regulated significantly and five were recovered to the normal levels. The major genes in the up-regulated categories included Serpina3n, Lcn2 and Slc5a8, whereas the major genes in the recovered categories were Tmem45a, Rerg and Rgc32. These results indicate that several gene functional groups and individual genes as constipation biomarkers respond to an AEtLP treatment in constipated model rats.

Relations between transit time, fermentation products, and hydrogen consuming flora in healthy humans.

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El Oufir, L; Flourié, B; Bruley des Varannes, S; Barry, J L; Cloarec, D; Bornet, F; Galmiche, J P

1996-06-01

To investigate whether transit time could influence H2 consuming flora and certain indices of colonic bacterial fermentation. Eight healthy volunteers (four methane excretors and four non-methane excretors) were studied for three, three week periods during which they received a controlled diet alone (control period), and then the same diet with cisapride or loperamide. At the end of each period, mean transit time (MTT) was estimated, an H2 lactulose breath test was performed, and stools were analysed. In the control period, transit time was inversely related to faecal weight, sulphate reducing bacteria counts, concentrations of total short chain fatty acids (SCFAs), propionic and butyric acids, and H2 excreted in breath after lactulose ingestion. Conversely, transit time was positively related to faecal pH and tended to be related to methanogen counts. Methanogenic bacteria counts were inversely related to those of sulphate reducing bacteria and methane excretors had slower MTT and lower sulphate reducing bacteria counts than non-methane excretors. Compared with the control period, MTT was significantly shortened (p < 0.05) by cisapride and prolonged (p < 0.05) by loperamide (73 (11) hours, 47 (5) hours and 147 (12) hours for control, cisapride, and loperamide, respectively, mean (SD)). Cisapride reduced transit time was associated with (a) a significant rise in faecal weight, sulphate reducing bacteria, concentrations of total SCFAs, and propionic and butyric acids and breath H2 as well as (b) a significant fall in faecal pH and breath CH4 excretion, and (c) a non-significant decrease in the counts of methanogenic bacteria. Reverse relations were roughly the same during the loperamide period including a significant rise in the counts of methanogenic bacteria and a significant fall in those of sulphate reducing bacteria. Transit time differences between healthy volunteers are associated with differences in H2 consuming flora and certain indices of colonic

Observational Study of Travelers' Diarrhea.

Science.gov (United States)

Meuris

1995-03-01

Background: European air travelers returning from Algeria, Egypt, Mexico, Morocco, and Tunisia were interviewed about their experience of travelers' diseases upon arrival in Brussels. Diarrhea was mentioned by 37% of the adults and 27% of the children. These subjects were questioned about the types of measures taken, type and duration of drug treatment (if any), and about duration of diarrhea and side effects experienced. Methods: Final analysis was performed based on 2160 interviews. The largest proportion of diarrhea was reported in the age group 15-24 years (46%). Results: The majority of the 2160 subjects had opted for drug treatment (81%): 927 subjects for loperamide alone, 235 for loperamide in combination with nifuroxazide, and 178 for nifuroxazide alone. Other drugs had been used less frequently. The median time to recovery was 2.4 days with loperamide compared to 3.2 days with nifuroxazide and to 3.4 days for the no-treatment group. Conclusions: A stratification of the results by severity of the diarrhea suggests a rank of antidiarrheal potency as follows: loperamide > nifuroxazide > no-drug treatment. The side effect with the highest incidence was constipation (2.4% with loperamide). (J Travel Med 2:11-15, 1995) Travelers' diarrhea is usually defined as the passage of at least three unformed stools per day or any number of such stools when accompanied by fever, abdominal cramping, or vomiting. The definition may be broadened to include more trivial bowel disturbance.1,2 The duration of this self-limited disease generally is 3 to 5 days. Medical intervention aims at shortening the duration of disease, thus allowing the sufferer to resume his or her usual activities at an early stage. A shortened period of recovery to physical well-being has obvious favorable economic implications if the traveler is on business and may help the maintenance of a desired level of quality of life while a traveler is on holiday. An observational study of various medical

Travellers' diarrhoea.

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Ericsson, Charles D

2003-02-01

Risk of travellers' diarrhoea is about 7% in developed countries and 20-50% in the developing world. Options for prevention include education and chemoprophylaxis. Vaccination is a promising but incomplete option. Achieving behaviour modification of food and water choices among tourists is difficult. Bismuth subsalicylate (BSS)-containing compounds are about 62% effective in the prevention of travellers' diarrhoea. Antibiotics are about 84% effective in preventing travellers' diarrhoea. Routine prophylaxis of travellers' diarrhoea, especially with antibiotics, should be discouraged. Oral rehydration is generally important in the treatment of diarrhoea, but travellers' diarrhoea is only infrequently dehydrating in adults. The addition of oral rehydration solutions confers no additional benefit to loperamide in the treatment of travellers' diarrhoea in adults. Presently, the most active of the antibiotics routinely available for treatment are members of the fluoroquinolone group. Antibiotics that are not absorbed such as aztreonam and a rifampicin-like agent, rifaximin, are both effective. The latter might become a therapy of choice once it is routinely available, due to predictably less adverse reactions with a non-absorbed antibiotic. Preliminary results with azithromycin look very promising. Less severe disease can be treated with a variety of non-antibiotic agents (e.g. BSS-containing compounds, loperamide and a calmodulin inhibitor, zaldaride). The combination of an antibiotic and loperamide is superior to treatment with either agent alone in a several studies and is arguably the treatment of choice for distressing travellers' diarrhoea.

Formulation and evaluation of analgesic activity of polysorbate 80 ...

African Journals Online (AJOL)

Abstract. Purpose: To deliver loperamide (Lp) into mice brain using polysorbate 80 (PS80)-coated liposomes that ... Due to P-gp mediated efflux, Lp ... Polysorbate 80 (PS80) enabled the drug dalargin to reach brain by ..... inflammatory pain.

Role of octreotide in chemo and radiotherapy induced diarrhea

International Nuclear Information System (INIS)

Farooqi, J.I.; Farooqi, R. J.

2000-01-01

An international, quasi-experimental, clinical trial of 'before-and-after type' was conducted to find out the role of octreotide in chemo and radiotherapy-induced diarrhea on thirty patients. Among these 19 patients had advanced cancer and 11 with acute leukemia. All patients were given IV fluids and Loperamide for 5 days. The patients who did not respond during this period were administered with octreotide subcutaneously for another 5 days and response against diarrhea was noted. We found that only 10% patients responded to loperamide therapy whereas in the remaining 90% patients an excellent response was noted as 96.29% of these patients responded to octreotide therapy which stopped their diarrhea (P<0.005) leading us to the conclusion that, octreotide is a safe and effective drug in the management of chemo and radiotherapy-induced diarrhea. (author)

Using Potentiometric Free Drug Sensors to Determine the Free Concentration of Ionizable Drugs in Colloidal Systems

DEFF Research Database (Denmark)

Tran, Thuy; Chakraborty, Anjan; Xi, Xi

2018-01-01

The present study investigates the use of free drug sensors (FDS) to measure free ionized drug concentrations in colloidal systems, including micellar solutions, emulsions, and lipid formulations during in vitro lipolysis. Diphenhydramine hydrochloride (DPH) and loperamide hydrochloride (LOP) wer...

A comprehensive comparison of the efficacy and tolerability of racecadotril with other treatments of acute diarrhea in adults

Directory of Open Access Journals (Sweden)

Wolfgang Fischbach

2016-10-01

Full Text Available Racecadotril is a guideline-recommended treatment to alleviate symptoms of acute diarrhea. A systematic review of randomized studies was performed comparing efficacy and safety of treatment with racecadotril to that with placebo or active treatments in adults. In five double-blind studies, racecadotril and placebo had comparable tolerability but racecadotril was more effective. This was consistent across multiple efficacy parameters including duration of diarrhea, number of diarrheic stools, abdominal pain and meteorism; it was also consistent across countries in Africa, Asia and Europe. In six randomized studies in outpatients comparing racecadotril to loperamide, resolution of symptoms occurred with similar speed and efficacy; however, racecadotril treatment was associated with less rebound constipation and less abdominal discomfort. A seventh comparative study performed in geriatric nursing home residents reported a superior efficacy of racecadotril. In direct comparison with Saccharomyces boulardii treatment, racecadotril exhibited similar tolerability but was more efficacious. One study compared racecadotril to octreotide in patients with acute diarrhea requiring hospitalization, rehydration and antibiotic treatment; in this cohort, octreotide was more efficacious than racecadotril. In conclusion, in adults with acute diarrhea racecadotril is more efficacious than placebo or Saccharomyces boulardii, similarly efficacious as loperamide and, in patients with moderate to severe disease as add-on to antibiotics, less than octreotide. The tolerability of racecadotril is similar to that of placebo or Saccharomyces boulardii and better than that of loperamide, particularly with regard to risk of rebound constipation. Taken together these data demonstrate that racecadotril is a suitable treatment to alleviate symptoms of acute diarrhea in adults.

Relationships between transit time in man and in vitro fermentation of dietary fiber by fecal bacteria.

Science.gov (United States)

Oufir, L E; Barry, J L; Flourié, B; Cherbut, C; Cloarec, D; Bornet, F; Galmiche, J P

2000-08-01

To assess the effects of drug-induced changes in mean transit time (MTT) on the activity of human fecal flora in vitro. The activity of fecal flora was estimated by the ability of a fecal inoculum to ferment a substrate (beet fiber) in vitro in a batch system for 24 h. The inoculum was collected from 8 healthy volunteers studied during three 3-week randomized periods, who received a controlled diet alone (control period) or the same diet with either cisapride or loperamide. Cisapride and loperamide were adjusted in order to halve and double MTT measured during the control period. At the end of each period, the percentage disappearance of the initial added substrate and the concentration and the profile of short-chain fatty acids (SCFAs), were determined. In the control period, the pH of the inoculum and SCFA concentration were inversely related to MTT (P=0.0001). Individual SCFA production was also significantly related to MTT (P<0.01). Cisapride-reduced transit time was associated with a significant rise in the concentrations of total SCFAs (P<0.05), propionic and butyric acids (P<0.05) and the percentage substrate disappearance (P<0.05). Inverse relations were observed during the loperamide period. Moreover, MTT was inversely related to the percentage substrate disappearance (P<0.001), SCFA production (P<0.001) and butyrate production (P<0.0005). Changes in MTT alter bacterial activity and modify the bacterial pathways affecting the proportion of individual SCFAs. European Journal of Clinical Nutrition (2000) 54, 603-609

On-chip electro membrane extraction with online ultraviolet and mass spectrometric detection

DEFF Research Database (Denmark)

Petersen, Nickolaj Jacob; Foss, Sunniva Taule; Jensen, Henrik

2011-01-01

(SLM) consisted of 2-nitrophenyl octyl ether (NPOE) immobilized in the pores of the membrane. The driving force for the extraction was a 15 V direct current (DC) electrical potential applied across the SLM. Samples containing the basic drugs pethidine, nortriptyline, methadone, haloperidol, loperamide...

Journal of Chemical Sciences | Indian Academy of Sciences

Indian Academy of Sciences (India)

Loperamide (LPR) is a synthetic, poorly water soluble, peripherally acting opiate agonist drug used for the treatment of diarrhea. Major challenges in formulating this drug for clinical applications include solubility enhancement and improved stability in biological systems. Cyclodextrins (CDs) are chiral, truncated cone ...

Liquid-phase microextraction in a microfluidic-chip

DEFF Research Database (Denmark)

Payán, María D. Ramos; Jensen, Henrik; Petersen, Nickolaj J.

2012-01-01

, methadone, haloperidol, loperamide, and pethidine were selected as model analytes, and they were extracted from alkaline sample solution, through the SLM, and into 10mM HCl or 100mM HCOOH functioning as acceptor phase. Subsequently, the acceptor phase was either analyzed off-line by capillary...

Journal of Pharmacy & Bioresources - Vol 9, No 2 (2012)

African Journals Online (AJOL)

Quality assessment of ten brands of loperamide hydrochloride marketed in Maiduguri Metropolitan Council (MMC) · EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. AA Sani, TE Alemika, S Zakama, PI Dike, MA Sani, RO Abdulraheem, SA Sani, RB Abdulraheem, M Ilyas, 67-74.

Gastric Emptying and Gastrointestinal Transit Compared among Native and Hydrolyzed Whey and Casein Milk Proteins in an Aged Rat Model.

Science.gov (United States)

Dalziel, Julie E; Young, Wayne; McKenzie, Catherine M; Haggarty, Neill W; Roy, Nicole C

2017-12-13

Little is known about how milk proteins affect gastrointestinal (GI) transit, particularly for the elderly, in whom digestion has been observed to be slowed. We tested the hypothesis that GI transit is faster for whey than for casein and that this effect is accentuated with hydrolysates, similar to soy. Adult male rats (18 months old) were fed native whey or casein, hydrolyzed whey (WPH) or casein (CPH), hydrolyzed blend (HB; 60% whey:40% casein), or hydrolyzed soy for 14 days then treated with loperamide, prucalopride, or vehicle-control for 7 days. X-ray imaging tracked bead-transit for: gastric emptying (GE; 4 h), small intestine (SI) transit (9 h), and large intestine (LI) transit (12 h). GE for whey was 33 ± 12% faster than that for either casein or CPH. SI transit was decreased by 37 ± 9% for casein and 24 ± 6% for whey compared with hydrolyzed soy, and persisted for casein at 12 h. Although CPH and WPH did not alter transit compared with their respective intact counterparts, fecal output was increased by WPH. Slowed transit by casein was reversed by prucalopride (9-h), but not loperamide. However, rapid GE and slower SI transit for the HB compared with intact forms were inhibited by loperamide. The expected slower GI transit for casein relative to soy provided a comparative benchmark, and opioid receptor involvement was corroborated. Our findings provide new evidence that whey slowed SI transit compared with soy, independent of GE. Increased GI transit from stomach to colon for the HB compared with casein suggests that including hydrolyzed milk proteins in foods may benefit those with slowed intestinal transit.

Pathophysiology and therapy of irinotecan-induced delayed-onset diarrhea in patients with advanced colorectal cancer: a prospective assessment.

Science.gov (United States)

Saliba, F; Hagipantelli, R; Misset, J L; Bastian, G; Vassal, G; Bonnay, M; Herait, P; Cote, C; Mahjoubi, M; Mignard, D; Cvitkovic, E

1998-08-01

Irinotecan (CPT-11), a camptothecin derivative, has shown efficacy against colorectal cancer. Delayed-onset diarrhea is its main limiting toxicity. The aim of this study was to determine the pathophysiology of CPT-11-induced delayed-onset diarrhea and assess the efficacy of combined antidiarrheal medication in a phase II, prospective, successive-cohorts, open study. Twenty-eight patients with advanced colorectal cancer refractory to fluorouracil (5-FU) therapy received CPT-11 350 mg/m2 every 3 weeks. The first cohort of 14 consecutive patients explored for the mechanism of diarrhea received acetorphan (a new enkephalinase inhibitor) 100 mg three times daily; the second 14-patient cohort received, in addition to acetorphan, loperamide 4 mg three times daily. Before treatment, and if late diarrhea occurred, patients underwent colon mucosal biopsies for CPT-11 and topoisomerase I levels; intestinal transit time; fecalogram; fat and protein excretion; alpha1-antitrypsin clearance; D-xylose test; blood levels for vasoactive intestinal polypeptide, glucagon, gastrin, somatostatin, prostaglandin E2, and carboxylesterase; CPT-11/SN-38 and SN-38 glucuronide pharmacokinetics; and stool cultures. Delayed-onset diarrhea occurred during the first three treatment cycles in 23 patients (82%). Electrolyte fecal measurements showed a negative or small osmotic gap in nine of nine patients and an increased alpha1-antitrypsin clearance in six of six patients. There were no modifications in stool cultures or hormonal dysfunction. Four of 11 patients (36%) with delayed-onset diarrhea in the first cohort responded to acetorphan, whereas nine of 10 patients (90%) responded to the combination of acetorphan and loperamide (P diarrhea is caused by a secretory mechanism with an exudative component. Early combined treatment with loperamide and acetorphan seems effective in controlling the diarrheal episodes.

Mechanism of antidiarrhoeal effect of ethanolic extract of Psidium ...

African Journals Online (AJOL)

CLEMENT O BEWAJI

received 80mg/kg b. wt.) of extract orally, group H received 10mg/kg b. wt. of loperamide while group I which received normal saline (5mls/kg body. weight.) served as control. After 5 minutes of drug administration 0.5 ml of. 5.0 % charcoal suspension in 10.0% aqueous solution of tragacanth powder was administered orally ...

Aqueous Root Extract in Loperamide- Induced Constipated Rats

African Journals Online (AJOL)

central nervous system (CNS) depressant action of the plant has ... administration was done using metal oropharyngeal ... weight of constipated rats before treatment. .... constipation, abdominal bloating and refractory ... found in the plasma membrane and endoplasmic .... induced production of prostaglandins in rat isolated.

Prospective, Controlled, Multicentre Study of Loperimide in Pregnancy

Directory of Open Access Journals (Sweden)

A Einarson

2000-01-01

Full Text Available BACKGROUND: Loperamide is a synthetic piperidine derivative used for the treatment of both acute and chronic diarrhea. Little is known about its safety and risk in pregnancy. Human data are limited to one surveillance study of Michigan Medicaid patients, with 108 women exposed in the first trimester. In this study there were six major birth defects, three of which were cardiovascular anomalies.

Effects of Hypericum perforatum extract on rat irritable bowel syndrome

Science.gov (United States)

Mozaffari, Shilan; Esmaily, Hadi; Rahimi, Roja; Baeeri, Maryam; Sanei, Yara; Asadi-Shahmirzadi, Azar; Salehi-Surmaghi, Mohammad-Hossein; Abdollahi, Mohammad

2011-01-01

Context: In irritable bowel syndrome (IBS), disturbance of bowel motility is associated with infiltration of inflammatory mediators and cytokines into the intestine, such as neutrophils, myeloperoxidase (MPO), tumor necrosis factor alfa (TNF-α), and lipid peroxide. Aims: Regarding promising anti-inflammatory and anti-oxidative effects of Hypericum perforatum (HP) extract, besides its anti-depressant effect, this study was designed to evaluate the effects of HP in an experimental model of IBS. Settings and Design: IBS was induced by a 5-day restraint stress in rats. The HP extract was administered by gavage in doses of 150, 300, and 450 mg/kg for 26 days. Fluoxetine and loperamide were used as positive controls. Gastric emptying and small bowel and colon transit, besides the levels of TNF-α, MPO, lipid peroxidation, and antioxidant power, were determined in colon homogenates. Statistical Analysis Used: Data were analyzed by one-way ANOVA followed by Tukey's post hoc test for multiple comparisons. Results: A significant reduction in small bowel and colonic transit (450 mg/kg), TNF-α, MPO, and lipid peroxidation and an increase in antioxidant power in all HP-treated groups (150, 300, and 450 mg/kg) were seen as compared with the control group. Gastric emptying did not alter significantly when compared with the control group. Treatment with loperamide (10 mg/kg) significantly inhibited gastric emptying and small bowel and colonic transit, while flouxetine (10 mg/kg) decreased gastric emptying, TNF-α, MPO, and lipid peroxidation and increased the antioxidant power of the samples in comparison with the control group. Conclusions: HP diminished the recruitment of inflammatory cells and TNF-α following restraint stress not in a dose-dependent manner, possibly via inhibition of MPO activity and increasing colon antioxidant power, without any difference with fluoxetine. The HP extract inhibits small bowel and colonic transit acceleration like loperamide but has minimal

Relations between transit time, fermentation products, and hydrogen consuming flora in healthy humans.

OpenAIRE

El Oufir, L; Flourié, B; Bruley des Varannes, S; Barry, J L; Cloarec, D; Bornet, F; Galmiche, J P

1996-01-01

BACKGROUND/AIMS: To investigate whether transit time could influence H2 consuming flora and certain indices of colonic bacterial fermentation. METHODS: Eight healthy volunteers (four methane excretors and four non-methane excretors) were studied for three, three week periods during which they received a controlled diet alone (control period), and then the same diet with cisapride or loperamide. At the end of each period, mean transit time (MTT) was estimated, an H2 lactulose breath test was p...

Management of chemotherapy induced diarrhea (abstract)

International Nuclear Information System (INIS)

Qureshi, A.M.

1998-01-01

Diarrhoea is seen with many tumors and following several chemotherapy regimen esp. those containing 5-fluorouracil and high dose folinic acid it causes debility even death, delays cancer treatment, reduces compliance increases cost. It causes dehydration, renal failure volume depletion. Quality of life is worsened and hospitalization may be needed in multifactorial, with secretion; absorption imbalance due to mucosal damage, necrosis or inflammation. Local infection is set up by opportunistic organism and cell necrosis. The large volume of fluid and electrolytes overwhelms colonic absorptive capacity. Agent usually used for treatment is opioids (such as Diphenoxylate / Loperamide]. Bismuth (for inflammatory diarrhea). NSAIDs or alpha 2-agonists. For optimal management, the cause and severity should be assessed and treatment planned. Advice is given about certain dietary restraints and avoidance of some drugs. Fever, infection, dehydration and electrolyte losses are treated, pain relieved. Diphenoxylate / Loperamide (later is more effective; 4 mg, STAT, then 2mg every 4 hours or even 2 hourly) may be used. It is moderately effective in CID. Octreotide is useful in carcinoid. VIPoma, AIDS idiopathic secretary diarrhea, ileostomy, dumping syndrome. It acts directly on epithelial cells to reduce secretin, motilin pancreatic polypeptide. It slows transit time, reduces fluid and electrolyte secretin, increases absorption of electrolytes. It is effective in 5 FU and high dose chemotherapy with a 90% response rates seen after 3 days treatment. High Dose Chemotherapy and total body irradiation - induced diarrhea usually resolves within 72 hours. (author)

Evaluation of the effects of Olea europaea L. subsp. africana (Mill.) P.S. Green (Oleaceae) leaf methanol extract against castor oil-induced diarrhoea in mice.

Science.gov (United States)

Amabeoku, George J; Bamuamba, Kapinga

2010-03-01

Olea europaea L. subsp. africana (Mill.) P.S. Green is widely used in South Africa by traditional medicine practitioners to treat diarrhoea. However, little is known scientifically about this South African species in the treatment of diarrhoea. The main aim of the study therefore was to investigate the antidiarrhoeal effect of the leaf methanol extract of the plant species in mice. The antidiarrhoeal activity of the leaf methanol extract of O. europaea subsp. africana was studied using a castor oil-induced diarrhoeal test. The antipropulsive activity of the plant extract was also investigated using the charcoal meal transit test. Standard methods were used to investigate the acute toxicity and effect of O. europaea subsp. africana on castor oil-induced intraluminal fluid accumulation. Leaf methanol extract of O. europaea subsp. africana and loperamide, a standard antidiarrhoeal drug, significantly reduced the number of diarrhoeal episodes induced by castor oil, significantly decreased the stool mass, significantly delayed the onset of the diarrhoea and protected the animals against castor oil-induced diarrhoea. Both O. europaea subsp. africana and loperamide significantly decreased the gastrointestinal transit of charcoal meal and castor oil-induced intraluminal fluid accumulation in mice. The LD50 value was found to be 3475 mg/kg (p.o.). The results obtained suggest that the leaf methanol extract of O. europaea subsp. africana has an antidiarrhoeal property and that, given orally, it may be non-toxic and/or safe in mice.

PLGA nanoparticles prepared by nano-emulsion templating using low-energy methods as efficient nanocarriers for drug delivery across the blood-brain barrier.

Science.gov (United States)

Fornaguera, C; Dols-Perez, A; Calderó, G; García-Celma, M J; Camarasa, J; Solans, C

2015-08-10

Neurodegenerative diseases have an increased prevalence and incidence nowadays, mainly due to aging of the population. In addition, current treatments lack efficacy, mostly due to the presence of the blood-brain barrier (BBB) that limits the penetration of the drugs to the central nervous system. Therefore, novel drug delivery systems are required. Polymeric nanoparticles have been reported to be appropriate for this purpose. Specifically, the use of poly-(lactic-co-glycolic acid) (PLGA) seems to be advantageous due to its biocompatibility and biodegradability that ensure safe therapies. In this work, a novel approximation to develop loperamide-loaded nanoparticles is presented: their preparation by nano-emulsion templating using a low-energy method (the phase inversion composition, PIC, method). This nano-emulsification approach is a simple and very versatile technology, which allows a precise size control and it can be performed at mild process conditions. Drug-loaded PLGA nanoparticles were obtained using safe components by solvent evaporation of template nano-emulsions. Characterization of PLGA nanoparticles was performed, together with the study of the BBB crossing. The in vivo results of measuring the analgesic effect using the hot-plate test evidenced that the designed PLGA loperamide-loaded nanoparticles are able to efficiently cross the BBB, with high crossing efficiencies when their surface is functionalized with an active targeting moiety (a monoclonal antibody against the transferrin receptor). These results, together with the nanoparticle characterization performed here are expected to provide sufficient evidences to end up to clinical trials in the near future. Copyright © 2015 Elsevier B.V. All rights reserved.

The application of 1,8-cineole, a terpenoid oxide present in medicinal plants, inhibits castor oil-induced diarrhea in rats.

Science.gov (United States)

Jalilzadeh-Amin, Ghader; Maham, Massoud

2015-04-01

1,8-Cineole, a terpene, characterized as a major constituent occurring in the essential oils of several aromatic plants. It is widely used in pharmaceutical industry, as a food additive and for culinary purposes. This study investigates the inhibitory effect of 1,8-cineole on transit time and diarrhea in animal models. Acute toxicity and lethality of 1-8-cineole was determined by Lork's guidelines. The antidiarrheal effect of 1,8-cineole was investigated by determining the intestinal transit and enterpooling in rats. In all experiments, different doses of 1,8-cineole (20-120 mg/kg), atropine, and loperamide were administered orally. The LD50 of 1,8-cineole for oral administration was estimated to be 1280 mg/kg. 1,8-Cineole (20-120 mg/kg) did not show a significant decrease in small intestine transit (p > 0.05); however, the highest dose displayed a significant decrease in comparison with atropine (p castor oil transit test. 1,8-Cineole significantly delayed the onset of diarrhea to -142.33 ± 6.08 min at 120 mg/kg, while the time was 103.66 ± 20.73 min for the control and >240 min for the loperamide. Moreover, 1,8-cineole significantly decreased intestinal fluid accumulation (p < 0.05). This study demonstrated antispasmodic and antisecretory activities of 1,8-cineole and rationalized the traditional use of the plant containing various levels of this terpene in the treatment of gastrointestinal complains such as diarrhea.

Nano-electromembrane extraction

DEFF Research Database (Denmark)

Payán, María D Ramos; Li, Bin; Petersen, Nickolaj J.

2013-01-01

as extraction selectivity. Compared with conventional EME, the acceptor phase volume in nano-EME was down-scaled by a factor of more than 1000. This resulted in a very high enrichment capacity. With loperamide as an example, an enrichment factor exceeding 500 was obtained in only 5 min of extraction...... electrophoresis (CE). In that way the sample preparation performed by nano-EME was coupled directly with a CE separation. Separation performance of 42,000-193,000 theoretical plates could easily be obtained by this direct sample preparation and injection technique that both provided enrichment as well...

Opposite Effect of Opuntia ficus-indica L. Juice Depending on Fruit Maturity Stage on Gastrointestinal Physiological Parameters in Rat.

Science.gov (United States)

Rtibi, Kais; Selmi, Slimen; Grami, Dhekra; Amri, Mohamed; Sebai, Hichem; Marzouki, Lamjed

2018-06-01

The phytochemical composition and the effect of the green and ripe Opuntia ficus-indica juice on some gastrointestinal (GI) physiological parameters such as stomach emptying and small-intestinal motility and permeability were determined in rats administered multiple concentrations of the prickly pear juice (5, 10, and 20 mL kg -1 , b.w., p.o.). Other separate groups of rats were received, respectively; sodium chloride (0.9%, b.w., p.o.), clonidine (α- 2 -adrenergic agonist, 1 mg kg -1 , b.w., i.p.), yohimbine (α- 2 -adrenergic antagonist, 2 mg kg -1 , b.w., i.p.), and loperamide (5 mg kg -1 , b.w., p.o.). In vivo reverse effect of juice on GI physiological parameters was investigated using a charcoal meal test, phenol-red colorimetric method, loperamide-induced acute constipation, and castor oil-caused small-bowel hypersecretion. However, the opposite in vitro influence of juice on intestinal permeability homeostasis was assessed by the Ussing chamber system. Mature prickly pear juice administration stimulated significantly and dose dependently the GI transit (GIT; 8-26%) and gastric emptying (0.9-11%) in a rat model. Conversely, the immature prickly pear juice reduced gastric emptying (7-23%), GIT (10-28%), and diarrhea (59-88%). Moreover, the standard drugs have produced their antagonistic effects on GI physiological functions. The permeability of the isolated perfused rat small-intestine has a paradoxical response flowing prickly pear juices administration at diverse doses and maturity grade. Most importantly, the quantitative phytochemical analyses of both juices showed a different composition depending on the degree of maturity. In conclusion, the prickly pear juice at two distinct phases of maturity has different phytochemical characteristics and opposite effects on GI physiological actions in rat.

Effects of Probiotic Lactobacillus Casei DN-114 001 in Prevention of Radiation-Induced Diarrhea: Results From Multicenter, Randomized, Placebo-Controlled Nutritional Trial

International Nuclear Information System (INIS)

Giralt, Jordi; Regadera, Jose Perez; Verges, Ramona; Romero, Jesus; Fuente, Isabel de la; Biete, Albert; Villoria, Jesus; Cobo, Jose Maria; Guarner, Francisco

2008-01-01

Purpose: To determine whether a probiotic drink containing Lactobacillus casei DN-114 001 reduces the incidence of radiation-induced diarrhea in patients with gynecologic cancer. Methods and Materials: Patients who were undergoing pelvic radiotherapy (45-50 Gy, conventional fractionation) for either cervical carcinoma (radiotherapy and weekly cisplatin) or endometrial adenocarcinoma (postoperative radiotherapy) were randomly assigned to a probiotic drink or placebo, in a double-blind fashion. The probiotic drink consisted of liquid yogurt containing L. casei DN-114 001 at 10 8 CFU/g. The patients recorded the daily the number of bowel movements and scored the stool consistency using the Bristol scale. Diarrhea was graded weekly according the Common Toxicity Criteria system. The primary endpoint was to reduce the incidence of diarrhea, defined by a Common Toxicity Criteria Grade of 2 or greater or the need for loperamide. Results: A total of 85 patients were enrolled. Grade 2 or greater diarrhea and/or the use of loperamide was observed in 24 of 41 patients in the placebo group and 30 of 44 in the probiotic group (p = 0.568). No differences were found in the median time to the presentation of the primary endpoint. Probiotic intervention had a significant effect on stool consistency (p = 0.04). The median time for patients to present with Bristol scale stools of Type 6 or greater was 14 days for patients receiving the probiotic drink vs. 10 days for those receiving placebo. Conclusion: Nutritional intervention with the probiotic drink containing L. casei DN-114 001 does not reduce the incidence of radiation-induced diarrhea as defined by a Common Toxicity Criteria Grade 2 or greater. However, it had a significant effect on stool consistency as measured by the Bristol scale

Existing and emerging therapies for managing constipation and diarrhea.

Science.gov (United States)

Bharucha, Adil E; Wouters, Mira M; Tack, Jan

2017-12-01

Functional bowel disorders (i.e., constipation and diarrhea) are characterized by abdominal pain, bloating, distention, and/or bowel habit abnormalities in the absence of obvious anatomic or physiologic abnormalities on routine diagnostic tests. These symptoms are attributable to gastrointestinal sensorimotor dysfunctions resulting from peripheral and/or central mechanisms. Available drugs target the underlying bowel disturbance (i.e., constipation, diarrhea, or both), supplemented when necessary by management of pain. Osmotic and stimulant laxatives, secretagogues, and serotonin 5-HT 4 receptor agonists are approved for treating constipation. Loperamide, anticholinergic agents, rifaximin, bile-acid binding agents, eluxadoline, and clonidine are used to treat diarrhea. Several exciting new compounds, some of which have been evaluated in humans, are currently under development. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chronic diarrhea caused by Blastocystis hominis and Cryptosporidium sp. in immunocompetent patient-a case report

Science.gov (United States)

Andriyani, Y.; Rozi, M. F.; Saragih, R. H.; Darlan, D. M.

2018-03-01

Blastocystis hominis and Cryptosporidium sp. are commonly associated with immunocompromised patients. Severe clinical manifestation can be produced by this organism. It varies according to immune status, and subtype of this organism. Unfortunately, we found an immunocompetent patient with chronic diarrhea caused by this organism. A 38- year old male was admitted to Adam Malik General Hospital because of watery diarrhea since four days ago. Administration of fluid replacement was done to this patient, but the frequency of diarrhea did not decrease. Loperamide as anti-spasmodic was also given in each episode of diarrhea. Surprisingly, fecal smear examination revealed that this patient positive for Blastocystis hominis and Cryptosporidium sp. Thus, diarrhea was resolved for four days without giving any anti-parasitic drugs to the patient.

Fitting the elementary rate constants of the P-gp transporter network in the hMDR1-MDCK confluent cell monolayer using a particle swarm algorithm.

Directory of Open Access Journals (Sweden)

Deep Agnani

Full Text Available P-glycoprotein, a human multidrug resistance transporter, has been extensively studied due to its importance to human health and disease. In order to understand transport kinetics via P-gp, confluent cell monolayers overexpressing P-gp are widely used. The purpose of this study is to obtain the mass action elementary rate constants for P-gp's transport and to functionally characterize members of P-gp's network, i.e., other transporters that transport P-gp substrates in hMDR1-MDCKII confluent cell monolayers and are essential to the net substrate flux. Transport of a range of concentrations of amprenavir, loperamide, quinidine and digoxin across the confluent monolayer of cells was measured in both directions, apical to basolateral and basolateral to apical. We developed a global optimization algorithm using the Particle Swarm method that can simultaneously fit all datasets to yield accurate and exhaustive fits of these elementary rate constants. The statistical sensitivity of the fitted values was determined by using 24 identical replicate fits, yielding simple averages and standard deviations for all of the kinetic parameters, including the efflux active P-gp surface density. Digoxin required additional basolateral and apical transporters, while loperamide required just a basolateral tranporter. The data were better fit by assuming bidirectional transporters, rather than active importers, suggesting that they are not MRP or active OATP transporters. The P-gp efflux rate constants for quinidine and digoxin were about 3-fold smaller than reported ATP hydrolysis rate constants from P-gp proteoliposomes. This suggests a roughly 3∶1 stoichiometry between ATP hydrolysis and P-gp transport for these two drugs. The fitted values of the elementary rate constants for these P-gp substrates support the hypotheses that the selective pressures on P-gp are to maintain a broad substrate range and to keep xenobiotics out of the cytosol, but not out of the

Proactive management strategies for potential gastrointestinal adverse reactions with ceritinib in patients with advanced ALK-positive non-small-cell lung cancer

International Nuclear Information System (INIS)

Schaefer, Eric S; Baik, Christina

2016-01-01

Anaplastic lymphoma kinase (ALK) gene fusions occur in 3%–7% of non-small-cell lung cancer (NSCLC) cases. Ceritinib, a once-daily, oral ALK inhibitor, has activity against crizotinib-resistant and crizotinib-naïve NSCLC, including brain metastases. Ceritinib (Zykadia™) was granted accelerated approval by the US Food and Drug Administration in 2014 for treating crizotinib-resistant ALK-positive NSCLC. Adverse events (AEs), particularly gastrointestinal (GI) AEs, are commonly experienced at the recommended dose of 750 mg/d and ∼38% of patients require dose interruption or reduction for GI AEs. This case study details our experience with the use of proactive GI AE management regimens in patients treated with ceritinib (750 mg/d) across two study sites. Proactive Regimens A and B were implemented in patients with metastatic ALK-positive NSCLC treated with ceritinib to manage drug-related GI AEs. Regimen A comprised ondansetron and diphenoxylate/atropine or loperamide, taken 30 minutes prior to ceritinib dose. Regimen B included dicyclomine (taken with the first ceritinib dose), ondansetron (taken 30 minutes prior to ceritinib dose for the first seven doses), and loperamide (taken as needed with the onset of diarrhea). The proactive medications were tapered off depending on patient tolerability to ceritinib. Nine patient cases are presented. Starting Regimens A or B before the first dose of ceritinib, or as soon as GI symptoms were encountered, prevented the need for dose reduction due to GI toxicity in eight of the nine patients. Using these regimens, 78% of patients were able to remain on 750 mg/d fasting. Two patients received 23 months and 16 months of therapy and remain on ceritinib 750 mg/d and 600 mg/d, respectively. Although not currently recommended or implemented in clinical studies, based on the patients evaluated here, upfront or proactive treatment plans that address AEs early on can allow the majority of patients to remain on the approved 750 mg

A pharmacological evaluation of antidiarrhoeal activity of leaves extract of Murraya koenigii in experimentally induced diarrhoea in rats

Directory of Open Access Journals (Sweden)

Praveen Sharma

2012-06-01

Full Text Available Objective: To evaluate anti-diarrhoeal activity of aqueous and alcoholic extract of the leaves of Murraya koenigii (M. koenigiiby using models of castor oil induced diarrhoea, charcoal meal test and PGE 2 induced diarrhoea. Methods: Alcoholic extract (400 mg/kg and aqueous extract (200 mg/kg of leaves of Murraya koenigii were used with loperamide as standard. Albino Wistar rats of both sexes weighing between 150-250 g were used for the anti-diarrhoeal activity. Results: The result suggested that it could act centrally and inhibit the PGE2 to give anti-diarrhoeal effects. Result of charcoal meal test also suggested its anti-muscarnic activity. Conclusions: These findings indicate that aqueous extract of the leaves of M. koenigii displays good antidiarrhoeal activity, corroborating the folk use of M. koenigii preparations and contributing for its pharmacological validation.

Acetylcholine serves as a derepressor in Loperamide-induced Opioid-Induced Bowel Dysfunction (OIBD) in zebrafish

OpenAIRE

Shi, Yanyan; Zhang, Yu; Zhao, Fangying; Ruan, Hua; Huang, Honghui; Luo, Lingfei; Li, Li

2014-01-01

The mechanisms underlying gut development, especially peristalsis, are widely studied topics. However, the causes of gut peristalsis-related diseases, especially Opioid-Induced Bowel Dysfunction (OIBD) disorder, have not been well defined. Therefore, our study used zebrafish, a popular model for studying both gut development and peristalsis, and DCFH-DA, a dye that clearly labels the live fish gut lumen, to characterize the formation process of gut lumen as well as the gut movement style in v...

Antidiarrhoeal and antimicrobial activity of Calpurnia aurea leaf extract

Directory of Open Access Journals (Sweden)

Umer Shemsu

2013-01-01

Full Text Available Abstract Background In Ethiopia, Calpurnia aurea is used for the treatment of syphilis, malaria, rabies, diabetes, hypertension, diarrhoea, leishmaniasis, trachoma, elephantiasis, fungal diseases and different swellings. However, despite its traditional usage as an antidiarrhoeal and antimicrobial agent, there is limited or no information regarding its effectiveness and mode of action in diarrhoea which may be caused by Shigella flexneri, Staphylococcus aureus, Escherichia coli and Salmonella typhi. Hence, we evaluated the 80% methanol (MeOH extract of dried and powdered leaves of C. aurea for its antidiarrhoeal and antimicrobial activities. Methods Swiss albino mice of either sex were divided into five groups (five/group: Group I served as control and received vehicle (1% Tween 80 at a dose of 10 ml/kg orally; Group II served as standard and received loperamide at the dose of 3 mg/kg orally; Groups III, IV and V served as test groups and received the 80% MeOH leaf extract of C. aurea at doses of 100, 200 and 400 mg/kg orally, respectively. Diarrhoea was induced by oral administration of 0.5 ml castor oil to each mouse, 1 h after the above treatments. During an observation period of 4 h, time of onset of diarrhea, total number of faecal output (frequency of defecation and weight of faeces excreted by the animals were recorded. Data were analyzed using one way analysis of variance followed by Tukey post test. Antimicrobial activity test was conducted using agar well diffusion assay. Clinical isolates tested were Salmonella typhi, Salmonella paratyphi, Salmonella typhimurium, Shigella species, Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli. Results In castor oil induced diarrhea model, the 80% methanol leaf extract of C. aurea at 100, 200 and 400 mg/kg and the standard drug loperamide (3 mg/kg significantly reduced the time of onset of diarrhea, the frequency of defecation (total number of faecal output and weight of faeces. C

Neratinib in HER-2-positive breast cancer: results to date and clinical usefulness.

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Chan, Arlene

2016-09-01

The management of HER-2-positive breast cancer has improved significantly with the use of targeted agents to the HER-2 signaling pathway. Despite the improved survival achieved with the use of trastuzumab and chemotherapy in both the adjuvant and metastatic setting, patients may still recur or progress; whilst preclinical data demonstrate that these cancer cells remain addicted to the HER-2 oncogene. Neratinib, an oral small molecule tyrosine-kinase inhibitor has efficacy in the metastatic and adjuvant setting of patients who have previously received trastuzumab-based treatment. Diarrhea, being a class effect of tyrosine-kinase inhibitor, is the most common side effect seen following neratinib administration, but recent data suggests that a prophylactic loperamide regimen can reduce the incidence of grade 3 diarrhea. Phase I through to III clinical trials of neratinib will be reviewed, with discussion of the postulated mechanism underlying diarrheal events and its management.

Antispasmodic activity of Symplocos paniculata is mediated through opening of ATP-dependent K+ channel

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Khalid Hussain Janbaz

2016-06-01

Full Text Available Symplocos paniculata is a medicinal plant used by native healers to manage gastrointestinal ailments. The crude methanolic extract of S. paniculata was screened pharmacologically both in vitro and in vivo for the validation of its therapeutic potential. It suppressed the spontaneous activity of isolated rabbit jejunum preparations and also caused inhibition of the low K+ (20 mM- induced spastic contractions in isolated rabbit jejunum preparations in a manner comparable to cromakalim. The relaxant effect was found to be blocked following glibenclamide exposure of the isolated tissue preparations similar to cromakalim, suggesting that observed response was likely to be mediated through opening of ATP dependent K+ channels. Following oral administration to mice provided protection against castor oil-induced diarrhea in a manner similar to loperamide. The plant material was found safe in toxicity study up to oral dose of 8 g/kg in mice. Hence, present study provides a scientific basis for the vernacular use of S. paniculata in gastro-intestinal system.

Antisecretory activity from the flowers of Chiranthodendron pentadactylon and its flavonoids on intestinal fluid accumulation induced by Vibrio cholerae toxin in rats.

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Velázquez, Claudia; Calzada, Fernando; Esquivel, Baldomero; Barbosa, Elizabeth; Calzada, Samuel

2009-12-10

The flowers of Chiranthodendron pentadactylon Larreat. (Sterculiaceae) has been traditionally used as folk medicine in Mexico for the treatment of gastrointestinal disorders such as diarrhea and dysentery. This study aimed to assess the antisecretory activity which supports the therapeutic use of Chiranthodendron pentadactylon and its flavonoids to treat diarrhea. The methanol extract of Chiranthodendron pentadactylon, subsequent fractions, and flavonoids were evaluated on cholera toxin-induced intestinal secretion in rat jejunal loops model. Three antisecretory flavonoids were isolated by bioassay-guided purification, namely, isoquercitrin 3, (+)-catechin 4 and (-)-epicatechin 5. Among them, epicatechin exhibited the most potent antisecretory activity with ID(50) of 8.3 microM/kg. Its potency was close that of to loperamide (ID(50) 6.1 microM/kg), drug used as control. Isoquercitrin (ID(50) 19.2 microM/kg) and catechin (ID(50) 51.7 microM/kg) showed moderate and weak activity, respectively. The results of the present study lend some support to the anecdotal report for the traditional use of the flowers of Chiranthodendron pentadactylon in the control of dysentery.

Radiation-induced gastrointestinal toxicity. Pathophysiologie, approaches to treatment and prophylaxis

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Classen, J.; Belka, C.; Paulsen, F.; Budach, W.; Hoffmann, W.; Bamberg, M.

1998-01-01

Background: Gastrointestinal toxicity is frequently observed during radiotherapy of malignancies in the abdomen and pelvis. The proposed pathophysiology of radiation enteritis is complex and a variety of different treatment strategies have been suggested for the management of acute radiation-induced diarrhea. Material and methods: Data are presented from an extensive review of the current literature. Results: Radiation-induced diarrhea results from a variety of different pathophysiological mechanisms including malabsorption of bile salts and lactose, imbalances in local bacterial flora and changes in the intestinal patterns of motility. Up to date acute radiation diarrhea is predominantly treated symptomatically using opioide derivates (loperamide) or adsorbants of bile salts such as smectite. Clinical trials have been performed using L. acidophilus, smectite or sucralfate for diarrhea prophylaxis with moderate reduction of acute symptoms. Conclusions: Further evaluation of strategies for diarrhea prophylaxis is warranted. Due to the complex nature of radiation enteritis a multimodal approach taking into account alterations in intestinal motility patterns, malabsorption of bile salts and an imbalance of mucosal bacterial flora may offer new perspectives. (orig.) [de

SYMPOSIUM REPORT: An Evidence-Based Approach to IBS and CIC: Applying New Advances to Daily Practice

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Chey, William D.

2017-01-01

Many nonpharmacologic and pharmacologic therapies are available to manage irritable bowel syndrome (IBS) and chronic idiopathic constipation (CIC). The American College of Gastroenterology (ACG) regularly publishes reviews on IBS and CIC therapies. The most recent of these reviews was published by the ACG Task Force on the Management of Functional Bowel Disorders in 2014. The key objective of this review was to evaluate the efficacy of therapies for IBS or CIC compared with placebo or no treatment in randomized controlled trials. Evidence-based approaches to managing diarrhea-predominant IBS include dietary measures, such as a diet low in gluten and fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs); loperamide; antispasmodics; peppermint oil; probiotics; tricyclic antidepressants; alosetron; eluxadoline, and rifaximin. Evidence-based approaches to managing constipation-predominant IBS and CIC include fiber, stimulant laxatives, polyethylene glycol, selective serotonin reuptake inhibitors, lubiprostone, and guanylate cyclase agonists. With the growing evidence base for IBS and CIC therapies, it has become increasingly important for clinicians to assess the quality of evidence and understand how to apply it to the care of individual patients. PMID:28729815

Quantification of total tannin, flavonoid contents and pharmacognostic study of the seeds of Swietenia mahagoni (Linn.

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Tasmia Rahman

2016-11-01

Full Text Available Objective: To justify the folkloric use of Swietenia mahagoni (S. mahagoni seeds, 90% ethanolic extract and their aqueous and organic partitioning substances were evaluated for their possible antidiarrhoeal and antimicrobial potentials in vivo. Methods: Crude ethanolic extract of S. mahagoni seeds were subjected and partitioned into fractions using solvents at different polarity. Antimicrobial and antidiarrheal activities were evaluated and subsequently outcomes were corresponded with the conventional standard drugs. Results: The antidiarrheal activity was assessed using mouse model, where unfractionated ethanolic extract significantly reduced, the number, onset, rate and weight of diarrheal episodes. This fraction showed the limited number of defecation episodes of 27.0% and 40.9% at dose of 200 mg/kg and 400 mg/kg body weight respectively and reference drug, loperamide, showed 53% at a dose of 50 mg/kg. All extract fractions exhibited the significant potential to kill or subside the growth of known Gram-positive and Gram-negative bacteria. Conclusions: Ethanolic extract and their aqueous and organic fractious revealed the seeds of S. mahagoni (Linn. have the potential to be used as a remedy for diarrhea and known pathogenic microbes which ensured the folkloric use of the seeds of S. mahagoni.

Effects of Lizhong Tang on gastrointestinal motility in mice.

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Lee, Min Cheol; Ha, Wooram; Park, Jinhyeong; Kim, Junghoon; Jung, Yunjin; Kim, Byung Joo

2016-09-14

To investigate the effects of Lizhong Tang, a traditional Chinese medicine formula, on gastrointestinal motility in mice. The in vivo effects of Lizhong Tang on GI motility were investigated by measuring the intestinal transit rates (ITRs) and gastric emptying (GE) values in normal mice and in mice with experimentally induced GI motility dysfunction (GMD). In normal ICR mice, the ITR and GE values were significantly and dose-dependently increased by Lizhong Tang (ITR values: 54.4% ± 1.9% vs 65.2% ± 1.8%, P Tang and 54.4% ± 1.9% vs 83.8% ± 1.9%, P Tang; GE values: 60.7% ± 1.9% vs 66.8% ± 2.1%, P Tang and 60.7% ± 1.9% vs 72.5% ± 1.7%, P Tang). The ITRs of the GMD mice were significantly reduced compared with those of the normal mice, which were significantly and dose-dependently reversed by Lizhong Tang. Additionally, in loperamide- and cisplatin-induced models of GE delay, Lizhong Tang administration reversed the GE deficits. These results suggest that Lizhong Tang may be a novel candidate for development as a prokinetic treatment for the GI tract.

Solanum paniculatum root extract reduces diarrhea in rats

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Jonh A.B. Tenório

Full Text Available Abstract Solanum paniculatum L., Solanaceae, locally known as "jurubeba", is widely used in Brazil for culinary purposes, and in folk medicine to treat of diverse disorder including gastric dysfunctions. In this study we investigated the antidiarrheal activity of S. paniculatum roots extract in rats at different concentrations (125, 250 and 500 mg/kg, p.o using different experimental models such as castor oil-induced diarrhea, enteropooling and gastrointestinal motility, determined by in vivo experimental models. The major compound of root extract was characterized as chlorogenic acid based in the IR, 1D and 2D NMR analysis. All the extract doses achieved antidiarrheal potency, as indicated by reduced weight of feces in castor oil-induced diarrhea, decreased intestinal motility and significantly inhibited castor oil-induced enteropooling compared to the vehicle group. The highest dose (500 mg/kg produced greater anti-motility effect and better reduction of enteropooling, similar to the reference drug Loperamide (5 mg/kg. Extract from S. paniculatum L. roots had antidiarrheal activity, as shown by the lower weight of the feces as well as decrease in the accumulation of intestinal fluid and slower transit, justifying the traditional use of plant for diarrhea.

Evaluation of the calcium-antagonist, antidiarrhoeic and central nervous system activities of Baccharis serraefolia.

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Tortoriello, J; Aguilar-Santamaría, L

1996-09-01

Baccharis serraefolia is a widely used plant to treat diarrhoea in Mexican traditional medicine. Although the methanolic extract of this plant has shown an important dose-dependent spasmolytic activity, its underlying mechanism has not been studied. In the present work, the methanolic extract of B. serraefolia significantly delayed the onset of tonic seizures induced by strychnine and pentylenetetrazol; besides, it diminished the death rate and number of animals that exhibited convulsions. It produced potentiation of the hypnotic effect of pentobarbital. Oral administration produced an inhibition of gastrointestinal transit in mice as effective as that produced by loperamide. As to the effect on smooth muscles, the active extract produced an inhibition of contraction induced electrically, which could not be reversed by naloxone. The calcium concentration-contraction curve showed a rightward displacement when the extract was added to isolated guinea pig ileum depolarized with high K+ and cumulative concentrations of Ca2+. The results suggest that the methanolic extract does not interact with classical opiate receptors and its effects, at least that produced on smooth muscle, may be due to a probable interference with calcium influx and/or calcium release from an intra-cellular store.

Electrokinetic migration across artificial liquid membranes. New concept for rapid sample preparation of biological fluids.

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Pedersen-Bjergaard, Stig; Rasmussen, Knut Einar

2006-03-24

Basic drug substances were transported across a thin artificial organic liquid membrane by the application of 300 V d.c. From a 300 microl aqueous donor compartment (containing 10 mM HCl), the drugs migrated through a 200 microm artificial liquid membrane of 2-nitrophenyl octyl ether immobilized in the pores of a polypropylene hollow fiber, and into a 30 microl aqueous acceptor solution of 10 mM HCl inside the lumen of the hollow fiber. The transport was forced by an electrical potential difference sustained over the liquid membrane, resulting in electrokinetic migration of drug substances from the donor compartment to the acceptor solution. Within 5 min of operation at 300 V, pethidine, nortriptyline, methadone, haloperidol, and loperamide were extracted with recoveries in the range 70-79%, which corresponded to enrichments in the range 7.0-7.9. The chemical composition of the organic liquid membrane strongly affected the permeability, and may serve as an efficient tool for controlling the transport selectivity. Water samples, human plasma, and human urine were successfully processed, and in light of the present report, electrokinetic migration across thin artificial liquid membranes may be an interesting tool for future isolation within chemical analysis.

Antispasmodic and Antidiarrheal Activities of Valeriana hardwickii Wall. Rhizome Are Putatively Mediated through Calcium Channel Blockade.

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Bashir, Samra; Memon, Raafia; Gilani, Anwar H

2011-01-01

Valeriana hardwickii is indigenous to Pakistan, Burma and Ceylon, where it is traditionally being used as an antispasmodic and antidiarrheal, besides its culinary use as spice. The aim of this paper was to provide pharmacological validation to these medicinal uses. The crude aqueous-methanolic extract of Valeriana hardwickii rhizome (Vh.Cr) was studied on isolated rabbit jejunum and castor oil-induced diarrhea in mice for spasmolytic and antidiarrheal properties, respectively. Vh.Cr caused concentration-dependent (0.01-1 mg/mL) relaxation of spontaneous contractions in isolated rabbit jejunum and inhibited K(+)-induced contractions (0.01-0.3 mg/mL), similar to verapamil, suggestive of calcium channel blockade (CCB). The CCB effect was confirmed when pretreatment of the jejunum preparations with Vh.Cr produced a concentration-dependent (0.03-0.1 mg/mL) rightward shift in the Ca(++) concentration-response curves, as caused by verapamil. Vh.Cr exhibited dose-dependent (100-300 mg/kg) protection against castor oil-induced diarrhea in mice. Loperamide, a standard antidiarrheal drug, similarly prevented the diarrhea. These data indicate the presence of CCB effect in the extract of Valeriana hardwickii rhizome, possibly mediating its antispasmodic and antidiarrheal activities and provide a scientific base for its traditional use in hyperactive gut disorders.

Hydrolysis of a series of parabens by skin microsomes and cytosol from human and minipigs and in whole skin in short-term culture

International Nuclear Information System (INIS)

Jewell, Christopher; Prusakiewicz, Jeffery J.; Ackermann, Chrisita; Payne, N. Ann; Fate, Gwendolyn; Voorman, Richard; Williams, Faith M.

2007-01-01

Parabens are esters of 4-hydroxybenzoic acid and used as anti-microbial agents in a wide variety of toiletries, cosmetics and pharmaceuticals. It is of interest to understand the dermal absorption and hydrolysis of parabens, and to evaluate their disposition after dermal exposure and their potential to illicit localised toxicity. The use of minipig as a surrogate model for human dermal metabolism and toxicity studies, justifies the comparison of paraben metabolism in human and minipig skin. Parabens are hydrolysed by carboxylesterases to 4-hydroxybenzoic acid. The effects of the carboxylesterase inhibitors paraoxon and bis-nitrophenylphosphate provided evidence of the involvement of dermal carboxylesterases in paraben hydrolysis. Loperamide, a specific inhibitor of human carboxylesterase-2 inhibited butyl- and benzylparaben hydrolysis in human skin but not methylparaben or ethylparaben. These results show that butyl- and benzylparaben are more selective substrates for human carboxylesterase-2 in skin than the other parabens examined. Parabens applied to the surface of human or minipig skin were absorbed to a similar amount and metabolised to 4-hydroxybenzoic acid during dermal absorption. These results demonstrate that the minipig is a suitable model for man for assessing dermal absorption and hydrolysis of parabens, although the carboxylesterase profile in skin differs between human and minipig

A comprehensive review of the pharmacodynamics, pharmacokinetics and clinical effects of the neutral endopeptidase inhibitor racecadotril

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Marion eEberlin

2012-05-01

Full Text Available Racecadotril, via its active metabolite thiorphan, is an inhibitor of the enzyme neutral endopeptidase (NEP, EC 3.4.24.11, thereby increasing exposure to NEP including enkephalins and atrial natriuretic peptide. Upon oral administration racecadotril is rapidly and effectively converted into the active metabolite thiorphan, which does not cross the blood-brain-barrier. Racecadotril has mainly been tested in animal models and patients of three therapeutic areas. As an analgesic the effects of racecadotril across animal models were inconsistent. In cardiovascular diseases such as hypertension or congestive heart failure results from animal studies were promising, probably related to increased exposure to atrial natriuretic peptide, but clinical results have not shown substantial therapeutic benefit over existing treatment options in cardiovascular disease. In contrast, racecadotril was consistently effective in animal models and patients with various forms of acute diarrhea by inhibiting pathologic (but not basal secretion from the gut without changing gastro-intestinal transit time or motility. This included studies in both adults and children. In direct comparative studies with loperamide in adults and children, racecadotril was at least as effective but exhibited fewer adverse events in most studies, particularly less rebound constipation. Several guidelines recommend the use of racecadotril as addition to oral rehydration treatment in children with acute diarrhea.

Comparison between narcotic 'receptors' in the guinea-pig ileum and the rat brain

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Terenius, L [Uppsala Univ. (Sweden)

1975-01-01

The receptors, i.e., specific binding molecules, for narcotic analgesics in the guinea-pig ileum and rat brain have been compared. The relative affinities of a number of narcotics for the two receptors were very similar and discrimination between stereoisomeric agents was identical. The dissociation constants for dihydromorphine binding were 0.78 nM for the ileum and 1.4 nM for the brain receptor, respectively. There was a good correspondance between receptor affinities on the ileum preparation and the literature data on biologic activity on the isolated ileum. Codeine, diphenoxylate, difenoxine and loperamide, which are used clinically for the treatment of diarrhoea showed no selectivity against the ileum receptor. The two latter drugs had a very high receptor affinity and their lack of narcotic activity after oral administration is probably attributable to lack of penetration of the CNS. Receptor binding in both ileum and brain preparations was inhibited by N-ethylmaleimide, Triton X-100, trypsin and phospholipase C. There were small quantitative differences in sensitivity to these agents but it is difficult to assess whether this is because of real differences between the receptor molecules or attributable to secondary effects. As previously described for the brain receptor, the ileum receptor appeared to be present in a fraction enriched in plasma membranes.

Pre-travel advice at a crossroad: Medical preparedness of travellers to South and Southeast-Asia - The Hamburg Airport Survey.

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Rolling, Thierry; Mühlenpfordt, Melina; Addo, Marylyn M; Cramer, Jakob P; Vinnemeier, Christof D

Specific travel-related recommendations exist for the prevention or self-treatment of infectious diseases contracted by travellers to the tropics. In the current study, we assessed the medical preparedness per these recommendations, focusing on whether travellers carried antidiarrheal and antimalarial medication with them stratified by type of pre-travel advice. We surveyed travellers departing from Hamburg International Airport to South or Southeast Asia, using a questionnaire on demographic, medical and travel characteristics. 975 travellers were analysed - the majority (817, 83%) being tourists. A large proportion packed any antidiarrheal medication (612, 63%) - most frequently loperamide (440, 72%). Only 176 of 928 (19%) travellers to destinations with low-to medium risk for malaria packed a recommended antimalarial medication. The majority (162, 17%) of them carried antimalarials as stand-by emergency treatment (SBET). 468 (48%) travellers had a pre-travel medical consultation. This lead to higher odds of carrying SBET- with the highest odds associated with a consultation at a travel medicine specialist (OR 7.83 compared to no consultation). Attending a travel medicine specialist was associated with better adherence to current recommendations concerning the carriage of stand-by emergency treatment of malaria. However, the proportion of travellers seeking pre-travel health advice was overall low in our population. Promoting pre-travel consultations may, therefore, lead to higher adherence to the current recommendations in travel medicine. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antispasmodic and Antidiarrheal Activities of Valeriana hardwickii Wall. Rhizome Are Putatively Mediated through Calcium Channel Blockade

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Samra Bashir

2011-01-01

Full Text Available Valeriana hardwickii is indigenous to Pakistan, Burma and Ceylon, where it is traditionally being used as an antispasmodic and antidiarrheal, besides its culinary use as spice. The aim of this paper was to provide pharmacological validation to these medicinal uses. The crude aqueous-methanolic extract of Valeriana hardwickii rhizome (Vh.Cr was studied on isolated rabbit jejunum and castor oil-induced diarrhea in mice for spasmolytic and antidiarrheal properties, respectively. Vh.Cr caused concentration-dependent (0.01–1 mg/mL relaxation of spontaneous contractions in isolated rabbit jejunum and inhibited K+-induced contractions (0.01–0.3 mg/mL, similar to verapamil, suggestive of calcium channel blockade (CCB. The CCB effect was confirmed when pretreatment of the jejunum preparations with Vh.Cr produced a concentration-dependent (0.03–0.1 mg/mL rightward shift in the Ca++ concentration-response curves, as caused by verapamil. Vh.Cr exhibited dose-dependent (100–300 mg/kg protection against castor oil-induced diarrhea in mice. Loperamide, a standard antidiarrheal drug, similarly prevented the diarrhea. These data indicate the presence of CCB effect in the extract of Valeriana hardwickii rhizome, possibly mediating its antispasmodic and antidiarrheal activities and provide a scientific base for its traditional use in hyperactive gut disorders.

Evaluation of antinociceptive and antidiarrhoeal properties of Manilkara zapota leaves in Swiss albino mice.

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Ganguly, Amlan; Al Mahmud, Zobaer; Kumar Saha, Sajal; Abdur Rahman, S M

2016-08-01

Context Manilkara zapota (L.). P. Royen. (Sapotaceae) has been used in folk medicine to treat pain, diarrhoea, inflammation, arthralgia, and other disorders. Objective Screening of Manilkara zapota leaves ethanol extract and its different solvent soluble fractions for possible antinociceptive and antidiarrhoeal activities in Swiss albino mice. Materials and methods The extract and various fractions (200 and 400 mg/kg body weight; p.o.) were tested for peripheral and central antinociceptive activity by acetic acid-induced writhing and radiant heat tail-flick method, respectively; castor oil-induced diarrhoeal model was used to evaluate antidiarrhoeal activity at both doses. All the samples were administered once in a day and the duration of study was approximately 5 h. Results Ethanol extract (400 mg/kg), petroleum ether fraction (400 mg/kg), and ethyl acetate fraction (400 mg/kg) showed significant peripheral antinociceptive activity having 59.89, 58.24, and 46.7% (p analgesic activity having 74.15 and 82.15% (p screening, ethanol extract (200 and 400 mg/kg) showed significant inhibition of defecation by 53.57 and 60.71%, respectively (p < 0.001) compared with that of loperamide (71.42%). Discussion and conclusion The findings of the studies demonstrated antinociceptive and antidiarrhoeal activities of M. zapota leaves which could be the therapeutic option against pain and diarrhoeal disease.

Pharmacodynamics, pharmacokinetics and clinical efficacy of neratinib in HER2-positive breast cancer and breast cancer with HER2 mutations.

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Kourie, Hampig Raphael; Chaix, Marie; Gombos, Andrea; Aftimos, Phillippe; Awada, Ahmad

2016-08-01

Despite the availability of several potent HER2-directed targeted agents, primary and acquired resistance continues to influence patient outcomes in HER2-positive breast cancer. Neratinib is an irreversible pan-HER tyrosine kinase inhibitor in late-phase clinical development. This review article focuses on neratinib in the treatment of HER2-positive breast cancer - early and metastatic stage - and HER2-mutant breast cancer, with particular emphasis on the pharmacokinetics and pharmacodynamics of the drug. The phase III ExteNET trial shows that neratinib improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in early-stage HER2-positive breast cancer, and in particular HER2+/HR+ tumors. Survival data are awaited. The investigational role of neratinib in high-risk patients or conversely in de-escalation dual regimens with other anti-HER2 therapies and without chemotherapy are of interest. Phase II trials show that neratinib has efficacy, either as monotherapy or in combination with other chemotherapeutic or endocrine agents, in patients with HER2-positive metastatic breast cancer and in tumors harboring HER2 mutations. The role of neratinib in therapeutic algorithms of HER2-positive patients, as well as delaying CNS events, awaits the results of ongoing trials such as NALA. Diarrhea, the main toxicity of neratinib, can be effectively managed with early loperamide prophylaxis.

Opioid transport by ATP-binding cassette transporters at the blood-brain barrier: implications for neuropsychopharmacology.

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Tournier, Nicolas; Declèves, Xavier; Saubaméa, Bruno; Scherrmann, Jean-Michel; Cisternino, Salvatore

2011-01-01

Some of the ATP-binding cassette (ABC) transporters like P-glycoprotein (P-gp; ABCB1, MDR1), BCRP (ABCG2) and MRPs (ABCCs) that are present at the blood-brain barrier (BBB) influence the brain pharmacokinetics (PK) of their substrates by restricting their uptake or enhancing their clearance from the brain into the blood, which has consequences for their CNS pharmacodynamics (PD). Opioid drugs have been invaluable tools for understanding the PK-PD relationships of these ABC-transporters. The effects of morphine, methadone and loperamide on the CNS are modulated by P-gp. This review examines the ways in which other opioid drugs and some of their active metabolites interact with ABC transporters and suggests new mechanisms that may be involved in the variability of the response of the CNS to these drugs like carrier-mediated system belonging to the solute carrier (SLC) superfamily. Exposure to opioids may also alter the expression of ABC transporters. P-gp can be overproduced during morphine treatment, suggesting that the drug has a direct or, more likely, an indirect action. Variations in cerebral neurotransmitters during exposure to opioids and the release of cytokines during pain could be new endogenous stimuli affecting transporter synthesis. This review concludes with an analysis of the pharmacotherapeutic and clinical impacts of the interactions between ABC transporters and opioids.

High-output stoma after small-bowel resections for Crohn's disease.

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Tsao, Stephen K K; Baker, Melanie; Nightingale, Jeremy M D

2005-12-01

A 56-year-old Caucasian woman with a history of Crohn's disease and multiple bowel resections resulting in a loop jejunostomy was referred to our Nutritional Unit from a neighboring district general hospital for further management. She was first seen in October 2001, and initial assessment indicated that she was malnourished with fluid depletion, evidenced by the high volume of stomal fluid produced. There had been no sudden change in her medication, her Crohn's disease was quiescent and there was no evidence of any intra-abdominal sepsis. Despite a high calorific intake through her diet, she continued to lose weight. Serum urea and electrolytes; magnesium; C-reactive protein; full blood count; urinary spot sodium; anthropometric measurements. High-output stoma with malabsorption as a consequence of repeated small-bowel surgery. The patient was treated with oral hypotonic fluid restriction (0.5 l/day), 2 l of oral glucose-saline solution per day, high-dose oral antimotility agents (loperamide and codeine phosphate), a proton-pump inhibitor (omeprazole) and oral magnesium replacement. A year later, the patient's loop jejunostomy was closed and an end ileostomy fashioned, bringing an additional 35 cm of small bowel into continuity; macronutrient absorption improved but her problem of dehydration was only slightly reduced. She was stabilized on a twice-weekly subcutaneous magnesium and saline infusion and daily oral 1alpha-hydroxycholecalciferol.

Gastrointestinal medications and breastfeeding.

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Hagemann, T M

1998-09-01

Medications used to treat gastrointestinal symptoms are increasingly being used as more have been gained nonprescription status. Most of the gastrointestinal medications, such as laxatives, antacids, and antidiarrheal agents, are used short term. Women who breastfeed should be aware of the risks of taking any medications, whether prescription or nonprescription. There is little information describing transfer into breast milk for many of these products. Cimetidine, atropine, cascara, cisapride, loperamide, magnesium sulfate, and senna are the only products identified by the AAP as compatible with breast feeding. Metoclopramide is listed by the AAP as a drug whose effect on nursing infants is unknown but may be of potential concern, although studies published to date have not reported any adverse effects. The safest laxatives and antidiarrheals are those that are not absorbed and should be considered first-line therapy for conditions of constipation or loose stools. Famotidine and nizatidine are excreted into breast milk to a lesser extent than cimetidine or ranitidine and may be the preferred histamine antagonists. Despite the limited data on the use of cisapride in nursing women, it is considered safe by the AAP and may be preferred over metoclopramide for first-line prescription treatment of heartburn. Although most of these agents appear safe in the nursing infant, caretakers should be aware of the potential adverse reactions that may occur in infants whose mothers require these products.

Antidiarrheal Activity of Three Medicinal Plants in Swiss Albino Mice

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MD. Ashrafuzzaman

2016-09-01

Full Text Available Background: Different parts of Allamanda neriifolia (AN, Crinum latifolium (CL, and Bruguiera cylindrical (BC are used in folk medicine to treat diarrhea. Therefore, the aim of this study was to investigate and compare possible antidiarrheal activity of methanol extracts from barks, stems, and roots of AL, CL, and BC in Swiss albino mice. Methods: Antidiarrheal activities of extracts were evaluated at three doses (100mg/kg, 200 mg/kg and 400mg/kg and compared with Loperamide in a castor oil-induced diarrhea and charcoal meal test model in the Swiss albino mice. Results: The aqueous extract of CL and BC administered at doses of 100, 200 and 400mg/kg showed 0%, 24.5%, 62.26% and 5.66%, 37.11%, and 62.26% diarrhea inhibition, respectively (Table 2. This reduction in diarrheal episodes is significant, and maximum effect was observed at the dose of 400mg/kg similarly in the alcohol extracts of both CL and BC. AN administered at the dose of 100, 200 and 400mg/kg showed 55.97%, 74.84% and 74.84% diarrhea inhibition, respectively. Conclusion: The antidiarrheal effect of the AN extract, in contrast to CL and BC, against the castor oil-induced diarrhea model prove its efficacy in an extensive range of diarrheal conditions.

Nanotechnology-based drug delivery systems

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Singh Baljit

2007-12-01

Full Text Available Abstract Nanoparticles hold tremendous potential as an effective drug delivery system. In this review we discussed recent developments in nanotechnology for drug delivery. To overcome the problems of gene and drug delivery, nanotechnology has gained interest in recent years. Nanosystems with different compositions and biological properties have been extensively investigated for drug and gene delivery applications. To achieve efficient drug delivery it is important to understand the interactions of nanomaterials with the biological environment, targeting cell-surface receptors, drug release, multiple drug administration, stability of therapeutic agents and molecular mechanisms of cell signalling involved in pathobiology of the disease under consideration. Several anti-cancer drugs including paclitaxel, doxorubicin, 5-fluorouracil and dexamethasone have been successfully formulated using nanomaterials. Quantom dots, chitosan, Polylactic/glycolic acid (PLGA and PLGA-based nanoparticles have also been used for in vitro RNAi delivery. Brain cancer is one of the most difficult malignancies to detect and treat mainly because of the difficulty in getting imaging and therapeutic agents past the blood-brain barrier and into the brain. Anti-cancer drugs such as loperamide and doxorubicin bound to nanomaterials have been shown to cross the intact blood-brain barrier and released at therapeutic concentrations in the brain. The use of nanomaterials including peptide-based nanotubes to target the vascular endothelial growth factor (VEGF receptor and cell adhesion molecules like integrins, cadherins and selectins, is a new approach to control disease progression.

Anticholinergic syndrome following an unintentional overdose of scopolamine

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Carmela E Corallo

2009-09-01

Full Text Available Carmela E Corallo1, Ann Whitfield2, Adeline Wu21Department of Pharmacy, The Alfred, Melbourne, Victoria, Australia; 2Intensive Care Unit, Box Hill Hospital, Melbourne, Victoria, AustraliaAbstract: Scopolamine hydrobromide (hyoscine is an antimuscarinic drug which is primarily used in the prophylaxis and treatment of motion sickness and as a premedication to dry bronchial and salivary secretions. In acute overdosage, the main clinical problem is central nervous system (CNS depression. In Australia, tablets containing scopolamine hydrobromide 0.3 mg are available over the counter in packs of ten. The recommended dose for adults is one to two tablets as a single dose, repeated four to six hours later, if required. The maximum dose stated on the pack is four tablets over a 24-hour period with a caution regarding drowsiness and blurred vision. We describe a patient who presented with symptoms of anticholinergic syndrome secondary to an unintentional overdose of scopolamine. Whilst at work, the patient noticed that he had forgotten his prescribed medication, domperidone, at home; a friend gave him some travel sickness medication which contained scopolamine for relief of nausea. On a previous occasion, he had experienced a similar, less severe reaction with another anticholinergic agent, loperamide. This report highlights the need to consider nonprescription products, ie, over the counter medications, herbal/nutritional supplements as causes of anticholinergic syndrome when a patient presents with symptoms suggestive of this diagnosis.Keywords: domperidone, scopolamine, nonprescription drugs, toxicity, anticholinergic syndrome

MSBIS: A Multi-Step Biomedical Informatics Screening Approach for Identifying Medications that Mitigate the Risks of Metoclopramide-Induced Tardive Dyskinesia

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Dong Xu

2017-12-01

Full Text Available In 2009 the U.S. Food and Drug Administration (FDA placed a black box warning on metoclopramide (MCP due to the increased risks and prevalence of tardive dyskinesia (TD. In this study, we developed a multi-step biomedical informatics screening (MSBIS approach leveraging publicly available bioactivity and drug safety data to identify concomitant drugs that mitigate the risks of MCP-induced TD. MSBIS includes (1 TargetSearch (http://dxulab.org/software bioinformatics scoring for drug anticholinergic activity using CHEMBL bioactivity data; (2 unadjusted odds ratio (UOR scoring for indications of TD-mitigating effects using the FDA Adverse Event Reporting System (FAERS; (3 adjusted odds ratio (AOR re-scoring by removing the effect of cofounding factors (age, gender, reporting year; (4 logistic regression (LR coefficient scoring for confirming the best TD-mitigating drug candidates. Drugs with increasing TD protective potential and statistical significance were obtained at each screening step. Fentanyl is identified as the most promising drug against MCP-induced TD (coefficient: −2.68; p-value < 0.01. The discovery is supported by clinical reports that patients fully recovered from MCP-induced TD after fentanyl-induced general anesthesia. Loperamide is identified as a potent mitigating drug against a broader range of drug-induced movement disorders through pharmacokinetic modifications. Using drug-induced TD as an example, we demonstrated that MSBIS is an efficient in silico tool for unknown drug-drug interaction detection, drug repurposing, and combination therapy design.

MSBIS: A Multi-Step Biomedical Informatics Screening Approach for Identifying Medications that Mitigate the Risks of Metoclopramide-Induced Tardive Dyskinesia.

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Xu, Dong; Ham, Alexandrea G; Tivis, Rickey D; Caylor, Matthew L; Tao, Aoxiang; Flynn, Steve T; Economen, Peter J; Dang, Hung K; Johnson, Royal W; Culbertson, Vaughn L

2017-12-01

In 2009 the U.S. Food and Drug Administration (FDA) placed a black box warning on metoclopramide (MCP) due to the increased risks and prevalence of tardive dyskinesia (TD). In this study, we developed a multi-step biomedical informatics screening (MSBIS) approach leveraging publicly available bioactivity and drug safety data to identify concomitant drugs that mitigate the risks of MCP-induced TD. MSBIS includes (1) TargetSearch (http://dxulab.org/software) bioinformatics scoring for drug anticholinergic activity using CHEMBL bioactivity data; (2) unadjusted odds ratio (UOR) scoring for indications of TD-mitigating effects using the FDA Adverse Event Reporting System (FAERS); (3) adjusted odds ratio (AOR) re-scoring by removing the effect of cofounding factors (age, gender, reporting year); (4) logistic regression (LR) coefficient scoring for confirming the best TD-mitigating drug candidates. Drugs with increasing TD protective potential and statistical significance were obtained at each screening step. Fentanyl is identified as the most promising drug against MCP-induced TD (coefficient: -2.68; p-valueTD after fentanyl-induced general anesthesia. Loperamide is identified as a potent mitigating drug against a broader range of drug-induced movement disorders through pharmacokinetic modifications. Using drug-induced TD as an example, we demonstrated that MSBIS is an efficient in silico tool for unknown drug-drug interaction detection, drug repurposing, and combination therapy design. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Abuse of Prescription Drugs in the Context of Novel Psychoactive Substances (NPS): A Systematic Review.

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Schifano, Fabrizio; Chiappini, Stefania; Corkery, John M; Guirguis, Amira

2018-04-22

Recently, a range of prescription and over-the-counter drugs have been reportedly used as Novel Psychoactive Substances (NPS), due to their potential for abuse resulting from their high dosage/idiosyncratic methods of self-administration. This paper provides a systematic review of the topic, focusing on a range of medications which have emerged as being used recreationally, either on their own or in combination with NPS. Among gabapentinoids, pregabalin may present with higher addictive liability levels than gabapentin, with pregabalin being mostly identified in the context of opioid, polydrug intake. For antidepressants, their dopaminergic, stimulant-like, bupropion activities may explain their recreational value and diversion from the therapeutic intended use. In some vulnerable clients, a high dosage of venlafaxine (‘baby ecstasy’) is ingested for recreational purposes, whilst the occurrence of a clinically-relevant withdrawal syndrome may be a significant issue for all venlafaxine-treated patients. Considering second generation antipsychotics, olanzapine appears to be ingested at very large dosages as an ‘ideal trip terminator’, whilst the immediate-release quetiapine formulation may possess proper abuse liability levels. Within the image- and performance- enhancing drugs (IPEDs) group, the beta-2 agonist clenbuterol (‘size zero pill’) is reported to be self-administered for aggressive slimming purposes. Finally, high/very high dosage ingestion of the antidiarrhoeal loperamide has shown recent increasing levels of popularity due to its central recreational, anti-withdrawal, opiatergic effects. The emerging abuse of prescription drugs within the context of a rapidly modifying drug scenario represents a challenge for psychiatry, public health and drug-control policies.

Evaluation of drug treatment in irritable bowel syndrome

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Talley, Nicholas J

2003-01-01

The irritable bowel syndrome (IBS) remains a therapeutic challenge in part because of the limited understanding of the pathophysiology. The placebo response rate varies in randomized controlled trials from 20 to 70%, and can persist for up to at least 1 year. It is contentious whether dietary fibre and bulking agents relieve the symptoms of IBS; constipation probably improves. Anticholinergic and antispasmodic agents are of questionable benefit in IBS despite positive meta-analyses of poor quality trials. A meta-analysis concluded that the tricyclic antidepressants were superior to placebo in IBS, although the individual trial results were variable. Selective serotonin reuptake inhibitors are of uncertain benefit. Laxatives are used for constipation but probably poorly control the IBS symptom complex. Loperamide is superior to placebo in improvement of diarrhoea but not abdominal pain in IBS. Tegaserod is a well- tolerated aminoguanidine indole derivative of serotonin that is a partial 5HT4–receptor agonist with prokinetic properties; a therapeutic gain over placebo of 5% to 15% has been observed in constipation-predominant IBS in females. Alosetron is a 5HT3-receptor antagonist that is efficacious in females with diarrhoea-predominant IBS, with a 12% to 17% therapeutic gain; the risk of ischaemic colitis is 1 in 350, with very severe constipation occurring in about 1 in 1000. Optimizing study design remains a challenge in IBS. New visceral analgesic and motility modifying agents, as well as anti-inflammatory agents are in trials, and hopefully additional efficacious therapeutic options for patients with IBS will soon emerge. PMID:12968980

A double-blind, placebo-controlled trial of dextromethorphan combined with clonidine in the treatment of heroin withdrawal.

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Lin, Shih-Ku; Pan, Chun-Hung; Chen, Chia-Hui

2014-08-01

Dextromethorphan has been reported to ameliorate opioid withdrawal symptoms in both animal and human subjects. In the present study, we investigated the efficacy of dextromethorphan as an add-on medication in heroin detoxification treatment in a double-blind, placebo-controlled design. Sixty-five heroin-dependent patients (male, 63; female, 2) participated in this inpatient detoxification trial after giving informed consent. Clonidine 0.075 mg 4 times a day was given as an antiwithdrawal medication at baseline. Each patient was then randomly assigned to treatment with either dextromethorphan 60 mg or placebo 4 times a day as additional medication. Flurazepam 30 mg was given before bedtime for insomnia. Other medications that were allowed included loperamide for diarrhea and lorazepam for agitation. Participants were monitored using the Objective Opioid Withdrawal Scale 3 times a day as the primary outcome to compare drug efficacy between groups. Generalized estimating equation model analysis revealed that the Objective Opioid Withdrawal Scale had no group difference between dextromethorphan and placebo group overall (P = 0.29), whereas a significant difference between groups was found during day 3 to day 6 (P = 0.04) by post hoc analysis. There was no difference in the Clinical Global Impression Scale, patient's impression of treatment, and use of ancillary medications between groups. No severe adverse effects were noticed. We suggest that dextromethorphan has some beneficial effect in attenuating the severity of opioid withdrawal symptoms and can be used as an adjunction medication in the treatment of opioid withdrawal, whereas the exact efficacy needs further investigation.

Development of in situ ion selective sensors for dissolution

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Bohets, Hugo; Vanhoutte, Koen; De Maesschalck, Roy; Cockaerts, Paul; Vissers, Bert; Nagels, Luc J.

2007-01-01

The dissolution of formulations of the drugs dapoxetine, paliperidone, cinnarizine, tetrazepam, mebeverine, loperamide, galantamine and ibuprofen was studied by an in-line potentiometric measurement system. The transpose of a Nikolskii-Eisenman type function performed the conversion of potential to percentage of dissolution. A novel gradient membrane electrode was developed especially for dissolution, varying continuously in composition from an ionically conducting rubber phase to an electronically conducting solid state PVC/graphite composite. The gradient part had a thickness of 200 μm. The electrodes life span exceeded 6 months. An ion exchange procedure was used to prepare them for one specific drug. This enabled us to use one universal electrode built to measure a wide array of drugs. The system parameters such as accuracy, reproducibility and linearity were presented with the data obtained for the drug dapoxetine. In dissolution, accurate measurements were possible from 10 -9 to 10 -3 M concentrations, for high log P drugs. The effect of t 90 response times on the measurement error was estimated. The t 90 response times of the electrodes were concentration dependent, and varied between 50 and 10 s for, respectively, 10 -6 and 10 -3 M concentrations. Potential drift was studied in detail. The measurements performed with these electrodes showed an accuracy of 1%, and inter- and intra electrode variabilities of 0.6 and 1.7%, respectively. The electrodes were successfully applied in colloidal media containing suspended matter, typically formed during dissolution of tablets. The advantages and pitfalls of potentiometry over the presently used techniques for dissolution testing are discussed

Evaluation of safety and protective effects of Potentilla fulgens root extract in experimentally induced diarrhoea in mice

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V. Tangpu

2014-06-01

Methods: The protective effects of P. fulgens root extract was investigated against experimentally induced diarrhoea in mice, using four experimental models, i.e. measurement of faecal output, castor oil model, prostaglandin E2 (PGE2 enteropooling assay and gastrointestinal transit test. The safety assessment of root extract was done in mice on the basis of general signs and symptoms of toxicity, food water intake and mortality of animals following their treatment with various doses of extract (100 and ndash;3200 mg/kg. In addition, the serum glutamate oxaloacetate transaminase (SGOT, serum glutamate pyruvate transaminase (SGPT, cholesterol and total protein of experimental mice were also monitored to assess the toxicity of root extract. Results: In the safety assessment studies, P. fulgens root extract did not showed any visible signs of toxicity, but mortality was observed in a single animal at 3200 mg/kg dose of extract. The extract also did not showed any adverse effects on the studied serum parameters of experimental animals. In the antidiarrhoeal tests, administration of 800 mg/kg dose of extract to mice showed 50% protection from diarrhoea evoked by castor oil. In addition, the extract also showed 29.27% reduction in PGE2-induced intestinal secretion as compared to 30.31% recorded for loperamide, a standard anti-diarrhoeal drug. Conclusions: The results of this study indicate that P. fulgens root extract possesses significant anti-diarrhoeal properties. Therefore, the roots of this plant can be an effective traditional medicine for the protection from diarrhoea. [J Intercult Ethnopharmacol 2014; 3(3.000: 103-108

Reverse Effect of Opuntia ficus-indica L. Juice and Seeds Aqueous Extract on Gastric Emptying and Small-Bowel Motility in Rat.

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Rtibi, Kaïs; Selmi, Slimen; Saidani, Khouloud; Grami, Dhekra; Amri, Mohamed; Sebai, Hichem; Marzouki, Lamjed

2018-01-01

This study was conducted to compare the effects of juice and seeds on gastric emptying, small-bowel motility and intestinal ion transport. Separate groups of rats were randomized to receive NaCl, increasing doses of juice (5, 10, and 20 mL/kg, b.w.) or seeds aqueous extract (100, 200, and 400 mg/kg, b.w.). Simultaneously, two other groups were received, the reference drugs; clonidine (1 mg/kg) and yohimbine (2 mg/kg). The charcoal meal was used as a suspension for gastrointestinal motility test. The purgative action of juice was confirmed using the loperamide (5 mg/kg, p.o.) induced constipation. To evaluate the antisecretory effect, we were used as a hypersecretion agent, the castor oil at the dose of 5 mL/kg. Compared to the control and standard groups, we were showed that the prickly pear has an opposite effect on small-bowel motility and gastric emptying. Indeed, the juice at various doses has a laxative effect of gastrointestinal transit in healthy and constipated-rats. However, the aqueous extract of the seeds leads to a reduction of motility in normal rats which gives it a remarkable antidiarrhoeal activity, a notable intestinal fluid accumulation decline and electrolyte concentrations reestablishment. Moreover, orally juice administered at different doses accelerated the stomach emptying time in contrast to the seeds aqueous extract. More importantly, a significant variation in the phytochemical constituents levels between juice and seeds was found. These findings confirm the reverse therapeutic effects of this fruit in the treatment of digestive disturbances such as difficulty stool evacuation and massive intestinal secretion, likewise, the gastric emptying process perturbation. © 2017 Institute of Food Technologists®.

Development of in situ ion selective sensors for dissolution

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Bohets, Hugo [Antwerp University, Chemistry Department, Groenenborgerlaan 171, B-2020 Antwerpen (Belgium); Vanhoutte, Koen [Johnson and Johnson Pharmaceutical Research and Development, Turnhoutseweg 30, B-2340 Beerse (Belgium); De Maesschalck, Roy [Johnson and Johnson Pharmaceutical Research and Development, Turnhoutseweg 30, B-2340 Beerse (Belgium); Cockaerts, Paul [Johnson and Johnson Pharmaceutical Research and Development, Turnhoutseweg 30, B-2340 Beerse (Belgium); Vissers, Bert [Antwerp University, Chemistry Department, Groenenborgerlaan 171, B-2020 Antwerpen (Belgium); Nagels, Luc J. [Antwerp University, Chemistry Department, Groenenborgerlaan 171, B-2020 Antwerpen (Belgium)]. E-mail: luc.nagels@ua.ac.be

2007-01-02

The dissolution of formulations of the drugs dapoxetine, paliperidone, cinnarizine, tetrazepam, mebeverine, loperamide, galantamine and ibuprofen was studied by an in-line potentiometric measurement system. The transpose of a Nikolskii-Eisenman type function performed the conversion of potential to percentage of dissolution. A novel gradient membrane electrode was developed especially for dissolution, varying continuously in composition from an ionically conducting rubber phase to an electronically conducting solid state PVC/graphite composite. The gradient part had a thickness of 200 {mu}m. The electrodes life span exceeded 6 months. An ion exchange procedure was used to prepare them for one specific drug. This enabled us to use one universal electrode built to measure a wide array of drugs. The system parameters such as accuracy, reproducibility and linearity were presented with the data obtained for the drug dapoxetine. In dissolution, accurate measurements were possible from 10{sup -9} to 10{sup -3} M concentrations, for high log P drugs. The effect of t {sub 90} response times on the measurement error was estimated. The t {sub 90} response times of the electrodes were concentration dependent, and varied between 50 and 10 s for, respectively, 10{sup -6} and 10{sup -3} M concentrations. Potential drift was studied in detail. The measurements performed with these electrodes showed an accuracy of 1%, and inter- and intra electrode variabilities of 0.6 and 1.7%, respectively. The electrodes were successfully applied in colloidal media containing suspended matter, typically formed during dissolution of tablets. The advantages and pitfalls of potentiometry over the presently used techniques for dissolution testing are discussed.

Posterior sagittal anorectoplasty in vestibular fistula: with or without colostomy.

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Karakus, Suleyman Cuneyt; User, Idil Rana; Akcaer, Vedat; Ceylan, Haluk; Ozokutan, Bulent Hayri

2017-07-01

The aim of this study is to compare the results and complications of one- and three-stage repairs in females with vestibular fistula (VF) and make contribution to the discussion of whether the disadvantages outweigh the protective effect of a colostomy from wound infection and wound dehiscence following posterior sagittal anorectoplasty (PSARP). Patients with a diagnosis of VF who underwent PSARP between October 2009 and November 2015 were retrospectively reviewed. The patients were divided into two groups: Group 1-patients treated by one-stage procedure (n = 30); Group 2-patients treated by three-stage procedure (n = 16). There were no statistically significant differences between the groups with respect to wound infection, recurrence of fistula and rectal mucosal prolapse. Minor wound dehiscence occurred slightly more common in Group 1, even if p value is not significant. No wound dehiscence has been observed since we switched to the protocol of keeping the child nil per oral for 5 postoperative days and loperamide (0.1 mg/kg) administration for 7 postoperative days. The mean time before resuming oral intake was 2.87 ± 1.7 and 1.19 ± 0.4 days in Group 1 and Group 2, respectively (p = 0.001). None developed major wound disruption or anal stenosis in either group. There were no statistical differences between the groups in terms of voluntary bowel movements, soiling and constipation. PSARP performed without a protective colostomy in patients with VF has low morbidity, good continence rates and obvious advantages for both the patients and their parents.

Laxative activities of Mareya micrantha (Benth. Müll. Arg. (Euphorbiaceae leaf aqueous extract in rats

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Djaman Joseph A

2010-02-01

Full Text Available Abstract Background Mareya micrantha (Benth. Müll. Arg. (Euphorbiaceae is a shrub that is commonly used in Côte d'Ivoire (West Africa for the treatment of constipation and as an ocytocic drug. The present study was carried out to investigate the laxative activity of Mareya micrantha in albino's Wistar rats. Methods Rats were divided in 5 groups of 5 animals each, first group as control, second group served as standard (sodium picosulfate while group 3, 4 and 5 were treated with leaf aqueous extract of Mareya micrantha at doses of 100, 200 and 400 mg/kg body weight (b.w., per os respectively. The laxative activity was determined based on the weight of the faeces matter. The effects of the leaves aqueous extract of Mareya micrantha and castor oil were also evaluated on intestinal transit, intestinal fluid accumulation and ions secretion. Results Phytochemicals screening of the extract revealed the presence of flavonoids, alkaloids, tannins, polyphenols, sterols and polyterpenes. The aqueous extract of Mareya micrantha applied orally (100, 200 and 400 mg/kg; p.o., produced significant laxative activity and reduced loperamide induced constipation in dose dependant manner. The effect of the extract at 200 and 400 mg/kg (p.o. was similar to that of reference drug sodium picosulfate (5 mg/kg, p.o. The same doses of the extract (200 and 400 mg/kg, p.o. produced a significant increase (p -, Na+, K+ and Ca2+ in the intestinal fluid (p Conclusions The results showed that the aqueous extract of Mareya micrantha has a significant laxative activity and supports its traditional use in herbal medicine.

The behaviour of health care providers in managing diarrheal disease in Palembang City, south Sumatera, Indonesia.

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Ismail, R; Bakri, A; Nazir, M; Pardede, N

1991-01-01

A study on knowledge, attitude and practice of health care providers in Palembang had been conducted at the end of 1989 and beginning of 1990. Four approaches were carried out: (1) by recording the help obtained by cases who consulted researchers for further help for the same diarrheal diseases (DD) episode, (2) by studying the medical records of DD cases admitted to three hospitals, (3) by studying prescriptions dispensed by three pharmacies and (4) by focus group discussions. The findings were analysed to evaluate the achievement of the Indonesian Diarrheal Diseases Control Program (CDD). ORT, avoiding antimotility drugs and appropriated feeding have been accepted and practiced by the providers in Palembang. The target of promotion now is to support the acquisition of these behaviours to be implemented as a routine habit of the providers and as a part of the ongoing system of health care delivery system. Specifically the danger of loperamide promotion to the policy on antimotility must be stressed. Rapid iv rehydration and avoiding surface precipitating agents have been accepted, but are not practiced consistently yet due to practical considerations. It seems that there is no impact at all of CDD towards the rate of antibiotic therapy in DD. Besides intensifying the campaign, enforcing group pressure, may be we have to elaborate more the perception of health care provider as a practitioner, and conforming the strategy of the CDD campaign towards the findings. Health education had not been practiced effectively yet. Morale and value system of the providers are important for the success of this program. In general the medical-technic aspect of the CDD has been accepted by the providers, but there is still a lot to do in communicating them to be adopted as an effective behaviour.

HALT-D: A Phase II Evaluation of Crofelemer for the Prevention and Prophylaxis of Diarrhea in Patients With Breast Cancer on Pertuzumab-Based Regimens.

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Gao, Jennifer J; Tan, Ming; Pohlmann, Paula R; Swain, Sandra M

2017-02-01

Approximately 40% to 80% of patients receiving pertuzumab-directed therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer will develop chemotherapy-induced diarrhea (CID). Loperamide and octreotide are frequently used to treat CID after diarrhea occurs, but neither is used prophylactically or targets the underlying mechanism. Previous studies suggest blocking epidermal growth factor receptor may cause excess chloride secretion, resulting in diarrhea. Crofelemer is derived from the red latex of the Croton lechleri tree, blocks gastrointestinal cystic fibrosis transmembrane regulator and calcium-activated chloride channels, and is U.S. Food and Drug Administration approved for relief of diarrhea in HIV/AIDS patients on anti-retroviral therapy. Crofelemer is not systemically absorbed, has relatively few side effects, and presents a targeted approach at preventing CID in patients receiving pertuzumab-based therapy. HALT-D (DiarrHeA Prevention and ProphyLaxis with Crofelemer in HER2-Positive Breast Cancer Patients Receiving Trastuzumab, Pertuzumab, and Docetaxel or Paclitaxel with or without Carboplatin, NCT02910219) is a phase II, randomized, open-label trial that aims to recruit 46 patients from 3 MedStar sites. Adults with HER2-positive breast cancer being treated with trastuzumab, pertuzumab, and docetaxel or paclitaxel (THP) or trastuzumab, pertuzumab, docetaxel, and carboplatin (TCHP) will be randomized to receive crofelemer or no medication for diarrhea prophylaxis. The primary endpoint is incidence of all grade diarrhea for ≥ 2 consecutive days during cycles 1 to 2 of THP or TCHP. Secondary endpoints include overall incidence, duration, and severity of diarrhea; time to onset of diarrhea; use of other anti-diarrheal medications; stool frequency and consistency; and quality of life. HALT-D will provide important information about the feasibility and tolerability of crofelemer in preventing diarrhea for patients receiving THP or TCHP

Cellular mechanisms underlying the laxative effect of flavonol naringenin on rat constipation model.

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Zi-Huan Yang

Full Text Available BACKGROUND & AIMS: Symptoms of constipation are extremely common, especially in the elderly. The present study aim to identify an efficacious treatment strategy for constipation by evaluating the secretion-promoting and laxative effect of a herbal compound, naringenin, on intestinal epithelial anion secretion and a rat constipation model, respectively. METHODS/PRINCIPAL FINDINGS: In isolated rat colonic crypts, mucosal addition of naringenin (100 microM elicited a concentration-dependent and sustained increase in the short-circuit current (I(SC, which could be inhibited in Cl- free solution or by bumetanide and DPC (diphenylamine-2-carboxylic acid, but not by DIDS (4, 4'- diisothiocyanatostilbene-2, 2'-disulfonic acid. Naringenin could increase intracellular cAMP content and PKA activity, consisted with that MDL-12330A (N-(Cis-2-phenyl-cyclopentyl azacyclotridecan-2-imine-hydrochloride pretreatment reduced the naringenin-induced I(SC. In addition, significant inhibition of the naringenin-induced I(SC by quinidine indicated that basolateral K+ channels were involved in maintaining this cAMP-dependent Cl- secretion. Naringenin-evoked whole cell current which exhibited a linear I-V relationship and time-and voltage- independent characteristics was inhibited by DPC, indicating that the cAMP activated Cl- conductance most likely CFTR (cystic fibrosis transmembrane conductance regulator was involved. In rat constipation model, administration of naringenin restored the level of fecal output, water content and mucus secretion compared to loperamide-administrated group. CONCLUSIONS: Taken together, our data suggest that naringenin could stimulate Cl- secretion in colonic epithelium via a signaling pathway involving cAMP and PKA, hence provide an osmotic force for subsequent colonic fluid secretion by which the laxative effect observed in the rat constipation model. Naringenin appears to be a novel alternative treatment strategy for constipation.

Pharmacological Approach for Managing Pain in Irritable Bowel Syndrome: A Review Article

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Chen, Longtu; Ilham, Sheikh J.; Feng, Bin

2017-01-01

Context Visceral pain is a leading symptom for patients with irritable bowel syndrome (IBS) that affects 10% - 20 % of the world population. Conventional pharmacological treatments to manage IBS-related visceral pain is unsatisfactory. Recently, medications have emerged to treat IBS patients by targeting the gastrointestinal (GI) tract and peripheral nerves to alleviate visceral pain while avoiding adverse effects on the central nervous system (CNS). Several investigational drugs for IBS also target the periphery with minimal CNS effects. Evidence of Acquisition In this paper, reputable internet databases from 1960 - 2016 were searched including Pubmed and ClinicalTrials.org, and 97 original articles analyzed. Search was performed based on the following keywords and combinations: irritable bowel syndrome, clinical trial, pain, visceral pain, narcotics, opioid, chloride channel, neuropathy, primary afferent, intestine, microbiota, gut barrier, inflammation, diarrhea, constipation, serotonin, visceral hypersensitivity, nociceptor, sensitization, hyperalgesia. Results Certain conventional pain managing drugs do not effectively improve IBS symptoms, including NSAIDs, acetaminophen, aspirin, and various narcotics. Anxiolytic and antidepressant drugs (Benzodiazepines, TCAs, SSRI and SNRI) can attenuate pain in IBS patients with relevant comorbidities. Clonidine, gabapentin and pregabalin can moderately improve IBS symptoms. Lubiprostone relieves constipation predominant IBS (IBS-C) while loperamide improves diarrhea predominant IBS (IBS-D). Alosetron, granisetron and ondansetron can generally treat pain in IBS-D patients, of which alosetron needs to be used with caution due to cardiovascular toxicity. The optimal drugs for managing pain in IBS-D and IBS-C appear to be eluxadoline and linaclotide, respectively, both of which target peripheral GI tract. Conclusions Conventional pain managing drugs are in general not suitable for treating IBS pain. Medications that target

Sildenafil normalizes bowel transit in preclinical models of constipation.

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Sarah K Sharman

Full Text Available Guanylyl cyclase-C (GC-C agonists increase cGMP levels in the intestinal epithelium to promote secretion. This process underlies the utility of exogenous GC-C agonists such as linaclotide for the treatment of chronic idiopathic constipation (CIC and irritable bowel syndrome with constipation (IBS-C. Because GC-C agonists have limited use in pediatric patients, there is a need for alternative cGMP-elevating agents that are effective in the intestine. The present study aimed to determine whether the PDE-5 inhibitor sildenafil has similar effects as linaclotide on preclinical models of constipation. Oral administration of sildenafil caused increased cGMP levels in mouse intestinal epithelium demonstrating that blocking cGMP-breakdown is an alternative approach to increase cGMP in the gut. Both linaclotide and sildenafil reduced proliferation and increased differentiation in colon mucosa, indicating common target pathways. The homeostatic effects of cGMP required gut turnover since maximal effects were observed after 3 days of treatment. Neither linaclotide nor sildenafil treatment affected intestinal transit or water content of fecal pellets in healthy mice. To test the effectiveness of cGMP elevation in a functional motility disorder model, mice were treated with dextran sulfate sodium (DSS to induce colitis and were allowed to recover for several weeks. The recovered animals exhibited slower transit, but increased fecal water content. An acute dose of sildenafil was able to normalize transit and fecal water content in the DSS-recovery animal model, and also in loperamide-induced constipation. The higher fecal water content in the recovered animals was due to a compromised epithelial barrier, which was normalized by sildenafil treatment. Taken together our results show that sildenafil can have similar effects as linaclotide on the intestine, and may have therapeutic benefit to patients with CIC, IBS-C, and post-infectious IBS.

Female sexual function and fertility after ileal pouch-anal anastomosis.

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Hor, Thevy; Lefevre, Jeremie H; Shields, Conor; Chafai, Najim; Tiret, Emmanuel; Parc, Yann

2016-03-01

A potential complication in women after ileal pouch-anal anastomosis (IPAA) is sexual impairment and reduced fertility. The aim was to evaluate sexual function and fertility after IPAA. All female patients who underwent an IPAA between 2004 and 2013 were retrospectively included. Sexual function, fertility, and continence were explored by the female sexual function index (FSFI), telephonic interview, and Wexner's score. Among 127 women included, 93 responded to the questionnaires (73.2%). Seventy five were sexually active, and 48 (64%) had normal sexual function (FSFI > 26). In univariate analysis, there was a significant relationship between ulcerative colitis (p = 0.0161), age > 40 years (p = 0.01311), number of bowel movements (p = 0.0238), nocturnal pouch activity (p = 0.0094), use of loperamide (p = 0.0283), and existence of sexual dysfunction. After multivariate analysis, age and nocturnal pouch activity were associated with a worse sexual function (p = 0.0235, OR = 3.3 (1.2-9.9) and p = 0.0094, OR = 4.1 (1.4-13.5)). Of 16 patients who wished to have children, 10 (63%) became pregnant without recourse to in vitro fertilization, of whom 3 had two or more pregnancies. In total, there were 13 children born after IPAA. The mean time between the first pregnancy and surgery was 24.8 ± 22 months. At 12 and 24 months after cessation of contraception, 57 and 67% had at least one pregnancy. While sexual function is impaired in a limited number of patients, the impact of surgery can be regarded as modest. Age and nocturnal pouch activity were some independent factors of worse sexual function. The risk of infertility should not preclude consideration of IPAA as a treatment option.

Transport inhibition of digoxin using several common P-gp expressing cell lines is not necessarily reporting only on inhibitor binding to P-gp.

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Annie Albin Lumen

Full Text Available We have reported that the P-gp substrate digoxin required basolateral and apical uptake transport in excess of that allowed by digoxin passive permeability (as measured in the presence of GF120918 to achieve the observed efflux kinetics across MDCK-MDR1-NKI (The Netherlands Cancer Institute confluent cell monolayers. That is, GF120918 inhibitable uptake transport was kinetically required. Therefore, IC50 measurements using digoxin as a probe substrate in this cell line could be due to inhibition of P-gp, of digoxin uptake transport, or both. This kinetic analysis is now extended to include three additional cell lines: MDCK-MDR1-NIH (National Institute of Health, Caco-2 and CPT-B2 (Caco-2 cells with BCRP knockdown. These cells similarly exhibit GF120918 inhibitable uptake transport of digoxin. We demonstrate that inhibition of digoxin transport across these cell lines by GF120918, cyclosporine, ketoconazole and verapamil is greater than can be explained by inhibition of P-gp alone. We examined three hypotheses for this non-P-gp inhibition. The inhibitors can: (1 bind to a basolateral digoxin uptake transporter, thereby inhibiting digoxin's cellular uptake; (2 partition into the basolateral membrane and directly reduce membrane permeability; (3 aggregate with digoxin in the donor chamber, thereby reducing the free concentration of digoxin, with concomitant reduction in digoxin uptake. Data and simulations show that hypothesis 1 was found to be uniformly acceptable. Hypothesis 2 was found to be uniformly unlikely. Hypothesis 3 was unlikely for GF120918 and cyclosporine, but further studies are needed to completely adjudicate whether hetero-dimerization contributes to the non-P-gp inhibition for ketoconazole and verapamil. We also find that P-gp substrates with relatively low passive permeability such as digoxin, loperamide and vinblastine kinetically require basolateral uptake transport over that allowed by +GF120918 passive permeability, while

Neratinib Efficacy and Circulating Tumor DNA Detection of HER2 Mutations in HER2 Nonamplified Metastatic Breast Cancer.

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Ma, Cynthia X; Bose, Ron; Gao, Feng; Freedman, Rachel A; Telli, Melinda L; Kimmick, Gretchen; Winer, Eric; Naughton, Michael; Goetz, Matthew P; Russell, Christy; Tripathy, Debu; Cobleigh, Melody; Forero, Andres; Pluard, Timothy J; Anders, Carey; Niravath, Polly Ann; Thomas, Shana; Anderson, Jill; Bumb, Caroline; Banks, Kimberly C; Lanman, Richard B; Bryce, Richard; Lalani, Alshad S; Pfeifer, John; Hayes, Daniel F; Pegram, Mark; Blackwell, Kimberly; Bedard, Philippe L; Al-Kateb, Hussam; Ellis, Matthew J C

2017-10-01

Purpose: Based on promising preclinical data, we conducted a single-arm phase II trial to assess the clinical benefit rate (CBR) of neratinib, defined as complete/partial response (CR/PR) or stable disease (SD) ≥24 weeks, in HER2 mut nonamplified metastatic breast cancer (MBC). Secondary endpoints included progression-free survival (PFS), toxicity, and circulating tumor DNA (ctDNA) HER2 mut detection. Experimental Design: Tumor tissue positive for HER2 mut was required for eligibility. Neratinib was administered 240 mg daily with prophylactic loperamide. ctDNA sequencing was performed retrospectively for 54 patients (14 positive and 40 negative for tumor HER2 mut ). Results: Nine of 381 tumors (2.4%) sequenced centrally harbored HER2 mut (lobular 7.8% vs. ductal 1.6%; P = 0.026). Thirteen additional HER2 mut cases were identified locally. Twenty-one of these 22 HER2 mut cases were estrogen receptor positive. Sixteen patients [median age 58 (31-74) years and three (2-10) prior metastatic regimens] received neratinib. The CBR was 31% [90% confidence interval (CI), 13%-55%], including one CR, one PR, and three SD ≥24 weeks. Median PFS was 16 (90% CI, 8-31) weeks. Diarrhea (grade 2, 44%; grade 3, 25%) was the most common adverse event. Baseline ctDNA sequencing identified the same HER2 mut in 11 of 14 tumor-positive cases (sensitivity, 79%; 90% CI, 53%-94%) and correctly assigned 32 of 32 informative negative cases (specificity, 100%; 90% CI, 91%-100%). In addition, ctDNA HER2 mut variant allele frequency decreased in nine of 11 paired samples at week 4, followed by an increase upon progression. Conclusions: Neratinib is active in HER2 mut , nonamplified MBC. ctDNA sequencing offers a noninvasive strategy to identify patients with HER2 mut cancers for clinical trial participation. Clin Cancer Res; 23(19); 5687-95. ©2017 AACR . ©2017 American Association for Cancer Research.

Translational Breast Cancer Research Consortium (TBCRC) 022: A Phase II Trial of Neratinib for Patients With Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer and Brain Metastases.

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Freedman, Rachel A; Gelman, Rebecca S; Wefel, Jeffrey S; Melisko, Michelle E; Hess, Kenneth R; Connolly, Roisin M; Van Poznak, Catherine H; Niravath, Polly A; Puhalla, Shannon L; Ibrahim, Nuhad; Blackwell, Kimberly L; Moy, Beverly; Herold, Christina; Liu, Minetta C; Lowe, Alarice; Agar, Nathalie Y R; Ryabin, Nicole; Farooq, Sarah; Lawler, Elizabeth; Rimawi, Mothaffar F; Krop, Ian E; Wolff, Antonio C; Winer, Eric P; Lin, Nancy U

2016-03-20

Evidence-based treatments for metastatic, human epidermal growth factor receptor 2 (HER2)-positive breast cancer in the CNS are limited. Neratinib is an irreversible inhibitor of erbB1, HER2, and erbB4, with promising activity in HER2-positive breast cancer; however, its activity in the CNS is unknown. We evaluated the efficacy of treatment with neratinib in patients with HER2-positive breast cancer brain metastases in a multicenter, phase II open-label trial. Eligible patients were those with HER2-positive brain metastases (≥ 1 cm in longest dimension) who experienced progression in the CNS after one or more line of CNS-directed therapy, such as whole-brain radiotherapy, stereotactic radiosurgery, and/or surgical resection. Patients received neratinib 240 mg orally once per day, and tumors were assessed every two cycles. The primary endpoint was composite CNS objective response rate (ORR), requiring all of the following: ≥ 50% reduction in volumetric sum of target CNS lesions and no progression of non-target lesions, new lesions, escalating corticosteroids, progressive neurologic signs/symptoms, or non-CNS progression--the threshold for success was five of 40 responders. Forty patients were enrolled between February 2012 and June 2013; 78% of patients had previous whole-brain radiotherapy. Three women achieved a partial response (CNS objective response rate, 8%; 95% CI, 2% to 22%). The median number of cycles received was two (range, one to seven cycles), with a median progression-free survival of 1.9 months. Five women received six or more cycles. The most common grade ≥ 3 event was diarrhea (occurring in 21% of patients taking prespecified loperamide prophylaxis and 28% of those without prophylaxis). Patients in the study experienced a decreased quality of life over time. Although neratinib had low activity and did not meet our threshold for success, 12.5% of patients received six or more cycles. Studies combining neratinib with chemotherapy in patients

Translational Breast Cancer Research Consortium (TBCRC) 022: A Phase II Trial of Neratinib for Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases

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Gelman, Rebecca S.; Wefel, Jeffrey S.; Melisko, Michelle E.; Hess, Kenneth R.; Connolly, Roisin M.; Van Poznak, Catherine H.; Niravath, Polly A.; Puhalla, Shannon L.; Ibrahim, Nuhad; Blackwell, Kimberly L.; Moy, Beverly; Herold, Christina; Liu, Minetta C.; Lowe, Alarice; Agar, Nathalie Y.R.; Ryabin, Nicole; Farooq, Sarah; Lawler, Elizabeth; Rimawi, Mothaffar F.; Krop, Ian E.; Wolff, Antonio C.; Winer, Eric P.; Lin, Nancy U.

2016-01-01

Purpose Evidence-based treatments for metastatic, human epidermal growth factor receptor 2 (HER2)–positive breast cancer in the CNS are limited. Neratinib is an irreversible inhibitor of erbB1, HER2, and erbB4, with promising activity in HER2-positive breast cancer; however, its activity in the CNS is unknown. We evaluated the efficacy of treatment with neratinib in patients with HER2-positive breast cancer brain metastases in a multicenter, phase II open-label trial. Patients and Methods Eligible patients were those with HER2-positive brain metastases (≥ 1 cm in longest dimension) who experienced progression in the CNS after one or more line of CNS-directed therapy, such as whole-brain radiotherapy, stereotactic radiosurgery, and/or surgical resection. Patients received neratinib 240 mg orally once per day, and tumors were assessed every two cycles. The primary endpoint was composite CNS objective response rate (ORR), requiring all of the following: ≥50% reduction in volumetric sum of target CNS lesions and no progression of non-target lesions, new lesions, escalating corticosteroids, progressive neurologic signs/symptoms, or non-CNS progression—the threshold for success was five of 40 responders. Results Forty patients were enrolled between February 2012 and June 2013; 78% of patients had previous whole-brain radiotherapy. Three women achieved a partial response (CNS objective response rate, 8%; 95% CI, 2% to 22%). The median number of cycles received was two (range, one to seven cycles), with a median progression-free survival of 1.9 months. Five women received six or more cycles. The most common grade ≥ 3 event was diarrhea (occurring in 21% of patients taking prespecified loperamide prophylaxis and 28% of those without prophylaxis). Patients in the study experienced a decreased quality of life over time. Conclusion Although neratinib had low activity and did not meet our threshold for success, 12.5% of patients received six or more cycles. Studies

Anti-spasmodic assessment of hydroalcoholic extract and essential oil of aerial part of Pycnocycla caespitosa Boiss. & Hausskn on rat ileum contractions.

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Sadraei, Hassan; Asghari, Gholamreza; Alipour, Mahdi

2016-01-01

Pycnocycla caespitosa is an essential oil-containing plant naturally growing in southwest of Iran. The extract of this plant has been used as remedy in traditional medicine. Another species of Pycnocyla (P. spinosa) possessed antispasmodic activity. The pharmacological objective of this study was to look for relaxant effect of hydroalcoholic extract and essential oil of P. caespitosa on rat isolated ileum contractions for comparison with loperamide. The essential oil and the hydroalcoholic extract were prepared by hydrodistillation and percolation techniques, respectively. For antispasmodic studies a section of rat ileum was suspended in an organ bath containing Tyrode's solution. The tissue was stimulated with electrical field stimulation (EFS), KCl (80 mM) and acetylcholine (ACh 0.5 μM). The tissue was kept under 1 g tension at 37°C and continuously gassed with O2. The essential oil content in the aerial parts of P. caespitosa was found to be 0.16 % ml/g. The essential oil was analyzed by gas chromatography and gas chromatography-mass spectrometry. Seventy constituents, representing 97 % of the oil were identified. The major components of the oil were carvacrol (7.1%), β-eudesmol (6.4 %), ρ-cymene (5.7%), caryophyllene oxide (3.6%), α-pinine (1.4%) and α-phelandrene (1.1%). The hydroalcoholic extract of P. caespitosa inhibited the response to KCl (IC50 = 48 ± 3 μg/ml), ACh (IC50 = 61 ± 14.7 μg/ml) and EFS (IC50 = 77 ± 17 μg/ml) in a concentration-dependent manner. The essential oil of P. caespitosa also inhibited rat ileum contractions. The IC50 values for KCl, ACh and EFS were 9.2 ± 1.2 μg/ml, 7.6 ± 0.8 μg/ml and 6.4 ± 0.8 μg/ml, respectively. The inhibitory effect of both the essential oil and the extract were reversible. This research confirms the anti-spasmodic activity of both the essential oil and the extract of P. caespitosa on smooth muscle contraction of ileum.

Pharmacological profile of DA-6886, a novel 5-HT4 receptor agonist to accelerate colonic motor activity in mice.

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Lee, Min Jung; Cho, Kang Hun; Park, Hyun Min; Sung, Hyun Jung; Choi, Sunghak; Im, Weonbin

2014-07-15

DA-6886, the gastrointestinal prokinetic benzamide derivative is a novel 5-HT4 receptor agonist being developed for the treatment of constipation-predominant irritable bowel syndrome (IBS-C). The purpose of this study was to characterize in vitro and in vivo pharmacological profile of DA-6886. We used various receptor binding assay, cAMP accumulation assay, organ bath experiment and colonic transit assay in normal and chemically constipated mice. DA-6886 exhibited high affinity and selectivity to human 5-HT4 receptor splice variants, with mean pKi of 7.1, 7.5, 7.9 for the human 5-HT4a, 5-HT4b and 5-HT4d, respectively. By contrast, DA-6886 did not show significant affinity for several receptors including dopamine D2 receptor, other 5-HT receptors except for 5-HT2B receptor (pKi value of 6.2). The affinity for 5-HT4 receptor was translated into functional agonist activity in Cos-7 cells expressing 5-HT4 receptor splice variants. Furthermore, DA-6886 induced relaxation of the rat oesophagus preparation (pEC50 value of 7.4) in a 5-HT4 receptor antagonist-sensitive manner. The evaluation of DA-6886 in CHO cells expressing hERG channels revealed that it inhibited hERG channel current with an pIC50 value of 4.3, indicating that the compound was 1000-fold more selective for the 5-HT4 receptor over hERG channels. In the normal ICR mice, oral administration of DA-6886 (0.4 and 2mg/kg) resulted in marked stimulation of colonic transit. Furthermore, in the loperamide-induced constipation mouse model, 2mg/kg of DA-6886 significantly improved the delay of colonic transit, similar to 10mg/kg of tegaserod. Taken together, DA-6886 is a highly potent and selective 5-HT4 receptor agonist to accelerate colonic transit in mice, which might be therapeutic agent having a favorable safety profile in the treatment of gastrointestinal motor disorders such as IBS-C and chronic constipation. Copyright © 2014 Elsevier B.V. All rights reserved.

Antibacterial, antidiarrhoeal, and cytotoxic activities of methanol extract and its fractions of Caesalpinia bonducella (L.) Roxb leaves.

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Billah, Muhammad Mutassim; Islam, Rafikul; Khatun, Hajera; Parvin, Shahnaj; Islam, Ekramul; Islam, Sm Anisul; Mia, Akbar Ali

2013-05-12

Caesalpinia bonducella is an important medicinal plant for its traditional uses against different types of diseases. Therefore, the present study investigated the antimicrobial, antidiarrhoeal, and cytotoxic activities of the methanol extract and ethyl acetate, chloroform, and petroleum ether (pet. ether) fractions of C. bonducella leaves. The antibacterial potentialities of methanol extract and its fractions of C. bonducella leaves were investigated by the disc diffusion method against four gram-positive and five gram-negative bacteria at 300, 500 and 800 μg/disc. Kanamycin (30 μg/disc) was used as the standard drug. Antidiarrhoeal activities of leaf extracts were evaluated at two doses (200 and 400 mg/kg) and compared with loperamide in a castor oil-induced diarrhoeal model in rat. The fractions were subjected to a brine shrimp lethality test to evaluate their cytotoxicity. The methanol extract and other three fractions exhibited better activities at higher concentrations. Amongst, the chloroform fraction showed maximum activity at all three concentrations (300, 500, and 800 μg/disc) against almost all bacteria. S. aureus and P. aeruginosa showed better sensitivities to all extracts at all three concentrations excluding the pet. ether fraction. Bacillus megaterium and Klebsiella spp. were two bacteria amongst nine that showed lowest sensitivity to the extracts. Maximum zone of inhibition (25-mm) was obtained by the methanol extract at an 800 μg/disc concentration against S. aureus. In the antidiarrhoeal test, all fractions exhibited dose-dependent actions, which were statistically significant (p extract and its three fractions compared with the standard drug vincristine sulfate in the brine shrimp bioassay. In the present study, the LC50 values of the methanol crude extract and ethyl acetate, chloroform, pet. ether fractions and vincristine sulfate were 223.87, 281.84, 112.2, 199.53, and 12.59 μg/mL, respectively. Therefore, the ethyl acetate fraction

Inconvenience due to travelers' diarrhea: a prospective follow-up study

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Soonawala Darius

2011-11-01

Full Text Available Abstract Background Limited data exist documenting the degree to which travelers are inconvenienced by travelers' diarrhea (TD. We performed a prospective follow-up study at the travel clinic of Leiden University Medical Center in The Netherlands to determine the degree of inconvenience and to determine how experiencing TD affects travelers' perception. Methods Healthy adults who intended to travel to the (subtropics for less than two months were invited to take part. Participants filled out a web-based questionnaire before departure and after returning home. TD was defined as three or more unformed stools during a 24-hour period. Results 390 of 776 Eligible travelers completed both questionnaires. Participants' median age was 31 years and mean travel duration 23 days. Of 160 travelers who contracted TD (incidence proportion 41%, median duration of TD episode 2.5 days the majority (107/160, 67% could conduct their activity program as planned despite having diarrhea. However, 21% (33/160 were forced to alter their program and an additional 13% (20/160 were confined to their accommodation for one or more daylight days; 53 travelers (33% used loperamide and 14 (9% an antibiotic. Eight travelers (5% consulted a physician for the diarrheal illness. When asked about the degree of inconvenience brought on by the diarrheal illness, 39% categorized it as minor or none at all, 34% as moderate and 27% as large or severe. In those who regarded the episode of TD a major inconvenience, severity of symptoms was greater and use of treatment and necessity to alter the activity program were more common. Travelers who contracted travelers' diarrhea considered it less of a problem in retrospect than they had thought it would be before departure. Conclusion Conventional definitions of TD encompass many mild cases of TD (in our study at least a third of all cases for which treatment is unlikely to provide a significant health benefit. By measuring the degree of

Inconvenience due to travelers' diarrhea: a prospective follow-up study.

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Soonawala, Darius; Vlot, Jessica A; Visser, Leo G

2011-11-20

Limited data exist documenting the degree to which travelers are inconvenienced by travelers' diarrhea (TD). We performed a prospective follow-up study at the travel clinic of Leiden University Medical Center in The Netherlands to determine the degree of inconvenience and to determine how experiencing TD affects travelers' perception. Healthy adults who intended to travel to the (sub)tropics for less than two months were invited to take part. Participants filled out a web-based questionnaire before departure and after returning home. TD was defined as three or more unformed stools during a 24-hour period. 390 of 776 Eligible travelers completed both questionnaires. Participants' median age was 31 years and mean travel duration 23 days. Of 160 travelers who contracted TD (incidence proportion 41%, median duration of TD episode 2.5 days) the majority (107/160, 67%) could conduct their activity program as planned despite having diarrhea. However, 21% (33/160) were forced to alter their program and an additional 13% (20/160) were confined to their accommodation for one or more daylight days; 53 travelers (33%) used loperamide and 14 (9%) an antibiotic. Eight travelers (5%) consulted a physician for the diarrheal illness. When asked about the degree of inconvenience brought on by the diarrheal illness, 39% categorized it as minor or none at all, 34% as moderate and 27% as large or severe. In those who regarded the episode of TD a major inconvenience, severity of symptoms was greater and use of treatment and necessity to alter the activity program were more common. Travelers who contracted travelers' diarrhea considered it less of a problem in retrospect than they had thought it would be before departure. Conventional definitions of TD encompass many mild cases of TD (in our study at least a third of all cases) for which treatment is unlikely to provide a significant health benefit. By measuring the degree of inconvenience brought on by TD, researchers and policy makers

Effective treatment of common variable immunodeficiency associated diarrhea Diarrea asociada a inmunodeficiencia común variable tratada con budesonida

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H. Córdova Guevara

2009-03-01

Full Text Available Common variable immunodeficiency disorder (CVID, the commonest symptomatic primary antibody deficiency syndrome, is characterised by recurrent bacterial infections, particularly of the upper and lower airways; it is also associated with an increased incidence of autoimmune and neoplastic disorders. CVID has a high prevalence of infectious, inflammatory and neoplastic gastrointestinal diseases. Up to 60% of the patients with non-treated CVID develop diarrhea and 10% associated idiopathic malabsorption with weight loss. The case of a 50-year-old woman with CVID-associated diarrhea, abdominal pain and bloating of one year's duration is reported. An exhaustive evaluation made for secondary causes of her symptoms was unrevealing; she was treated with loperamide and diet, without improvement. She later followed a course of oral budesonide for 3 months; her clinical symptoms disappeared and her quality of life improved. In conclusion, we report the case of a patient with CVID-related chronic diarrhea who responded well to oral budesonide treatment. This outcome provides the gastroenterologist with a new therapeutic option in this difficult group of patients.La inmunodeficiencia común variable (IDCV es la deficiencia primaria de anticuerpos sintomática más frecuente y está caracterizada por infecciones bacterianas recurrentes, especialmente de las vías aéreas superiores e inferiores, y también asociada a incremento de enfermedades autoinmunes y neoplasias. Presenta alta prevalencia de enfermedades gastrointestinales infecciosas, inflamatorias y neoplásicas. Hasta el 60% de los pacientes con IDCV no tratados desarrollan diarrea y el 10% desarrollan malabsorción idiopática asociado a pérdida de peso. Presentamos el caso de una mujer de 50 años con IDCV que presenta diarrea crónica, con dolor y distensión abdominal desde hace 1 año. Realizándose múltiples exploraciones y descartando causas secundarias de diarrea crónica, se inicia

Postoperative outcomes and functional results after Deloyer's procedure – a retrospective cohort study

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Noel Salgado-Nesme

2017-04-01

Full Text Available Introduction: The objective of our study was to describe surgical outcomes of Deloyers procedure in our referral center, and to compare the results of patients with and without protective ileostomy. Methods: Patients undergoing a Deloyers procedure from 2013 to 2016 were prospectively included. General characteristics, intraoperative variables, postoperative course, and functional outcomes were analyzed. Patients were compared into two groups: group (1 patients undergoing Deloyers procedure without ileostomy, and group (2 Deloyers procedure with protective ileostomy. Results: Sixteen patients undergoing isoperistaltic transposition of the right colon remnant were included, of which 9 (63% were males with a median age of 47 (range 22–76 years. The main surgical indication was the restoration of bowel transit (62.5%. There was higher major morbidity rate in the Deloyers procedure with protective ileostomy group, but without statistical significance (20% vs. 9%, p = 0.92. No leaks or deaths were reported. The length of hospital stay was 7 days. The mean number of bowel movements per day was 4 at 18 months of follow up. Only four (25% patients used irregularly loperamide. Conclusions: The Deloyers procedure has satisfactory results and is reproducible with low morbidity. The major and minor morbidity rates were similar between groups, suggesting that the costs and risks of a second procedure can be avoided by providing a safe primary anastomosis. Resumo: Introdução: O objetivo de nosso estudo foi descrever os resultados cirúrgicos do procedimento de Deloyer em nosso centro de referência e comparar os resultados de pacientes com e sem ileostomia de proteção. Métodos: Pacientes submetidos ao procedimento de Deloyer de 2013 a 2016 foram incluídos prospectivamente. Foram analisadas as características gerais, as variáveis intraoperatórias, o curso pós-operatório e os desfechos funcionais. Os pacientes foram comparados em dois grupos