Antidiarrheal Research Articles

MECHANISMS OF ANTIDIARRHEAL EFFECT BY PROBIOTICS

Gastroenteritis is a major cause of morbidity and mortality worldwide. Several microbial pathogens cause secretory diarrhea such as Vibrio cholerae and enterotoxigenic Escherichia coli as well as enteric viruses such as Rotavirus (RV) and Norovirus and parasites including Cryptosporidium. Other agents induce inflammatory diarrhea such as Clostridium difficile, Shigella and selected strains of pathogenic E. coli.Gastroenteritis is the result of multiple mechanisms that may mainly be summarized in enterotoxic (secretory diarrhea) or cytotoxic (osmotic diarrhea) as a consequence of ion secretion and epithelial damage, respectively. Other indirect mechanisms of infectious diarrhea include inflammation or altered regulatory processes involving hormones and neurotransmitters.The first‐line treatment of acute gastroenteritis in children is the administration of oral rehydration solution (ORS) but this neither shortens the duration of diarrhea nor reduces the frequency of stool outputs. Therefore, active therapies are now recommended in adjunct to ORS for children with gastroenteritis.The use of the specific probiotic strains, namely Lactobacillus rhamnosus GG (LGG) and Saccharomyces boulardii, is included ESPGHAN/ESPID guidelines for the management of children with AGE as an adjunct to rehydration therapy.Antidiarrheal drugs act at the luminal side of intestinal epithelium and modulate apical pathways, induce ion absorption or limit secretion, influence microbiome, modulate permeability, bind secretory moieties such as enterotoxins or bile acids. Probiotics are not drugs, but are rapidly effective in acute diarrhea reducing its duration and their effects have been linked to intestinal permeability and the modulation of intestinal microbiota and‐ indirectly‐ of inflammation. Those mechanisms are not consistent with the rapid effects of probiotics observed in children with acute diarrhea within hours since their initial administration. Evidence exists in favor of direct effects induced by probiotics on the enterocyte. Saccharomyces boulardii secreted moieties prevented RV‐induced oxidative stress and chloride secretion in human enterocytes. LGG exerted an ion proabsorptive effect through a direct antioxidant mechanisms and also promoted cell growth and differentiation acting on MAPKs. Those data indicate that the rapid and effective clinical effects by probiotics on acute diarrhea are probably the results of the direct microbe‐enterocyte rather than to the microbe‐microbiota or microbe‐immune interaction. This data provide an entirely new scenario for understanding the antidiarrheal mechanisms of probiotics in diarrhea.

Journal Digest

Journal Digest

Investigating a Syndromic Surveillance Signal with Complimentary Data Systems

In early June, the New York City syndromic surveillance system detected five signals in sales of over-the-counter antidiarrheal medications. To determine if this increase reflected a concerning cluster of diarrheal illness, we examined multiple communicable disease surveillance data systems. After further investigation of syndromic and other systems, we determined that findings possibly reflected sales promotions but did not suggest increased diarrheal illness in NYC.

Identifying factors associated with clinical success in patients treated with NASHA(®)/Dx injection for fecal incontinence.

PurposeInjection with the bulking agent consisting of non-animal stabilized hyaluronic acid/dextranomer (NASHA®/Dx) is well tolerated and efficacious for the treatment of fecal incontinence (FI); however, the patient population that may derive maximum benefit has not been established. This post hoc responder analysis assessed demographic and baseline characteristics predictive of responsiveness to NASHA/Dx treatment.MethodsAdults with a Cleveland Clinic Florida fecal incontinence score (CCFIS) ≥10 were randomized to receive NASHA/Dx or sham treatment. The primary end point was response to treatment (ie, decrease from baseline of ≥50% in number of FI episodes) at 6 months; a prespecified secondary end point was change in fecal incontinence quality of life (FIQL) score at 6 months. Post hoc subgroup analyses were performed for baseline and demographic characteristics and prior FI treatments.ResultsOverall, response to treatment was significantly greater with NASHA/Dx versus sham injection (52.7% vs 32.1%; P=0.0089). All subgroups analyzed demonstrated evidence of improvement, favoring NASHA/Dx versus sham treatment for both response to treatment and change in the FIQL coping/behavior subscale score. For the primary end point, a significantly greater percentage of patients with CCFIS ≤15, FI symptoms ≤5 years’ duration, or obstetric causes of FI responded to NASHA/Dx treatment versus patients receiving sham treatment (51.1% vs 28.3%, P=0.0169; 55.4% vs 25.7%, P=0.0026; and 53.6% vs 23.1%, P=0.0191, respectively). The mean change in the FIQL coping/behavior score significantly favored NASHA/Dx versus sham treatment for patients with CCFIS ≤15 (P=0.0371), FI symptoms ≤5 years’ duration (P=0.0289), or obstetric causes of FI (P=0.0384). Patients without a history of specific FI treatments (eg, antidiarrheal medications, biofeedback, surgery) were more likely to respond to NASHA/Dx versus sham treatment for both end points.ConclusionAlthough all subgroups analyzed showed evidence of quantitative and qualitative benefit from NASHA/Dx therapy, patients with characteristics indicative of mild-to-moderate FI may exhibit the greatest benefit.

Phase Ib study of cancer stem cell (CSC) pathway inhibitor BBI-608 administered in combination with FOLFIRI with and without bevacizumab (Bev) in patients (pts) with advanced colorectal cancer (CRC).

569 Background: BBI-608 is an oral first-in-class cancer stemness inhibitor that blocks STAT3-mediated transcription of cancer stemness genes. Potent anti-CSC activity was observed in vitro and in vivo,in mono and combination therapy. In phase I studies, BBI-608 was generally well tolerated with encouraging signs of anti-tumor activity. Methods: A phase Ib open label, multi-center study in pts with advanced CRC was undertaken to confirm the RP2D of BBI-608 in combination with FOLFIRI with or without BEV. BBI-608 was administered at 240 mg BID in combination with FOLFIRI (5-FU 400 mg/m2 bolus with 2400 mg/m2, irinotecan 180 mg/m2, and leucovorin 400 mg/m2infusion) with or without BEV 5 mg/kg, administered bi-weekly until progression of disease, unacceptable toxicity, or other discontinuation criterion was met. Results: 18 heavily pretreated pts with an average of > 3 prior lines of therapy of which 10 pts (56%) previously progressed on FOLFIRI were enrolled. Of the 17 pts evaluable for response, 8 pts received FOLFIRI and 9 pts received FOLFIRI with BEV in combination with BBI-608. Most common adverse events included grade 1 and 2 diarrhea, abdominal pain, nausea, vomiting and anorexia. No dose limiting toxicity or new adverse events were seen, and the safety profile was similar to that of each regimen as monotherapy. Grade 3 events related to protocol therapy included diarrhea occurring in 3 pts, fatigue in 2 pts and dehydration in 1 pt. All events resolved after dose reduction and/or start of anti-diarrheal medications. No significant pharmacokinetic interactions were observed. Disease control (PR+SD) was observed in 16 of 17 evaluable pts (94%) with 2 PR (per RECIST 1.1 criteria: 44% and 33% regression) and 14 SD (of which 13 (93%) had tumor regression < 25%). In the evaluable pts, median progression free survival was 5.54 months. Of 17 pts, 7 (41%) had prolonged SD of > 6 months. Conclusions: This phase Ib study confirmed that BBI-608 at 240 mg bid can be safely combined with FOLFIRI with and without BEV, and shows encouraging anti-tumor activity in heavily pretreated CRC pts, even in pts with prior progression on FOLFIRI-based therapy. Clinical trial information: NCT02024607.

Evaluation of knowledge, attitude, and practice of community pharmacists toward administration of over-the-counter drugs for the treatment of diarrhea in children: A pretest-posttest survey.

Objective:In this study, we aimed to assess knowledge, attitude, and practice of community pharmacists toward administration of over-the-counter (OTC) antidiarrheal drugs in our city pharmacies, Shiraz, Iran.Methods:In this descriptive cross-sectional study, 90 pharmacies among 128 pharmacies in our city were randomly chosen. The study was designed into two phases: A standard questionnaire to determine the level of knowledge and attitude of pharmacists and a simulated client method to evaluate practice among them. An educational pamphlet was then given to the pharmacists. One month later, knowledge, attitude, and performance of studied pharmacists were evaluated again using the same method.Findings:Our results showed that an average consultation time by female pharmacists was considerably more than male pharmacists (P < 0.001). Before intervention, only 37.8% of pharmacists performed appropriately by prescribing the proper medicine while this increased to 58.44% after intervention. The average score of pharmacists’ knowledge was statistically increased (P < 0.001) and the pharmacists’ performance was significantly improved (P < 0.001) after the educational intervention. In related to the attitude, pharmacists’ tendency toward prescribing oral rehydration salt solutions (ORS) (P < 0.001) and their belief about the great effect of ORS on the treatment of diarrhea increased significantly after the intervention.Conclusion:It is concluded that training programs such as educational pamphlets and continuing educational seminars may play important roles in increasing pharmacists’ knowledge and therefore improving their performance in prescribing OTC medicines.

A Comparative study between infant and neonate patient suffering from diarrhea in Dhaka city of Bangladesh

Diarrheal diseases remain important causes of childhood morbidity and mortality in developing countries. Most of the diarrheal diseases in developing countries are symptomatic. For this reason, this study was designed to find out the specific symptoms, treatment pattern and recovery time of the affected children, infant and neonate. A retrospective study was performed on 50 patients suffering from diarrhea. The study period was from January, 2009 - June, 2009 at Institute of Child health of Shishu Sasthya Foundation Hospital, Mirpur-2, Dhaka - 1216. The Information of the anthropometric measurements, type of feeding, duration of diarrhea, number of stools during the last 24 hours, dehydration status etc. were collected from the hospital records. The oral rehydration solution (ORS), antibiotic therapy or antidiarrhoeal drugs were given to the patients having age range 24 months also considered. It was found that among 50 patients, 80% infant was affected by diarrhea. Common symptoms for infants were loose watery stool (84.38%), vomiting (80%), fever (87.5%) and loose motion (81.82%). Most of the infant about 87.5% received antibiotic therapy. The treatment provided other than antibiotic therapy was koloride, NPO (Nothing per oral), ORS (Oral Rehydration Solution) etc. After taking the antibiotic therapies with other treatment, 85% infants and 100% neonates were recovered within 1-3 days. This scenario gives a partial feature of diarrhea disease in developing country like Bangladesh. But the further study is required to find out the full status of the symptomatic childhood diarrhea disease.

Editor's Choice

Eating marshmallows reduces ileostomy output: A randomised crossover trial. Clarebrough E, Guest G, Stupart D. 1 The management of the high output ileostomy remains a challenge – the review by Baker et al in this journal in 2011 remains one of our most downloaded and most cited papers. Some treatments undoubtedly have an excellent evidence base, whereas others have become ingrained within the everyday practice of our specialty but are based on little more than anecdote and folklore. Critically appraising the information given to patients with ostomies for their accuracy is every bit as important as the readability. When evidence is lacking to support the statements made, what should we do? Clarebrough et al have provided the answer – perform the study to answer the question and help eliminate uncertainty. Marshmallows (and related gelatin containing products) have often been advocated by stoma care nurses, gastroenterologists and colorectal surgeons alike. Clarebrough et al designed a randomised crossover trial to assess the effect of marshmallows on stoma output. Importantly, they assessed not only the volume of stoma output but also the patient centred outcomes of number of bag changes and subjective questionnaire assessment of qualitative effluent changes and acceptability for future use. Marshmallows did reduce stoma output, albeit only by a median of 75 ml and the clinical utility of this is uncertain. Perhaps more importantly marshmallows reduced the number of bag changes per day from a median of six to five. What may perturb some is that only seven out of the 28 patients who completed the trial were taking regular antidiarrhoeal medication. Regular loperamide may be far more effective than marshmallow ingestion and better for dental health too. The relatively low proportion of patients taking loperamide may reflect differences in healthcare systems. Nevertheless, we may now have greater confidence when giving dietary advice to reduce stoma output to patients with ileostomies.

Assessment of Prescription of Metronidazole among the Doctors of District Mirpurkhas.

Background: Metronidazole is a Nitroimidazole antibiotic medication used particularly for anaerobic bacteria andprotozoa. It is on the WHO’s list of essential medicines (a list of most important medication needed in a basichealth system)Objectives: Aim was to assess the indications with which metronidazole is being prescribed by the doctors ofMirpurkhas. To set necessary recommendations regarding prescription of drug and emergence of drug resistance. Methodology: A cross sectional study was conducted among the doctors of Mirpurkhas in which pretested questionnaire was distributed to 80 doctors which are practicing in different hospitals of Mirpurkhas.Results: There were 56 medical officers and 24 Postgraduates. 53/80 thought that it was anti diarrheal, 50/80said anti bacterial, 46/80 said anti protozoal, 27/80 said anti helminthic, 12/80 said anti fungal, 6/80 said antiviral,3/80 said mucosal protective agent. 75/80 said that they would prescribe metronidazole in any type of diarrhoea,56/80 said Food poisoning, 29/80 said IBS and amoebiasis, 26/80 anaerobic Bacterial infection, 24/80 IBD, 15/80said intra abdominal infection 12/80 said bacterial septicemia, 7/80 said skin infection, 3/80 Said bones and jointinfection &amp; CNS infection, 1/80 said Trichomoniasis, 1/80 RTI. 43/80 knew the side effects of the drugs (skin allergy, bitter taste, nausea, vomiting, vertigo, constipation) 27/80 didn’t. 39/80 knew about the contraindications(hepatitis, pregnancy, unconsciousness, Constipation), 41/80. Regarding the Substitute of metronidazole 62/80said other antibiotics (Levofloxacin, moxifloxacin) 18/80 said antifungal.Conclusion: This study reflects that there is unnecessary prescription of Metronidazole among the doctors ofMirpurkhas. Most commonly being prescribed for diarrhea, Food poisoning, Amebiasis and IBS. It is critical that27 doctors didn’t know the side effects and 41 were not aware of the contraindications.Key Words: Metronidazole, Antibiotic, Abuse, Diarrhea.

Comparative Antidiarrheal Activity of Three Bangladeshi Medicinal Plants Using in Vivo Animal Model Study

Diarrhea is a worldwide concern. So this study investigated the antidiarrheal effect of methanol extract of leaves of Podocarpus neriifolius D. Don., Mangifera sylvatica Roxb. and Ficus sagittata Vhal. using in vivo animal model. These plants have history of ethnobotanical use. Antidiarrheal effect was assessed in Castor oil induced diarrheal test model in Swiss Albino mice. Lopramide (5 mg/kg) was used as standard drug. The animals were treated with doses of 200 and 400 mg/kg of the plant extracts. All data were analyzed by the software, statistical package for social science (SPSS), Version 18.0. The extracts (200 and 400 mg/kg) showed a remarkable antidiarrheal activity by reducing the number of defecation and maintaining the consistency of faeces. All the extracts significantly (P < 0.001) inhibited the diarrheal incidence at the dose of 200 and 400 mg/kg. Mangifera sylvatica showed the highest percent of inhibition of 72.37% at dose of 400 mg/kg and Ficus sagittata showed the lowest (52.63%) percent of inhibition at dose of 200 mg/kg while the standard Loperamide showed 77.63% of diarrheal inhibition. The results suggest the potentiality of Podocarpus neriifolius, Mangifera sylvatica and Ficus sagittata as antidiarrheal drugs but further investigations are required to find out the exact mechanism of action and the chemicals responsible for the effect.

Electrophysiological Studies into the Safety of the Anti-diarrheal Drug Clotrimazole during Oral Rehydration Therapy.

Background and AimsMorbidity and mortality from acute diarrheal disease remains high, particularly in developing countries and in cases of natural or man-made disasters. Previous work has shown that the small molecule clotrimazole inhibits intestinal Cl- secretion by blocking both cyclic nucleotide- and Ca2+-gated K+ channels, implicating its use in the treatment of diarrhea of diverse etiologies. Clotrimazole, however, might also inhibit transporters that mediate the inwardly directed electrochemical potential for Na+-dependent solute absorption, which would undermine its clinical application. Here we test this possibility by examining the effects of clotrimazole on Na+-coupled glucose uptake.Materials and MethodsShort-circuit currents (Isc) following administration of glucose and secretagogues were studied in clotrimazole-treated jejunal sections of mouse intestine mounted in Ussing chambers.ResultsTreatment of small intestinal tissue with clotrimazole inhibited the Cl- secretory currents that resulted from challenge with the cAMP-agonist vasoactive intestinal peptide (VIP) or Ca2+-agonist carbachol in a dose-dependent fashion. A dose of 30 μM was effective in significantly reducing the Isc response to VIP and carbachol by 50% and 72%, respectively. At this dose, uptake of glucose was only marginally affected (decreased by 14%, p = 0.37). There was no measurable effect on SGLT1-mediated sugar transport, as uptake of SGLT1-restricted 3-O-methyl glucose was equivalent between clotrimazole-treated and untreated tissue (98% vs. 100%, p = 0.90).ConclusionTreatment of intestinal tissue with clotrimazole significantly reduced secretory responses caused by both cAMP- and Ca2+-dependent agonists as expected, but did not affect Na+-coupled glucose absorption. Clotrimazole could thus be used in conjunction with oral rehydration solution as a low-cost, auxiliary treatment of acute secretory diarrheas.

Efficacy of Encapsulated Lactobacillus casei Probiotics as Anti Diarrheal Agent on Sprague Dawley Rats

Efficacy of Encapsulated Lactobacillus casei Probiotics as Anti Diarrheal Agent on Sprague Dawley Rats

Efficacy of the Natural Clay, Calcium Aluminosilicate Anti-Diarrheal, in Reducing Medullary Thyroid Cancer-Related Diarrhea and Its Effects on Quality of Life: A Pilot Study.

Medullary thyroid cancer (MTC)-related diarrhea can be debilitating, reduces quality of life (QOL), and may be the only indication for initiating systemic therapy. Conventional antidiarrheal drugs are not always helpful and may have side effects. Calcium aluminosilicate antidiarrheal (CASAD), a natural calcium montmorrilonite clay, safely adsorbs toxins and inflammatory proteins associated with diarrhea. It was hypothesized that CASAD would reduce the severity of diarrhea and improve QOL in MTC patients. This was a prospective pilot trial (NCT01739634) of MTC patients not on systemic therapy with self-reported diarrhea of three or more bowel movements (BMs) per day for a week or more. The study design included a one-week run-in period followed by one week of CASAD ± a two-week optional continuation period. The primary endpoint was efficacy of one week of CASAD treatment in decreasing the number of BMs per day by ≥20% when compared with the baseline run-in period. Secondary objectives included tolerability and safety and the impact on QOL using the MD Anderson Symptom Inventory-Thyroid questionnaire (MDASI-THY). Ten MTC patients (median age = 52 years, 70% female, 80% white) were enrolled. All had distant metastases, and median calcitonin was 5088 ng/mL (range 1817-42,007 ng/mL). Ninety percent had received prior antidiarrheals, and 40% of these had used two or more drugs, including tincture of opium (30%), loperamide (50%), diphenoxylate/atropine (20%), colestipol (10%), or cholestyramine (10%). Of seven evaluable patients, four (56%) had ≥20% reduction in BMs per day. Six out of seven patients discontinued their prior antidiarrheals. Best response ranged from 7% to 99% reduction in mean BMs/day from baseline. Five out of seven patients considered CASAD a success, and they opted for the two-week continuation period. Improvements in diarrhea and all six interference items assessed by MDASI-THY were noted at weeks 1 and 3. Total interference score was significantly improved at three weeks compared with baseline (p = 0.05). An oral levothyroxine absorption test was performed in one patient; malabsorption of levothyroxine was not observed. Adverse events included flatulence (40%), bloating (10%), heartburn (10%), and constipation (10%). CASAD is a promising strategy for treatment of MTC-related diarrhea. In this small pilot study, improvements in frequency and quality of diarrhea as well as QOL were noted. Further studies in this population are warranted.

Saccharomyces boulardii and bismuth subsalicylate as low-cost interventions to reduce the duration and severity of cholera

We conducted a randomised single-blinded clinical trial of 100 cholera patients in Port-au-Prince, Haiti to determine if the probiotic Saccharomyces cerevisiae var. boulardii and the anti-diarrhoeal drug bismuth subsalicylate (BS) were able to reduce the duration and severity of cholera. Subjects received either: S. boulardii 250 mg, S. boulardii 250 mg capsule plus BS 524 mg tablet, BS 524 mg, or two placebo capsules every 6 hours alongside standard treatment for cholera. The length of hospitalisation plus the number and volume of emesis, stool and urine were recorded every 6 hours until the study subject was discharged (n = 83), left against medical advice (n = 11), or requested removal from the study (n = 6). There were no reported deaths or adverse study-related events. There were no statistically significant differences between the study arms and the outcomes of interest.

Anti-Diarrheal Activity of the Aqueous Leaf Extract of &lt;i&gt;Ageratum Conyzoides&lt;/i&gt; in Wistar Rats

The leaves of Ageratum conyzoides had been reportedly used in traditional medicine in the treatment of diarrhea. Thus its aqueous leaf extract was investigated for its possible anti-diarrheal property using castor oil induced diarrheal, charcoal meal intestinal transit and castor oil-induced enteropooling models in Wistar rats to substantiate its folklore claim. In castor oil induced diarrheal model, 500 mg/kg and 1000 mg/kg body weight doses of the extract showed dose dependent remarkable anti-diarrheal activity evidenced by delay in diarrheal latency, reduction in the rate of defecation and consistency, although it was not comparable to that loperamide which elicited absent of diarrheal. In charcoal meal intestinal transit models, extract doses (500 mg/kg and 1000 mg/kg) also elicited dose dependent anti-diarrheal activity, evidenced by reduction in distance travelled by charcoal meal. Although, it was not also comparable to that of intraperitoneal injection of standard drug, Atropine sulphate at a dose of 0.1 mg/kg body weight. Experimental findings showed that aqueous leaf extract of Ageratum conyzoides possess anti-diarrheal activity and may be a potential source of anti-diarrheal drug in future. Higher doses may possess better anti-diarrhoeal properties.KEY WORDS: Ageratum conyzoides, anti-diarrheal activity, loperamide, castor oil, atropine sulphate. activated charcoal, enteropooling, Wistar rats.

PTU-256 New pelvic radiotherapy techniques do not eliminate gastrointestinal toxicity: Abstract PTU-256 Table 1

Introduction Volumetric Modulated Arc Therapy (VMAT) is a recent technique of external beam radiotherapy. VMAT delivers less radiation dose to the bowel than traditional conformal therapy. This should lessen gastrointestinal (GI) acute toxicity however this has not yet been shown. We aimed to determine the rate of GI toxicity in the treatment of gynaecological malignancy with VMAT. Method This prospective study included patients commencing radiotherapy from December 2013 to July 2014. Patients completed questionnaires prior to commencing radiotherapy, on their final day of treatment (end of week 4) and at 8 weeks (median 57 days) following the end of treatment. The questionnaire used was a validated patient reported questionnaire derived from the CTCAE (Common Terminology Criteria for Adverse Events) grading system. Results See Table 1for patient demographics. All patients had 20 fractions of radiotherapy over 4 weeks with the exception of 1 patient who only completed 17 fractions. Of the 62 eligible patients 57 completed baseline questionnaires, 60 at end of treatment and 50 completed them 8 weeks later. At baseline 32% of patients reported diarrhoea, this rose to 75% at end of treatment and fell to 33% 8 weeks later. In line with this 11% of patients reported taking anti-diarrhoeal medication at baseline, 73% at end of treatment and 14% at the 3 rd time point. Forty percent of patients had grade 3–4 faecal urgency at baseline, 70% at end of treatment and 53% at the 3 rd time point. Grade 3–4 tenesmus was present in 15% at baseline, 27% at end of treatment and 8% 8 weeks later. No patients reported faecal incontinence at baseline. Faecal incontinence of any grade was reported by 29% at end of treatment and by 12% at the 3 rd time point. Patients reported whether difficulty controlling their bowels affected their daily activities. At baseline 2% reported that this was the case compared with 30% at end of treatment and 10% 8 weeks later. Rectal bleeding was reported by 5% at baseline and by 8% at end of treatment and at the 3 rd time point. Conclusion Our data suggest that VMAT does cause acute GI toxicity during radiotherapy treatment although at early follow up much of this has improved. Future work is planned to demonstrate whether VMAT confers benefit over conformal treatment in terms of GI late effects. Disclosure of interest None Declared.

Antidiarrheal activity of fractions from aqueous extract of Detarium senegalense

Summary The aim of this study was to evaluate the effect of different fractions of the aqueous crude extract of Detarium senegalense stem bark on castor oil-induced diarrhea. Castor oilinduced diarrhea, gastrointestinal motility and castor oil-induced enteropooling methods were used to evaluate the antidiarrheal effects of the fractions. Castor oil was used to induce diarrhea and the effect of all the fractions (chloroform, ethyl acetate, n-butanol, methanol and residual aqueous) were evaluated at the doses of 200 and 400 mg/kg body weight. The results show that all fractions significantly (p&lt;0.05) decreased the frequency of defecation in rats following the induction of diarrhea with castor oil. Ethyl acetate which produced the highest antidiarrheal activity was further subjected to gastrointestinal motility and castor oil-induced enteropooling tests. In the gastrointestinal motility, two test doses of the extract (200 and 400 mg/kg) were administered orally to two groups of rats (n=5), while the third group of rats (control), were treated with normal saline, and the fourth group were treated with diphenoxylate, a conventional anti-diarrheal drug. In the castor oil-induced enteropooling experiment, normal saline was used for the control animals, while 200 and 400 mg/kg of the extract was administered to groups two and three, respectively and atropine, a standard drug, was administered to rats in group four. The ethyl acetate fraction significantly (p&lt;0.05) decreased the gastro-intestinal motility, as shown by the extent of movement of the charcoal meal in the treated rats. It also significantly inhibited the fluid accumulation within the intestine. These findings suggest that the ethyl acetate fraction possess antidiarrheal effect, which may be due to the presence of some phytochemical constituents (alkaloids, flavonoids and tannins) in the plant, which may either be working alone or in combination with each other. This study has demonstrated that D. senegalense fractions, especially the ethyl acetate fraction, possess antidiarrheal activity thus supporting the use of the plant in the treatment of diarrheal diseases.

Difference between patients' and clinicians' perception of pouch dysfunction and its impact on quality of life following restorative proctocolectomy.

The Pouch Dysfunction Score (PDS) is a five-item instrument that evaluates bowel function and quality of life following restorative proctocolectomy for ulcerative colitis. The PDS includes items that have a significantly negative impact on quality of life from the patient's point of view. The study aimed to establish how pouch dysfunction is perceived by clinicians in relation to patients experience. Fifty-eight leading clinicians in the field of inflammatory bowel disease were invited to complete two PDS-based exercises. In part 1, they received a list of the 12 bowel symptoms from which the PDS had been developed and were asked to identify and rank (in order of severity) the five they thought had the most significantly negative impact on quality of life. In part 2, they were given the list of symptoms perceived by patients to be most troublesome and were then required to enter a score that they thought was appropriate for each item according to the impact on quality of life. Forty-three clinicians responded, and each correctly identified one to three items selected by patients and included in the PDS. Severity of urgency was selected by 29 (67%) clinicians, and four (9%) rated it to be the most important. Incomplete emptying after defaecation was selected by 10 (23%). Frequency of defaecation and the use of anti-diarrhoeal medication were selected by 14 (33%) and three (7%) clinicians, respectively. Twenty-six (60%) did not include incomplete emptying and 25 (58%) did not include uncontrolled loss of stool in their selection. This study demonstrates that clinicians do not have a great understanding of the symptoms of pouch dysfunction that really matter to the patient.

Bioactive compounds in Magnifera indica demonstrates dose-dependent anti- inflammatory effects

Magnifera indica (MI) is one of the notable medicinal plants use for the treatment of inflammatory diseases in folkloric medicine. Recent studies by present author demonstrated anti-inflammatory effects of Mangifera indica to have dose-dependent effects, pointing out this single effect to be relevant to therapeutics findings. However, as far as we know, Mangifera indica has one or no translational drugs or products already established in clinical trials or pharmaceutical practice. This is rather a concern in drug discovery and optimization, particularly for Magnifera indica plant which has various medicinal efficacies been ascribed to its properties. It has been investigated already that, Mangiferin a very potent bioactive compound found inside extracts of Magnifera indica , being a polyphenolic and a glucosyl xanthone has strong antioxidant and anti-inflammatory properties. Various effects like antibacterial, antipyretic, anti diarrhoeal, anti allergic, immunomodulation, anti microbial, gastroprotective have also been ascribed to medicinal use of Mangifera indica . Other phytochemistry found in Mangifera indica includes; Saponin, tannins, steroids, flavoniod, alkaloids, cardiac glycosides, reducing sugar and anthraquinone. All these have been seen to be useful in herbal medicine and cosmetics. Thus, this paper focus on the need to encourage the lead optimization and to adequately promote further research that will formulate bioactive compounds in Magnifera indica for the purpose of treating inflammatory diseases, and the need to conduct more clinical trials using Mangifera indica bioactive compounds for variety of conditions in human volunteers.

Treatment of Clostridium difficile infection in a French university hospital

The management of Clostridium difficile infection (CDI) has become very daunting over the past decade because of increased incidence and severity both in hospital and the community. Guidelines recommend metronidazole, vancomycin, or fidaxomicin, depending on clinical presentation. Objective. Our objective was to describe CDI management and assess empirical CDI therapy complying with practice guidelines. Methods. We performed a 2-year prospective cohort study in a university teaching hospital in Lyon, France. Criteria assessing the conformity of CDI patient management were: time elapsed between testing and start of treatment specific to CDI, antibiotics to fight CDI and treatment duration according to infection severity, concomitant therapy, and use of antidiarrheal drugs. Results. Among 118 patients with confirmed CDI, 98 (83%) were specifically treated for CDI. Severe CDI was observed in 63 patients (53.9%). Treatment included metronidazole alone in 72 patients (73.5%), vancomycin alone in 1 patient (1%), and both in 25 patients (25.5%). The percentage of CDI treatment compliance with published guidelines in our hospital at the study period varied between 22% and 93%. A total of 16 patients (13.6%) died within 30 days after diagnosis. Death was related to CDI in nine patients (56.3% of deceased cases). Conclusion. This study identified significant gaps in our knowledge of CDI treatment. Increasing disease severity highlights the need to investigate antibiotic treatment in severely ill CDI patients, as data on this group are currently lacking.