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Probiotics have been reported to be associated with the alleviation of constipation. The aim of this study was to detect and determine the effect of Bifidobacterium animalis subsp. lactis MN-Gup (MN-Gup) on the alleviation of constipation in BALB/c mice and humans, and to elucidate the mechanisms underlying its effect by measuring changes in the concentration of short-chain fatty acids and the composition of microbes in human faeces. BALB/c mice were given MN-Gup by gavage for 14 days. On the 8th day of this treatment, constipation was induced by the application of diphenoxylate via gavage. The results showed that MN-Gup significantly decreased the first black stool defecation time, and significantly increased black faecal wet weight, black faecal number and the gastric-intestinal transit rate (P

Background. Maren pills have been used to treat constipation. Aquaporin 3 (AQP3) plays a vital role in regulating water transfer in the colon. It has been reported that the downregulation of AQP3 can regulate liquid water metabolism and intestinal permeability in irritable bowel syndrome (IBS) rats’ colon via NF-κB pathway. In this study, we investigated whether the laxative effect of Maren pills is associated with the regulation of AQP3 and NF-κB signaling pathway in the colon. Methods. The compound diphenoxylate suspension-induced STC rats received Maren pills intragastrically for 1 consecutive week to evaluate the laxative effect of Maren pills involving the regulation of AQP3 and NF-κB signaling pathway. Moreover, human intestinal epithelial cells (HT-29) were treated with drug serum to obtain in vitro data. Results. Our results revealed that treatment with Maren pills increased the stool number, moisture content of feces, and intestinal transit rate in a dose-dependent manner. Maren pills significantly increased the AQP3, fibrosis transmembrane conductance regulator (CFTR), and protein kinase A (PKA) proteins in the colon of rats and in HT-29 cells. Mechanistically, Maren pills obviously inhibited the activation of NF-κB pathway in the colon of rats and in HT-29 cells. Conclusion. These results suggest that the laxative effect of Maren pills is associated with the increased expression of AQP3 by downregulating NF-κB signal pathway.

To observe the effects of electroacupuncture (EA) of different frequencies on transmission function, electromyography, nitric oxide synthase (NOS) content and interstitial cells of Cajal (ICC) expression of colon in rat models with slow transit constipation (STC). Of the 50 healthy male Wistar rats, 10 were randomly selected as a normal group and fed with ordinary diet, and the remaining 40 rats were fed with the diet added with the compound diphenoxylate at a dose of 8 mg/(kg·bw) each day for continuous 120 d. The 40 successfully established STC rat models were randomly divided into a model group, a low-frequency EA group (2 Hz), a high-frequency EA group (100 Hz), and a variable-frequency EA group (2 Hz/100 Hz), with 10 rats in each group. Rats in the normal and the model groups were not given any treatment; the low-frequency EA and the high-frequency EA groups were given EA at Tianshu (ST 25), Zusanli (ST 36) and Zhigou (TE 6) with continuous wave at the designated frequency, and the variable-frequency EA group received sparse-dense wave (2 Hz/100 Hz) EA at the same acupoints, once a day for a total of 15 d. After treatment, the colonic transmission function, electromyography, NOS content and ICC expression (calculated by the difference in the area of the C-kit positive cells) of the rats in each group were measured. For the colonic transmission function, compared with the normal group, the first black stool excretion durations of rats in the other groups were significantly prolonged (all P

Background: Opioid addiction is a serious and growing global concern. Recently, herbal medicine has been popular for the treatment of opioid abusers worldwide. Unfortunately, the adulteration of herbal remedies with undeclared synthetic pharmaceuticals has been reported. In Iran, there are few reports on the adulteration of herbal remedies by synthetic pharmaceuticals sold as opioid addiction treatment. The aim of this study was to analyze herbal products used in opioid addiction treatment for the identification of synthetic pharmaceuticals as adulterants in the remedies.Methods: Forty commonly-used handmade herbal products for the treatment of opioid addiction were collected from herbal shops in Kermanshah (western area of Iran). After organoleptic examinations, the samples were prepared and analyzed by high-performance liquid chromatography and gas chromatography-mass spectrometry for detecting probable synthetic pharmaceutical adulterants.Results: The chromatographic analysis of the samples showed that 90% of the products had at least one undeclared pharmaceutical ingredient as an adulterant. The majority of the samples (n=19, 47.5%) had only one undeclared pharmaceutical. Diphenoxylate (n=24, 39.3%), tramadol (n=16, 26.2), methadone (n=8, 13.2%), and the combination of these drugs were reported as common adulterants. We detected the presence of buprenorphine and sildenafil as adulterating agents in the herbal formulations for the first time.Conclusion: According to the presence of undeclared synthetic pharmaceuticals in opioid addiction herbal products, as well as their threats to public health, awareness, in this case, is necessary.

Introduction Herbal medicines are used to address some of the problems experienced by individuals addicted to drugs, but there are also many reports about the adulteration of products sold as medicinal herbs for addiction treatment or opioid withdrawal. The aim of the present study was to explore the products sold as herbal medicines by herbal remedy shops in Iran. Method Fifty samples of medicinal herbs were collected from herb shops located in different parts of Iran. Samples were coded according to their brand name and included: Dragon tablets, Deta capsules, compound capsules and Vincamin DF. Samples were transferred to the toxicology laboratory of the Medical Jurisprudence Organization of Mashhad and the samples were analyzed for their physical and chemical properties. Results Out of the samples, 74% contained illegal or chemical drugs. In most of the counterfeit samples, we found a high dose of tramadol, methadone, and diphenoxylate. In some samples, small amounts of nicotine, barbiturate, acetaminophen, diclofenac, lysergic acid diethylamide, diphenhydramine, codeine were detected. An investigation of the physical properties (smell) indicated the presence of fragrant compounds in some samples such as ginger, Peganum harmala, and pepper. Conclusions Nearly all of the handmade and illegally distributed herbal medicines for the treatment of drug withdrawal contained at least one opioid or illegal drug, indicating that there was evidence of adulteration and highlighting the dangers to users. It is important to raise awareness of people, particularly warning them against the use of such products sold by herbal shops for the treatment of addiction.

Poisoning is a type of accidental injury and it is considered a major public health problem worldwide. Oral drug poisoning in children is an important cause of accidental injury and even death. It is a common critical emergency in the field of pediatrics. Once a child unintentionally takes an overdose, regardless of whether it caused poisoning or not, they should be admitted to the hospital for emergency treatment. Acute poisoning in children most frequently occurs through the digestive tract. Drug poisoning can happen in children of all ages. In children younger than 1 year, drug poisoning is mostly caused by the parents during feeding, while in children aged 1–3 years, it predominantly occurs as a result of an accident. A case of diagnosis and treatment of a child with diphenoxylate-atropine poisoning is reported herein. The early manifestation of this child was acute toxic encephalopathy with clinical manifestations of a coma, convulsions, and respiratory depression. A brain MRI showed extensive damage to the bilateral caudate nucleus, lenticular nucleus, parietal lobe, precuneus lobe, and occipital lobe. Accidental administration of a large dose of diphenoxylate results in severe clinical symptoms and can cause obvious diffuse brain damage.

Slow transit constipation (STC) has become an epidemic medical problem. There are several kinds of drugs for constipation; however, each drug has its limitations. The gut microbiota has a close relationship with STC. Lactulose is an effective drug for constipation because it is a kind of bulking laxative and microbioecologic, and it relieves the syndromes of STC. We found that the Chinese Herb Solid Drink (CHSD), which contains medicine food homologous materials such as psyllium husk, sweetalmond, semen sesami nigrum, and hemp seed, has a similar effect on relieving constipation as lactulose, although it has different effects on the gut microbiota. We investigated the mechanisms of CHSD in rats with STC, induced by diphenoxylate, via constipation index and enzyme linked immunosorbent assay (ELISA) analyses using serum and 16S rDNA amplicon and gas chromatography-mass spectroscopy (GC-MS). CHSD enhanced the relative abundance of some types of gut microbiota, such as Blautia, Ruminococcus, Roseburia, Coprococcus, Lachnospira, and Phascolarctobacterium, while lactulose enhanced the relative abundance of Blautia, Phascolarctobacterium, Eubacterium, and Akkernansia in diphenoxylate-induced STC rats. Both CHSD and lactulose enhanced the level of short-chain fatty acids in the faeces of rats; however, the composition of those were different between the two drugs. From the perspective of the gut neuroendocrine system, both CHSD and lactulose could elevate neurotransmitters, such as motilin (MTL) and substance P (SP), which promote intestinal peristalsis and reduce the expression of vasoactive intestinal peptide, which inhibits intestinal peristalsis in the serum of STC rats. CHSD could elevate gastrin expression, which also promoted intestinal peristalsis in serum, while lactulose did not have this effect. Our findings suggest that CHSD may be an effective and safe therapeutic choice for STC.

Constipation is characterized by reduced number of bowel movements, dry stools, and difficult defecation. Yangyin Tongmi capsule (YTC), a traditional Chinese formula, is used in the treatment of constipation, while the underlying mechanisms remain unknown. Herein, this work attempted to prove the effects of YTC on constipation treatment and its possible mechanisms. KM mice were randomly divided into four groups (n = 10/group) and treated with double distilled water (Control), diphenoxylate (Model: 10 mg/kg), or diphenoxylate plus low-dose YTC (L-YTC: 0.6 g/kg) or high-dose YTC (H-YTC: 1.2 g/kg). The data indicated that YTC can significantly shorten the discharge time of the first black stool, improve intestinal propulsion rate, and increase the water content and quantity of feces in mice. ELISA suggested that YTC regulate the content of intestinal hormones and neurotransmitters, such as motilin (MTL), gastrin (GT), somatostatin (SST), substance P (SP), acetylcholine (Ach), and nitric oxide (NO). The expression levels of aquaporin 3 (AQP3) and aquaporin 8 (AQP8) in the colon were examined by immunohistochemistry. In the meantime, the expression levels of P2X2, C-kit, and stem cell factor (SCF) in the colon were examined by western blot analysis. The results of this study suggest that YTC has mitigative effects on diphenoxylate-induced constipation by regulating the content of intestinal hormones and neurotransmitters and regulating the expression of related proteins in the colon.

Objective To explore the short and long-term efficacy of combining electroacupuncture (EA) and Qibei mixture in the treatment of irritable bowel syndrome (IBSD). Methods Six hundred and forty-four patients with confirmed IBSD from the Department of Gastroenterology, the First Affiliated Hospital of Xinxiang Medical University in China, recruited from July 2012 to June 2016, were randomly divided into four groups, the EA group, Qibei mixture group, combination group and medication group with 161 patients in each group. The patients in the EA group were treated with EA at zusānlǐ (足三里ST36), Gān shu (肝俞BL18), Pǐshu (脾俞BL20), Taichōng (太冲LR36) and Qizhōngsibiān (脐中四边) once daily for 4 weeks, while the patients in the Qibei mixture group were treated with 50 mL of Qibei mixture twice daily, the combination group with the above-mentioned EA and Qibei mixture, and the medication group with 1 tablet compound diphenoxylate twice, 3 g montmorillonite powder three times and 25 mg amitriptyline twice daily. The defecation frequencies, stool properties, accompanying symptom score, life quality score and adverse reactions were recorded pre-treatment, at the end of treatment and 6 weeks post-treatment for the four groups. Results Compared with pre-treatment, the defecation frequencies, stool property score and accompanying symptom score were all decreased significantly at the end of treatment in each group (all P 0.05), but these indices all recurred significantly in the group given Qibei mixture and the medication group (P Conclusion EA and Qibei mixture can decrease defecation frequencies, improve stool properties, and alleviate accompanying symptoms to increase life quality, but the therapeutic effect of combination therapy is greater, with better reliability and long-term efficacy.

Background: Substance abuse is among the main causes of preventable diseases and premature deaths worldwide. Despite legal efforts to prevent substance abuse, it has increased and imposed significant economic costs on societies. This analytical cross-sectional study aimed to explore the rate of substance abuse-induced mortality in the provinces of Iran, in 2017. We elaborated an evaluation structure to identify nationwide different substance abuse-related mortality rates. Methods: We employed the retrospective data extracted from autopsy, forensic medicine examination, and demographic characteristics from the recordings in the Iranian Legal Medicine Organization (ILMO). Stata and ArcGIS were applied for data analysis. Results: Nationwide, 3089 substance abuse-related deaths were recorded in the ILMO; the incidence rate was 38.17 per million subjects. The deaths mostly occurred in the 30-39 age group and males accounted for 90% of cases. The provinces of Kermanshah, Lorestan, Fars, Hamadan, and Semnan reported significantly higher rates, compared with the provinces of Mazandaran, West-Azerbaijan, and Golestan with the lowest mortality rates per million (74.72, 69.81, 63.42, 61.70, 58.53 vs. 10.82, 12.11, 14.30, respectively). Mortality rates due to the abuse of methadone (20.29), morphine (12.34), amphetamine (5.32), methamphetamine (7.05), codeine (4.21), tramadol (5.96), benzodiazepine (1.47), and diphenoxylate (0.05) were calculated per million populations of Iran.Conclusion: The obtained data suggested that preventive interventions should focus on the 20-40 age group. Methadone, morphine, and methamphetamine were associated with the highest mortality, compared to other substances; thus, they require effective treatment and preventive programs. Iranian Drug Control Headquarters, police department, and policymakers should act more efficiently regarding a preventive strategic plan in this respect.

Acute noninfectious diarrhea is a common phenomenon in intensive care unit patients. Multiple treatments are suggested but the most effective management is unknown. A working group of the Eastern Association for the Surgery of Trauma, aimed to evaluate the effectiveness of loperamide, diphenoxylate/atropine, and elemental diet on acute noninfectious diarrhea in critically ill adults and to develop recommendations applicable to daily clinical practice.The literature search identified 11 randomized controlled trials (RCT) appropriate for inclusion. The Grading of Recommendations Assessment, Development, and Evaluation methodology was applied to evaluate the effect of loperamide, diphenoxylate/atropine, and elemental diet on the resolution of noninfectious diarrhea in critically ill adults based on selected outcomes: improvement in clinical diarrhea, fecal frequency, time to the diarrhea resolution, and hospital length of stay.The level of evidence was assessed as very low. Analyses of 10 RCTs showed that loperamide facilitates resolution of diarrhea. Diphenoxylate/atropine was evaluated in three RCTs and was as effective as loperamide and more effective than placebo. No studies evaluating elemental diet as an intervention in patients with diarrhea were found.Loperamide and diphenoxylate/atropine are conditionally recommended to be used in critically ill patients with acute noninfectious diarrhea.Systematic Review/Guidelines, level III.

Mulberry (Morus atropurpurea) has long been used to treat gastro-intestinal ailments; however, the functional basis of its therapeutic effects remains unclear. The aim of this study was to measure the effects of mulberry (administered by gavage) on diphenoxylate-induced constipation in mice and elucidate the mechanisms underlying these effects using constipation and physicochemical indexes, histological morphology and 16S rDNA amplicon analysis of fecal microbiota. Sixty Kunming mice were randomly divided into the following six groups (n = 10 per group): normal control, constipation model, positive control, and low-, mid- and high-dose mulberry groups. After 14 days of treatment, constipation was induced over 5 days and measurements were conducted. The results show that mulberry treatment prevented constipation by increasing the fecal water content, shortening the first red fecal defecation time, promoting gastric evacuation, and increasing the gastric-intestinal transit rate (P < 0.05). Compared with the constipation model group, the mulberry-treated groups showed decreased aquaporin gene expression (Aqp3, Aqp4, Aqp8 and Aqp9), decreased serum levels of inhibitory neurotransmitters (nitric oxide and vasoactive intestinal peptide) (P < 0.05), and increased serum levels of excitability neurotransmitters (acetyl choline, substance P, and motilin). The histological morphology of the colon showed that mulberry treatment increased the number of mucus cells (P < 0.05). Mulberry treatment also increased the concentrations of acetic, propionic, butyric, valeric and isovaleric acids (P < 0.05), increased the abundance of Lactobacillus and Bifidobacterium in feces, and decreased the abundance of Helicobacter and Prevotellaceae in feces. Our findings indicate that mulberry consumption effectively prevents constipation in mice and is a promising therapeutic candidate for constipation.

BACKGROUND: Pharmacologic therapies for management of heroin withdrawal have been studied and reviewed widely. Opium dependence is generally associated with less severe dependence and milder withdrawal symptoms than heroin. The evidence on withdrawal management of heroin might therefore not be exactly applicable for opium. OBJECTIVES: To assess the effectiveness and safety of various pharmacologic therapies for the management of the acute phase of opium withdrawal. SEARCH METHODS: We searched the following sources up to September 2017: CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, regional and national databases (IMEMR, Iranmedex, and IranPsych), main electronic sources of ongoing trials, and reference lists of all relevant papers. In addition, we contacted known investigators to obtain missing data or incomplete trials. SELECTION CRITERIA: Controlled clinical trials and randomised controlled trials on pharmacological therapies, compared with no intervention, placebo, other pharmacologic treatments, different doses of the same drug, and psychosocial intervention, to manage acute withdrawal from opium in a maximum duration of 30 days. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 13 trials involving 1096 participants. No pooled analysis was possible. Studies were carried out in three countries, Iran, India, and Thailand, in outpatient and inpatient settings. The quality of the evidence was generally very low. When the mean of withdrawal symptoms was provided for several days, we mainly focused on day 3. The reason for this was that the highest severity of opium withdrawal is in the second to fourth day. Comparing different pharmacological treatments with each other, clonidine was twice as good as methadone for completion of treatment (risk ratio (RR) 2.01, 95% confidence interval (CI) 1.69 to 2.38; 361 participants, 1 study, low‐quality evidence). All the other results showed no differences between the considered drugs: baclofen versus clonidine (RR 1.06, 95% CI 0.63 to 1.80; 66 participants, 1 study, very low‐quality evidence); clonidine versus clonidine plus amantadine (RR 1.03, 95% CI 0.86 to 1.24; 69 participants, 1 study); clonidine versus buprenorphine in an inpatient setting (RR 1.04, 95% CI 0.90 to 1.20; 1 study, 35 participants, very low‐quality evidence); methadone versus tramadol (RR 0.95, 95% CI 0.65 to 1.37; 1 study, 72 participants, very low‐quality evidence); methadone versus methadone plus gabapentin (RR 1.17, 95% CI 0.96 to 1.43; 1 study, 40 participants, low‐quality evidence), and tincture of opium versus methadone (1 study, 74 participants, low‐quality evidence). Comparing different pharmacological treatments with each other, adding amantadine to clonidine decreased withdrawal scores rated at day 3 (mean difference (MD) ‐3.56, 95% CI ‐5.97 to ‐1.15; 1 study, 60 participants, very low‐quality evidence). Comparing clonidine with buprenorphine in an inpatient setting, we found no difference in withdrawal symptoms rated by a physician (MD ‐1.40, 95% CI ‐2.93 to 0.13; 1 study, 34 participants, very low‐quality evidence), and results in favour of buprenorpine when rated by participants (MD ‐11.80, 95% CI ‐15.56 to ‐8.04). Buprenorphine was superior to clonidine in controlling severe withdrawal symptoms in an outpatient setting (RR 0.35, 95% CI 0.19 to 0.64; 1 study, 76 participants). We found no difference in the comparison of methadone versus tramadol (MD 0.04, 95% CI ‐2.68 to 2.76; 1 study, 72 participants) and in the comparison of methadone versus methadone plus gabapentin (MD ‐2.20, 95% CI ‐6.72 to 2.32; 1 study, 40 participants). Comparing clonidine versus buprenorphine in an outpatient setting, more adverse effects were reported in the clonidine group (1 study, 76 participants). Higher numbers of participants in the clonidine group experienced hypotension at days 5 to 8, headache at days 1 to 8, sedation at days 5 to 8, dizziness and dry mouth at days 1 to 10, and nausea at days 1 to 9. Sweating was reported in a significantly higher number of participants in the buprenorphine group at days 1 to 10. We found no difference between groups for all the other comparisons considering this outcome. Comparing different dosages of the same pharmacological detoxification treatment, a high dose of clonidine (1 to 1.2 mg/day) did not differ from a low dose of clonidine (0.5 to 0.6 mg/day) in completion of treatment in an inpatient setting (RR 1.00, 95% CI 0.84 to 1.19; 1 study, 68 participants), however a higher number of participants with hypotension was reported in the high‐dose group (RR 3.25, 95% CI 1.77 to 5.98). Gradual reduction of methadone was associated with more adverse effects than abrupt withdrawal of methadone (RR 2.25, 95% CI 1.02 to 4.94; 1 study, 20 participants, very low‐quality evidence). AUTHORS' CONCLUSIONS: Results did not support using any specific pharmacological approach for the management of opium withdrawal due to generally very low‐quality evidence and small or no differences between treatments. However, it seems that opium withdrawal symptoms are significant, especially at days 2 to 4 after discontinuation of opium. All of the assessed medications might be useful in alleviating symptoms. Those who receive clonidine might experience hypotension.

The effect of bisacodyl on the treatment of rats with slow transit constipation (STC) was studied. Forty-five female Wister rats were divided into control group, STC group, and STC bisacodyl group. The immunohistochemical method was used to determine interstitial cells of Cajal (ICC) and the expression of c-Kit protein. Body mass and the number of defecations were significantly decreased in the STC group compared with the control group on the 100th day after diphenoxylate administration, while dry weight of feces was significantly increased and the intestinal transit time was prolonged. There were significant differences in the number of defecations, dry weight of feces, and intestinal transit time among the three groups. The number of defecations was higher, dry weight of feces was lower, and intestinal transit time was shorter in the STC bisacodyl group compared to the STC group. In addition, ICC basement membrane dissolution occurred in the colon wall of the STC group. The connection between ICC and surrounding cells was destroyed, and the nucleus shrunken to different degrees. Moreover, c-Kit expression in the STC group was significantly lower than the control group. The connection between ICC and surrounding cells in the STC bisacodyl group was significantly stronger than the STC group, and the number of ICC and the expression of c-Kit were increased. Bisacodyl could reduce the severity of STC in rats by increasing the number of ICC and the expression of c-Kit.

Objectives Constipation can adversely affect children's health, with disorders of host immunity and enhanced oxidative stress. As nondigestible carbohydrates, prebiotics can affect the host with constipation; however, whether the prebiotics have effects on the content of intestinal secretory immunoglobulin A (sIgA) and the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in constipation has not been fully clarified. Methods In the present study, constipation was induced in female Sprague-Dawley rats by diphenoxylate, and the prebiotics dissolved in milk were used as an intervention. The indicators of intestinal peristalsis, including the time of passing black stool initially, the grains of black stool in 24 hours, and the advance rate of ponceau, were measured. The content of intestinal sIgA was detected by enzyme-linked immunosorbent assay. The contents of SOD and MDA in serum and intestinal tissue were analyzed by their detection kits. Results The changes in intestinal peristalsis show obvious constipation. The content of intestinal sIgA decreases, the content of SOD decreases, but the content of MDA increases in constipated rats. Prebiotics can attenuate the constipation-caused abnormal indicators significantly. Conclusions Prebiotics can attenuate decreased intestinal immunity and enhanced oxidative stress, in addition to reduced intestinal peristalsis and of the constipated rats.

Aim: To assess the efficacy of a probiotic preparation on the prevention of radiation-induced diarrhoea in cancer patients.Methods: Group of 42 radio-oncology patients who had undergone adjuvant post-operative radiation therapy (RT) after abdominal and pelvic cancer were randomised to receive either the probiotic preparation “5” Strain Dophilus (twice per day; L-Group), or the preparation Hylak Tropfen Forte (40 drops, three times per day; H-Group). Supplementation started on the first day and lasted until the end of RT. Efficacy endpoints were the incidence and the severity of the radiation-induced diarrhoea. All patients received a paper form in which they recorded monitored parameters on a daily basis during RT.Results: The mean daily number of bowel movements during the whole period was 4.16 in the L-Group and 2.52 in the H-Group; 62.5% of patients in L-Group and 81% in H-Group had a mean daily number of bowel movements of ≤4/day. Abdominal pain was recorded in 25% of the patients in L-Group and 22% of the patients in H-Group. Blood in the bowel movement was found in one patient from H-Group (9 days). Of patients in L-Group, 27% required diphenoxylate treatment during pelvic radiotherapy, compared with 55% in H-Group. Of patients from L-Group, 9% required antibiotics administration, compared with 25% in H-Group.Conclusion: We concluded that the prophylactic probiotic therapy produced a highly favourable benefit/risk ratio. Supplementation with the probiotic preparation is an easy and safe approach to protect cancer patients from the risk of radiation-induced diarrhoea and carry out improvement in their quality of life.

OBJECTIVES: The aim of the present study was to investigate the effect of an antidiabetic polysaccharide (IJP) from Inula japonica on gastrointestinal transit in normal mice and on constipation in two models of constipated mice. METHODS: Two models of constipation in mice were respectively induced by fasted water for 4 days or induced by diphenoxylate. The normal and constipated mice were administered IJP once at doses of 100 and 400 mg/kg (p.o.), the gastrointestinal vermicular motion, start time of defecation, number and weight of stool were investigated. RESULTS: After administration of IJP, the gastrointestinal propulsive rate was increased by 9.79% and 10.42%, the start time of defecation was shortened by 37.27% and 44.06%, the number of feces increased by 115.4% and 130.8% in normal mice. In fasting-water constipated mice, the start time of defecation was shortened by 9.69% and 30.52% by IJP, defecation granules raised by 22.09% and 39.53%, wet feces weights were increased by 23.50% and 39.14% compared with the untreated constipated mice. In diphenoxylate-induced mice, the start time of defecation was shortened by 25.48% and 28.13%, defecation granules raised by 100.0% and 118.0%. CONCLUSIONS: Consumption of IJP effectively improved bowel movement, stool output observed in this study. IJP may be practical in relieving constipation in the elderly diabetic population. Copyright © 2010 John Wiley & Sons, Ltd.

Loperamide was compared double-blind with diphenoxylate and a placebo in 59 women with diarrhoea due to prostaglandin administration for mid-trimester abortion. Treatment was started with the intake of two capsules two hours before the first intramuscular injection of 15(S-)15 methyl prostaglandin F2alpha and was then adapted individually, i.e. one capsule after each unformed stool, with a maximum of ten per 24 hours. Both antidiarrhoeals were significantly more effective than the placebo in preventing diarrhoea, and loperamide was found to be more active than diphenoxylate. The course of abortion, BP and vital signs, or prostaglandin side-effects other than diarrhoea were not affected by either antidiarrhoeal, nor could any adverse experience be specifically attributed to them.

The objective of this study was to measure the anticholinergic activity (AA) of medications commonly used by older adults. A radioreceptor assay was used to investigate the AA of 107 medications. Six clinically relevant concentrations were assessed for each medication. Rodent forebrain and striatum homogenate was used with tritiated quinuclidinyl benzilate. Drug-free serum was added to medication and atropine standard-curve samples. For medications that showed detectable AA, average steady-state peak plasma and serum concentrations (C(max)) in older adults were used to estimate relationships between in vitro dose and AA. All results are reported in pmol/mL of atropine equivalents. At typical doses administered to older adults, amitriptyline, atropine, clozapine, dicyclomine, doxepin, L-hyoscyamine, thioridazine, and tolterodine demonstrated AA exceeding 15 pmol/mL. Chlorpromazine, diphenhydramine, nortriptyline, olanzapine, oxybutynin, and paroxetine had AA values of 5 to 15 pmol/mL. Citalopram, escitalopram, fluoxetine, lithium, mirtazapine, quetiapine, ranitidine, and temazepam had values less than 5 pmol/mL. Amoxicillin, celecoxib, cephalexin, diazepam, digoxin, diphenoxylate, donepezil, duloxetine, fentanyl, furosemide, hydrocodone, lansoprazole, levofloxacin, metformin, phenytoin, propoxyphene, and topiramate demonstrated AA only at the highest concentrations tested (patients with above-average C(max) values, who receive higher doses, or are frail may show AA). The remainder of the medications investigated did not demonstrate any AA at the concentrations examined. Psychotropic medications were particularly likely to demonstrate AA. Each of the drug classifications investigated (e.g., antipsychotic, cardiovascular) had at least one medication that demonstrated AA at therapeutic doses. Clinicians can use this information when choosing between equally efficacious medications, as well as in assessing overall anticholinergic burden.

Objective: To investigate the effects of acupuncture on constipation in rats. Method:Compound diphenoxylate was used to set up rat model of constipation. After needling "Hegu"and "Housanli", the time to first bowel movement, and stool grains quantity and weight in 12 rats were observed. Results: The time to first bowel movement was delayed, and the stool grains quantity and weight were reduced in the model rats. Acupuncture could significantly shorten the time to first bowel movement, and increase stool grains quantity and weight.Conclusion: Acupuncture can improve the defecating abilities in rats model of constipation.

Fecal incontinence is a common clinical problem that often is frustrating to the patient and treating physician. Nonsurgical management for fecal incontinence includes dietary manipulation, Kegel exercises, perianal skin care, and biofeedback therapy. Pharmacotherapies often are used to assist in management of fecal incontinence. A variety of pharmacotherapies have been utilized for the management of fecal incontinence; limited data from randomized, placebo-controlled trials are available. This is a review of the existing literature on clinical trials of several classes of drugs and other medical therapies that may be beneficial for patients with fecal incontinence. The information in this article was obtained by a MEDLINE search for all clinical trials of drug therapy for fecal incontinence. These treatments and the existing data on their use are summarized. Treatments reviewed include stool bulking agents, with an emphasis on the most promising effect obtained with calcium polycarbophil, constipating agents, including loperamide, codeine, amitriptyline, atropine, and diphenoxylate agents injected into the anal sphincter, drugs to enhance anal sphincter function, including topical phenylepherine and oral sodium valproate, and trials of fecal disimpaction. A new classification to easily remember the treatment categories for this condition, based on the "ABCs of treatment for fecal incontinence," has been introduced into the structure of this review.

Background: Lomotil (diphenoxylate atropine combination) has been in use as an antidiarrhoeal agent. Due to presence of opioid (diphenoxylate), there are chances of abuse. The reports of abuse of lomotil have been few in published literature. This chart review aimed to evaluate the characteristics of patients with dependence on lomotil coming to our centre. Materials and Methods: This retrospective chart review was conducted at the Drug De-addiction and Treatment Centre of PGIMER, Chandigarh, India. The records of patients who had presented to the centre with dependence on Lomotil in the last five years were identified, and clinical details were extracted from the records. Results: We identified 41 patients who had presented to our centre with dependence upon lomotil as the primary substance of abuse. The cases were typically married and employed males, educated up to 10 th grade, belonging to a rural Sikh extended or joint family. Most of the patients had taken other opioids too. The number of tablets taken in a day varied from 3- to 250 (median 25). The reasons of initiation were to relieve withdrawals, as a cheap substitute opioid, curiosity, and on suggestion of friends. Conclusion: Lomotil is a medication with a potential of abuse and regulatory controls are required to prevent escalation of misuse of this easily available prescription drug. Lomotil (diphenoxylate and atropine combination) has been used since a long time as an anti-diarrheal agent. Reports of abuse of diphenoxylate had surfaced. We present a series of 41 cases of opioid dependence presenting with the use of the diphenoxylate as the primary substance. The cases were typically married and employed males, educated up to 10 th grade, belonging to a rural Sikh extended or joint family. Most of the patients had taken other opioids too. The number of tablets taken in a day varied from 3 to 250 (median 25). The reasons of initiation of diphenoxylate were to relieve withdrawals, as a cheap substitute opioid, curiosity, and suggestion of friends. Regulatory controls are needed to prevent escalation of use of this easily available prescription opioid.

Objectives To describe the dietary and pharmacologic management of acute CTID. Data sources Primary and secondary literature, and clinical experience. Conclusion When dietary strategies do not work, or when patients present with grade 3/4 diarrhea, pharmacologic intervention is required. First-line therapy should be initiated quickly with loperamide or diphenoxylate/atropine in recommended doses. Somatostatin analogues are effective as second-line therapy or as first-line therapy for patients with grade 3/4 diarrhea. Implications for nursing practice Oncology nurses should strive to match treatment with the severity of symptoms of CTID. Whatever therapy is chosen, the goal must be to quickly control this debilitating and potentially life-threatening side effect so that primary chemotherapy and/or radiation therapy may be resumed and completed.

Water channels play important role in colon, and might be involved in constipation disease. To understand the mRNA expression changes of aquaporin protein 1 and 7 (AQP1, AQP7) in a rat model of slow transit constipation (STC), a rat model of slow transit constipation was designed, and the correlated changes of aquaporin protein 1 and 7 at the mRNA level were examined. The rat model of slow transit constipation was produced with diphenoxylate administration. The mRNA expression of AQP1 and 7 from STC rats and control rats were examined with reverse transcription polymerase chain reaction (RT-PCR). AQP1 was expressed in ascending and descending colon of both control and STC rats. For the ascending colon, the AQP1 grayscale ratio in control and STC rats were 0.602 ± 0.239 and 0.344 ± 0.212 (P 0.05), respectively in descending colon. AQP7 was also expressed in ascending and descending colon of both control and STC rats, with 0.776 ± 0.642 and 0.764 ± 0.147 in ascending colon (P > 0.05), and 0.736 ± 0.42 and 0.759 ± 0.629 in descending colon (P > 0.05), respectively. We did not examine the changes of the AQPs at the protein level. The downregulation of AQP1 rather than AQP7 might be involved in the development and progression of STC. Key words: Aquaporin protein, AQP1, AQP7, slow transit constipation, mRNA.

Background: Diarrheal diseases cause significant morbidity in developing countries and are the leading cause of death in children. The study was undertaken to assess drug utilization patterns in patients with gastroenteritis in a private setting.Methods: The in-patient data records of 208 patients (96 males, 112 females) admitted with acute gastroenteritis in a private hospital in Mumbai over 2 years were analysed. WHO core drug prescribing indicators - average number of drugs per prescription, percentage of drugs prescribed by generic name, percentage of encounters resulting in prescription of an antibiotic, percentage of encounters resulting in prescription of an injection were assessed. Patient demographics and trends in use of antibiotics, antiemetics and antidiarrheals were assessed.Results: The average total number of drugs prescribed per patient was 6.33 and average number of antibiotics was 1.61. 99% of drugs were prescribed using brand names. Percentage of encounters resulting in prescription of injection was 97.11%. Cephalosporins were the most commonly used group of antimicrobials (62.5%) followed by fluroquinolones (49.03%) and antiamoebic drugs (35.58%). Diphenoxylate was the most commonly prescribed antidiarrheal drug and ondansetron was the most commonly prescribed antiemetic agent. Cephalosporins were the most commonly used antimicrobials in patients diagnosed with enteric fever.Conclusions: Emperical irrational use of antibiotics was observed. There was paucity of stool culture for identification of causative agents. Review of antibiotic susceptibility patterns needs to be done on a regular basis. Educational programmes to reinforce the need for ORS and zinc supplementation are necessary.

Case Study Mr. D., a 55-year-old male, presented to the medical oncology service with a diagnosis of stage III adenocarcinoma of the sigmoid colon. He presented 7 weeks post sigmoid colectomy with lymph node resection and was initiated on adjuvant chemotherapy with CAPOX (capecitabine [Xeloda] and oxaliplatin [Eloxatin]). Standard dosing was used: oxaliplatin at 130 mg/m(2) on day 1 and capecitabine at approximately 2,000 mg/m(2)/day (rounded to the nearest 500-mg tablet size) for 14 days on and 7 days off (1 cycle = 21 days). A capped body surface area of 2.4 m2 was used, due to the patient's body habitus. Adverse Effects Mr. D. did not report any complications of therapy during cycle 1, days 1-7, other than grade 1 diarrhea, which was amenable to diphenoxylate/atropine when taken. The next week, he reported significant malaise and fatigue associated with persistent diarrhea occurring every 30 minutes for 5 days. Mr. D. was instructed to go to the emergency room for an immediate evaluation, but he refused. Mr. D. presented to the clinic in poor condition on day 14 of cycle 1. His diarrhea had increased to grade 3 and was not controlled with either loperamide or diphenoxylate/atropine, though he was not taking his medications as directed. He had been instructed to take two 2-mg loperamide tablets after the first loose stool, followed by 1 tablet of diphenoxylate/atropine 2 hours later. He could then alternate this with loperamide every 2 hours as needed, not to exceed 8 tablets of loperamide per day. Instead, he had taken 2 tablets of loperamide after the first loose stool, but either waited 6 hours to take 1 tablet of diphenoxylate/atropine or otherwise chose not to alternate the medications at all despite continued diarrhea, depending on the day. Mr. D.'s timing in taking his supportive medications was inconsistent, and his explanations of this timing were not exact. He also reported persistent grade 3 nausea with vomiting for 5 days, which did not improve with ondansetron and prochlorperazine, though he again did not take these consistently. He was advised to alternate ondansetron and prochlorperazine every 4 hours as needed, but only took one or the other medication approximately 3 times per day. According to Mr. D., his adverse effects initially began on day 9 of cycle 1. He had lost approximately 14 kg (31 lb) during cycle 1. Clinically, he was found to have grade 2 mucositis and grade 1 hand-foot syndrome. At the time of this visit, his absolute neutrophil count was 3,000/iL, his hemoglobin was 14.4 g/dL, his hematocrit 42.2%, and his platelet count was 139,000/iL. His kidney function was within the normal range. Mr. D. refused hospitalization despite the primary team's recommendation. He also refused to undergo stool sampling for Clostridium difficile. He was given IV fluids along with adjustments in supportive medications, including a prescription for 10% tincture of opium. He was instructed to use 0.6 mL every 6 hours in addition to alternating loperamide with diphenoxylate/atropine as noted previously. He was advised to rinse his mouth with a baking soda solution for relief of his grade 1 mucositis, and alternation of antiemetics every 4 hours was reiterated. He was to return prior to initiation of cycle 2 for further evaluation. Worsening Symptoms The next day, Mr. D.'s wife called the clinic to report that her husband's diarrhea continued despite the use of tincture of opium and that it was associated with hematochezia. He was also experiencing a worsening of his mucositis, with an associated swelling of the tongue. He was instructed to present to the emergency center, which he did on day 16 of cycle 1. By then, he was found to be febrile at 39.5°C. He was tachycardic, with a heart rate of 126, and he was experiencing significant abdominal pain associated with the diarrhea. The mucositis was worsening, with new odynophagia. At this time, Mr. D.'s absolute neutrophil count had dropped dramatically to 160/iL, his hemoglobin was 13.1 g/dL, his hematocrit was 39.2%, and his platelet count was 68,000/iL. He was admitted to the inpatient service and started on empiric antibiotics. His blood cultures remained negative during hospitalization, but stool cultures were positive for C. difficile. His antimicrobial regimen was deescalated to oral vancomycin once his stool volume decreased. He was treated with an institutional compounded mouthwash of diphenhydramine, aluminum/magnesium hydroxide, and viscous lidocaine for the mucositis, which also slowly improved. He was given a dose of growth factor. Neutropenia eventually resolved, with an absolute neutrophil count of 4,820/iL on the day of discharge. He was discharged 26 days after initiating cycle 1, at which time his myelosuppression and mucositis were also resolved. Throughout his course, he did not report any neurotoxicity. DPD Testing Due to his severe symptoms of neutropenia, mucositis, and diarrhea, Mr. D. was tested for dihydropyrimidine dehydrogenase (DPD) deficiency. Testing confirmed a heterozygous IVS14+IG>A mutation. For this reason, all further adjuvant therapy was withheld, and he was followed on clinical surveillance only.

Presentation of Case A 74-year-old woman was admitted to the hospital because of diarrhea and fever followed by multiple cranial-nerve palsies. She had a one-week history of fever (temperature, 40°C), watery diarrhea, nausea, abdominal pain, weakness, and fatigue. Her physician prescribed diphenoxylate hydrochloride–atropine sulfate. At 9 p.m. on the day before admission, the patient was speaking normally. She later applied a benzocaine–eugenol preparation to her gingiva because of several hours of dental pain. At 3 a.m. on the next day, her speech became severely slurred. The patient was taken to another hospital. She was able to drink water and to . . .

Presentation of Case A 70-year-old man was admitted to the hospital because of polyarthritis. The patient had been well until 13 days earlier, when he began a 3-day course of treatment with cefixime because of a root-canal operation. Watery diarrhea developed four days later. He took diphenoxylate and then flew to Europe for a one-week vacation. Mild diarrhea continued. Five days before admission, while the patient was still on vacation, his left knee became stiff, painful, and swollen. The next day, these symptoms were worse, and chilliness and night sweats developed. He began a two-day course of treatment with azithromycin. . . .

Background Faecal incontinence (leakage of bowel motions or stool) is a common symptom which causes significant distress and reduces quality of life. Objectives To assess the effects of drug therapy for the treatment of faecal incontinence. In particular, to assess the effects of individual drugs relative to placebo or other drugs, and to compare drug therapy with other treatment modalities. Search methods We searched the Cochrane Incontinence Group Specialised Register of Trials, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and MEDLINE in process, and handsearching of journals and conference proceedings (searched 21 June 2012) and the reference lists of relevant articles. Selection criteria All randomised or quasi-randomised controlled trials were included in this systematic review. Data collection and analysis Two review authors independently screened abstracts, extracted data and assessed risk of bias of the included trials. Main results Sixteen trials were identified, including 558 participants. Eleven trials were of cross-over design. Eleven trials included only people with faecal incontinence related to liquid stool (either chronic diarrhoea, following ileoanal pouch or rectal surgery, or due to use of a weight-reducing drug). Two trials were amongst people with weak anal sphincters, one in participants with faecal impaction and bypass leakage, and one in geriatric patients. In one trial there was no specific cause for faecal incontinence. Seven trials tested anti-diarrhoeal drugs to reduce faecal incontinence and other bowel symptoms (loperamide, diphenoxylate plus atropine, and codeine). Six trials tested drugs that enhance anal sphincter function (phenylepinephrine gel and sodium valproate). Two trials evaluated osmotic laxatives (lactulose) for the treatment of faecal incontinence associated with constipation in geriatric patients. One trial assessed the use of zinc-aluminium ointment for faecal incontinence. No studies comparing drugs with other treatment modalities were identified. There was limited evidence that antidiarrhoeal drugs and drugs that enhance anal sphincter tone may reduce faecal incontinence in patients with liquid stools. Loperamide was associated with more adverse effects (such as constipation, abdominal pain, diarrhoea, headache and nausea) than placebo. However, the dose may be titrated to the patient's symptoms to minimise side effects while achieving continence. The drugs acting on the sphincter sometimes resulted in local dermatitis, abdominal pain or nausea. Laxative use in geriatric patients reduced faecal soiling and the need for help from nurses. Zinc-aluminium ointment was associated with improved quality of life, with no reported adverse effects. However, the observed improvement in quality of life was seen in the placebo group as well as the treatment group. It should be noted that all the included trials in this review had small sample sizes and short duration of follow-up. 'Risk of bias' assessment was unclear for most of the domains as there was insufficient information. There were no data suitable for meta-analysis. Authors' conclusions The small number of trials identified for this review assessed several different drugs in a variety of patient populations. The focus of most of the included trials was on the treatment of diarrhoea, rather than faecal incontinence. There is little evidence to guide clinicians in the selection of drug therapies for faecal incontinence. Larger, well-designed controlled trials, which use the recommendations and principles set out in the CONSORT statement, and include clinically important outcome measures, are required.

Objective: To describe the effect of low-dose subcutaneous octreotide on refractory diarrhea associated with capecitabine. Case Summary: A 67-year-old white woman with recurrent metastatic breast cancer received monotherapy with capecitabine after failing docetaxel. The first 2 consecutive capecitabine cycles were well tolerated. The patient, however, developed severe watery diarrhea after the third cycle. Diphenoxylate, atropine, loperamide, and attapulgite, along with conventional supportive measures, did not significantly improve the diarrhea, resulting in prolonged hospitalization. Octreotide 100 μg every 8 hours was administered subcutaneously. Immediate relief in stool frequency was observed during the first day. The stool became more formed on the next day. The patient was ready for discharge after learning how to perform subcutaneous injections. Octreotide was continued at home for 3 more days. After discontinuation of octreotide, no recurrent diarrhea occurred. Capecitabine was not reinitiated. Discussion: Diarrhea is a potentially life-threatening complication from treatment with capecitabine, an oral fluoropyrimidine analog. Octreotide has shown efficacy for diarrhea from many conditions, including chemotherapy with irinotecan and intravenous fluoropyrimidines such as fluorouracil. Our report suggests that octreotide also is effective for diarrhea associated with capecitabine. The patient's rapid response shortened her hospital stay and improved her quality of life. Conclusions: In our patient, subcutaneous octreotide, along with other conventional antidiarrheal therapies, was associated with rapid resolution of refractory diarrhea attributed to capecitabine.

Background Constipation is a very common health problem in the world. Intake of sufficient amount of dietary fibers is a cornerstone in the prevention and treatment of constipation. As a traditional medicine, flaxseed has been used to treat constipation for centuries, but the controlled trials are rare. The purpose of the present study was to assess that whether partially defatted flaxseed meal (PDFM) has the potential role to facilitate fecal output in normal and experimental constipated mice. Methods After supplemented with 2.5%, 5% and 10% (w/w) PDFM (L-, M- and H -PDFM) for 14 days, the constipation models of mice were induced by atropine-diphenoxylate. The small intestinal transit rates, start time of defecation, amount of defecation and wet weight of feces were researched in normal and constipation model mice. Results M- and H-PDFM significantly increase small intestinal transit rates in constipation model mice. All dose of PDFM markedly shortened the start time of defecation and M- and H-PDFM significantly increase stool frequency and weight in both normal and constipation model mice. Conclusions PDFM may be a useful laxative to facilitate fecal output in normal and constipation conditions.

The hypertonicity of liquid medications must be evaluated in conjunction with the required dosage volume. Some medications require a minimal dosing volume and can be adequately diluted in gastric fluids or tube-flush volumes to a tolerable osmotic load. Other medications such as diphenoxylate, loperamide, and paregoric have a pharmacologic influence on motility and can be administered undiluted into the small bowel. Still others can require dilution to a final volume of 4 to 10 oz to reduce osmolality to a level tolerable by the GI tract. Bolus administration of a large volume of medication is impractical for many patients, especially if it must be administered three or four times a day. For these patients, an alternate route of drug administration is often preferable. In some instances, the IV route is most appropriate. In others, crushing the appropriate oral form, mixing it in a slurry with a suitable diluent, and administering the slurry through the feeding or NG tube can be an acceptable alternative. Regardless of the method of drug delivery, one must be cognizant of the limitations of the administration strategy, the potential for complications that can result from the administration of a medication by the enteral route, and alternative means of medication administration, should complications ensue. A vast number of pharmaceutical products are marketed in a wide array of dosage forms. For these reasons, a pharmacist or other knowledgeable healthcare provider should be consulted for information regarding product availability, bioavailability, compatibility, and potential for drug-nutrient interactions when drugs are given in conjunction with enteral feeding.

Antidiarrhoeal activities of Aqueous extract of Occimum. Gratissimum leaves in rats were evaluated. These studies were carried out to determine the folkoric medicinal values of the plant leaves. Extraction of crude extract was done using standard method. LD50 was determined using the Locke Dietrich Method. Antidiarrhoeal activities of the extract were carried out using albino rats. It was observed that the aqueous extract of O. gratissimum showed no protective effects against castor oil induced diarrhea when compared with the standard drug, diphenoxylate. The extract showed some antibacterial activities in vitro. Therefore the extract possesses antidiarrhoeal property as accorded to it by ethnomedicine and that justifies the folkore use of the Ocimum gratissimum in the treatment of diarrhea.

Antimicrobial and antimotility agents are not recommended for the treatment of Shiga toxin-producing Escherichia coli O157 infection. In our study, many persons with Shiga toxin-producing E. coli O157 infection took antimicrobial (62%) and antimotility agents (32%); 43 (29%) of 146 reported commencing antimicrobial treatment after laboratory confirmation. Efforts are needed to promote practice guidelines.

Although oral rehydration and antimicrobials constitute the main therapy of bacterial diarrheas, symptomatic relief is also important to patients. Combinations of antibacterials and anti-diarrheals have been shown to be of value in such patients. This multicentric, open study involving medical practitioners in India evaluated Lomofen®, a combination of furazolidone (FRZ) and diphenoxylate (DPH), in 681 patients with bacterial diarrhea. The median dose of Lomofen used was 6 tablets/day. Each tablet contained 2.5 mg of DPH, 0.025 mg of atropine sulfate, and 50 mg of FRZ. Of the 403 patients evaluable for efficacy, 93.05% obtained complete symptomatic relief at the end of 3 days of treatment. These patients also showed relief of accompanying symptoms (ie, abdominal cramps, nausea, and vomiting). Only 41 (6%) of the total 681 patients reported side effects; the most commonly reported side effects were abdominal distention (1.62%), nausea (1.32%), and dryness of mouth (1.32%). This study indicates that an antidiarrheal/antibacterial drug combination can be used safely in adults as an adjunct to rehydration therapy in the treatment of bacterial diarrhea.

A 31-year-old man was hospitalized for evaluation of chronic diarrhea accompanied by profound dehydration, abdominal pain, nausea, vomiting, and low-grade fever. He had been identified as hepatitis B surface antigen-positive in 1983 and HIV antibody-positive two years later. In 1987, after a diagnosis of Pneumocystis carinii pneumonia, he had been placed on zidovudine and prophylactic pentamidine. Subsequently, thrush developed, which was treated with nystatin. The patient's gastrointestinal symptoms were of about six months' duration and originally had responded fairly well to diphenoxylate. More recently, however, he had been losing weight steadily and had required emergency room rehydration on two occasions. A search for stool ova and parasites and routine enteric pathogens, conducted by the outpatient department, had revealed Cryptosporidium cysts.

Recently, we have studied the pathophysiological significance of H 2 S in the gastrointestinal diseases such as slow transmit constipation, intestinal I/R injury, abdominal infection, and omental arteries of human. We applied in vitro vascular ring tension measurement techniques by the means of measuring the tension of H 2 S and NO effects on human omental arteries ring tension, to reach the aims of exploring Regulation of H 2 S and NO in the blood vessels of adult omentum. The results showed that H 2 S and NO can relaxed human omental arteries with concentration-dependent; We also explore the possible relationship between H 2 S and the pathology of slow transmit constipation. We compound Diphenoxylate to set up the mice models of STC, and recorded the area under the curve (AUC) of spontaneous contractions and contraction frequency after drug additional to study the contraction of colonic tissues in vitro. The evidences showed that H 2 S has an obvious effect on colon smooth muscle contraction, and can increase the intestinal movements in slow transmit constipation. Our experiment states that H 2 S has anti-inflammation effect in prophase of acute peritoneal cavity infection. We used cecal ligation and puncture (CLP) to make up the rat models of acute peritoneal cavity infection, gave them different dispose include giving the donor of H 2 S, then observed the contents of TNF- α and H 2 S in serum and the content of MPO in intestinal tissues. And stated that H 2 S could alleviated CLP-induced inflammation obviously, decreased the content of TNF- α in serum when inflammation, and attenuate the infiltration of neutrophilic granulocyte in small intestine.

Purpose Compound diphenoxylate (diphenoxylate–atropine) poisoning can cause toxic encephalopathy in children, and magnetic resonance imaging (MRI) of the brain in this condition has not been reported. This study is to analyze brain MRI findings and to investigate the relations between MRI features and possible pathophysiological changes in children. Methods Six children accidentally swallowed compound diphenoxylate, 4 males, 2 females, aged 20–46 months, average 33 months. Quantity of ingested diphenoxylate–atropine was from 6 to 30 tablets, each tablet contains diphenoxylate 2.5 mg and atropine 0.025 mg. These patients were referred to our hospital within 24 h after diphenoxylate–atropine ingestion, and underwent brain MRI scan within 24–72 h after emergency treatment. The characteristics of conventional MRI were analyzed. Results These pediatric patients had various symptoms of opioid intoxication and atropine toxicity. Brain MRI showed abnormal low signal intensity on T1-weighted images (T1WI) and abnormal high signal intensity on T2-weighted images (T2WI) and fluid-attenuated inversion recovery (FLAIR) imaging in bilateral in all cases; abnormal high signal intensity on T1WI, T2WI and FLAIR in 4 cases. Encephalomalacia was observed in 3 cases during follow-up. Conclusion In the early stage of compound diphenoxylate poisoning in children, multiple extensive edema-necrosis and hemorrhagic-necrosis focus were observed in basic nucleus, pallium and cerebellum, these resulted in the corresponding brain dysfunction with encephalomalacia. MRI scan in the early stage in this condition may provide evidences of brain impairment, and is beneficial for the early diagnosis, treatment and prognosis assessment.

Introduction: The crude extract of the plant Zingiber officinale has a high folkloric reputation for anti-diarrhea activity. This study investigated the scientific basis of this folkloric claim. Materials and Methods: Diarrhea was induced in albino mice and albino wistar rats using Castor-oil. The animals (mice) were offered the acetone extracts of the plant at 20 and 40mg/kg body weight. The albino rats (wistar) received water dose extracts of the plant. The level of protection offered by the extracts was compared with a standard anti-diarrhea agent (Diphenoxylate). The effect of the extract on the intestinal motility was also investigated. Results: The crude extract of Z. officinale produced a comparatively high protection against castor oil- induced diarrhea in rats relative to the positive control animals that were treated with diphenoxylate. The extract shows a reduction in the transit time of ingested charcoal indicating a reduction in the intestinal motility. Conclusion: The crude extract of Z. officinale showed a promising anti-diarrhea activity. Inhibition of the intestinal motility by the extract may underlie the observed anti-diarrhea action but previous reports show that the extracts have anti-microbial action as well. High secretions largely underlie the pathophysiology of diarrhea. Keywords : Zingiber officinal, anti-diarrhea, rodents Tropical Journal of Medical Research Vol. 12 (1) 2008: pp.18-21

SUMMARY Individualization of treatment for patients with IBS is predicated on a thorough analysis of the patient's symptoms, consideration of the reasons for seeking health care, evaluation of symptom-precipitating factors, elimination of confounding features, and the absolute knowledge of the absence of organic illness. Collecting and codifying appropriate historical data allow the physician to educate the patient with respect to the origin of his symptoms, and to enlist the patient as a partner in his future health care. There is no single, universally accepted therapeutic agent available for the treatment of the IBS patient. As a result, treatment is directed at reducing the frequency and intensity of triggering factors as well as ameliorating the symptoms when they arise. Symptoms evoked by psychologic factors may be effectively reduced by psychotherapy or hypnotherapy. Situational anxiety may be treated for brief periods by using antianxiety agents such as diazepam, chlordiazepoxide, buspirone, or similar agents. Depressive reactions may be reduced with suitable doses of antidepressant agents such as amitriptyline. Smooth muscle hyperreactivity may be dulled with small amounts of selected anticholinergics, which are usually most effective in reducing mealinduced discomfort. Peppermint oil may be of additional benefit. Gas-related symptoms require elimination of contributory dietary factors, such as lactose-containing foods, sorbitol, or fructose, as well as certain oligosaccharides. Simethecone, charcoal, or beanase may be helpful. Functional constipation is best treated with graded doses of insoluble or soluble fiber. Diarrheal episodes may be reduced with either loperamide or diphenoxylate. Careful, continued follow-up assessment of therapeutic endeavors, a sincere interest in the patient's concerns, and surveillance for intercurrent organic illness are the cornerstones of complete ongoing care.

Rhus semialata Murr. (Anacardiaceae) is a deciduous tree of north eastern India. The fruit of this plant is traditionally used to control diarrhoea and dysentery. The Present study was undertaken to evaluate anti-diarrhoeal potency of methanol extract of fruits of R. semialata using Wister albino rats to substantiate folklore claims. The extract at graded doses (100, 200, 400 and 600 mg/kg body weight) was investigated for anti-diarrhoeal activity in term of reduction in the rate of defecation in castor oil induced diarrhoea. To understand the mechanism of its anti-diarrhoeal activity, the gastrointestinal transit and PGE2-induced intestinal fluid accumulation (enteropooling) were further evaluated. At graded doses, the extract showed a remarkable anti-diarrhoeal activity evidenced by the reduction in the rate of defecation up to 80.70 % of control diarrhoeal animals at the dose of 600 mg/kg body weight. Results are comparable to that of standard drug diphenoxylate (50 mg/kg body weight). Extract produced profound decrease in intestinal transit (8.02 – 47.05 %) at selected doses comparable to that of single intraperitoneal injection of standard drug atropine sulphate at doses of 0.1 mg/kg body weight. It significantly inhibited PGE2 -induced enteropooling (21.98 – 56.03 %). The results indicated that the methanol extract of the fruits of R. semialata possesses significant anti-diarrhoeal effect and substantiated the use of this herbal remedy as a non-specific treatment for diarrhoea in folk medicine.

Background AIDS-related diarrhoea is a common cause of morbidity and mortality in HIV positive individuals, especially in the sub-Saharan Africa where 70% of deaths from HIV occur. It often compromises quality of life both in those receiving antiretroviral therapy (ART) and the ART naive. Empirical antidiarrhoeal treatment may be required in about 50% of cases which are non-pathogenic or idiopathic and in cases resulting from antiretroviral therapy. Antimotility agents (Loperamide, Diphenoxylate, Codeine) and adsorbents (Bismuth Subsalicylate, Kaolin/Pectin, Attapulgite) are readily available, and have been found to be useful in this condition and so, are often used. Antimotilitics are opioids, decreasing stool output by reducing bowel activity thereby increasing fecal transit time in the gut, promoting fluid and electrolyte retention while adsorbents act by binding to fluids, toxins and other substances to improve stool consistency and eliminate the toxins. Due to its potential impact on the management of chronic diarrhoea in persons with HIV/AIDS, we reviewed the effectiveness of antimotility agents in controlling chronic diarrhoea in immunocompromised states caused by HIV/AIDS. Objectives To assess the effectiveness of antimotility agents in controlling chronic diarrhoea in people with HIV/AIDS. Search strategy We searched Medline, EMBASE, the Cochrane Controlled Trials Register, the Cochrane HIV/AIDS Register and AIDSearch databases in November 2006. We also contacted WHO, CDC, pharmaceutical companies and experts in the field for information on previous or on-going trials and checked reference list from retrieved studies, irrespective of language and publication status. Selection criteria Randomised controlled trials comparing an antimotility agent or an adsorbent with another antimotility agent, placebo, an adsorbent or no treatment in children and adults diagnosed with HIV and presenting with diarrhoea of three or more weeks duration. Data collection and analysis Two authors independently undertook study selection and examined full articles of potentially eligible studies. Main results One trial was found assessing the use of an adsorbent (attapulgite) compared to a placebo for chronic diarrhoea in people with HIV/AIDS. It included 91 adults (Aged 18 to 60), diagnosed with AIDS and experiencing diarrhoea for at least 7 days. There was no evidence that attapulgite is superior to placebo in controlling diarrhoea by reducing stool frequency and normalising stool consistency on days 1 (0.34 (95% CI 0.01 - 8.15)), 3 (1.35 (95% CI 0.51 - 3.62)) and 5 (1.74 (95% CI 0.89 - 3.38)). This was a small trial and may not have had enough power to show evidence of effects. Five deaths were reported which was not classified according to the arms of the study.Studies assessing the use of antimotility agents were not found. Authors' conclusions This review highlights the absence of evidence for the use of antimotility agents and adsorbents in controlling diarrhoea in people with HIV/AIDS. While no trials assessing the use of Antimotilitics were found, the retrieved study showed that attapulgite was not better than placebo in controlling diarrhoea in HIV/AIDS patients . For optimum patient care, these agents can still be used, with greater emphasis placed on adjunct therapies like massive fluid replacement while evidence for practice is awaited from further studies and reviews.

Physiologic uptake of 2-[(18)F]-fluoro-2-deoxy-D: -glucose (FDG) by bowel can confound positron emission tomography/computed tomography (PET/CT) assessment for abdominal pathology, particularly within the bowel itself. We wished to determine if oral administration of the antimotility agent, Lomotil (5 mg diphenoxylate hydrochloride/0.05 mg atropine sulfate; G.D. Searle and Company, a division of Pfizer), prior to PET/CT scanning would reduce physiologic uptake of FDG by the small bowel and colon (lower gastrointestinal [GI] tract).Patients undergoing PET/CT scans for lymphoma were enrolled in a prospective, randomized, double-blinded study and received either 10 mL water (control group) or 10 mL Lomotil (experimental group) orally 30-60 min prior to scanning. Scans were reviewed independently by two blinded experienced readers and scored for the degree of FDG activity in the lower GI tract relative to liver activity.The administration of Lomotil prior to PET/CT scanning did not reduce physiologic FDG activity in the small bowel and colon. In contrast, increased radiotracer uptake by the lower GI tract was observed in the Lomotil group compared to the control group.Pretreatment with Lomotil prior to PET/CT scanning confers no benefit toward the reduction of physiologic FDG uptake by the small bowel and colon.

Drug treatment of gastrointestinal diseases, which was previously limited to the use of antacids, anticholinergics, antispasmodics, cathartics and laxatives, has changed markedly over the past decade. Histamine H2-receptor antagonists (e.g. cimetidine, ranitidine and more recently famotidine and nizatidine) have revolutionised the treatment of peptic acid disorders, but their role is currently challenged by muscarinic-M1-receptor antagonists (e.g. pirenzepine), proton pump inhibitors (e.g. omeprazole), prostaglandin analogues and site-protective drugs (e.g. colloidal bismuth subcitrate and sucralfate). Newer anti-emetics with prokinetic properties (e.g. metoclopramide, domperidone and cisapride) have also been introduced in the management of gastrointestinal motility disturbances, and new anti-inflammatory salicylates (e.g. olsalazine and mesalazine) have been developed for the treatment of chronic inflammatory bowel diseases. Finally, diphenoxylate and loperamide have gained wide clinical application as nonspecific antidiarrhoeal agents. The basic pharmacokinetic properties of the above agents are briefly reviewed with the main emphasis on the newer and more important drugs in current use. Furthermore, the effects of age and disease on pharmacokinetics, in addition to drug interaction potentials and pharmacokinetic-pharmacodynamic relationships, are discussed. The anti-inflammatory salicylates, nonspecific antidiarrhoeal agents, laxatives and cathartics will be dealt with in Part II.

Loperamide is a safe and effective antidiarrheal for the treatment of acute diarrhea. Efficacy data suggest that loperamide is more effective than the prescription drug diphenoxylate and an over-the-counter bismuth subsalicylate preparation. Loperamide is a safe drug, with few adverse reactions reported worldwide. It also lacks significant abuse potential. Loperamide may prove to be the antidiarrheal agent of choice when compared with currently available nonprescription treatments for acute diarrhea.

Chemotherapy-induced diarrhea (cid) is a common side effect of cancer treatment and can cause significant morbidity and mortality. Diarrhea is frequently severe enough to require a dose reduction of, a delay in, or a discontinuation of chemotherapy. Diarrhea-associated mortality has been reported to be as high as 3.5% in clinical trials of irinotecan and bolus 5-fluorouracil in colorectal cancer. The frequency of cid and its impact on patient management are frequently under-recognized in clinical practice. A Canadian working group, consisting of medical oncologists and an oncology pharmacist, was formed in 2001 to review the optimal approach to managing cid and to identify and implement new areas of research. The recommendations that follow are the result of the group’s work. Acute medical management of cid includes loperamide or diphenoxylate as first-line agents. Subcutaneous octreotide is recommended for intractable grade 2 diarrhea and may be considered for grade 1 cid that does not resolve with high-dose loperamide. Hospitalization is recommended for patients with grades 3 and 4 cid; in-hospital care includes rehydration, antibiotic therapy, and octreotide. A chemotherapy dose reduction is generally advised for patients who have experienced grade 3 or 4 diarrhea in a previous chemotherapy cycle. If a dose reduction is not desired, prophylaxis with intramuscular long-acting release octreotide may be considered. The foregoing recommendations are based on expert opinion and require validation in prospective clinical trials.