Gastrointestinal Transit Test Research Articles

Recurrent spontaneous pneumoperitoneum secondary to intestinal dilatation caused by allied disorders of Hirschsprung’s disease: a case report

BackgroundAllied disorders of Hirschsprung’s disease (ADHD) mainly present with bowel obstruction, intestinal dilatation, and chronic constipation, while recurrent spontaneous pneumoperitoneum was rarely reported. We aimed to report a case of recurrent spontaneous pneumoperitoneum caused by ADHD.Case presentationA 59-year-old female patient presented with progressive and severe constipation in the past 30 years. She suffered from abdominal discomfort, which was described as ‘gurgling’ during the last three years. Radiography showed free-air and intestinal dilatation, without any other diseases, and she was identified with recurrent spontaneous pneumoperitoneum. Gastrointestinal transit test indicated gastrointestinal motility disorder, and anorectal manometry confirmed the presence of rectal anus-suppressing reflex. Subtotal colectomy was performed to relieve apparent constipation, and the postoperative pathological examination of the colon demonstrated proliferation of nerve fibers and hyperplasia of myenteric plexuses, as well as a relatively scarcity of ganglion cells in the myenteric plexus. Based on the presentations and the postoperative pathology, she was diagnosed with ADHD. The recurrent spontaneous pneumoperitoneum was regarded as the gas escape from dilated intestines, which was in high pressure. All the symptoms and her mental state were improved after the treatment with gastrointestinal decompression and enteral nutrition. However, during follow-up visits, she had intestinal infection, and suffered from severe diarrhea and water-electrolyte imbalance, and the patient eventually died at 17 months after the diagnosis.ConclusionADHD could be a rare cause of recurrent spontaneous pneumoperitoneum, and are mainly undiagnosed or misdiagnosed. A full-thickness biopsy of the gastrointestinal tract (especially the small intestine and sigmoid colon) and differential diagnosis are recommended for the definitive diagnosis. While the ADHD have shown a poor prognosis, timely and long-term treatment with intestinal decompression and nutritional therapy could help relieve symptoms and provide a better quality of life for such patients.

Effect of Aqueous Ethanol Stem Extract of Entada africana Guill. Et Perrott. on Castor Oil and Magnesium Sulphate-Induced Diarrhoea Models in Mice

This study investigated the phytochemical, elemental analysis, acute toxicity study of aqueous ethanol stem bark extract of Entada africana, as well as its antidiarrhoeal activity in mice and its effects on isolated rabbit jejunum. The preliminary phytochemical screening revealed the presence of alkaloids, flavonoids, cardiac glycosides, phenols, saponins, steroids, tannins and terpenoids. Elemental analysis of the extract showed the presence of magnesium (Mg), manganese (Mn), iron (Fe), copper (Cu), lead (Pb), zinc (Zn) and sodium (Na) while acute toxicity study revealed intraperitoneal median lethal dose (LD50) values for the extract to be 774.6 mg/kg body weight. The antidiarrheal effect of the extract was studied using castor-oil and magnesium sulphate induced diarrhoeal models (dropping test) and gastrointestinal transit test in mice. The result showed that the extract produced a dose-dependent protection against diarrhoea induced by castor oil and magnesium sulfate, with the highest protection (80 and 100%), obtained at 100 and 200 mg/kg. The extract significantly (p≤0.01) reduced the small intestinal transit of charcoal meal in mice at all doses tested. The extract (0.4-3.2 mg/ml) produced a concentration dependent relaxation of the rabbit jejunum, and the effects were blocked by propranolol (0.04 and 0.64 μg/ml). The results of this study showed that the extract contain pharmacologically active substance with antidiarrhoeal properties mediated through inhibition of hyper secretion and reduced gastrointestinal motility. These properties may explain the rationale for use of it’s stem bark as antidiarrhoeal remedy in traditional medicine.

Central and peripheral modulation of gastrointestinal transit in mice by DN-9, a multifunctional opioid/NPFF receptor agonist.

The nonapeptide DN-9 functions as a multifunctional agonist to opioid and neuropeptide FF (NPFF) receptors and exhibits antinociceptive effects at the central and peripheral levels. The effects of DN-9 on small and colonic intestinal transit were evaluated using the upper gastrointestinal (GI) transit test and colonic bead expulsion assay, respectively. Opioid and NPFF receptor antagonists were used to investigate the mechanisms of DN-9-induced GI inhibition. Furthermore, the agonism of the DN-9 analog [Phg9 ]-DN-9 to opioid and NPFF receptors was tested by the cAMP assay. Intracerebroventricular administration of DN-9 dose-dependently slowed upper GI transit and colonic expulsion via mu- and kappa-opioid receptors in the brain, independent of the delta-opioid receptor. Similarly, intraperitoneal injection of DN-9 dose-dependently inhibited GI propulsion via the peripheral opioid receptors. DN-9-induced GI transit inhibitions were significantly aggravated by the NPFF receptor antagonist RF9. Moreover, the DN-9 analog [Phg9 ]-DN-9, an agonist at mu-, delta-, and kappa-opioid receptors but not NPFF receptors, inhibited GI more potently than DN-9. In addition, intracerebroventricular NPFF significantly attenuated the central inhibitory effects induced by [Phg9 ]-DN-9 and morphine. However, central and peripheral injections of NPFF or RF9 almost had no significant effects on GI transit by itself. Intracerebroventricular and intraperitoneal administrations of DN-9 inhibit GI transit via opioid receptors in mice by central and peripheral mechanisms, respectively. In addition, the NPFF agonism of DN-9 possesses antiopioid effects on GI transit, which might explain the reduced constipation at the antinociceptive doses.

Electroacupuncture promotes the gastrointestinal motility of diabetic mice by CNP/NPR-B-cGMP and PDE3A-cGMP signaling.

Electroacupuncture (EA) can promote gastrointestinal (GI) motility of diabetic mice, but the mechanism is not clearly elucidated. Natriuretic peptides (NPs) were related to the diabetes-induced gut dysfunction of mice, which may be associated with ICC (interstitial cells of cajal). Besides, EA could increase the ICC of diabetic mice. Our aim was to explore whether EA can promote the gut motility by CNP/NPR-B-cGMP and PDE3A-cGMP signaling in diabetic mice, and the relationship between NPs and ICC. Wild C57BL/6 male mice were divided into five groups: control group, diabetic mellitus (DM group), diabetic mellitus plus sham EA group (SEA), diabetic mellitus plus low-frequency EA group (LEA), and diabetic mellitus plus high-frequency group (HEA). Gastrointestinal motility was assessed by gastric emptying and GI transit test. Immunofluorescence staining was applied to assess the expression level of CNP, NPR-B, and c-Kit. Western blot, PCR, and ELISA were used to detect the level of CNP, NPR-B, PDE2A, PDE3A, c-Kit, mSCF, and cGMP content. The correlativity between NPR-B and mSCF was evaluated by Pearson's correlation and linear regression analyses. (a) EA could improve the GI dysfunction of diabetic mice. (b) CNP, NPR-B, and cGMP contents were decreased, but the level of PDE3A, c-Kit, and mSCF was increased in the EA groups. (c) There was a negative correlation between NPR-B and mSCF among the groups. Electroacupuncture promotes the GI function by CNP/NPR-B-cGMP and PDE3A-cGMP signaling in diabetic mice; up-regulated mSCF/c-Kit signaling by EA may be mediated partially via down-regulation of CNP/NPR-B signaling.

In Vivo Anti-diarrheal Activity of Methanolic Extract of Streblus asper Leaves Stimulating the Na+/K+-ATPase in Swiss Albino Rats.

Streblus asper Lour., traditionally used for anti-diarrheal effects as like dysentery and diarrhea. The present study aims to prove the anti-diarrheal activities of methanolic extract of leaves of S. asper in animal models. The anti-diarrheal activity was evaluated using castor oil-induced diarrhea and magnesium sulphate-induced diarrhea models whereas anti-motility activities were investigated using gastrointestinal transit test examined in animal models. In castor oil-induced diarrhea model, methanolic extract of S. asper (MESA) at the doses of 100, 200, and 400mg/kg produced statistically significant (P < 0.001) decreased the number of diarrheal feces of rats against castor oil-induced diarrhea as well as magnesium sulphate-induced diarrhea model also showed the same manner. In gastrointestinal transit test, delayed gastric emptying time decreased significantly (P < 0.001), the propulsion of charcoal meal in the gastrointestinal tract which also showed a dose-dependent manner in rats. The recent study indicates that MESA possesses anti-diarrheal property. The findings represent a rational explanation for its use in traditional medicine for the management of diarrhea management.

Neuronal Nitric Oxide Synthase Is a Novel Biomarker for the Interstitial Cells of Cajal in Stress-Induced Diarrhea-Dominant Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder involving changes in normal bowel movements. The pathophysiology of IBS is not clearly understood owing to the lack of identifiable pathological abnormalities and reliable biomarkers. The aim of this study was to discover the novel and reliable biomarker for IBS. In this study, neonatal maternal separation (NMS) stress model was used for the IBS mouse model. Further assessment was conducted with whole gastrointestinal transit test, quantitative RT-PCR, histological examination, and western blot. Male pups developed symptoms similar to those of human IBS with diarrhea (IBS-D), such as low-grade inflammation, stool irregularity, and increased bowel motility. NMS stress influenced to the interstitial cells of Cajal (ICC) and induced altered bowel motility, resulting in IBS-D-like symptoms. In addition, we found neuronal nitric oxide synthase (nNOS) to be a novel biomarker for ICC under NMS stress. nNOS expression was only observed in the ICC of the submucosal plexus of IBS-D mice, and the inhibition of nNOS changed the phenotype from IBS-D to IBS with constipation. Our study demonstrates that early-life stress can influence to ICC and modulate bowel activity and that nNOS might be used as a biomarker for ICC stimulation in IBS.

Antidiarrheal activities of hydroalcoholic extract of Sida cordifolia roots in Wister albino rats

Sida cordifolia Linn. (Malvaceae) traditionally used for the treatment of chronic dysentery, diarrhea, and dyspepsia. The core aim of the present study is to evaluate the antidiarrheal activity of hydroalcoholic extract of roots of Sida cordifolia (HESC) in animal models. The antidiarrheal activity was evaluated using castor oil-induced diarrhea and magnesium sulphate-induced diarrhea models whereas Anti-secretory and anti-motility activities were investigated using castor oil-induced enteropooling assay and gastrointestinal transit test examined in animal models respectively. Antidiarrheal activities compared to loperamide, a positive control. The acute toxicity effect of the hydroalcoholic extract of S. cordifolia also investigated. S. cordifolia (100-400mg/kg) produced dose-dependent and significant protection of rats against castor oil-induced diarrhea, magnesium sulphate-induced diarrhea, delayed gastric emptying and inhibited intestinal transit. HESC, dose-dependently and significantly delayed the onset of castor-oil induced diarrhea and magnesium sulphate-induced diarrhea, decreased the frequency of defecation, and reduced the severity of diarrhea in the rats as well as loperamide (5mg/kg). Furthermore, HESC produced dose-dependent and significant anti-motility effect, caused inhibition of castor-oil-induced enteropooling in rats, almost similar to loperamide. Additionally, castor oil-induced enteropooling assay, HESC dose-dependently and significantly decreased the volume of castor oil-induced intestinal fluid secretion compared with the control group. In gastrointestinal transit test, delayed gastric emptying and decreased the propulsion of charcoal meal through the gastrointestinal tract also observed. The effect of HESC significant and dose-dependent when compared with the control group. There was no deaths or abnormalities in behavior seen in the acute toxicity test. The experimental findings indicate that HESC possesses antidiarrheal property in rats. These activities confirm the ethnomedicinal use of S. cordifolia roots a valuable natural remedy for the treatment, management, and control of diarrhea.

Antidiarrheal and antinociceptive activities of ethanol extract and its chloroform and pet ether fraction of Phrynium imbricatum (Roxb.) leaves in mice.

The objective of the study was to evaluate the antidiarrheal and antinociceptive activities of ethanol extract and its chloroform and pet ether fraction of Phrynium imbricatum (Roxb.) leaves in mice. In the present study, the dried leaves of P. imbricatum were subjected to extraction with ethanol, and then it was fractioned by chloroform and pet ether solvent. Antidiarrheal effects were tested by using castor oil-induced diarrhea, castor oil-induced enteropooling, and gastrointestinal transit test. Antinociceptive activity was evaluated by using the acetic acid-induced writhing test and formalin-induced paw licking test. The standard drug loperamide (5 mg/kg) showed significant (p<0.001) inhibitory activity against castor oil-induced diarrhea, in which all the examined treatments decreased the frequency of defecation and were found to possess an anti-castor oil-induced enteropooling effect in mice by reducing both weight and volume of intestinal content significantly, and reducing the propulsive movement in castor oil-induced gastrointestinal transit using charcoal meal in mice. The results showed that the ethanol extract of P. imbricatum leaves has significant dose-dependent antinociceptive activity, and among its two different fractions, the pet ether fraction significantly inhibited the abdominal writhing induced by acetic acid and the licking times in formalin test at both phases. These findings suggest that the plant may be a potential source for the development of a new antinociceptive drug and slightly suitable for diarrhea, as it exhibited lower activity. Our observations resemble previously published data on P. imbricatum leaves.

Spasmolytic Action of Preparations and Compounds from Hofmeisteria schaffneri

Hofmeisteria schaffneri is used in Mexican folk medicine for treating painful gastric complaints. Therefore, in this paper the smooth muscle relaxant effect of the essential oil, and an infusion of the whole plant were evaluated using the gastrointestinal transit test in mice. The results revealed that both preparations at 316 mg/kg inhibited gastrointestinal transit by 47.5 and 52.1%, respectively. The common component of the infusion and essential oil was 8.9 -epoxy-10-acetoxythymol angelate (2), which inhibited the gastrointestinal transit by 53.4% at a dose of 31.6 mg/kg. An HPLC-UV method was developed and validated to quantify 2. The chromatographic conditions were: A LiChrospher® 100 RP-18 column (250 x 4 mm i.d., 5μm) with a mobile phase composed of CH₃CN-H₂O, in a gradient run at a flow rate of 0.6 mL/min, using a wavelength of 215 nm. The method was linear, precise, accurate, and showed excellent recovery. According to the results, compound 2 can be used as a marker for the quality control procedures of the crude drug of H. schaffneri.

Antioxidant, antidiarrheal, hypoglycemic and thrombolytic activities of organic and aqueous extracts of Hopea odorata leaves and in silico PASS prediction of its isolated compounds.

Background Hopea Odorata, locally known as Telsur (Bangladesh), has some traditional uses as folk medicine. This study aims to investigate the antioxidant, antidiarrheal, hypoglycemic and thrombolytic activities of H. odorata leaf extracts as new therapeutic prospects predicting the activity of some of the isolated compounds of this plant.MethodsLeaves of Hopea odorata was extracted with pure methanol (MEHO), ethanol (EEHO) and water (AEHO). The extract was tested for antioxidant activity by using reducing power and H2O2 scavenging assay. Antidiarrheal effects were assayed by three standard methods of bioassay: Castor oil-induced diarrhea, Castor oil induced enteropooling and gastrointestinal transit test. Hypoglycemic effect was determined by normoglycemic model of mice. Thrombolytic activity was evaluated by clot lyses test for human and mice blood. In silico PASS prediction was applied for phytoconstituents namely Balanocarpol, Hopeaphenol and Ampelopsin H isolated from this plant. ResultAmong the all extracts, MEHO exhibited strong antioxidant activity in both reducing power and H2O2 scavenging assay. Phenol content of MEHO was 297.22 ± 0.78 mg/g and flavonol content was 91.53 ± 1.82 mg/g. All the experiment of extracts at dose of 200 and 400 mg/kg and the standard drug loperamide (5 mg/kg) showed significant (p < 0.001) inhibition against castor oil induced diarrhea and castor oil induced enteropooling in mice. There were also significant (p < 0.01) reduction in gastrointestinal motility in the charcoal meal test. Leaf extract showed no significant (P < 0.01) decrease of blood glucose compared to Glibenclamide in normoglycemic mice. Using an in vitro thrombolytic model, MEHO showed the highest and significant clot lysis of human and mice blood compared to Streptokinase. PASS predicted the wide range of antioxidant, free radical scavenger, Nitric oxide scavenger, cardioprotectant, hepatoprotectant, thrombolytic, fibrinolytic, antibacterial, antifungal, anticarcinogenic, anthelmintic and anti-inflammatory activity of examined phytoconstituents.ConclusionThese findings suggest that the plant may be a potential source of new antidiarrheal, thrombolytic and antioxidative agents but it is found to have no antidiabetic capability. PASS prediction matched with present study for the extracts. Further study needs to identify the PASS predicted biological actions of the phytoconstituents.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-016-1461-x) contains supplementary material, which is available to authorized users.

Laparoscopic-assisted subtotal colectomy combined with modified Duhamel procedure for mixed constipation.

Background and Objectives:To evaluate the effects of subtotal colectomy combined with the modified Duhamel procedure on mixed constipation.Methods:A total of 16 female patients with mixed constipation were enrolled and underwent subtotal colectomy combined with the modified Duhamel procedure under laparoscopy from April 2010 to April 2012. Before surgery, physical examinations such as the gastrointestinal transit test, barium enema, and defecography were performed for all the patients. After surgical treatment, 2-year follow-up was performed using questionnaires to assess the effect of treatment.Results:All 16 cases were treated successfully, with a mean operation time of 230 minutes (range, 180–290 minutes). No intraoperative or postoperative complications were found, and no deaths occurred. Constipation and relevant symptoms were relieved, and all patients were satisfied with their quality of life. The gastrointestinal quality-of-life score was significantly increased 6 months postoperatively (mean, 102) compared with preoperatively (mean, 75).Conclusion:Subtotal colectomy combined with the modified Duhamel procedure under laparoscopy is effective and safe for the treatment of mixed constipation.

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

Aim:The roots of Potentilla fulgens Wall. ex Hook. (Rosaceae) have been used in the indigenous system of medicine in Northeast India to treat diarrhea. The aim of this study was to investigate the safety and protective effects of P. fulgens root extract in experimentally induced diarrhea in mice.Materials and Methods:The protective effects of P. fulgens root extract was investigated against experimentally induced diarrhea in mice, using four experimental models, that is the measurement of fecal output, castor oil model, prostaglandin E2 (PGE2) enteropooling assay, and gastrointestinal transit test. The safety assessment of root extract was done in mice on the basis of general signs and symptoms of toxicity, food water intake and mortality of animals following their treatment with various doses of extract (100-3200 mg/kg). In addition, the serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, cholesterol and total protein of experimental mice were also monitored to assess the toxicity of root extract.Results:In the safety assessment studies, P. fulgens root extract did not showed any visible signs of toxicity, but mortality was observed in a single animal at 3200 mg/kg dose of extract. The extract also did not showed any adverse effects on the studied serum parameters of experimental animals. In the antidiarrheal tests, administration of 800 mg/kg dose of extract to mice showed 50% protection from diarrhea evoked by castor oil. In addition, the extract also showed 29.27% reduction in PGE2-induced intestinal secretion as compared with 30.31% recorded for loperamide, a standard antidiarrheal drug.Conclusions:The results of this study indicate that P. fulgens root extract possesses significant antidiarrheal properties. Therefore, the roots of this plant can be an effective traditional medicine for protection from diarrhea.

Clinical features and related factors of severe functional constipation

Objective To analyze the clinical characteristics and related factors of severe functional constipation (FC) and explore the correlation between the severity of FC and colonic motility and anorectal function of patients.Methods From March 2010 to March 2012,patients with FC met Rome Ⅲ criteria were selected.A questionnaire survey was carried out and gastrointestinal transit test (GITT),anorectal manometry (ARM) and defecography were examined.The measurement data were analyzed by t test or rank sum and chi-square test was used for rate compare.Results Among 242 FC patients (male 69,female 173),179 cases (74.0％) were severe FC.The body mass index (BMI) of severe FC patients was (21.52±2.55) kg/m2,which was higher than that of non-severe FC patients ((20.72±2.46) kg/m2) and the difference was statistically significant (t=2.148,P=0.033).The rate of natural delivery in severe FC patients was 80.2％ (89/111),which was higher than that of non-severe FC patients (63.6％,21/33),and the difference was statistically significant (x2 =3.860,P=0.049).There were no significant differences in GITT,ARM and defecography between severe FC patients and non-severe FC patients (all P＞0.05).The weekly frequency of defecation of patients with abnormal GITT was 1.0 (0.5,2.0),which was less than that of patients with normal GITT (1.5(0.9,2.9)),and the difference was significant (Z=-2.612,P=0.009).Conclusions Severe FC is related to BMI and natural delivery.There is no correlation between anorectal function and severity of FC.The defecation frequency is correlated with colonic transit time. Key words: Constipation; Body mass index; Natural childbirth; Colon; Defecation

Solid gastric emptying mediated by the serotonin (5-HT)3 receptor in mice is a simple marker to predict emesis

Nausea and emesis are often observed as side effects with many medicines and may lead to poor treatment compliance. In the present study, we aimed to establish simple methods for predicting nausea and/or emesis in mice, which do not vomit, using drugs and chemicals known to evoke nausea and/or emesis. The gastrointestinal transit test, the liquid gastric emptying by phenol red solution (Phenol red method) and the solid gastric emptying by resin beads (Beads method) were used and the effects of antispasmogenics (atropine, 0.1-3 mg/kg i.p.; salmon calcitonin, 1-30 units/kg i.m.), nauseants (copper sulfate, 1-30 mg/kg p.o.; apomorphine, 0.01-0.3 mg/kg s.c.) and chemotherapeutics (cisplatin, 0.3-10 mg/kg i.v.; doxorubicin, 0.3-10 mg/kg i.v.) were evaluated. In addition, the effects of ondansetron, a serotonin (5-HT)(3) receptor antagonist, on the inhibition of solid gastric emptying induced by salmon calcitonin, copper sulfate, cisplatin and doxorubicin were also assessed. Only the solid gastric emptying method could detect changes of gastric emptying by all drugs and chemicals. We also found that the inhibition of solid gastric emptying induced by cisplatin and doxorubicin was dose-dependently antagonized by ondansetron. However, ondansetron failed to antagonize the salmon calcitonin-induced delay, but exerted only very weak effects with copper sulfate. Solid gastric emptying may be more suitable than gastrointestinal intestinal transit or liquid gastric emptying in mice to predict nausea and/or emesis. Our results also suggest that chemotherapeutic-induced delay of solid gastric emptying mediated via 5-HT(3) receptors in mice could also be useful for prediction purposes.

Antidiarrhoeal activity of &amp;lt;i&amp;gt;Cistus ladaniferus&amp;lt;/i&amp;gt; aqueous extract

AIM: Cistus ladaniferus L. (Cistaceae) is a plant which is traditionally used for the treatment of intestinal pain and diarrhea in Morocco. The aim of this study is to evaluate antidiarrhoeal activity of aqueous extract of this plant. METHODS: Aqueous extract of aerial part (stems and leaves) of Cistus ladaniferus was decocted and evaporated to give a crude residue (yield: 18%). It is bioassayed for their antidiarrhoeal effect by the two standard methods of bioassay of the antidiarrheal activity: Castor oil-induced diarrhoea and Gastrointestinal transit test. RESULTS: The aqueous extract of Cistus ladaniferus L. given orally at the dose 300 and 600 mg/kg, showed significant antidiarrhoeal activity in castor oil induced diarrhoea and reduced the frequency of diarrhoeal episodes in rat. At 600 mg/kg it decreased the propulsion of charcoal meal through the gastrointestinal tract in mice by 30.71%. COCLUSION: These results suggested that the extract may contain biologically active components that may be useful against diarrhoea, thereby justifying its use in ethnomedical practice.

Preparation and evaluation of a novel gastric mucoadhesive sustained-release acyclovir microsphere

Objective: The objective of this study was to prepare a novel gastric mucoadhesive sustained-release acyclovir (AV)-resinate microsphere. Methods: First, AV absorption ratio was quantified in a rat gastrointestinal (GI) tract model. AV-resinate was prepared by bath method and used as cores to prepare microspheres by an emulsion solvent diffusion technique with carbopol 934 as coating material. GI transit test of the prepared microspheres was carried out in rats and beagle dogs, followed by the in vivo bioavailability evaluation of the microspheres in beagle dogs. Results: The AV absorption ratio in different segments of rat's GI track for 3 hours was as following: stomach 9.46 ± 0.62%, duodenum 20.22 ± 1.50%, jejunum 15.7 ± 1.33%, ileum 9.15 ± 1.01%, and colon 4.59 ± 0.48%. These results showed that AV was mainly absorbed in the stomach and upper intestine. The average diameter of the microspheres was 115.3 μm. The microspheres had a drug content of 33.3 ± 0.7% (w/w) and a sustained-release profile for 12 hours in vitro. The mucoadhesive test in rats and beagle dogs showed that most of the microspheres were retained in the stomach 6 hours after oral administration. The in vivo pharmacokinetics test revealed that the microsphere and reference (AV tablets) preparations have no significant difference for Cmax. The tmax has increased from 2.33 hours (reference) to 5 hours (test). Meanwhile, the relative bioavailability of AV microspheres was 145%. Conclusion: A novel AV-resinate microsphere was prepared. The microspheres were proved to be gastric mucoadhesive and sustained-release with higher bioavailability.

Categorization of dysmotility in patients with chronic constipation and its significance for management

Chronic constipation is a common gastrointestinal symptom with different patterns of dysmotility for which there is not one simple and effective diagnostic method for categorization. The present study assessed the diagnostic method used in patients with chronic constipation and its significance for clinical management. The study group comprised 210 consecutive patients with chronic constipation who underwent history, digital anorectal examination (DARE), gastrointestinal transit test (GITT) and anorectal manometry (ARM) to determine the pattern of dysmotility. Symptoms and the examinations were summarized for establishing the diagnostic method and evaluation of the role of the examinations. Outlet obstructive constipation (OOC), slow transit constipation (STC) and mixed constipation (MC) accounted for 50.8%, 10.2% and 39.0% of cases, respectively. The stool was harder in STC or MC than in OOC (P = 0.036). The presence of a paradoxical inverse contraction of anal sphincter when straining to defecate during DARE or ARM was significant for the diagnosis of OOC (P < 0.001). The distribution of the residual markers on abdominal plain film after 48 h GITT was significant for the diagnosis of STC (P < 0.001). The sensitivity of DARE, GITT and ARM was 82.5%, 89.1% and 94.4%, and specificity was 95.2%, 87.9% and 82.6%, respectively. Clinical management was modified in 69.5% of patients after categorizing the constipation pattern. The symptoms, DARE, GITT and ARM are effective methods of evaluating the dysmotility patterns in patients with chronic constipation. DARE and ARM could improve the diagnostic rate of OOC, and GITT assists in diagnosis of STC. Proper categorization of the dysmotility pattern is important for the clinical management of chronic constipation.

Evaluation of poly(vinyl alcohol)-gel spheres containing chitosan as dosage form to control gastrointestinal transit time of drugs.

Two types of poly(vinyl alcohol)-gel spheres were prepared with chitosan (CS/PVA-GS) and without chitosan (PVA-GS), and comparative studies were performed using these gel spheres (GSs). No change in particle size was observed by the addition of chitosan: nearly 45% of both particles were in the 5-10 microm range. In an in vivo gastrointestinal transit test, CS/PVA-GS prolonged the small-intestinal transit time more than PVA-GS. In an in vitro intestinal perfusion study, the mean transit time of these GSs was markedly reduced by pretreatment of the intestinal surface with a mucolytic agent, N-acetyl-L-cysteine, suggesting that the mucous layer on the intestinal surface plays an important role in controlling the transit rate of these GSs. The oral administration of aminophylline (theophylline) and ampicillin as model drugs incorporated in PVA-GS and CS/PVA-GS was examined in rats. While theophylline absorption from PVA-GS was not affected by the addition of chitosan, the improvement of ampicillin absorption by PVA-GS was enhanced by the chitosan combination.

Measurement of Small Bowel and Colonic Transit: Indications and Methods

In this article, we review the currently available techniques for measuring small intestinal and colonic transit. In addition, we describe the characteristics of an ideal test that provided the rationale for the development and validation of a gastrointestinal and colonic transit test at the Mayo Clinic. This new technique assesses regional transit of solid radiolabeled particles of the same size through the entire digestive tract and provides further insights into motor physiologic processes of the gut. By means of a delayed-release methacrylate-coated capsule, isotopically labeled pellets are delivered to the colon as a single bolus; thereby, dispersion of isotope throughout the small bowel is avoided because of the gradual emptying of chyme from the stomach. Similar pellets labeled with a different isotope can be used to assess gastric and small bowel transit. These new methods for measuring transit have also led to insights into the pathogenesis of unexplained gastrointestinal symptoms and disease states. Thus, we demonstrated that in healthy subjects, ileocolonic transfer of chyme occurs in boluses; this transfer is impaired in patients with myopathic pseudo-obstruction. The emptying rate of the proximal colon is an important determinant of the pathophysiologic features of colonic disease; thus, colonic transit is delayed in cases of severe idiopathic constipation. In contrast, rapid emptying of the proximal colon influences stool weight in diarrhea-predominant irritable bowel syndrome. An integrated approach for studying gastric, small bowel, and colonic transit by using the same radiolabeled particle provides a useful, clinically applicable method for evaluating gastrointestinal symptoms and for measuring motor function of the entire digestive tract without need for intubation; cost and radiation exposure are acceptable.