Relative efficacy of some prokinetic drugs in morphine-induced gastrointestinal transit delay in mice

AIM:To study the relative efficacy of cisapride, metoclopramide,domperidone,erythromycin and mosapride on gastric emptying(GE)and small intestinal transit(SIT) in morphine treated mice. METHODS:Phenol red marker meal was employed to estimate GE and SIT in Swiss albino mice of either sex.The groups included were control,morphine 1 mg/kg(s.c.15 rain before test meal)alone or with(45 rain before test meal p.o.)cisapride 10 mg/kg,metoclopramide 20 mg/kg, domperidone 20 mg/kg,erythromycin 6 mg/kg and mosapride 20 mg/kg. RESULTS:Cisapride,metoclopramide and mosapride were effective in enhancing gastric emptying significantly(P<0.001) whereas other prokinetic agents failed to do so in normal mice.Metoclopramide completely reversed morphine induced delay in gastric emptying followed by mosapride. Metoclopramide alone was effective when given to normal mice in increasing the SIT.Cisapride,though it did not show any significant effect on SIT in normal mice,was able to reverse morphine induced delay in SIT significantly(P<0.001) followed by metoclopramide and mosapride. CONCLUSION:Metoclopramide and cisapride are most effective in reversing morphine-induced delay in gastric emptying and small intestinal transit in mice respectively.

Effect of lipopolysaccharide on diarrhea and gastrointestinal transit in mice: Roles of nitric oxide and prostaglandin E_2

AIM: To investigate the effect of lipopolysaccharide (LPS)on the diarrheogenic activity, gastrointestinal transit (GIT),and intestinal fluid content and the possible role of nitric oxide (NO) and prostaglandin E2 (PGE2) in gastrointestinal functions of endotoxin-treated mice.METHODS: Diarrheogic activity, GIT, and intestinal fluid content as well as nitric oxide and PGE2 products were measured after intraperitoneal administration of LPS in mice.RESULTS: LPS dose-dependently accumulated abundant fluid into the small intestine, induced diarrhea, but decreased the GIT. Both nitric oxide and PGE2 were found to increase in LPS-treated mice. Western blot analysis indicated that LPS significantly induced the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 in mice intestines. Pretreatment with NG-nitro-L-arginine-methyl ester (L-NAME, a non-selective NOS inhibitor) or indomethacin (an inhibitor of prostaglandin synthesis) significantly attenuated the effects of LPS on the diarrheogenic activity and intestine content, but reversed the GIT.CONCLUSION: The present study suggests that the pathogenesis of LPS treatment may mediate the stimulatory effect of LPS on nitric oxide and PGE2 production and NO/prostaglandin pathway may play an important role on gastrointestinal function.

Effect of explosive noise on gastrointestinal transit and plasma levels of polypeptide hormones

AIM： To investigate the effect of firing noise on gastrointestinal transit and probe its mechanism by measuring the levels of plasma polypeptide hormones. METHODS： A total of 64 SD rats were randomly divided into a control group and three stimulating groups. Firing noise of different intensity by sub-machine guns was used as inflicting factor. The effect of firing noise on liquid substance gastrointestinal transit and solid substance gastrointestinal transit was observed by measuring the ratio of carbon powder suspension transmitting and barium sticks transmitting respectively. Plasma levels of polypeptide hormones were measured by radio-immunoassay. RESULTS： The noise accelerated gastrointestinal transit of solid food by more than 80 db;and accelerated gastrointestinal transit of liquid food significantly by more than 120 db. Meantime, plasma levels of plasma motilin （MTL）（157.47±16.08; 151.90±17.08）, somatostatin （SS）（513.97±88.77; 458.25±104.30）, substance P （SP）（115.52±20.70; 110.28±19.96） and vasoactive intestinal peptide （VIP） （214.21±63.17; 251.76±97.24） remarkably changed also. CONCLUSION： Within a certain intensity range, the firing noise changes the levels of rat plasma gastrointestinal hormones, but the gastrointestinal transit is still normal. Beyond the range, the noise induces plasma hormone levels disturbance and gastrointestinal transit disorder. ~

Effects of progesterone on gastric emptying and intestinal transit in male rats

AIM: To study the dose-dependent of progesterone (P) effect and the interaction between the oxytocin (OT) and P on gastrointestinal motility. METHODS: In order to monitor the gastric emptying and intestinal transit, the SD male rats were intubated via a catheter with normal saline (3 ml/kg) containing Na(2)(51)CrO(4) (0.5 microCi/ml) and 10% charcoal. OT was dissolved into normal saline and P was dissolved into 75% alcohol. RESULTS: Low does of P (1 mg/kg, i.p.) enhanced the gastric emptying (75+/-3%, P【0.05) and high dose of P (5 mg/kg, i.p.) inhibit it (42+/-11.2%, P【0.01). P (1 mg/kg) increased the intestinal transit (4.2+/-0.3, P【0.05) while the higher dose (10-20 mg/kg) had no effect. OT (0.8 mg/kg, i.p.) inhibited the gastric emptying (23.5+/-9.8%, P【0.01). The inhibitory effects of P(20 mg/kg) (32+/-9.7%, P【0.05) and OT (0.8 mg/kg) on gastric emptying enhanced each other when the two chemicals were administrated simultaneously (17+/-9.4%, P【0.01). CONCLUSION: Low dose of P increased GI motility while high dose of P decreased it. During the later period of pregnancy, elevated plasma level of OT may also participate in the gastrointestinal inhibition.

STUDIES ON THE RELATIONSHIP BETWEEN SUBSTANCE P AND ABNORMAL GASTROINTESTIANL TRANSIT

Objective To realize the relationship between substance P(SP) and abnormal gastrointestinal transit.Methods By radioimmunoassay, concentration of SP in sigmoid mucosa was determined in 12 healthy volunteers, 15 slow and 10 fast transit patients.Results The concentration was (27.68±15.42)μg/g,(24.07±5.76)μg/g and (28.61±18.34)μg/g,respectively.They had no statistical difference.Conclusion There was no relationship between concentration of SP in sigmoid mucosa and abnormal gastrointestinal transit.

Study on efficacy and safety of acupuncture for treatment of functional constipation

Objective To explore clinical efficacy and safety of acupuncture in treatment of functional constipation.Methods One hundred and twenty cases were randomly divided into an observation group and a control group,60 cases in each group.The patients in the observation group were treated with acupuncture at Tiānshū（天枢 ST 25）,Shàngjùxū（上巨虚 ST 37）,Zúsānlǐ（足三里 ST 36）,Dàchángshū（大肠俞 BL 25）,etc.,and the control group was treated with oral administration of Macrogol 4000 and Mosapride.Defecation frequency,stool property,constipation symptom score,accompanying symptom score,gastrointestinal transit time and adverse reaction were observed before treatment,at the end of treatment and 4 weeks after treatment in the two groups.Results Compared with those before treatment,defecation frequency was increased significantly at the end of treatment in the two groups,while stool property,constipation symptom score,accompanying syndrome score and gastrointestinal transit time all were decreased significantly（all P0.01）,with no significant difference in these indexes between the two groups at the end of treatment （all P0.05）.Compared with the end of treatment,the above-mentioned indexes did not significantly recur in the observation group 4 weeks after the treatment （all P0.05）,but the therapeutic effects were unstable with decreased to some extent in the control group （all P0.05）.No serious adverse reaction was found in the two groups.Conclusion In the patients with functional constipation,acupuncture can significantly increase defecation frequency,change stool property,alleviate constipation and accompanying symptoms,and shorten gastrointestinal transit time with better safety and tolerance,and the therapeutic effect is more stable than that of Macrogol 4000 and Mosapride.

Short and long-term efficacy of combining Fuzhengliqi mixture with acupuncture in treatment of functional constipation

OBJECTIVE: To explore the short and long-term efficacy of combining Fuzhengliqi mixture (FLM) with acupuncture in treating functional constipation (FC). METHODS: The 560 patients with confirmed diagnosis of FC were randomly assigned to four groups: FLM group, acupuncture group, combined therapy group, and control group. There were 140 cases in each group. The FLM group was administered FLM 60 mL twice a day, while the acupuncture group was treated with acupuncture at acupoints Tianshu (ST 25), Shangjuxu (ST 37), Zusanli (ST 36), Dachangshu (BL 25), and Zhigou (TE 6) twice a day, the combined therapy group with FLM and acupuncture, and the control group was administered mosapride (5 mg thrice a day) and Macrogol 4000 (10 g twice a day). The treatment lasted 6 weeks. The defecation interval, stool property, constipation symptoms, and accompanying symptomswere recorded, graded, and scored.The gastrointestinal transit time (GITT) and motilin (MTL) level in serum and life quality score were detected at three time points (pre-treatment, at the end of treatment, and 60 weeks post-treatment). Moreover, the adverse reactions were also observed. RESULTS: In the FLM group 2 cases were eliminated for not taking medication strictly according to the research plan and 1 case was lost to follow-up, while 2 cases in the acupuncture group and 2 cases in the combined therapy group were lost to follow-up. Compared with those detected pre-treat- ment, the defecation interval, stool property, consti- pation symptom grade, accompanying symptom grade, and GITT were all decreased markedly at the end of treatment in every group, while the MTL levels in serum and life quality score were increased markedly (P<0.01), the above-mentioned detecting indices were better in the combined therapy group than those in other groups (P<0.05). Compared with the end of treatment, above-mentioned detecting indices all recurred significantly in the FLM group and control group 60 weeks post-treatment (P>0.05), but these indices recurred insignificantly in the acupuncture and combined therapy groups (P>0.05). The short and long-term total effective rates in the combined therapy group were significantly different from those in other groups (P<0.05 or P<0.01). No serious adverse reactions were found in four groups. CONCLUSION: Both FLM and acupuncture can significantly shorten the defecation interval and GITT, increase MTL levels in serum, decrease the scores of stool property, constipation symptoms, and accompanying symptoms in patients with FC to increase their life quality. The combined therapy is much better in long-term efficacy and the safety is also good, worth spreading in clinical practice.