Effects of Zuojin pill on depressive behavior and gastrointestinal function in rats with chronic unpredictable mild stress: Role of the brain-gut axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Zoujin pill (ZJP), a medication used to treat gastrointestinal disorders since the 15th Century in China, have been reported to exert anti-depressant effects in various models. STUDY AIM: To assess the effects of ZJP on gastrointestinal function and depressive behavior in rats under chronic unpredictable mild stress (CUMS), and to examine the underlying mechanisms related to brain-gut axis. METHODS: The rats suffered the stressor once daily for 5 weeks. ZJP (0.6 and 1.2 g/kg) and fluoxetine (15 mg/kg) as positive control were administered to the rats through gastric intubation once daily for 5 consecutive weeks. The anti-depression effects were compared by performing sucrose preference tests and open field tests. Gastrointestinal motility was investigated by determining the gastrointestinal transit rate and by electrogastrogram. The serum levels of the gastrointestinal hormone (GAS, MOT, VIP, SP), inflammatory cytokine (IL-1ß, IL-6; , TNFα) and glucagon-like peptide-1 (GLP-1) were assayed by enzyme-linked immunosorbent assay. For monoamine neurotransmitters (NE, 5-HT, DA), the levels were determined by high-performance liquid chromatography and electrochemical detection in conjunction, which was applied on the samples taken from the hypothalamus, hippocampus, and striatum. RESULTS: The depression-like symptoms among rats under CUMS were significantly relieved by ZJP administration (0.6 and 1.2 g/kg). Gastrointestinal motility was also improved by restoring gastric electrical rhythm and promoting gastrointestinal propulsion. The ZJP at 0.6 g/kg dosage obviously up-regulated 5-HT and DA levels in hippocampus. The ZJP at 1.2 g/kg dosage could increase 5-HT and DA levels in hypothalamus, striatum, and hippocampus, while down-regulated the NE level in hypothalamus and hippocampus. ZJP also reversed the alterations in serum gastrointestinal hormones. Furthermore, treatment with ZJP significantly reduced levels of IL-1ß, IL-6 and TNF-α and increased serum GLP-1 compared with the CUMS group. Fluoxetine also exerted similar anti-depressant effects in the absence of effects on gastrointestinal motility and the levels of serum hormone, inflammatory cytokine and GLP-1. CONCLUSION: ZJP imposed anti-depressant and gastrointestinal regulating functions in rats under CUMS, suggesting potential clinical application. .

Identification and quantification of the quality markers and anti-migraine active components in Chuanxiong Rhizoma and Cyperi Rhizoma herbal pair based on chemometric analysis between chemical constituents and pharmacological effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Chuanxiong Rhizoma and Cyperi Rhizoma (CRCR), an ancient and classic herbal pair, has been used in herbal medicines for treating migraine, but its effective components are not clear. AIM OF THE STUDY: The present study aimed to identify and quantify the quality markers and anti-migraine active components in CRCR based on chemometric analysis between chemical constituents and pharmacological effects. MATERIALS AND METHODS: The HPLC fingerprints of eight batches of CRCR samples were obtained, and their characteristic common peaks were identified by HPLC-ESI-Q-TOF-MS/MS. The therapeutic effects of eight batches of CRCR samples on nitroglycerin-induced migraine rats were evaluated by migraine-related neurotransmitters and neuropeptides. Similarity analysis, hierarchical cluster analysis and principal component analysis were applied to screen the quality markers. Artificial neural network and partial least squares regression models were used to screen the anti-migraine compounds by correlating the chemical constituents in HPLC fingerprints and pharmacological indicators. RESULTS: Eighteen characteristic common peaks were found in the HPLC fingerprints, including eleven known compounds and seven unknown compounds. Ferulic acid (FA), senkyunolide I (SI), senkyunolide A (SA), 3-n-butylphthalide (NBP), Z-ligustilide (LIG), Z-3-butylidenephthalide (BDPH), nookatone (NKT), levistilide A (LA), α-cyperone (CYP) and other five unknown compounds (P1, P2, P7, P8 and P9) were identified as quality markers. SA, NBP, LIG, NKT, CYP and other three unknown compounds (P1, P4 and P9) can be considered as anti-migraine prototype compounds. The quality markers and anti-migraine active components were further quantified in CRCR extract, rat serum and cerebral cortex by UPLC-MS/MS, which gives a clue to track the dynamic changes of the contents of the main constituents. CONCLUSIONS: Our study explored the anti-migraine material basis, and could lay a foundation for the improvement of the quality control of CRCR in practice.

Efficacy of High Specific Volume Polysaccharide - A New Type of Dietary Fiber - On Molecular Mechanism of Intestinal Water Metabolism in Rats With Constipation.

BACKGROUND The aim of this study was to evaluate the effects of a new type of dietary fiber - high specific volume polysaccharide (HSVP) - on fecal properties, serum vasoactive intestinal peptide (VIP) concentration, intestinal flora count, and expression of the VIP-cAMP-PKA-AQP3 signaling pathway. MATERIAL AND METHODS Compound diphenoxylate was used in 48 healthy Wistar rats to establish a constipation model. Rats were divided into a normal control group, a constipation model group, an HSVP low-dose group, an HSVP medium-dose group, an HSVP high-dose group, and a fructose control group. We used colony count method, ELISA, WB, and RT-PCR to determine fecal moisture content, fecal hardness, fecal passage time, serum VIP concentration, number of intestinal bacteria, and VIP-cAMP-PKA-AQP3 signal pathway protein expression. RESULTS The constipation model was established successfully. HSVP (the medium dose was 10% and the high dose was 15%) improved fecal moisture content, reduced hardness, shortened fecal emptying time, increased intestinal bacteria, reduced serum VIP concentration, downregulated cAMP and PKAm RNA transcription, reduced protein expression, and reduced intestinal AQP3 expression. CONCLUSIONS HSVP improved constipation, increased the number of intestinal bacteria, and elevated expression of the VIP-cAMP-PKA-AQP3 signaling pathway. The mechanism of HSVP in regulating intestinal water metabolism in constipated rats may occur through the VIP-cAMP-PKA-AQP3 signaling pathway, and be closely related to changes in intestinal bacteria. The important role of the brain-gut-microbiome axis in the pathogenesis of constipation has been confirmed in this study.

Evaluation of a modified rat model for functional dyspepsia.

Background/Aim: The purpose of this study was to establish a modified rat model with functional dyspepsia (FD) and analyze the changes in gastrointestinal motility and brain-gut peptide levels in serum and brain-gut axis. Materials and Methods: Male Wistar rats were divided into control group (Con) and FD model group. FD model was established by stimulating semi-starvation rats via tail damping, provocation, and forced exercise fatigue until gastrointestinal motility disorder appeared, and then levels of motilin, leptin, cholecystokinin (CCK), and vasoactive intestinal peptide (VIP) were detected in serum by enzyme linked immunosorbent assay and in duodenum, antrum, and hypothalamus by immunohistochemistry, reverse transcriptase-polymerase chain reaction, and Western blot. Results: The results showed rates of intestinal propulsion and gastric emptying slowed down markedly compared to Con (P < 0.05), the gastrointestinal electric activity attenuated, and migrating motor complex (MMC) interrupted in the model group. The levels of leptin and VIP markedly increased, but motilin decreased as compared to the Con (P < 0.05) in serum and in the above tissues. It is interesting that the level of CCK decreased in the antrum and duodenum but increased in the hypothalamus as compared to Con (P < 0.05). Conclusions: The modified rat model meets the diagnostic criteria of FD and can be used as a method for studying FD in animals.

Er Shen Wan extract reduces diarrhea and regulates AQP 4 and NHE 3 in a rat model of spleen-kidney Yang deficiency-induced diarrhea.

INTRODUCTION: Er Shen Wan (ESW), a traditional Chinese medicinal formula comprised of Psoraleae Fructus (Babchi seeds, from Psoralea corylifolia Linn.) and Myristicae Semen (Nutmeg, from Myristica fragrans Houtt.), is widely used to treat spleen-kidney Yang deficiency (SKYD)-induced diarrhea. Previous studies have demonstrated preliminarily that the petroleum ether extract of ESW (ESWP) exhibits significant anti-diarrheal activity. The present study aimed to evaluate the anti-diarrhea activity of ESWP and to explore the underlying mechanisms with respect to fluid metabolism in a rat model of SKYD-induced diarrhea. MATERIALS AND METHODS: A high-performance liquid chromatography-diode array detector (HPLC-DAD) approach was developed and validated for qualitative and quantitative analyses of the main constituents of ESWP. SKYD model rats were established and treated with an effective dose (3.5?g/kg) of the extract for two weeks. Anti-diarrheal activity and stool properties were observed. After the experiment, the appearance and histology of the intestines were evaluated. Serum levels of neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) were also determined. Furthermore, to characterize the regulation of aquaporin-4 (AQP 4) and Na+/H+ exchanger isoform 3 (NHE 3) in the colon, quantitative real-time RT-PCR (qRT-PCR), immunohistochemistry (IHC) and Western blotting (WB) were employed to detect mRNA and protein expression levels. RESULTS: In the rat models, oral ESWP administration significantly reduced the diarrhea score and the number and weight of wet stools. Jejunal and ileac histological damage was impeded, and the histology score decreased. Serum VIP levels were significantly decreased, in contrast to NPY levels. In addition, AQP 4 and NHE 3 expression levels increased significantly. CONCLUSIONS: These results showed that ESWP's anti-diarrheal effect might at least partially involve the regulation of hormones intimately involved in maintaining fluid and electrolyte levels, as well as by increasing AQP 4 and NHE 3 expression levels and enhancing the absorption of Na+ and water.

[Effects of Different Acupuncture and Moxibustion Methods on Plasma NO, NOS and VIP Contents and the Expression of Colonic VIP Protein in Functional Constipation Rats].

OBJECTIVE: To compare the effects of filiform needling, electroacupuncture, and moxibustion on functional constipation in rats, and to explore the possible mechanism of these three different methods. METHODS: Male SD rats were randomly divided into blank control group (n=8), model group (n=11), medication group (n=8), filiform needling group (n=11), electroacupuncture group (n=11), and moxibustion group (n=11). Functional constipation model was established by intragastric administration with the suspension of loperamide hydrochloride, daily for six days in a week. One hour after each gavage, the medication group was treated with cisapride suspension, while the other three groups were treated with filiform needling, electroacupuncture, and moxibustion, respectively, at "Tianshu"(ST 25), "Shangjuxu" (ST 37) acupoints. The first defecation time was recorded. NO, NOS and VIP (vasoactive intestinal peptide) levels in plasma were detected by ELISA. Immuohistochemical and Western blot methods were applied to test VIP expression in the colonic tissue. RESULTS: Compared with the blank control group, the first defecation time was prolonged, and the NO, NOS and VIP contents in plasma were increased in the model group (P<0.05, P<0.01), accompanied with increased score of VIP in the smooth muscle of colonic wall(P<0.05)and elevated VIP expression in colonic tissue(P<0.01). Compared with the model group, the first defecation time was shortened in the medication, filiform needling, electroacupuncture, and moxibustion groups(P<0.05), while decreased NO, NOS and VIP contents in plasma (P<0.01,P<0.05), decreased score of VIP in the smooth muscle of colonic wall(P<0.05), and lower expression level of VIP in colonic tissue(P<0.01)were observed in the four treatment groups. In contrast, the plasma VIP content in the electroacupuncture group was lower than that in the medication group (P<0.01), while colonic VIP expression decreased in the moxibustion group(P<0.01). The NO, NOS and VIP contents in plasma and score of VIP in the smooth muscle of colonic wall in the electroacupuncture group were lower than those in the filiform needling group and the moxibustion group(P<0.01, P<0.05), but the colonic VIP expression in the moxibustion group was lower than that in the filiform needling group(P<0.05)and electroacupuncture group(P<0.01). CONCLUSIONS: All the three different kinds of acupuncture and moxibustion methods have positively regulatory effect on functional constipation; electroacupuncture is the best for the regulation of plasma NO, NOS and VIP contents, while moxibustion is the best for the regulation of VIP expression in colonic tissue.

Effect of XiangBin granules on post-operative gastrointestinal function and brain-gut peptides after transabdominal gynecological surgery.

OBJECTIVES: We conducted a prospective clinical randomized single-blind placebo-controlled trial (ChiCTR-TRC-14004156) to observe the effect of XiangBin granules on the recovery of gastrointestinal function and levels of brain-gut peptide motilin (MTL); vasoactive intestinal peptide (VIP); growth hormone releasing peptide-ghrelin, GHRP-ghrelin, and corticotropin releasing hormone (CRH), after transabdominal gynecological surgery. STUDY DESIGN: Patients undergoing gynecologic abdominal surgery were randomly divided in a 2:1 ratio (according to the data of pre-trial which was a small sample randomized trial in gynecology inpatient) into two groups: the larger treatment group taking XiangBin granules, and the smaller placebo group taking Chinese herbal placebo. The aim was to observe anal exhaust time, time to defecation, and the change in level of brain-gut peptide. RESULT: A significantly shorter time to first postoperative anal exhaust was observed in the treatment group. In the placebo group, the MTL level on the first day after surgery was lower than the preoperative level (P<0.05). In both groups, the GHRP-ghrelin level on the first postoperative day was lower than the preoperative level (P<0.05). In the treatment group, the GHRP-ghrelin level of the third day after surgery was higher than the first day after surgery (P<0.05). The CRH level on the first postoperative day was lower in the treatment group compared to the placebo group (P<0.05). CONCLUSION: XiangBin granules can effectively promote the recovery of gastrointestinal function after surgery for gynecologic abdomen and promote GHRP-ghrelin and MTL recovery, and reduce the postoperative secretion of CRH.

Modulation of circulating vasoactive peptides and extracellular matrix proteins are two novel mechanisms in the cardioprotective action of acarbose.

BACKGROUND: Acarbose, an alpha-glucosidase inhibitor, unexpectedly reduced the incidence of hypertension and cardiovascular endpoints in the STOP-NIDDM study. Based on the growing evidence of a link between vasoregulatory peptides and metabolic traits, we hypothesized that changes of the Glycemic Index by acarbose may modulate vasoregulatory peptide levels via regulation of postprandial metabolism. METHODS: Subjects with type 2 diabetes and with metabolic syndrome were treated with acarbose (12 weeks, 300mg/d) in a double-blind, placebo-controlled, cross-over intervention. Changes in fasting and postprandial levels of midregional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-endothelin-1 (CT-proET-1) and midregional pro-adrenomedullin (MR-proADM), WNT1 Inducible Signaling Pathway Protein 1 (WISP1) as well as fasting and postprandial glucose/insulin levels in the liquid meal test were assessed. RESULTS: Acarbose strongly decreased postprandial insulin concentrations in subjects with metabolic syndrome (P=0.004), and postprandial glucose excursions in both groups. Postprandial MR-proANP and CT-proET-1 levels increased after acarbose treatment (P<0.01 and P<0.05, respectively) in subjects with metabolic syndrome only. No effect of acarbose treatment on MR-prADM was observed in both groups. All three peptides were correlated with each over, but neither with insulin sensitivity in euglycemic clamps, nor with adiponectin levels. WISP1 decreased after acarbose treatment in subjects with metabolic syndrome. CONCLUSIONS: Plasma MR- proANP and CT-proET-1 concentrations, but not MR-prADM concentrations, were affected by treatment with acarbose over 12 weeks. Our findings provide new possible mechanisms of acarbose action in diabetes and metabolic syndrome.

Clinical study of electro-acupuncture treatment with different intensities for functional constipation patients.

Functional constipation (FC) is a common functional bowel disorder disease that affects life quality of a large number of people. This study aimed to explore the impact of different intensities of electro-acupuncture (EA) treatment for FC patients. Totally, 111 patients with FC meeting the Rome III criteria were randomly assigned to different intensities of EA groups (low and high intensity of EA groups) and medicine-controlled (MC) group. In EA groups, patients were treated with EA at quchi (LI11) and shangjuxu (ST37) bilaterally for 4 weeks, 5 times/week in the first 2 weeks, and 3 times/week in the last 2 weeks. In MC group, 5 mg mosapride citrate was administered orally 3 times/day for 4 weeks. Spontaneous bowel movement frequency each day was recorded using a constipation diary. Self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were used to assess the patients' psychological state. Cortisol (CORT), substance P (SP), and vasoactive intestinal polypeptide (VIP) were evaluated at baseline and at the end of 4 weeks after treatment. As compared with the baseline, there was statistically significant increase in stool frequency every week (P<0.01), but there was no statistically significant difference among the three groups. As compared with the baseline, after 4 weeks of EA therapy, the scores of SDS and serum levels of CORT were decreased significantly in low intensity of EA group (P<0.01), and the serum levels of SP and VIP were increased significantly (P<0.05); the scores of SAS and SDS and serum levels of CORT were decreased significantly in high intensity of EA group (P<0.05), and the serum levels of SP and VIP were increased significantly (P<0.05); the serum levels of CORT and VIP were increased significantly in MC group (P<0.05). As compared with MC group, after 4 weeks of treatment, the serum levels of SP were signifcicantly increased in low intensity of EA group (P<0.01). Low and high intensities of EA could increase the stool frequency, improve the FC patient's anxiety and depression, reduce the serum levels of CORT, and increase the serum levels of SP and VIP effectively. It is concluded that both low and high intensities of EA are effective for FC patients, but there is no significant difference between the low and high intensities of EA.

Age-related changes in gonadal and serotonergic axes of broiler breeder roosters.

Fertility of domestic roosters decreases at ≈ 50 wk of age. In a previous study on aging white leghorn roosters, low fertility was accompanied by low levels of both hypothalamic vasoactive intestinal peptide (VIP) and pituitary prolactin (PRL) mRNA expression; however, their role in aging broiler breeder rooster reproduction is still unclear. In this study we compared reproductive activities of young (35-wk-old) and aging (73-wk-old) broiler breeder roosters. Weekly semen volume; concentration and ejaculation grade; and concentrations of plasma testosterone, estradiol, and PRL were examined. Every other week, 10 roosters from each group were euthanized, their testes weighed, and hypothalamus and pituitary removed to determine mRNA expression of hypothalamic GnRH-I, pituitary FSH, pituitary LH, hypothalamic VIP, and pituitary PRL. Aging roosters had significantly lower testis weight and semen volume, sperm concentration, ejaculation grade and plasma testosterone and low hypothalamic GnRH-I, pituitary FSH, and pituitary LH mRNA expression than young roosters (P ≤ 0.05). Aging roosters had higher concentrations of plasma estradiol and PRL and higher hypothalamic VIP and pituitary PRL mRNA expression than young roosters (P ≤ 0.05). We suggest that PRL, which is known to inhibit the gonadal axis, and its releasing factor, VIP, play an important role in the reproductive failure associated with age in broiler breeder roosters.

Prolonged treatment with transcutaneous electrical nerve stimulation (TENS) modulates neuro-gastric motility and plasma levels of vasoactive intestinal peptide (VIP), motilin and interleukin-6 (IL-6) in systemic sclerosis.

PURPOSE: We assessed the effects of transcutaneous electrical nerve stimulation (TENS) on neurogastric functioning in scleroderma patients. METHODS: Seventeen SSc patients underwent 30 min TENS treatment >10Hz at GI acupuncture points PC6 and ST36, once (acute TENS) and then after two weeks of TENS sessions for 30 min twice daily (prolonged TENS). Data collected at Visits 1 and 2 included gastric myoelectrical activity (GMA) by surface electrogastrography (EGG), heart rate variability (HRV) by surface electrocardiography (EKG), GI specific symptoms and health related SF-36 questionnaires. Plasma VIP, motilin and IL-6 levels were determined. Statistical analyses were performed by Student's t-test, Spearman Rank and p-values <0.05 were considered significant. RESULTS: 1. Only after prolonged TENS, the percentages of normal slow waves and average slow wave coupling (especially channels 1, 2 reflecting gastric pacemaker and corpus regions) were significantly increased; 2. the percentage of normal slow waves was significantly correlated to sympathovagal balance; 3. Mean plasma VIP and motilin levels were significantly decreased after acute TENS, (vs. baseline), generally maintained in the prolonged TENS intervals. Compared to baseline, mean plasma IL-6 levels were significantly increased after acute TENS, but significantly decreased after prolonged TENS. 4. After prolonged TENS, the frequency of awakening due to abdominal pain and abdominal bloating were significantly and modestly decreased, respectively. CONCLUSIONS: In SSc patients, two weeks of daily TENS improved patient GMA scores, lowered plasma VIP, motilin and IL-6 levels and improved association between GMA and sympathovagal balance. This supports the therapeutic potential of prolonged TENS to enhance gastric myoelectrical functioning in SSc.

Comparison of the effects of pantethine and fursultiamine on plasma gastrointestinal peptide levels in healthy volunteers.

Pantethine and fursultiamine have been evaluated for their clinical usefulness in the treatment and prevention of uncomplicated postoperative adhesive intestinal obstruction. In recent years, the actions of drugs used to treat gastrointestinal diseases have been elucidated pharmacologically from the viewpoints of gastrointestinal peptide levels. We examined the effects of pantethine and fursultiamine on plasma levels of calcitonin gene-related peptide (CGRP)-, vasoactive intestinal polypeptide (VIP)-, motilin- and substance P (SP)-like immunoreactive substances (IS) in healthy subjects. An open-labeled study was conducted on five healthy volunteers. Each subject was administered a single oral dose of pantethine, fursultiamine and placebo at intervals of one month. Venous blood samples were collected before and at 20, 40, 60, 90, 120, 180 and 240 min after each administration. Plasma peptide levels were measured using a highly sensitive enzyme immunoassay. A single oral dose of pantethine resulted in significant increases of plasma CGRP- and VIP-IS levels compared to placebo. Furthermore, areas under the plasma concentration-time curves (AUC(0-240)) of CGRP- and VIP-IS were significantly higher after pantethine administration compared with placebo. On the other hand, fursultiamine had no effect on plasma levels and AUC(0-240) of CGRP-, VIP-, motilin- and SP-IS. This study demonstrated the different effects of pantethine and fursultiamine from the viewpoint of plasma gastrointestinal peptide changes. The pharmacological effects of pantethine may be closely related to the changes in plasma CGRP- and VIP-IS levels.

[Effect and mechanism of reserpine for changing salivary protein secretion in Pi-deficient rats].

OBJECTIVE: To study the effect of reserpine (RSP) for changing salivary protein secretion in Pi-deficient rats and to explore its possible mechanism. METHODS: Twenty rats allocated in the RSP group were given subcutaneous injection of RSP [0.4 mg/(kg x d)] for 9 successive days, while the other 20 rats in the control group were injected with same volume of saline instead. On the 10th day, ten rats randomly selected from each group were subjected for extracting saliva to detect salivary amylase activity (sAA) before and after an acid stimulation; and drawing blood from the orbital vein to measure the contents of vasoactive intestinal peptide (VIP) and cyclic adenosine monophosphate (cAMP). Then they were sacrificed and their parotids were taken out for pathological examination with HE staining, as well as for VIP and cAMP measuring, and zymogen granules counting under a transmission electron microscope. The remainder animals were stopped injecting and normally fed to 40 days, then subjected to be detected as above-mentioned. RESULTS: Food intake and body weight reduction were more significantly in the RSP group than in the control group. On the 10th day, the ratio of sAA before/after stimulation in the RSP group was 0.39 +/- 0.18, significantly lower than that in the control group (0.80 +/- 0.21, P < 0.01), but it was restored rapidly, reaching the normal range on the 25th day, on the 40th day, it became significantly different to the level on the 10th day (P < 0.05) and approached the level in the control group (P > 0.05). No significant pathological change of parotid was found in both groups; but the number of zymogen granules in the RSP group was remarkably more than that in the control group (41.4 +/- 4.9 vs 34.6 +/- 5.2, P < 0.01). Serum level of VIP in the RSP group was significantly less while that of cAMP was higher than that in the control group (22.5 +/- 13.1 mg/L vs 38.5 +/- 14.1 mg/L, and 125.8 +/- 15.5 micromol/L vs 105.3 +/- 16.7 micromol/L, both P < 0.05), but no inter-group difference was found in parotid tissue contents of both VIP and cAMP. All the indices detected became equivalent in the two groups on the 40th day. CONCLUSION: The reduction of salivary protein in Pi-deficient rats induced by RSP may be related to the regulatory pathway of VIP and cAMP.

Reproductive hormones, hepatic deiodinase messenger ribonucleic acid, and vasoactive intestinal polypeptide-immunoreactive cells in hypothalamus in the heat stress-induced or chemically induced hypothyroid laying hen.

Heat stress (HS) effects on reproductive and thyroid hormones have been well documented; however, mechanisms of action are not well understood. Two studies were conducted to determine whether HS-induced and hypothyroid-induced effects are similar in the laying hen, with regard to reproductive hormones and vasoactive intestinal polypeptide (VIP)-immunoreactive cells in the hypothalamus. In study 1, thirty 32-wk-old Hy-Line W-36 laying hens, housed at 22 degrees C, were cannulated. On d 0 and then on d 1 to 5 of HS (35 degrees C, 50% RH), a daily blood sample was obtained and assayed for triiodothyronine (T(3)), thyroxine (T(4)), 17beta-estradiol (E(2)), progesterone (P(4)), prolactin (PRL), and VIP, and T(3):T(4)was calculated. On d 0, 1, 3, and 5, livers were obtained for hepatic type I deiodinase mRNA (cDI-1) determination. In study 2, eighty 32-wk-old hens were randomly assigned to 4 treatments of 20 birds each: 1) HS (36.5 degrees C, 50% RH), 2) thiouracil-induced hypothyroidism (HY), 3) HY + T(4) administration, and 4) control (22 degrees C). Beginning on d 1 of the 5-d study, daily blood samples (3.0 mL) were removed and assayed as in study 1. On d 5, brains were removed from 3 hens/treatment and immunoreactivity of VIP cells was determined. In study 1, HS reduced E(2), P(4), T(3) (P = 0.0001), T(3):T(4) ratio (P = 0.0078), and hepatic type I deiodinase mRNA (P = 0.0204) and increased T(4) (P = 0.0013); there was no effect on VIP or PRL. In study 2, HS and HY reduced T(3), T(3):T(4) ratio, and E(2) (P = 0.0001) and increased PRL (P = 0.0045); HS alone decreased P(4) (P = 0.0001). In HY + T(4), plasma E(2) and PRL were similar to control. Vasoactive intestinal polypeptide increased in plasma of HY birds, but there was no effect of HS or HY + T(4). Immunoreactive VIP cells increased (P = 0.0036) in nucleus inferior hypothalami of HS and HY brains. In HY + T(4), VIP immunoreactive cell numbers were similar to control. It appears that HY induced chemically or by HS exerts similar effects on reproductive hormones in the hen; the results suggest involvement of the VIP-PRL pathway even though peripheral blood concentrations were not consistent between studies.

[Influence of electroacupuncture of "Daling"(PC 7) on heart rate, duration of arrhythmia and plasma vasoactive intestinal peptide contents in ventricular tachycardia rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on heart rate (HR), arrhythmia duration, and plasma vasoactive intestinal peptide (VIP) level in ventricular tachycardia (VT) rats so as to study its underlying adjustment mechanism. METHODS: A total of 70 SD rats were randomly divided into normal control, model (VT), "Daling" (PC 7, EA-PC 7) and "Taiyuan" (LU 9, EA-LU 9) groups. VT model was duplicated by injection of CsCI (2 mol/L, 1.6 mmoL/kg, femoral vein). EA (2 Hz/15 Hz, 1 mA) was applied to "Daling" (PC 7) and "Taiyuan" (LU 9) for 5 min after inserting acupuncture needles. BL-410 Biofunctional System was used to record the ECG of the standard limb lead II, and plasma VIP content assayed by using radioimmunoassay. RESULTS: Following intravenous injection of CsCI, HR increased significantly in model, EA-PC 7 and EA-LU 9 groups (P < 0.05). Compared to model group, HR at 5 min, 10 min and 15 min after administration of CsCI and the duration of arrhythmia in EA-PC 7 group decreased considerably (P < 0.01). No significant differences were found between EA-LU 9 and model groups in HR and the duration of arrhythmia (P > 0.05). Compared with normal group, the content of plasma VIP in model group decreased apparently (P < 0.05), while in comparison with model group, plasma VIP level in EA-PC 7 group increased considerably (P < 0.01). CONCLUSION: Electroacupuncture of "Daling" (PC7) can effectively suppress CsCI-induced tachycardia which may be closely associated with its effect in reducing plasma VIP level.

[Effects of eye-acupuncture therapy on serum and colonic SP and VIP contents in rats with irritable bowel syndrome].

OBJECTIVE: To observe the effect of the eye-acupuncture therapy on serum and colonic substance P (SP) and vasoactive intestinal peptide (VIP) contents in rats with irritable bowel syndrome (IBS) so as to explore its underlying mechanism. METHODS: Forty male Wistar rats were equally randomized into control group, IBS model group, eye-acupuncture group and medication (Pinaverium bromide, 7.5 mg/kg, twice daily, intragastric administration) group. IBS model was established by giving the rat with chronic stress stimulation (cold-water swimming, tail clamping, electrical shock, etc.) for 18 days. Eye-acupuncture of Xiajiao (Low Energizer) Area, Pi (Spleen) Area, Gan (Liver) Area and Dachang (Large Intestine) Area was given to the rat 20 min, twice daily for 7 d. Histopathological changes of the colon tissue were displayed by HE staining; and serum and colonic SP and VIP contents were detected by enzyme linked immunosorbent assay (ELISA). RESULTS: No significant difference was found among 4 groups in the histopathological changes of the colon. In comparison with normal control group, both serum and colonic SP and VIP contents in model group increased significantly (P < 0.01), while compared with model group, those in eye-acupuncture and medication groups lowered considerably (P < 0.01). CONCLUSION: Eye-acupuncture can reduce serum and coIonic SP and VIP contents in IBS rats, which may play a role in relieving IBS in eye-acupuncture clinic.

[Effect of rheum on gastrointestinal hormones in rats with severe scald injury].

OBJECTIVE: To observe the changes in motilin (MTL), substance P (SP), vasoactive intestinal peptide (VIP) and somatostatin (SS) in plasma of rats with severe scald injury at early stage and the effect of rheum on their changes. METHODS: Eighty-eight Wistar rats were randomly divided into normal control group (NC, n = 8), scald group (S, gavage of distilled water after full-thickness scald, n = 40), therapeutic group (T, gavage of rheum solution after full-thickness scald, n = 40). The blood samples were harvested from inferior vena cava at 6, 12, 24, 48, 72 post scald hours (PSH) to determine the levels of MTL, SS, SP and VIP with radioimmunoassay. RESULTS: (1) The levels of MTL and SP were (198 +/- 28), (61 +/- 10) ng/L, respectively, in NC group. The levels of MTL and SP in S group reached their minimum values [(110 +/- 15), (30 +/- 5) ng/L, respectively] at 6 PSH, then ascended slowly, peaked at 72 PSH but still lower than those in NC group (P < 0.05). The levels of MTL and SP slowly descended in T group, reached normal levels at 48 PSH, and obviously higher than those in NC group at 72 PSH [(232 +/- 32), (73 +/- 11) ng/ L, respectively, P < 0.05], which were higher than those in S group at 6 -72 PSH. (2) The levels of VIP and SS were (35 +/- 6), (30 +/- 5) ng/L, respectively, in NC group. The levels of VIP and SS in S group were (70 +/- 12), (49 +/- 9) ng/L at 6 PSH, which were obviously higher than those in NC group (P < 0.01), then descended slowly, but still higher than normal level at 72 PSH (P < 0.05). The levels of VIP and SS in T group ascended slowly, reached the normal level at 48 PSH, which were lower than those in S group at each time points, and VIP reached peak value at 12 PSH. CONCLUSION: Rheum may regulate secretion and release of gastrointestinal hormones to plasma in rats with severe scald injury at early stage.

Different effects of electroacupuncture on esophageal motility and serum hormones in cats with esophagitis.

We aim to investigate the effects of different electroacupuncture (EA) frequencies at ST-36 on esophageal motility, and to compare the effect of EA on serum gastrin (GAS), motilin (MTL), and vasoactive intestinal peptide (VIP). Thirty-two cats were divided into four equal groups. All animals underwent a Heller myotomy. After esophagitis developed two frequencies (2/15 Hz or 2/100 Hz) of EA were delivered into ST-36 (LEA group [low EA], HEA group [high EA]). Animals submitted to EA on a non-point region (EANP) were used as controls (LEANP group, HEANP group), respectively. Esophageal motility was continuously monitored. The lower esophageal sphincter pressure (LESP) decreased significantly after myotomy. The LESP decreased in both LEA and LEANP cats, and in LEA cats the pressure decrease was greater. The LESP increased in the HEA group, which was higher than that in the HEANP group (P < 0.05). High-frequency EA significantly increased the peak amplitude in esophageal peristalsis. There was a decrease in serum GAS and MTL in LEA cats compared with LEANP cats (both P < 0.01). GAS and MTL were higher in the HEA group than in the HEANP group (both P < 0.01). Serum VIP decreased in the HEA group (P < 0.05), while it increased in the LEA group (P < 0.05), compared with EANP groups, respectively. EA with a high frequency at ST-36 enhances LESP as well as esophageal motility, while EA with a low frequency decreases LESP. The effect of EA is acupoint-specific, and this effect appears to be mediated through GAS, MTL and VIP.

Effects of cinacalcet on gastrointestinal hormone release in patients with secondary hyperparathyroidism undergoing dialysis.

UNLABELLED: Objective. Our aim has been evaluating the influence of an acute dose of cinacalcet on the gastrointestinal hormonal responses to a test meal in uraemic patients with secondary hyperparathyroidism undergoing peritoneal dialysis (PD) or haemodialysis (HD). METHODS: Twenty patients (11 PD, 9 HD) on cinacalcet treatment (30-120 mg/day) were studied. Twelve patients (1 PD, 11 HD) who never received cinacalcet were studied as control group. Each patient received a test meal with blood samples at 0, 2 and 4 h. At 0 time, patients in the cinacalcet group received their usual oral dose of this calcimimetic. Plasma concentrations of intact parathyroid hormone (PTH), vasoactive intestinal peptide (VIP), ghrelin, substance P, serotonin, cholecystokinin (CCK) and gastrin were quantified at 0, 2 and 4 h. RESULTS: No significant differences in baseline concentrations of serum VIP, ghrelin, substance P, serotonine, CCK and gastrin were found between controls and cinacalcet-treated patients. In comparison with the control group, cinacalcet administration was followed by a significant decrease in VIP concentration at 4 h and a significant increase in substance P at 4 h. However, the areas under the curves of all studied gut hormones were similar in both groups. CONCLUSION: An acute dose of cinacalcet exerts minimal influence on gut hormone responses to a mixed meal in dialysis patients on chronic therapy with this drug. The small but significant differences between control subjects and patients on cinacalcet in VIP and substance P levels at 4 h should be investigated in symptomatic patients.

[Effect of electroacupuncture on gastrointestinal dynamics in acute pancreatitis patients and its mechanism].

OBJECTIVE: To investigate the therapeutic effect and mechanism of electroacupuncture (EA) in treating gastrointestinal disorder in acute pancreatitis (AP) patients. METHODS: A total of 94 cases of AP patients were divided into acupuncture group (n=56) and control group (n=38). The severity of AP was evaluated according to APACHE II and Balthazar CT scoring system. EA (4 Hz, 4-6 V) was applied to bilateral Zusanli (ST 36), Shangjuxu (ST 37), Xuanzhong (GB 39), Taichong (LR 3), and Gongsun (SP 4) for 60 min, twice a day, 5 days altogether. Total and segmental colonic transit time (CTT) were determined by using ingestion of radiopaque markers (SITZMARKS) according to the modified Metcalf's method, serum motilin (MTL), cholecystokinin (CCK), vasoactive intestinal peptide (VIP) contents were assayed using enzyme linked immunosorbent assay (ELISA). RESULTS: Compared with normal values, total and segmental CTT of AP patients (control group) increased apparently (P < 0.05), especially in right colon, serum MTL and CCK contents in both control and treatment groups on the 1st day decreased considerably (P < 0.05), while serum VIP levels of both control and treatment groups on the 1st day increased markedly (P < 0.05). In comparison with control group, total and segmental CTT of treatment group decreased significantly (P < 0.05). Auto-comparison of both control and treatment groups showed that serum MTL and CCK contents on day 9 were significantly higher than those on day 1 (P < 0.05), while serum VIP contents on day 9 in these two groups were both obviously lower than those on day 1 (P < 0.05). No significant differences were found between treatment group and control group in serum MTL, CCK and VIP levels on the 9th day after the treatment (P > 0.05). CONCLUSION: Acupuncture is able to enhance the gastrointestinal dynamics, improve its motor activity.