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Neonatal androgenization increases vasoactive intestinal peptide levels in rat anterior pituitary: possible involvement of vasoactive intestinal peptide in the neonatal androgenization-induced hyperprolactinemia.

Accumulating evidence suggests that vasoactive intestinal peptide (VIP) may be a physiological PRL-releasing factor. In the present study, we examined a possible involvement of VIP in the neonatal androgenization (NA)-induced hyperprolactinemia. Twenty-four hours after birth, newborn female rats were injected sc with 1,000 micrograms of testosterone (NA) or with oil vehicle only (control). Both groups were sacrificed at 8 weeks of age. Compared to controls, NA rats showed significantly higher plasma PRL levels (7.3 fold), anterior pituitary (AP) PRL content (2.1 fold) and plasma estradiol levels (2.1 fold). AP VIP content was extremely higher (61 fold) in NA rats than in controls. However, NA did not affect VIP content in the suprachiasmatic nucleus, paraventricular nucleus or median eminence. These results suggest that the NA-induced hyperprolactinemia may be mediated, at least in part, by paracrine and/or autocrine effects of the increased AP VIP on PRL secretion. However, since the potentiation by NA of the AP VIP content was extremely marked compared to those of the other parameters, the possibility was also raised that the increased AP VIP may be involved in other endocrine and/or nonendocrine events occurring in the AP.

Androgens↗

Intestinal motility and jejunal feeding in children with chronic intestinal pseudo-obstruction.

BACKGROUND/AIMS: Total parenteral nutrition is responsible for most of the morbidity and mortality of childhood chronic intestinal pseudo-obstruction (CIP). The aim of this study was to determine if there are manometric patterns associated with the success of jejunal feedings in children with CIP. METHODS: Eighteen children with CIP (age range, 1-9 years; mean, 4 years; 11 boys and 7 girls) were studied. All patients required parenteral nutrition or failed to thrive while receiving gastrostomy feedings. All underwent an antroduodenal manometry before surgical placement of a jejunostomy. Continuous drip jejunal feeding with an elemental formula was subsequently initiated. Follow-up after jejunal feeding was 1.6 years (range, 6 months to 4 years). Jejunal manometry was performed 2 months to 1 year after jejunostomy. RESULTS: Jejunal feeding eliminated the need for parenteral nutrition in all 9 patients with migrating motor complex (MMC) and in 3 of 9 patients without MMC (P < 0.01). The MMC was present or absent in both antroduodenal and jejunal manometry in 14 of 18 children (77.7%). In 10 of 18 children (55%), duodenal and jejunal manometry showed similar qualitative abnormalities. CONCLUSIONS: In selected children with CIP who fail gastrostomy feeding, jejunal tube feeding is an alternative to parenteral nutrition. The presence of MMCs is associated with a successful adaptation to jejunal feeding.

Child↗

Immunoepidemiology of intestinal helminthic infections. 1. The global burden of intestinal nematode disease.

Estimates of the world-wide prevalence of intestinal nematode infections indicate that there are more than 1000 million people infected, and several million cases of clinical helminthiases. Recent studies suggest that the morbidity has been underestimated and that moderate intensities of infection may have important developmental consequences, particularly for children of school age.

Ascariasis↗

Vasoactive intestinal polypeptide decreased in cerebrospinal fluid (CSF) in atypical depression. Vasoactive intestinal polypeptide, cholecystokinin and gastrin in CSF in psychiatric disorders.

Vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK) and gastrin in the cerebrospinal fluid (CSF) were studied in patients with endogenous depression, non-endogenous depression, mania, schizophrenia and a control group. All patients were classified according to ICD-9 and the group of depressions was further classified according to the Newcastle Rating Scales for depression (Carney et al. 1965) (N-I). In the group of non-endogenously depressed patients, CSF-VIP levels (median 16 pmol/l) were found to be significantly lower than those of controls (median = 32 pmol/l) and endogenous depressives (36 pmol/l). In the non-endogenous group, it appeared that the low CSF-VIP was due to a group of patients who, during a past or present depressive episode, had been diagnosed as suffering from endogenous depression. Moreover, this group was clinically characterized by 'dysphoric/hysterical features', 'reversed diurnal variation' (i.e. worse in the evening), and 'lack of clearly circumscribed episodes'. In many aspects this group seems similar to the atypical depressives described as monoamine oxidase inhibitor responders. Concerning CSF-CCK and CSF-gastrin, no significant differences between the examined groups were demonstrated.

Adult↗

Optimization of the intestinal lavage procedure for determination of intestinal immune responses.

Optimal conditions to process, concentrate and store intestinal lavage fluid were studied in samples collected from volunteers before and after oral immunization with a prototype vaccine against enterotoxigenic Escherichia coli (ETEC) diarrhoea. Total IgA and specific IgA antibody titres against enterotoxin and colonization factor antigen were determined in 22 lavage samples which were either enzyme-inhibited or heat-inactivated and then subjected to different long-term storage conditions. Samples were analysed within 1 month of collection and also after 3, 6 and 24 months of storage. Total IgA concentrations and specific IgA antibody levels were higher in lavage samples treated with enzyme inhibitors (soybean trypsin inhibitor and phenylmethylsulfonyl fluoride) than in those heat-inactivated. Similarily, concentration of the lavage fluid by freeze-drying was superior to concentration against polyethylene glycol. Specific antibody titres remained elevated after storage for at least 6 months but declined after 2 years in frozen compared with freeze-dried samples.

Administration, Oral↗

Distribution of vasoactive intestinal peptide, bombesin, and gastrin-cholecystokinin like peptides in the avian intestinal tract and brain.

The distribution of vasoactive intestinal peptide (VIP), bombesin and gastrin-cholecystokinin in the chicken was studied by radioimmunoassay of tissue extracts. VIP was present in high concentrations in colon (186 +/- 29 pmol/g), cloaca (116 +/- 27 pmol/g), jejunum (97 +/- 14 pmol/g) and pancreas (15 +/- 3 pmol/g) but not detected in lung, liver or thymus. The highest concentration of bombesin was in the proventriculus (92 +/- 13 pmol/g), negligible in remaining gut but found in brain. Gel chromatography indicated two forms of bombesin: one form eluting with bombesin-14 and the other with gastrin releasing peptide. Gastrin-like immunoreactivity was found in low levels in the gut and brain. The concentrations were higher with an antiserum which cross reacted with the carboxy terminus common to gastrin-17 and CCK compared to a gastrin specific antisera (P less than 0.01). This suggests that the carboxy terminal region has been conserved during evolution. Each distribution pattern of bombesin, VIP and gastrin CCK is different, and distinct from that found in mammals, suggesting specific roles for these peptides in birds.

Animals↗

Effect of intestinal fluid flux on ibuprofen absorption in the rat intestine.

Previously the apparent permeability coefficient (P(app)) of ibuprofen was observed to vary depending on the perfusion medium employed. The present work explores the possible contributions to these differences. Studies were undertaken using an in situ single pass rat gut technique. Lumenal drug concentrations and plasma drug levels were assayed by HPLC. Absorption rate constants (k(0)) were determined from fractions of drug unabsorbed from the intestineat steady state. Plasma data were fitted to a two compartment open model with zero-order input. Significant differences in net fluid flux were observed between the various buffered perfusion media, with fluxes varying from -0.044+/-0.006 ml min(-1) to +0.057+/-0.013 ml min(-1), the lower and negative values occurring for lower pH media and the larger positive values tending to occur with media of higher pH. A linear relationship was found between the P(app) of ibuprofen and net water flux (y=1.13+11.3x; r(2)=0.80). Apparent zero-order rate constants for ibuprofen appearance in plasma correlated well with absorption rate constants estimated from steady state lumenal drug concentration [k(0(gut))]. From the linear relationship between P(app) and fluid flux a normalized P(app) for ibuprofen (i.e. the P(app) in the absence of net fluid flux) of 1.1 x 10(-4)cms(-1) was determined Net lumenal fluid flux is dependent on perfusion medium composition and significantly alters ibuprofen absorption. The differences observed for P(app) were reflected in systemic drug absorption concentrations. The findings of these studies underline the importance of standardizing the osmolarity of experimental media used for the determination of intestinal permeability data.

Animals↗

Dual actions of S-nitrosylated derivative of vasoactive intestinal peptide as a vasoactive intestinal peptide-like mediator and a nitric oxide carrier.

Vasoactive intestinal peptide (VIP) has been postulated as a non-adrenergic non-cholinergic (NANC) transmitter in the relaxation of vascular and non-vascular systems. In order to synergize the vasoactivities of VIP with nitric oxide (NO), we synthesized a S-nitrosylated derivative of VIP, VIP-Gly-Cys-NO (VIPGC-NO). On aortic rings, VIPGC-NO exhibited a dose-dependent vasorelaxation similar to S-nitrosoglutathione (GSNO), and both induced complete vasorelaxation at 1 microM, whereas, VIP at 1 microM only produced 19% relaxation. The degree of vasorelaxation was proportional to the increases in cyclic GMP with no significant enhancement in cyclic AMP (cAMP) level. On precontracted tracheal rings, VIP, VIPGC-NO, VIPGC and GSNO produced relaxation with EC50 of 74+/-5, 32+/-6, 59+/-9, and 251+/-32 nM, respectively, which was consistent with increases in cyclic GMP (cGMP). A marked increase in cAMP was observed from the tracheal rings pretreated with VIP, VIPGC-NO and its parent VIP-Gly-Cys (VIPGC) as well as isoproterenol. Propranolol only blocked the airway relaxation induced by isoproterenol, but did not antagonize the relaxation induced by VIP, VIPGC and VIPGC-NO. On rabbit sphincter of Oddi, VIP, VIPGC-NO and VIPGC inhibited both basic and acetylcholine-induced contraction frequency and amplitude, whereas, GSNO was less potent than VIP and its derivatives over a range of 2 log units in this respect. On rat gastric fundus, these compounds inhibited contraction amplitude and frequency induced with 5-hydroxytryptamine (5-HT) in the order of inhibitory potency VIP > VIPGC-NO > VIPGC > isoproterenol > GSNO. Our data suggest that: (1) NO is selective in relaxing vascular smooth muscle via the cGMP pathway, whereas VIP is selective in relaxing non-vascular smooth muscles via the activation of both cGMP and cAMP pathways; (2) VIPGC-NO preserves the intrinsic function of VIP but acquires NO-like vasoactivities.

Animals↗

5-Fluorouracil-induced intestinal toxicity: what determines the severity of damage to murine intestinal crypt epithelia?

To elucidate the relationship between 5-fluorouracil (5-FU) distribution and 5-FU-induced apoptosis and/or cell cycle arrest, microautoradiography was applied to murine intestinal crypts exposed to [14C] 5-FU by intravenous infusion. The histologic location of apoptotic cells in the crypt did not correlate to that of 5-FU. The temporal profiles of apoptotic and/or mitotic indexes corresponded to those of orally administered 5-FU in a previous study. Two cell cycle-related proteins, p21(WAF/Cip1) and bax, were also investigated in the present study. With time, p21(WAF/Cip1)-positive nuclei apparently migrated up the crypt. Bax-positive cytoplasm was observed throughout the crypt epithelial cells, accompanied by the occurrence of apoptosis, and remained until 48 h when the control level recovered. The findings demonstrate that 5-FU mainly exerts an apoptotic effect and/or cell cycle arrest by systemic exposure, and p21 and bax expression determine an individual cell's fate.

Animals↗

Covalent structure of a group-specific protease from rat small intestine. Appendix: crystallographic data for a group specific protease from rat intestine.

"Group-specific" protease (GSP) is a serine protease, obtained from rat small intestine, which preferentially inactivates the apo forms of certain pyridoxal phosphate requiring enzymes. The enzyme contains 224 amino acid residues in a single polypeptide chain and three disulfide bonds. In the present work the covalent structure has been determined and its homologous relationship to those of chymotrypsin, trypsin, and elastase has been established (approximately 33% identity with each). The residues forming the "charge-relay" system of the active site of chymotrypsin (His-57, Asp-102, and Ser-195) are found in corresponding regions in GSP, whereas an alanyl residue at position 176 of GSP corresponds to a residue which participates in the primary substrate binding site in serine proteases (Asp-177 in trypsin; Ser-189 in chymotrypsin). Three disulfide bonds in GSP occur in similar positions in chymotrypsin, trypsin, and elastase. However, GSP lacks a disulfide bond which is present in all known serine proteases (linking Cys-191 to Cys-220 in chymotrypsin). In view of the close proximity of this bond to both the primary and the antiparallel binding sites of various serine proteases, it is likely that its absence in GSP is related to the substrate specificity of this enzyme. It is concluded that GSP diverged from a common ancestor preceding chymotrypsin but following trypsin.

Amino Acid Sequence↗

Heparin absorption across the intestine: effects of sodium N-[8-(2-hydroxybenzoyl)amino]caprylate in rat in situ intestinal instillations and in Caco-2 monolayers.

PURPOSE: The effects of sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC) on heparin intestinal absorption were studied using rat in situ ileal and colonic instillations and Caco-2 monolayers. METHODS: The flux of heparin was tested in the following groups: i) heparin alone, ii) heparin in the presence of SNAC, iii) heparin in the presence of propylene glycol (PG), and iv) heparin in the presence of SNAC and PG. Heparin absorption was measured by the APTT assay in the in situ models and by the anti-Factor Xa assay in Caco-2. SNAC and [3H]-SNAC fluxes were assessed by HPLC and by scintillation counting respectively. RESULTS: In the rat ileal and colonic in situ instillations SNAC (17-35 mg) promoted heparin absorption in the presence and absence of PG without damaging the tissue. PG alone did not alter heparin absorption in situ, but it amplified the effect of SNAC. In Caco-2, enhanced heparin fluxes were variable in the presence of non-cytotoxic concentrations of SNAC (< 10 mg/ml) and these effects could not be discriminated from those of PG. Papp values for SNAC alone were 2.2 x 10(-5) cm/s and 2.0 x 10(-5) cm/s in the mucosal-to-serosal and serosal-to-mucosal directions respectively, suggesting a substantial passive transcellular flux. Transport of SNAC was significantly reduced in the presence of heparin and/or PG, perhaps indicating physical association between the agents. CONCLUSIONS: SNAC augmented heparin absorption alone and in combination with PG in the rat in situ models without causing toxicity. Caco-2 had limitations for testing increased heparin absorption due to cytotoxic effects of high concentrations of SNAC and PG. However, SNAC itself was well absorbed across Caco-2 and its mechanism of permeation was determined.

Animals↗

Fixing the intestinal mucosa in the bone marrow transplant patient: lessons from other intestinal immunodeficiencies and inflammatory disorders.

Gastrointestinal inflammation is common following bone marrow transplantation. Key pathogenetic events, such as major histocompatibility complex (MHC) expression on intestinal epithelial cells and local production of cytokines in the gastrointestinal mucosa, are common features of many gastrointestinal inflammatory disorders. Drawing from clinical experience of the treatment of other disorders associated with gastrointestinal inflammation, such as ulcerative colitis and Crohn's disease, a number of therapeutic alternatives may be relevant for the bone marrow transplant patient with significant graft-vs.-host disease (GvHD). Options to consider include therapeutics that alter inflammatory cell migration, anti-inflammatory cytokines, direct neutralization of proinflammatory cytokines, and cytokines that promote epithelial restitution in the gastrointestinal mucosa. In addition, a variety of nutritional and other novel treatments are available, which may improve epithelial function or which have anti-inflammatory actions. Prospective studies of combined nutrient and cytokine-modulating treatments for the bone marrow transplant patient are warranted.

Bone Marrow Transplantation↗

New insights into spontaneous intestinal perforation using a national data set (3): antenatal steroids have no adverse association with spontaneous intestinal perforation.

OBJECTIVE: To examine whether antenatal steroids (ANS), alone or with early indomethacin, are associated with spontaneous intestinal perforation (SIP). SIP is a known complication of concurrent post-natal administration of glucocorticoid and indomethacin in extremely low birth weight (ELBW) infants. STUDY DESIGN: A large de-identified national data set was retrospectively examined for infants with SIP without any report of other malformation or necrotizing entrocolitis. A control group was then derived matching for gender and birth weight (+/- 20 g). Pre- and post-natal variables were tested by both univariate and multivariate analysis to identify associations with SIP. RESULTS: From January 1996 to June 2004, there were 2 27 711 discharges from Pediatrix neonatal intensive care unit sites. From this population 388 infants with SIP associated with ELBW were compared to matched controls. Infants with SIP were more likely to have received early indomethacin and to have received a combination of early indomethacin with post-natal glucocorticoids (P < 0.05 for both). When used alone (without subsequent indomethacin), ANS showed no association with SIP. When used in conjunction with indomethacin, ANS did not increase the rate of SIP beyond indomethacin alone. CONCLUSION: ELBW Infants that acquire SIP were more likely to have been exposed to early indomethacin and post-natal glucocorticoids. However, no association was found between SIP and ANS within a well-powered cohort.

Case-Control Studies↗

Biosynthesis of intestinal microvillar proteins. Characterization of intestinal explants in organ culture and evidence for the existence of pro-forms of the microvillar enzymes.

Explants of pig small intestine were maintained at 37 degrees C in organ culture for periods up to 24 h in a system using Trowell T-8 medium supplemented with 10% foetal-calf serum. The mucosal morphology was well preserved during culture, as judged by light and electron microscopy. The explant contents of protein and two brush-border enzymes, microvillus aminopeptidase (EC 3.4.11.2) and dipeptidyl peptidase IV (EC 3.4.14.5), were not significantly modified during culture compared with controls, but a moderate, continuous release of both protein and enzyme activities into the medium was observed. Continuous labelling with [35S]methionine resulted in an even incorporation of radioactivity in the protein components, and the rate of labelling only moderately decreased over the 24 h period. The polypeptide compositions of sucrase (EC 3.2.1.48)--isomaltase (EC 3.2.1.10), maltase--glucoamylase (EC 3.2.1.20) lactase (EC 3.2.1.23)--phlorizin hydrolase (EC 3.2.1.62), microvillus aminopeptidase and aspartate aminopeptidase (EC 3.4.11.7) synthesized during culture were studied, and some were found to be similar to those of the pro-forms of the enzymes isolated from animals that had had their pancreatic duct disconnected 3 days before being killed. These results confirmed earlier findings of the existence of pro-forms of some of the microvillar enzymes and thus indicate a low activity of pancreatic proteinases in the culture system.

Animals↗

The contribution of the pancreas and the intestine to the regulation of lipolysis in birds. 2. Impaired lipolytic activity of pancreatic glucagon in the absence of either the pancreas or the intestine in the chicken.

Adipose tissue was removed from five-day old chickens after a) an overnight fast, b) total pancreatectomy and c) partial evisceration and digested with collagenase. The adipocytes were incubated with pancreatic glucagon (Novo) and the glycerol released into the medium taken as the index of lipolytic activity. A moderate fast, while being without effect on basal lipolysis, slightly decreased adipocyte sensitivity to glucagon. Pancreatectomy and evisceration significantly reduced both basal lipolysis and the response to glucagon: the impairment was most evident just at the concentration found in the plasma of such operated animals. It seems clear that normal lipolysis is under the control not only of pancreatic factors, but also of those of intestinal origin, and can only proceed normally when both are present.

Adipose Tissue↗

Closed loop intestinal obstruction due to vitello-intestinal remnants.

Two young children presented with acute small bowel obstruction associated with closed loop ileal obstruction caused by Meckel's diverticulum and vitello-intestinal duct remnant respectively. In each, resection of the vitelline remnant and ischaemic ileum with primary small bowel anastomosis resulted in good recovery.

Child, Preschool↗

Vasoactive intestinal polypeptide and cholinergic mechanisms in cat nasal mucosa: studies on choline acetyltransferase and release of vasoactive intestinal polypeptide.

Quantitative immunohistochemical analysis of the sphenopalatine ganglion in normal cats revealed that virtually all ganglion cells (98.5%) were immunoreactive to vasoactive intestinal polypeptide (VIP). After surgical removal of this ganglion, the content of both VIP and choline acetyltransferase (acetyl-CoA:choline O-acetyltransferase, EC 2.3.1.6), a specific marker for cholinergic neurons, was decreased to about 70-80% in the nasal mucosa. In contrast, in animals subjected to sympathectomy combined with sensory (trigeminal) denervation, no significant change in VIP or choline acetyltransferase was found in the nasal mucosa. The present findings strongly suggest that a large proportion of the VIP neurons in the sphenopalatine ganglion contain choline acetyltransferase. This further supports the view that VIP is present in a population of autonomic cholinergic neurons innervating exocrine glands in the cat. In contrast, the ciliary ganglion contained high levels of choline acetyltransferase but no VIP. Parasympathetic nerve stimulation (15 Hz) caused a maximal vasodilation and a 500-fold increase in VIP output from the nasal mucosa. The plasma VIP immunoreactivity eluted at the same position as porcine VIP on gel permeation chromatography. Atropine pretreatment, which is known to abolish nasal secretion, caused a further 3-fold increase in VIP output during the nerve stimulation (15 Hz). Simultaneously, a markedly prolonged duration of the vasodilatory response was observed. The increased output of VIP during parasympathetic nerve stimulation by atropine pretreatment suggests that the transmitter acetylcholine may inhibit the release of the coexisting peptide--i.e., VIP--via muscarinic autoreceptors.

Animals↗