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At least 1,189 records · Page 66Linked to original sources
PubMed1996

Release of serotonin from RBL-2H3 cells by the Escherichia coli peptide toxin STb.

Heat-stable enterotoxin b (STb) of Escherichia coli is a 48-amino acid basic, disulfide-bonded peptide that causes intestinal secretion in experimental animal models. Recent evidence suggests that the in vivo mechanism of STb action involves release of 5-hydroxytryptamine (5-HT) and production of prostaglandin E2 (PGE2). Here we show STb-mediated release of 5-HT from rat basophilic leukemic cells (RBL-2H3), a mast cell line model used extensively to study 5-HT release. Increasing concentrations of biologically active STb resulted in a dose-dependent release of 5-HT from RBL-2H3 cells. In contrast to these results, reduced and alkylated STb had no effect on 5-HT release. Release of 5-HT from RBL-2H3 cells was independent of extracellular calcium ions and did not involve changes in the intracellular concentration of free Ca2+. In addition, pertussis toxin treatment completely blocked 5-HT release, indicating a role for a pertussis toxin-sensitive G-protein in the mechanism of 5-HT release from this cell type.

Animals↗
PubMed1993

Oral immunization with recombinant BCG induces cellular and humoral immune responses against the foreign antigen.

It has been shown recently that BCG can be used as a live recombinant vaccine to stimulate immune responses. Proliferative or cytotoxic T-cell responses against several viral proteins such as HIV Gag, Env or Nef were obtained after parenteral immunization with BCG expressing these proteins. Antibody responses were also obtained after immunization of mice with recombinant BCG strain which expressed lac Z under the control of a promoter sequence isolated from Mycobacterium paratuberculosis. We have used this recombinant vaccine in guinea-pigs to investigate the influence of various routes of immunization on the immunogenicity of a foreign antigen expressed by recombinant BCG. Guinea-pigs were immunized by oral, respiratory or intradermal routes and proliferative responses, delayed-type hypersensitivity and antibody responses specific for beta-galactosidase were followed for 16 weeks. Results demonstrated that humoral and cellular immune responses specific for beta-galactosidase can be produced in all groups of guinea-pigs. However, the respiratory and especially the oral route of administration induced higher local and systemic immune responses than the intradermal route of immunization. Moreover, the oral immunization of mice with this recombinant BCG induced IgA responses which could be detected in both sera and intestinal secretions. Therefore, this study demonstrates for the first time that oral immunization with recombinant BCG can induce strong cellular and humoral immune responses.

Administration, Inhalation↗
PubMed1984

Relationship of histamine in tissues and antiparasitic substances in gastrointestinal mucus to the development of resistance to trichostrongyle infections in young sheep.

The development of resistance to nematode infection and self-cure in a flock of young grazing sheep were examined in relation to changes in the levels of histamine in tissues and levels of antiparasitic substances in gastrointestinal mucus. Analysis of faecal egg counts showed that when the sheep were ranked according to individual mean monthly egg counts there was a significant trend to similar rankings in successive months. Sheep with high and low egg counts were slaughtered at monthly intervals for examination and comparison. Histamine levels in blood and intestinal content fluids were similar in both groups of sheep and were highest during maximum challenge by larval nematodes. Antiparasite activity of the intestinal mucus was significantly higher in sheep with low egg counts than those with high counts, between January and May, and was associated with significantly lower burdens of fourth stage larvae.

Abomasum↗
PubMed1994

Sources of heterogeneous contrast enhancement in the gastrointestinal tract.

Water soluble gadolinium chelates demonstrate heterogeneous enhancement of the gastrointestinal tract (GI) when administered orally. To investigate the causes, ProHance (2.0 mM) was administered orally to rats. There was a dramatic enhancement of rat GI lumen signal intensity in T1-weighted MR images which provided increased contrast relative to the adjacent abdominal tissues. Heterogeneity of MRI signal enhancement along the rat GI tract was investigated by sampling rat GI fluid at various times post-ingestion and at different locations along the GI tract. The corresponding T1 and T2 relaxation times, Gd concentrations, and viscosities of each GI fluid sample revealed that changes in each of these parameters contribute to the observed heterogeneity of MRI signal enhancement.

Abdomen↗
PubMed1988

The effects of chronic vitamin D deficiency on the skeleton in the adult rabbit.

Albino rabbits were fed a 1.0% Ca, 0.5% P, vitamin D-deficient diet for 11.7 to 31.3 mo. Control rabbits were fed either this diet with the addition of 2.2 units/gm of vitamin D3 or a standard laboratory rabbit ration. Serum levels of 25-OH-D and 1,25-(OH)2D were both undetectable in all vitamin D-deficient rabbits but were present at levels typically found in other species in the control rabbits. Vitamin D deficiency resulted in elevated serum PTH values but did not produce significant changes in serum Ca levels, femur length, femur ash weight to body weight ratio, or tibial breaking strength. The vitamin D-deficient rabbits could be readily separated into two distinct subgroups. Four of these rabbits were normophosphatemic (P = 3.7 +/- 0.4 mg/dl) whereas the other five were severely hypophosphatemic (P = 0.8 +/- 0.2 mg/dl). During the last 10 days of the study the control and normophosphatemic vitamin D-deficient rabbits were in positive Ca and zero P balance. The hypophosphatemic vitamin D-deficient rabbits were in zero Ca and negative P balance. This negative P balance resulted from a net intestinal secretion, as urinary P excretion was negligible. Femur ash weight as a percentage of dry weight was decreased in hypophosphatemic but not the normophosphatemic vitamin D-deficient rabbits. Histomorphometric analyses indicated the bones from the normophosphatemic vitamin D-deficient rabbits were normal. In contrast, vertebral trabecular bone from the hypophosphatemic rabbits contained large amounts of osteoid that was not mineralizing, as indicated by a failure to take up the fluorescent label calcein.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

New drug targets for cholera therapy.

Intestinal infection with Vibrio cholerae results in secretory diarrhea with potentially massive fluid losses and volume depletion. Morbidity and mortality associated with cholera remain a major problem in the developing world despite the success of oral rehydration therapy. New research aiming to inhibit cholera toxin binding to receptors in the intestine provides an attractive strategy for cholera therapy. Together with anti-secretory agents, including inhibitors of enkephalinase and of the cystic fibrosis transmembrane conductance regulator, new treatment options for managing severe diarrhea in cholera could soon be available.

Animals↗
PubMed2005

Induction of protective immunity against toxoplasmosis in mice by immunization with Toxoplasma gondii RNA.

Toxoplasma gondii enters the mucosal surfaces of the host, and so immunity at these sites is of major interest. Due to the compartmentalization of the immune response, systemic immunization does not induce high levels of immunity at mucosal surfaces. Intranasal immunization has been shown to be very effective in inducing both systemic and mucosal immune responses. Immunization with mRNA can induce both humoral and cell-mediated immune responses, both of which are important in conferring immunity to T. gondii. The efficacy of RNA vaccination by the nasal route with T. gondii RNA was evaluated. We assessed the percentage of cumulative survival after an oral challenge with a lethal dose of T. gondii cysts (40 cysts), and the number of brain cysts following a challenge with a sublethal dose of T. gondii 76 K cysts (15 cysts). Vaccinated mice were found to be significantly better protected than non-immunized mice after a challenge with a lethal dose of cysts; and a challenge with a sublethal dose also resulted in fewer brain cysts than in non-immunized mice. Sera and intestinal secretions of immunized mice recognized T. gondii antigens, suggesting that a specific humoral immune response may occur. Moreover, a specific lymphoproliferative response observed in cervical lymph nodes may confer protection. These preliminary findings suggest that RNA vaccination by a mucosal route could be feasible.

Animals↗
PubMed2005

A novel, quantitative bio-assay for cholecystokinin type-1 receptor activity in the anaesthetised rat.

INTRODUCTION: Cholecystokinin type-1 (CCK(1)) receptors mediate many of the physiological functions of CCK including delay of gastric emptying, pancreatic enzyme secretion, intestinal motility and gallbladder contractility. Existing in-vivo assays for the quantitative measurement of CCK(1) receptor mediated function are generally variable, limited in precision and require a relatively large number of animals to obtain statistically meaningful data. We found that they did not provide robust pharmacokinetic-pharmacodynamic data for profiling compounds acting at these receptors. Accordingly, here we describe a novel rat duodenal contractility assay that addresses these problems. METHODS: Rats were anaesthetised and a saline-filled balloon was inserted through the body of the stomach and secured in the duodenum approximately 1 cm from the pyloric sphincter for measurement of intra-lumenal pressure. Studies were performed to determine a dose, rate and frequency of administration of CCK8S that produced a readily quantifiable response. RESULTS: Initial experiments revealed that sustained exposure to CCK8S resulted in the rapid development of tachyphylaxis. After investigating different dosing paradigms, it was found that pulsatile delivery of CCK8S (intravenous infusion for 1 min every 10 min) produced a readily quantifiable contractile response that did not exhibit tachyphylaxis. The assay response output was defined as the number of contractions >5 mm Hg over baseline. The contractions were blocked in a dose-dependent manner by intravenous bolus injections of the CCK(1) receptor antagonists, dexloxiglumide (2 and 20 micromol/kg), and devazepide (3-100 nmol/kg) but not by the CCK(2) receptor antagonist gastrazole (10 micromol/kg). CONCLUSION: A novel, simple, high quality assay for the quantification of the in-vivo activity of CCK(1) receptor ligands is described. CCK8S delivered by pulsatile intravenous infusion to anesthetized rats produced a burst of contractile activity of the duodenum mediated by CCK(1) receptors. This activity was highly reproducible and sustained for more than 3 h providing an assay that circumvents problems associated with agonist-induced tachyphylaxis.

Anesthesia↗
PubMed1999

Serum squalene in postmenopausal women without and with coronary artery disease.

Squalene, found in earlier studies in human atherosclerotic plaques, was measured in the serum of postmenopausal women with coronary artery disease (CAD) (n = 25) and randomly chosen age-matched healthy controls (n = 30). The squalene concentrations of the whole population ranged from 37.5 to 115.5 microg/dl, and were higher in serum of the CAD than healthy women (91.4+/-2.6 versus 65.2+/-2.6 microg/dl, P = 0.000), a finding observed also in relation to cholesterol (43.8+/-1.8 versus 32.9+/-1.1 10(2)x mmol/mol of cholesterol, P = 0.000). The squalene concentration was also increased in chylomicrons, VLDL and d>1.006 g/ml lipoproteins, and the proportions to cholesterol in VLDL and d>1.006 g/ml lipoproteins. The respective squalene and cholesterol concentrations were related to each other in serum, VLDL and d>1.006 g/ml lipoproteins (r = 0.52, 0.85 and 0.55, respectively), whereas the correlation with triglycerides was seen only in VLDL (r = 0.84) over the whole population. Besides enhanced intestinal secretion, it remains to be shown whether higher serum squalene in postmenopausal coronary women is due to increased cholesterol synthesis or a defect in squalene conversion to lanosterol.

Biomarkers↗
PubMed1979

A clinical study of young infants after small intestinal resection.

We prospectively studied 15 infants who, before 3 months of age, underwent resection of the small intestine-proximal in 3 infants, mid in 6, and distal in 6. Two died before one year of age. Many required prolonged parenteral nutrition, but by one year, 12 of the 13 survivors were on oral feedings only, and seven were above the third percentile for height and weight. Developmental delay occurred in the early postoperative period but diminished with time. There was compensatory adaptation of the remaining gut, shown by improving fat and B12 absorption and duodenal bile-salt concentrations. Bacterial contamination complicating end-to-side anastomoses occurred in two cases (P), gastric hyperacidity in four of 12 (1P, 3M), and hyperoxaluria in eight of 14 (1P, 5M, 2D). Studies of immune competence revealed normal cellular immune function (11/11), transient hypogammaglobulinemia (3/14), hypocomplementemia (1/12), and serum autoantibodies (3/10). Thus, massive resection of the small intestine did not preclude spontaneous improvement in absorptive function, growth, and development.

Child Development↗
PubMed1983

Diarrhoea in vipoma patients associated with cosecretion of a second active peptide (peptide histidine isoleucine) explained by single coding gene.

Peptide histidine isoleucine (PHI), first isolated from pig intestine, is distributed identically to vasoactive intestinal peptide (VIP) in all mammals. 42 patients with high plasma VIP secondary to VIPoma also had very high plasma PHI-like immunoreactivity, in a constant ratio to VIP. None of 125 patients with other endocrine tumours had high levels of either peptide. VIPoma tissue from 20 patients also contained PHI shown by immunocytochemistry to be produced by the same cell as VIP. Messenger RNA(mRNA) from one of these tumours contained the codes for VIP and a separate PHI-like sequence. Human PHI-like sequence differed from porcine PHI in only two aminoacid residues. A single cell thus produces two separate regulatory peptides with apparently similar potencies but different spectra of activity. In normal tissue the constant coproduction of two active neuropeptides by a single neuron provides further evidence against the doctrine of one neuron producing only one neurotransmitter.

Adenoma, Islet Cell↗
PubMed1994

Cancer mortality in chronic typhoid and paratyphoid carriers.

It has been shown in vitro that bacteria are able to form or release carcinogens, mutagens, or promoters from intestinal secretions such as bile, or from excretions such as urine. It is, therefore, of interest to find out whether chronic infection of the gallbladder is associated with carcinogens, as in chronic infection of the urinary bladder. A study of cancer risk in chronic typhoid and paratyphoid carriers showed a large excess (observed/expected cases) for cancer of the gallbladder (167.0; 95% confidence interval 54.1-389) and also excess risks of cancer of the pancreas (8.1), colorectum (3.0), lung (2.5), and all neoplasms (2.6). There was no similar excess risk in a group of 386 people with typhoid from the 1964 Aberdeen outbreak. This indicates that it is long-term typhoid carriage, not acute infection, which is the risk factor. This has important implications for cancer prevention. Eradication of chronic carriage, by use of antibiotics or elective cholecystectomy, should be re-emphasised, and the need for good documentation of carriers is, therefore, of great importance.

Adult↗
PubMed1998

Bioactivity of intraduodenally and intravenously infused fragments of luminal cholecystokinin releasing factor (LCRF).

A luminal cholecystokinin releasing factor (LCRF), has been purified from intestinal secretion and found to have a mass of 8136 daltons. The amino-terminal 41 residues have been sequenced. Previous studies showed that intraduodenal infusion of the synthetic amino-terminal 35 amino acid peptide, LCRF1-35 significantly stimulated pancreatic protein and fluid secretion in conscious rats, but the peptide did not stimulate amylase release from isolated, dispersed pancreatic acini. In the present study, several fragments of LCRF were synthesized and tested for CCK-releasing activity (pancreatic protein secretion) to determine whether shorter fragments of LCRF exhibit the characteristic biological activity of native LCRF and synthetic LCRF1-35. Compounds tested were LCRF1-41, LCRF1-35, LCRF1-65 and LCRF11-25. Of the fragments shorter than LCRF1-35, only LCRF11-25 but not LCRF1-6 had significant CCK releasing activity. LCRF1-41 was equivalent to LCRF1-35 in potency and efficacy. Intravenous and intraduodenal infusion of LCRF1-35 elicited nearly identical dose-response curves.

Animals↗
PubMed1999

Biological relevance of pituitary adenylate cyclase-activating polypeptide (PACAP) in the gastrointestinal tract.

Since its initial discovery in 1989, pituitary adenylate cyclase activating peptide (PACAP) has been noted to distribute widely in the brain, the respiratory and the gastrointestinal system. It occurs in two bioactive molecules, PACAP-27 and the C-terminally extended PACAP-38, which evoke activity by binding to three distinct types of high-affinity, G-protein coupled membrane receptors. It is present throughout the entirety of the gut but is rare in certain areas such as the intestinal mucosa and islets of Langerhans. PACAP-induced biological effects are protean and include alterations of motility in the bowel and the gallbladder, stimulation of gastric acid and intestinal secretion, hormone/enzyme release from the exocrine and endocrine pancreas, and the induction as well as inhibition of proliferation in neuroendocrine cells and tumors. Its hepatic activity has to date not been elucidated in detail. One of the interesting features of PACAP is the species and organ dependent variation of its biological effects. Of particular note is its superior potency when compared with other neuropeptides identified in the gut, and the involvement of a number of different second messenger systems upon PACAP receptor activation.

Animals↗
PubMed1997

Neuropeptide Y family of hormones: receptor subtypes and antagonists.

Neuropeptide Y (NPY) is the most abundant peptide present in the mammalian central and peripheral nervous system. NPY exhibits a variety of potent central and peripheral effects including those on feeding, memory, blood pressure, cardiac contractility and intestinal secretions. Classical pharmacological studies have shown that NPY effects are mediated by four different receptor subtypes, Y-1, Y-1-like, Y-2, and Y-3. However, the existence of numerous atypical activities provide strong evidence for the occurrence of additional NPY receptor subtypes. Pharmacological studies have further been facilitated by the recent cloning and expression of Y-1, Y-2, Y-4 (PP-1) and Y-5 receptors. Moreover, the cloned Y-5 receptor has been suggested to be the long awaited Y-1-like receptor involved in feeding. Structure-activity studies have laid a good foundation towards the development of receptor selective compounds, and to date potent Y-1 selective peptide and nonpeptide antagonists have been developed. The need to clone numerous receptor subtypes and to develop receptor selective compounds for physiological and perhaps clinical use is expected to keep NPY research active for many years to come.

Animals↗