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Gastrointestinal colonization and systemic dissemination by Candida albicans and Candida tropicalis in intact and immunocompromised mice.

Gastrointestinal colonization and systemic dissemination by Candida albicans and Candida tropicalis were compared in intact and immunocompromised mice. Five-day-old CFW mice were inoculated by the oral-intragastric route with 1.0 x 10(7) CFU of two C. albicans and two C. tropicalis strains isolated from the blood of patients with acute leukemia and with C. albicans 4918 and its cerulenin-resistant mutant 4918-10. C. albicans and C. tropicalis spread to the lungs, liver, and kidneys within 30 min postinoculation, and organ CFU of the two species were comparable over the following 10 days. Close association of blastoconidia with the villous surface of the small intestine resulted in lysis of microvilli and then progressive invasion of villi. Blastoconidia within villi were surrounded by a conspicuous zone of clearing. Persistent colonization of the small and large intestines by C. albicans blood isolates and strains 4918 and 4918-10 was similar for 31 days after inoculation, but consistently exceeded that of C. tropicalis. In mice colonized with C. albicans, immunosuppression with cortisone acetate and cyclophosphamide on days 30 and 33 after inoculation increased stomach CFU 40- to 370-fold and intestinal CFU 30- to 80-fold. In contrast, persistent colonization by C. tropicalis was undetectable before immunosuppression and only became apparent after treatment. C. albicans disseminated more frequently and with higher organ CFU than C. tropicalis. Despite this fact, 20% of mice infected with C. tropicalis died, compared with 4% infected with C. albicans blood isolates. Indirect immunofluorescence revealed penetrative growth by Candida hyphae exclusively in the mucosa and submucosa of the stomach from immunosuppressed, persistently colonized mice. Taken together, the data indicate that C. tropicalis appears to be more virulent than C. albicans and that factors responsible for gastrointestinal colonization, systemic dissemination, and mortality in immunocompromised mice may not be identical.

Animals↗

Analysis of the cellular expression pattern of beta-CGRP in alpha-CGRP-deficient mice.

In this study we compared the alpha-calcitonin gene-related peptide (alphaCGRP) and betaCGRP expression patterns in wild-type and knockout mice by using quantitative reverse transcriptase polymerase chain reaction and immunohistochemistry. In dorsal root ganglia and spinal cord of wild-type animals, alphaCGRP mRNA was about two times more abundant than betaCGRP mRNA. The betaCGRP mRNA was the only isoform expressed in the intestine. In alphaCGRP knockout mice, we found no change in betaCGRP mRNA levels in dorsal root ganglia and spinal cord compared with wild-type controls, but a twofold decrease in the intestine. CGRP immunoreactivity (IR) was detected in many small and some large neurons in the dorsal root ganglia, was found in sensory fibers and motor neurons in the spinal cord, and labeled neuromuscular junctions in wild-type mice. In the dorsal root ganglia of alphaCGRP knockout mice, punctate betaCGRP-IR again was predominantly found in small neurons. In the spinal cord, betaCGRP-IR fibers were localized to the outermost layer of the dorsal horn. IR was found in the cell bodies of motor neurons, but it was undetectable in neuromuscular junctions. In the intestine, CGRP-IR was localized to neurons of the myenteric plexus and to fibers in the mucosal folds, with similar staining intensity in both wild-type and knockout mice. Finally, CGRP-IR was undetectable in preganglionic fibers and postganglionic sympathetic neurons in mice from both genotypes. Our results indicate that alphaCGRP and betaCGRP are variably coexpressed in different functional aspects of the mouse nervous system. This pattern suggests distinct roles for betaCGRP in pain, neuromuscular, and gastrointestinal systems.

Animals↗

Voluntary control of electrogastric activity.

The tonic component of the electrogastrogram (EGG) has been shown to differentiate duodenal ulcer patients from healthy individuals (15). It has therefore been of considerable interest to investigate the possibility that individuals can learn to modify electrogastric activity. Using a discriminative conditioning paradigm with analogue feedback (Experiment I), subjects were generally unsuccessful at controlling tonic EGG activity. However, when the conditioning paradigm was altered (Experiment II) it was clear that subjects were able to modify specific electrogastric changes. In addition to EGG, heart rate, respiration, abdominal muscle activity, and digital blood flow were measured in order to assess the physiological concomitants of learned control of gastrointestinal activity. Subjects who evidenced discriminative control also showed the least amount of abdominal muscle activity and reported being the most relaxed. The results of these studies suggest that exploration of the physiological processes underlying the electrical activity of the gastrointestinal system and the ability of individuals to modify this activity may lead to significant clinical and theoretical advances.

Abdominal Muscles↗

Systemic distribution of somatostatin receptor subtypes in human: an immunohistochemical study.

Somatostatin is well known to inhibit the hormone secretion of various peptides. This action has been considered to be generally mediated via six different specific somatostatin receptors (sstr), sstr1, sstr2A, sstr2B, sstr3, sstr4, and sstr5. It then becomes very important to demonstrate the localization of these sstr subtypes in order to elucidate the possible biological and/or clinical significance of somatostatin actions. These sstr subtypes have been demonstrated to be expressed throughout the human body, including the central nervous system, gastrointestinal tract, pancreas, kidney, and other organs, but its details, especially its systemic distribution and localization in tissue compartments, have yet to be examined thoroughly in human. Therefore, in this study, we examined the systemic localization of all six somatostatin receptors in normal human organs using immunohistochemistry with recently developed specific antibodies against these receptor subtypes. In all of the human tissues examined, various sstr subtypes were detected not only in parenchymal cells but also in various stromal cells such as lymphocytes, fibroblasts, and endothelial cells. Among human tissues in which the presence of sstr has not been previously reported, the parotid gland demonstrated immunoreactivity for sstr2B and sstr5, bronchial gland for sstr1, 2B, 3, 4, 5, parathyroid gland for sstr1, 3, 4, and duodenum for all subtypes immunoreactivity. The great majority of other organs examined demonstrated results consistent with those of previously reported biochemical studies. In pancreatic islet cells, only sstr2A was positive in all the cases but other sstr subtypes were associated with marked intraislet heterogeneity in their distribution. In stomach, all subtypes of receptor were detected in various cell types of the mucosa, but none in ECL cells of fundic gland. These findings demonstrated the broad systemic actions of somatostatin in non-endocrine cells.

Cell Membrane↗

[Gastrointestinal stromal tumor of small intestine--case report].

Gastrointestinal stromal tumor is a form of mesenchimal neoplasm that may be present in all parts of gastrointestinal system. We are reviewing diagnostic and therapeutic algorithms for patient with diagnosed gastrointestinal neoplasm of small intestine, experiencing repeated episodes of painful bleeding from gastrointestinal trackt.

Gastrointestinal Hemorrhage↗

[Congenital developmental defects in children in the southern Ukraine].

The authors analyze clinical material and autopsy findings of fetuses and children dying at the age from 0 to 15 years during the last 15 years. For etiological evaluation of developmental congenital malformations the authors analyzed anamnesis, genealogy, dermatoglyphics, table materials, biochemical examination, karyotyping. The most frequent organs involved were the central nervous system, cardiovascular system, gastrointestinal tract and to a lesser degree--the genitourinary, osseous and respiratory systems. Congenital developmental malformations were registered in 10.2% of cases: in the prenatal period from 13.1 to 16.2% at different age. Among the children who died with developmental congenital malformations most were in the first year of their life.

Abnormalities, Multiple↗

News in gut-brain communication: a role of peptide YY (PYY) in human obesity and following bariatric surgery?

Recent advances in obesity research focused on neuroendocrine control of food intake, appetite and body weight balance. Gut hormones, which are sequentially released from different regions of the gut, send signals to the areas of appetite control in the central nervous system causing a release of counter-regulatory hormones also originating from the gastrointestinal system. Ghrelin, a peptide secreted from the gastric fundus is released just before meal intake and stimulates hunger and food intake. Recently, peptide YY has been suggested to counteract ghrelin by inducing satiety and reducing appetite and caloric intake. While the effects of PYY on various gastrointestinal functions are well described, its action on weight loss is less known. Controversial results on the effect of exogenous administration of PYY(3-36) opened the discussion on the respective roles of PYY and/or PYY(3-36) in body weight homeostasis in man.

Appetite Regulation↗

Particulate oral NMR contrast agents.

Insoluble paramagnetic compounds in suspension can be used to achieve visualization of the gastrointestinal system on magnetic resonance imaging (NMR). Particulate preparations of these agents decrease the T1 and T2 of solutions to which they are added. Gadolinium oxalate, a prototype of these particulate agents, was evaluated in vitro and in vivo (in rabbits) by NMR imaging. The effect of this compound upon T1 and T2 in vitro was also quantitated by NMR spectroscopy. Opacification of the upper gastrointestinal tract was achieved with gadolinium oxalate following oral administration. The colon was visualized following rectal administration.

Administration, Oral↗

The 2.3 kb smooth muscle myosin heavy chain promoter directs gene expression into the vascular system of transgenic mice and rabbits.

BACKGROUND: Smooth muscle cells (SMC) are a preferential target for gene therapeutic approaches in atherosclerosis and restenosis. However, the undesirable expression of putative therapeutic genes in tissues other than the vascular wall is a considerable safety limitation for clinical trials, thus requiring the identification of a smooth-muscle-specific promoter sequence. Since the 2.3 kb rabbit Smooth Muscle Myosin Heavy Chain (SMHC) promoter was shown to be transcriptionally active in primary vascular but not visceral or other non-SMC in vitro, this fragment was chosen for in vivo analysis. METHODS AND RESULTS: Transgenic mice and rabbits were established expressing a luciferase reporter gene under control of the 2.3 kb rabbit SMHC promoter. In contrast to the endogenous expression pattern of the SMHC gene both species revealed light emission predominantly in the arterial system including coronary arteries. Low activities were measured in large veins and the gastrointestinal system. In situ hybridization of murine embryos using a luciferase riboprobe confirmed reporter gene expression in large arteries with no detectable mRNA in the viscera. Unlike adult animals, ectopic luciferase activities were found in ventricular myocardium during murine development ceasing 1 week post partum. CONCLUSIONS: In two animal species, the 2.3 kb SMHC promoter appeared to be effective in discriminating between the pathways regulating vascular and visceral smooth muscle gene expression. The vascular-specific expression profile of the 2.3 kb SMHC promoter suggests that the 2.3 kb SMHC promoter contains the regulatory elements necessary for selective gene targeting into vascular SMC of large arteries including coronary arteries in vivo.

Animals↗

Clinicopathological report: mucinous carcinoma of the eyelid.

BACKGROUND: Mucinous carcinoma of the skin is a rare tumour that may involve the peri-ocular region. METHODS/RESULTS: A case report is presented of a 73-year-old woman with a right upper lid tumour, initially diagnosed as a basal cell carcinoma. Excisional biopsy of the residual tumour revealed mucinous carcinoma. Re-examination of the original pathology proved to be mucinous carcinoma, originating in the eyelid skin. Further treatment involved wide local resection and reconstruction. Systemic investigations were undertaken to exclude the possibility of metastatic mucinous carcinoma. CONCLUSION: This case is presented to alert ophthalmologists to the occurrence of this tumour in the periocular region, to highlight the importance of surgical excision with wide margins and the need for systemic investigation to exclude a primary malignancy in other sites, in particular the gastrointestinal system and breast.

Adenocarcinoma, Mucinous↗

Calcium Channel Blockers and the Gastrointestinal Tract.

Calcium ions play an important role in the normal functioning of the gastrointestinal system. The calcium channel blockers appear to affect all the organs of the gastrointestinal tract and may have therapeutic efficacy on esophageal spasm, irritable bowel syndrome, mesenteric vascular insufficiency, dyskinesis of the Sphincter of Oddi, and insulinoma. Adverse effects are limited predominantly to constipation and some aggravation of ethanol-induced ulcer disease. In addition, the drugs continue to serve as important biologic probes for understanding the normal and abnormal functioning of the gastrointestinal tract.

Journal Article↗

Pulmonary manifestations of gastrointestinal disease.

The respiratory and gastrointestinal systems share several functional similarities. In health, the two systems remain structurally distinct and functionally integrated, so as to maintain physiologic homeostasis. However, in the setting of disease, pathophysiologic alterations in one system may be reflected in the other. This article focuses upon the nonmalignant gastrointestinal causes of respiratory illness. Using an anatomic approach, the pulmonary manifestations of selected gastrointestinal diseases are outlined. Emphasis is placed on the distinguishing features, pathophysiology, and therapy of the pulmonary sequelae of digestive diseases.

Esophageal Diseases↗

Protein losing enteropathy as the initial manifestation of childhood systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multisystem organ disease, and involvement of the gastrointestinal system is relatively rare. We describe a 13-year-old girl who presented initially with abdominal pain, diarrhea, edema, and hypoalbuminemia. She was diagnosed with protein losing enteropathy (PLE) based on the significant increase of alpha 1-antitrypsin clearance in the stool. Two weeks after admission she developed clinical and serological findings that fulfilled the ACR criteria for SLE. Over 22 cases of lupus associated PLE have now been reported, but only 3 in children. Children with PLE should be evaluated for SLE. In addition, PLE should be suspected as a possible cause of unexplained edema and/or hypoalbuminemia in SLE.

Adolescent↗

Comparative gastrointestinal and biliary tract effects of morphine and butorphanol (Stadol).

Butorphanol, levo-N-cyclobutylmethyl-3,14 beta-dihydroxy-morphinan, is a new agonist-antagonist type analgetic agent which is 4 to 8 times more potent than morphine in experimental animals and man. Butorphanol and morphine were evaluated in mice and dogs for their gastrointestinal and biliary tract smooth muscle effects. Morphine decreased the propulsion of a charcoal meal through the gastrointestinal tract of the mouse in a dose related manner with the maximal inhibition obtainable being 90%. Butorphanol produced a maximal inhibition of motility of only 40% with very high doses producing less of an inhibitory effect than lower doses. In dogs, morphine caused a dose-dependent increase in duodenal smooth muscle activity and a dose-dependent decrease in bile duct flow. A clinically effective i.v. dose of morphine (0.1 mg/kg) produced a statistically significant spasmogenic effect on dog biliary tract and gastrointestinal smooth muscle, while a clinically effective equianalgetic i.v. dose of butorphanol (0.025 mg/kg i.v.) had little or not effect on the biliary or gastrointestinal systems. These findings indicate that at equianalgetic doses, butorphanol should produce less constipation and less biliary tract and gastrointestinal smooth muscle spasm than morphine.

Analgesics↗

Pharmacodynamic effects of Sandostatin in the gastrointestinal tract.

Somatostatin (SST) is widely distributed throughout the human gastrointestinal system. There, it is found in neurons and fibers of both the submucosal and myenteric plexus and the pancreas, and also in the D cells of the stomach, gut, and pancreatic islets. Whereas in the intestinal nervous system, duodenum, and pancreas, somatostatin-14 (SST-14) appears to be the predominant molecular form, the endocrine-type D cells of the intestine primarily contain somatostatin-28 (SST-28). SST peptides may act very differently at different sites, as hormones, paracrine substances, or neurotransmitters. Because of this complexity of action, very little is known about the physiological effects of SST in the gastrointestinal tract. In contrast, the pharmacological actions of natural synthetic SST have been thoroughly studied and have given rise to many therapeutic applications. Octreotide, an analogue with a longer half-life and higher potency, has greatly facilitated the clinical application of SST. This review deals with the pharmacological effects of octreotide on different gastrointestinal functions. The SST analogue exerts a long-lasting inhibitory action on gastric acid, pancreatic enzyme, bicarbonate secretion, and on bile flow. It also inhibits stimulated intestinal secretion, ie, the release of neuropeptides from the gut and pancreas. It can also prolong orocecum transit time and prevent gallbladder contraction. It inhibits absorption of nutrients and exerts inhibitory effects on splanchnic hemodynamics. It is because of these actions that SST has attracted so much attention in the treatment of different gastrointestinal disorders.

Biological Transport↗

Gastrointestinal transit times of radiolabeled meal in progressive systemic sclerosis.

Gastrointestinal transit times were measured in 12 patients with progressive systemic sclerosis. The CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) was found in all patients. None of the patients reported complaints referable to specific gastric, small intestinal, or colonic involvement. The patient group had an increased mean gastric emptying time of 99mTc-labeled cellulose fiber when compared with 16 healthy controls [1.17 (0.89-1.38) hr [median (range)] vs 0.84 (0.56-1.88) hr; P less than 0.02], whereas mean gastric emptying time of 2- to 3-mm 111In-labeled plastic particles was unaffected [1.86 (0.99-2.74) hr vs 1.50 (0.92-2.51) hr; NS]. No difference was observed in mean small intestinal transit time of cellulose fiber [4.33 (0.50-7.04) hr vs 3.74 (2.09-7.59) hr; NS] or plastic particles [4.21 (2.00-6.25) hr vs 3.53 (1.50-6.70) hr; NS] between patients and controls. The patient group had an increased mean colonic transit time of plastic particles [47 (24-116) hr vs 29 (18-46) hr; P less than 0.01]. These findings suggest that asymptomatic delay in gastric emptying and colonic transit is frequent in patients with progressive systemic sclerosis.

Adult↗

The nerve-heart connection in the pro-oxidant response to Mg-deficiency.

Magnesium is a micronutrient essential for the normal functioning of the cardiovascular system, and Mg deficiency (MgD) is frequently associated in the clinical setting with chronic pathologies such as CHF, diabetes, hypertension, and other pathologies. Animal models of MgD have demonstrated a systemic pro-inflammatory/pro-oxidant state, involving multiple tissues/organs including neuronal, hematopoietic, cardiovascular, and gastrointestinal systems; during later stages of MgD, a cardiomyopathy develops which may result from a cascade of inflammatory events. In rodent models of dietary MgD, a significant rise in circulating levels of proinflammatory neuropeptides such as substance P (SP) and calcitonin gene-related peptide among others, was observed within days (1-7) of initiating the Mg-restricted diet, and implicated a neurogenic trigger for the subsequent inflammatory events; this early "neurogenic inflammation" phase may be mediated in part, by the Mg-gated N: -methyl-D-aspartate (NMDA) receptor/channel complex. Deregulation of the NMDA receptor may trigger the abrupt release of neuronal SP from the sensory-motor C-fibers to promote the subsequent pro-inflammatory changes: elevations in circulating inflammatory cells, inflammatory cytokines, histamine, and PGE(2) levels, as well as formation of nitric oxide, reactive oxygen species, lipid peroxidation products, and depletion of key endogenous antioxidants. Concurrent elevations of tissue CD14, a high affinity receptor for lipopolyssacharide, suggest that intestinal permeability may be compromised leading to endotoxemia. If exposure to these early (1-3 weeks MgD) inflammatory/pro-oxidant events becomes prolonged, this might lead to impaired cardiac function, and when co-existing with other pathologies, may enhance the risk of developing chronic heart failure.

Animals↗

Distribution and activity of dogfish NPY and peptide YY in the cardiovascular system of the common dogfish.

Neuropeptide Y is present in sympathetic nerves in the mammalian cardiovascular system. This study has investigated the distribution of neuropeptide Y in the cardiovascular and gastrointestinal systems and the effect of dogfish neuropeptide Y and related peptides on cardiovascular tissue of an elasmobranch fish, the common dogfish (Scyliorhinus canicula). Neuropeptide Y-like immunoreactivity is present in varicose nerve fibers innervating dogfish gut and cardiovascular tissue and in endocrine cells of the dogfish spiral intestine. Dogfish neuropeptide Y, dogfish peptide YY, and porcine neuropeptide Y contract the dogfish afferent branchial artery in a concentration-dependent manner. The effect is not inhibited by the presence of tetrodotoxin or by removal of the endothelium. The mammalian Y1 receptor selective agonist [Leu31Pro34]NPY but not the mammalian Y2 receptor selective agonist neuropeptide Y-(13-36) peptide has vasoconstrictor properties in this system, suggesting that the receptor mediating the vasoconstriction resembles the mammalian Y1 receptor more than the Y2 receptor.

Absorption↗