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Biomedical subjects

S Guandalini

Publications and source records attributed to S Guandalini.

At least 73 records · Page 4Linked to original sources

Production of Escherichia coli STa-like heat-stable enterotoxin by Citrobacter freundii isolated from humans.

Citrobacter species are often present in the stools of children and are generally considered a normal component of the intestinal microflora. Previous reports suggested that they might act as enteric pathogens. Aiming at defining the role of Citrobacter species in inducing diarrhea, we looked for their presence in the stools of 328 children with diarrhea and in 108 controls. Citrobacter strains were isolated from 46 patients (14%) and 7 controls (6.5%) (P less than 0.05). All isolates were tested for heat-stable (ST) and heat-labile (LT) enterotoxin. No LT-producing organisms were found. Three C. freundii strains, all isolated from children with diarrhea, elaborated an enterotoxin detected by the suckling mouse assay. A crude extract was prepared by acetone precipitation and a sequential ultrafiltration technique. The enterotoxin was heat stable, and its estimated molecular weight was between 2,000 and 10,000. Citrobacter enterotoxin was soluble in methanol and stable at acid and neutral pHs but not above pH 8, and its activity was destroyed by treatment with 2-mercaptoethanol. Citrobacter enterotoxin was inactive in the 18-h rabbit ileal loop test. All these characteristics closely resemble STa produced by Escherichia coli. The time course of Citrobacter enterotoxin-induced intestinal secretion in suckling mice was similar to that of E. coli STa. The enterotoxin produced by C. freundii cross-reacted with monoclonal antibodies raised against E. coli STa. These results suggest that C. freundii is capable of inducing diarrhea through the production of an E. coli-like STa, and its presence in the stools of patients with diarrhea should be considered as that of a possible etiologic agent.

Bacterial Toxins↗

Role of IgE in the pathogenesis of milk allergy in infancy: reassessment by a new ELISA technique.

An ELISA technique using labelled antigen for the determination of cow's milk specific IgE in serum is described. The use of labelled antigen, rather than labelled antibody as in the RAST, permits avoidance of interference by antibodies other than IgE, such as IgG, at times responsible for a negative RAST. The results obtained with the 2 techniques in 43 infants with a positive cow's milk challenge showed a positive RAST in 28%, a positive ELISA in 35% and a positive RAST or ELISA in 42%. These findings suggest that the use of both ELISA and RAST permits in vitro diagnosis of cow's milk allergy in more patients than either test alone.

Animals↗

Acute childhood diarrhoea in Naples: an aetiologic study.

A potential aetiologic agent was detected in the stools of 56% of 118 children hospitalized in Naples for acute diarrhoea. Rotavirus and Salmonella were the agents most commonly associated with disease, accounting for 23 and 17 percent of cases, respectively. Campylobacter jejuni, enterotoxigenic Escherichia coli, Yersinia and Shigella were less frequently isolated (total, 11% of cases). These findings fit well with the epidemiological picture described for other developed countries, except for the isolation rate of Salmonella which widely exceeds that reported in other investigations. Cytotoxic strains of E. coli and other Gram-negative bacilli were identified in the stools of 18 children; the possible pathogenic role of these strains is unknown and needs further investigation.

Acute Disease↗

Enteric infections, cow's milk intolerance and parenteral infections in 118 consecutive cases of acute diarrhoea in children.

One hundred and eighteen consecutive cases of childhood acute diarrhoea (mean age: 10.5 months) were studied after admission to our Pediatric Unit in Naples over a 13-month period. A diagnosis was established in 92 patients (78%): 55% of patients were found to have an infectious enteritis (among them, 5 had ETEC infections and 1 had an ST-producing Klebsiella infection), 12% a parenteral infection, 11% cow's milk intolerance. The occurrence of gross blood (P less than 0.01), leukocytes, and reducing substances in the stools was more commonly associated with infectious enteritis than with diarrhoea due to all other causes. In 14 patients (8 of whom were malnourished), diarrhoea ran a prolonged course. In all, the eventual outcome was favourable. Our findings, while confirming that infectious enteritides account for most of acute diarrhoeas in children, stress the importance of parenteral infections and cow's milk intolerance in this condition. Also, the need for an accurate search for enterotoxigenicity of enterobacteria before ruling out their pathogenetic role is stressed.

Bacterial Infections↗

Effects of loperamide on intestinal ion transport.

The synthetic opiate loperamide (LPMD) is an antidiarrheal compound which affects both intestinal motility and the transport of water and electrolytes. We have investigated its effects on ion transport in the stripped ileal mucosa of rabbits, mounted in Ussing chambers in vitro. Addition of LPMD to serosal bathing medium resulted in a dose-dependent decrement of short-circuit current (Isc). LPMD (50 microM) significantly increased net Cl absorption (JClnet) and JRnet (assumed to represent HCO3 secretion). LPMD also inhibited the Isc increments evoked either by agents that increase 3',5'-cyclic adenosine monophosphate (cAMP) content (theophylline and prostaglandin E2) or by the Ca2+ ionophore A23187; the opiate, however, did not prevent the Isc change induced by 3',5'-cyclic guanosine monophosphate (cGMP)-related agents such as 8-Br-cGMP and Escherichia coli heat-stable enterotoxin. LPMD did not alter basal or secretagogue-stimulated tissue cAMP. In contrast, LPMD caused a small increase in cGMP content of stripped ileal mucosa, but not in that of isolated enterocytes. The role of Ca2+ in LPMD action is suggested by the significantly different effect of the drug on JClnet in the presence and in the absence of Ca2+ in the serosal solution.

Animals↗

Chronic diarrhea and failure to thrive in an infant with Campylobacter jejuni.

We report the case of an infant with chronic diarrhea and failure to thrive. Campylobacter jejuni was isolated from stools and treatment with erythromycin resulted in eradication of infection and prompt resolution of symptoms. A 22-month-old girl was referred to our University Hospital because of weight loss and chronic diarrhea, which did not respond to repeated dietetic trials that excluded milk, gluten, and other foodstuffs. Microscopic examination of the jejunal biopsy specimen revealed a mild degree of partial mucosal atrophy with inflammatory infiltrates in the lamina propria without any hallmarks of celiac disease. Repeated stool cultures on Butzler medium were positive for C. jejuni. This finding was associated with a high titer of specific serum antibodies. Erythromycin therapy without any other form of therapy led to prompt improvement, and the patient reached her "own" 50th centile as weight/height ratio. The aim of this report is to alert pediatric gastroenterologists of the possibility that Campylobacter may be associated with chronic diarrhea and failure to thrive.

Campylobacter Infections↗

Sigmoidoscopy, colonoscopy, and radiology in the evaluation of children with rectal bleeding.

The authors evaluated the diagnostic role of sigmoidoscopy, colonoscopy, and double contrast radiology in 103 children with rectal bleeding, with or without other gastrointestinal symptoms. The children's mean age was 44 months, with a range from 1 month to 12 years. In 74.5% of the subjects investigated, visual inspection of the anus and sigmoidoscopy with rectal biopsy disclosed a positive diagnosis. Of the remaining patients, a conclusive diagnosis was reached by either colonoscopy or double contrast radiology in all but six patients. These six, with mild painless hematochezia, remained without a diagnosis. The diagnostic procedure in pediatric patients with rectal bleeding should include an initial visual inspection of the anus, and sigmoidoscopy; air contrast enema and colonoscopy should be performed only in children whose sigmoidoscopy is negative, in diagnostic assessment of inflammatory bowel disease, and in cases of recurrent bleeding after removal of rectal polyps. Colonoscopy is important also in the follow-up examination of children with inflammatory bowel disease and allows the removal of polyps located in the proximal colon.

Barium Sulfate↗

In vitro effects of conalbumin on iron transport by rat intestinal mucosa.

The possible effects of conalbumin (a glycoprotein closely resembling lactoferrin) on iron transport across the brush border of intestinal cells of the rat were evaluated in vitro. Iron influx was measured in proximal and distal tracts of small intestine from either normal or iron-deprived rats, both in the presence of 1 or 10 mg/ml conalbumin and in its absence. Conalbumin did not affect iron uptake at any concentration and in any intestinal segment, either in normal or in iron-deprived animals. It was concluded that the luminal presence of conalbumin, even at a relatively high concentration, does not interfere with iron intestinal transport.

Animals↗

cGMP modulation of ileal ion transport: in vitro effects of Escherichia coli heat-stable enterotoxin.

Diarrheagenic strains of Escherichia coli have been shown to produce a heat-stable enterotoxin (ST) that simulates guanylate cyclase, increases short-circuit current (Isc), and inhibits active Cl absorption in the intestine. In rabbit ileum, the ion transport effects are smaller than those produced by cAMP-related agonists. Because ST may be a selective cGMP agonist, we further explored its mode of action in rabbit ileum. ST inhibits net Na and net Cl absorption. ST also inhibits the same fraction of Cl influx across the brush border that theophylline inhibits. At maximal doses, ST and 8-bromo-cGMP (8-Br-cGMP) had nearly equal, nonadditive effects of Isc that were about 66% of that produced by 8-Br-cAMP. ST increased mucosal cGMP concentration 16-fold, whereas epinephrine, an inhibitor of secretion, increased cGMP concentration by only 30%. This is insufficient to alter ion transport because doses of ST that increased cGMP concentration by 100% failed to alter Cl fluxes. Furthermore, epinephrine did not increase cGMP concentration in isolated enterocytes. We conclude that 1) cGMP mediates ST effects on ion transport, and 2) although ST and cAMP-related agonists have the same antiabsorptive effects, ST is less effective in stimulating electrogenic Cl secretion.

Animals↗

Mode of action of heat-stable Escherichia coli enterotoxin. Tissue and subcellular specificities and role of cyclic GMP.

Some enteric strains of Escherichia coli release a heat-stable enterotoxin which, in contrast to cholera and heat-labile E. coli enterotoxins, stimulates guanylate cyclase (GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2). We have examined the tissue spcificity of its action and the relation of its action to those of the 8-bromo analogues of cyclic GMP and cyclic AMP. Heat-stable enterotoxin stimulated guanylate cyclase activity and increased cyclic GMP concentration throughout the small and large intestine. It increased transepithelial electric potential difference and short-circuit current in the jejunum, ileum and caecum but not in the duodenum or distal colon. This pattern of electrical responses was mimicked by 8-bromo-cyclic GMP. However, 8-bromo-cyclic AMP produced an electrical response in all intestinal segments. The enterotoxin failed to stimulate guanylate cyclase inliver, lung, pancreas or gastric antral mucosa. In the intestines, it stimulated only the particulate and not the soluble form of the enzyme. Preincubation of the toxin with intestinal membranes did not render it capable of stimulating pancreatic guanylate cyclase. Cytosol factors did not enhance the toxin's stimulation of intestinal guanylate cyclase. This study supports the role of cyclic GMP as intracellular mediator for heat-stable enterotoxin and suggests that the toxin affects a membrane-mediated mechanism for guanylate cyclase activation that is unique to the intestines.

Animals↗