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Biomedical subjects

R L Guerrant

Publications and source records attributed to R L Guerrant.

At least 163 records · Page 9Linked to original sources

Sulfamethoxazole-trimethoprim-resistant Shigella flexneri in northeastern Brazil.

In contrast to prior experience in northeastern Brazil, three of four Shigella flexneri strains recently isolated from patients with acute inflammatory diarrhea in this setting were found to be resistant to sulfamethoxazole-trimethoprim. The resistant strains contained large, different plasmids, two of which were transferred with sulfamethoxazole-trimethoprim resistance to Escherichia coli K-12 recipient strains.

Anti-Bacterial Agents↗

Does enteropathogenic Escherichia coli produce heat-labile enterotoxin, heat-stable enterotoxins a or b, or cholera toxin A subunits?

Although most enteropathogenic Escherichia coli strains do not produce recognized enterotoxins, we wished to examine whether they produce any factors like heat-stable enterotoxin b or cholera toxin active subunits that might be missed by conventional assay methods. E. coli strains E851 (O142) and E2348 (O127) that had caused diarrhea in volunteers were negative for heat-labile enterotoxin and heat-stable enterotoxin a in Chinese hamster ovary cell and suckling mouse assays, failed to cause secretion in ligated small bowel loops from 6- to 8-week-old pigs after 4 to 5 h (used to show heat-stable enterotoxin b), and did not activate adenylate cyclase in pigeon erythrocyte lysates (used to demonstrate cholera toxin A subunit). We conclude that crude, unconcentrated culture filtrates and sonicates do not mimic heat-labile or heat-stable enterotoxins or cholera toxin or its A subunit and that enteropathogenic strains of E. coli probably have yet another mechanism or group of mechanisms by which they cause diarrhea.

Animals↗

Effects of Escherichia coli heat-stable enterotoxin STb on intestines of mice, rats, rabbits, and piglets.

There are at least two classes of Escherichia coli heat-stable enterotoxins, STa and STb. Unlike STa, which is active in suckling mice and piglets, STb is inactive in suckling mice but active in piglets and older, weaned pigs. This study examined the activity of STb in several animals and its effect on intestinal histology and cyclic GMP levels in intestinal mucosal cells. STb did not cause fluid secretion in suckling mice up to 12 days old or in rat or rabbit intestinal-loop preparations. STb-induced fluid secretion in weaned-pig intestinal loops occurred by 30 min and became maximal by 3 to 6 h. STb did not disrupt intestinal histology and did not alter cyclic GMP levels in intestinal mucosal cells from piglet intestinal loops after 0.5- and 6-h incubations. Our studies support the concept that STb is a second heat-stable E. coli enterotoxin with properties and a mechanism of action unlike those of STa.

Animals↗

Economical, simple method for production of the gaseous environment required for cultivation of Campylobacter jejuni.

Campylobacter jejuni is an enteric pathogen recognized worldwide as a cause of diarrhea. Its isolation from stool samples requires a microaerophilic environment that heretofore has been expensive and cumbersome to create. An economical, portable, and simple method is described which involves the production of appropriate concentrations of oxygen and carbon dioxide. Inside a plastic bag are placed two cups, one containing fine steel wool (grade 0) previously soaked in a 2.5% aqueous solution of copper sulfate and the other containing an Alka-Seltzer tablet in tap water. As suggested by Jurgensen et al. (Rev. Bras. Pat. Clin. 18:58-63, 1982), we used the effervescent antacid to generate CO2. By plate counts, we found this method to be as reliable in the cultivation of 20 isolates of C. jejuni in pure and mixed fecal culture as the reference gas method (85% N2, 10% CO2, and 5% O2). Analyses of the gas mixture inside the bag after up to 24 h of incubation confirmed the creation of an atmosphere of reduced O2 and increased CO2 concentrations. This method is eminently suitable for field situations in which more costly supplies are not available.

Aspirin↗

NIH conference. Cyclic nucleotides: mediators of bacterial toxin action in disease.

In several bacterial diseases, the clinical, laboratory, and histologic findings result from the elaboration by the organism of a toxic product that binds to and may enter the host cell to alter its metabolism. In some cases, the intracellular mediators of toxin action are the cyclic nucleotides, cyclic adenosine 5'-monophosphate (cAMP) and cyclic guanosine 5'-monophosphate (cGMP), the ubiquitous second messengers through which numerous hormones, neurotransmitters, and drugs exert their effects. Certain toxins act by enhancing the activity of cellular enzymes that synthesize cAMP or cGMP; and others, by themselves catalyzing cAMP synthesis after entering the cell. Studies of the mechanism of action of these toxins have helped in deciphering the enzymatic components within animal cells that are responsible for cyclic nucleotide synthesis, degradation, and function as well as in understanding the pathogenesis of the diseases in which they are involved.

Adenosine Diphosphate Ribose↗

Giardia lamblia infection of suckling mice.

Axenically cultured Giardia lamblia trophozoites (2 x 10(5)) were inoculated by gavage into suckling mice. All mice three, seven, and 14 days old became infected, with the peak trophozoite count in the small bowel of 5.3 +/- 1.1 x 10(6) occurring seven days after inoculation of three-day-old mice. In addition to infecting each of 65 challenged mice, G. lamblia was able to complete its life cycle by encysting and, as cysts, to infect previously unchallenged animals. Control mice given culture medium alone, mice challenged with trophozoites when older than 14 days of age, and mothers of infected mice did not become infected. There was no difference in body weight between infected mice and control mice, nor were histopathologic changes in the small bowel noted at the time of peak infection. Infection was cleared in all mice by 17-21 days. Thus, axenically cultured G. lamblia trophozoites are capable of infecting and completing their life cycle in suckling mice. The susceptibility of mice to infection is remarkably age specific, and the infection is apparently without adverse effects on the murine host.

Aging↗

Prospective study of diarrheal illnesses in northeastern Brazil: patterns of disease, nutritional impact, etiologies, and risk factors.

Diarrhea is a leading cause of death in tropical countries. One of the highest childhood mortalities is in northeastern Brazil, where little is known about the morbidity, etiology, and risk factors of diarrhea. Prospective village surveillance over 30 months revealed diarrhea attack rates of more than seven episodes per child-year at six to 11 months of age among the children of the poorest families. Other risk factors included early weaning and the lack of toilets. Diarrhea led to weight loss and stunted growth. Enterotoxigenic Escherichia coli and rotaviruses were the most common pathogens, accounting for 21% and 19% of cases, respectively, followed by Shigella species (8.0%), Campylobacter jejuni (7.5%), Giardia species (6.7%), Strongyloides species (5.3%), and enteropathogenic E coli serotypes (4.6%). Most (84%) enterotoxigenic E coli were isolated during the rainy season of October to March (P less than 0.03), whereas 71% of rotaviral illnesses occurred during the drier months of June to October (P less than 0.03). In the present study, the early occurrence and nutritional impact of diarrhea and weaning, as well as the major etiologic agents of diarrhea and their different seasonal patterns have been defined for this region in which life-threatening diarrhea is endemic.

Adolescent↗

Induction of a novel morphological response in Chinese hamster ovary cells by pertussis toxin.

Exposing Chinese hamster ovary cells in culture to pertussis toxin resulted in a novel clustered growth pattern. The specificity of the response for pertussis toxin was shown by neutralization of the activity with specific anti-toxin antibody, heat lability (80 degrees C for 15 min), and absence of such activity by culture media from nontoxigenic Bordetella species. Although a lag of at least 16 h was required before clustered growth was seen, exposure to the toxin for as little as 10 min resulted in a full response 24 h later. The morphological effect appeared to be independent of the cyclic AMP-mediated cell elongation elicited by the heat-labile enterotoxin from Vibrio cholerae in that the pertussis toxin effect was seen in both the presence and absence of elongation. Although the mechanism by which this effect is mediated remains to be determined, it is already providing a useful in vitro assay for pertussis toxin.

Animals↗

Reduction of the secretory response to Escherichia coli heat-stable enterotoxin by thiol and disulfide compounds.

We examined the effects of disulfide and thiol compounds on Escherichia coli heat-stable enterotoxin (ST) and cyclic GMP-induced secretion. Both cystamine and cystine (disulfide compounds) reduced the secretory responses to submaximal doses of ST in suckling mice (at 0.5 mumol per mouse) and reduced ST activation of guanylate cyclase (by 33 to 73% at 1 mM). In higher doses, cystamine completely eradicated a maximally effective ST dose as well. In addition, the sulfhydryl (thiol) compounds cysteamine, cysteine, and acetylcysteine strikingly reduced the secretory response and the guanylate cyclase response to ST. Neither the disulfide nor the thiol compounds tested reduced cyclic GMP-induced secretion. These studies suggest that disulfide and thiol compounds both block ST-induced secretion before its activation of guanylate cyclase. Taken with the work of others, these findings suggest that disulfide compounds may alter the oxidation reduction state of a cell or act directly on the guanylate cyclase enzyme, whereas thiol compounds may inactivate ST itself by breaking its disulfide bridges, or it may alter guanylate cyclase activation by ST. Both families of compounds deserve further consideration among potential antisecretory agents for application in the control of ST-induced diarrhea.

Acetylcysteine↗

Praziquantel: a major advance in anthelminthic therapy.

Praziquantel recently has been approved in the United States for use against a broad range of trematodes and cestodes. The drug is highly effective against all Schistosoma species that infect humans as well as other flukes and tapeworms, including the larval stage of Taenia solium, which causes cysticercosis. In addition, praziquantel is relatively nontoxic, well accepted by patients, and can be given orally in one dose or several doses in a single day. Praziquantel lowers or abolishes the threshold for treating persons with these infections, and, if costs can be contained, may help in the global control of serious systemic helminthic infections.

Animals↗

Inhibition of Escherichia coli heat-stable enterotoxin effects on intestinal guanylate cyclase and fluid secretion by quinacrine.

Enterotoxigenic Escherichia coli may produce a heat-stable enterotoxin (ST) that causes diarrheal disease in humans and in animals ST activates particulate guanylate cyclase in intestinal mucosal cells and causes intestinal fluid secretion. In this study, we examined the effects of quinacrine on ST activation of guanylate cyclase and ST-mediated intestinal fluid secretion. Quinacrine significantly reduced ST activation of particulate guanylate cyclase in rat intestinal tissue. Additionally, quinacrine reduced ST-mediated fluid secretion in a rat intestinal loop assay (P less than 0.05). In the suckling mouse model, subcutaneous quinacrine (0.1 mumole/mouse) reduced ST-induced fluid secretion at a submaximally effective dose of the toxin, but it did not reduce ST-mediated fluid secretion at a near maximally effective dose. Quinacrine (0.1 mumole/mouse) did not significantly reduce intestinal fluid secretion induced by the analog of cyclic GMP, 8-bromo cyclic GMP. However, at a higher concentration of quinacrine (1 mumole/mouse), significant inhibition of 8-bromo cyclic GMP-induced secretion was observed. Inhibition by the antimalarial agent quinacrine of ST-induced fluid secretion, by a block prior to guanylate cyclase activation, suggests a possible role for a phospholipase early in the sequence of events of ST activation of guanylate cyclase. The results suggest that ST may activate membrane phospholipases prior to ST activation of guanylate cyclase.

Animals↗

Effect of ion channel inhibitors on the cytopathogenicity of Entamoeba histolytica.

Entamoeba histolytica (axenic strain HM1-IMSS), a cytolytic enteric pathogen, kills target Chinese hamster ovary cells in two discrete steps: (1) carbohydrate-specific adherence of amoebae to target cells, followed by (2) cytolysis of adherent target cells. Both steps require intact amoebic microfilament function. The effects of the fast Na+ channel blocker tetrodotoxin and the slow Na+-Ca++ channel blockers verapamil (10(-5) M) and bepridil (10(-5) M) on amoebic killing were evaluated. Verapamil and bepridil both decreased amoebic killing (P less than 0.001); tetrodotoxin had no effect. Bepridil, but not verapamil, inhibited amoebic adherence at 37 C (P less than 0.001). Both verapamil and bepridil inhibited amoebic lysis of cells after adherence occurred (P less than 0.001). Verapamil protected target cells from lysis by amoebae (P less than 0.005), whereas bepridil reduced the capacity of amoebae to kill Chinese hamster ovary cells (P less than 0.001). These findings suggest that changes in transmembrane ion flux in both the amoeba and the target cell are involved in amoebic killing of target cells.

Adhesiveness↗

Susceptibility of Shigella species to erythromycin.

Two of the most common causes of inflammatory enteritis are Campylobacter fetus subsp. jejuni and Shigella species. No single antimicrobial agent is recommended for treatment of both diseases. Erythromycin is used to treat C. fetus subsp. jejuni infections but has not been studied in shigellosis. For this reason, we determined the susceptibility of 22 strains of Shigella to erythromycin and found that Shigella species are susceptible to concentrations of erythromycin which are obtainable in stool.

Dose-Response Relationship, Drug↗

Lanthanum chloride inhibition of the secretory response to Escherichia coli heat-stable enterotoxin.

Escherichia coli heat-stable enterotoxin (ST) appears to cause intestinal fluid secretion by activating intestinal particulate guanylate cyclase. Recent studies suggest that chlorpromazine and quinacrine reduce the intestinal secretory response to ST and activation of guanylate cyclase by ST. We have examined the effects of lanthanum chloride, another agent that has been shown to inhibit calcium-dependent cellular processes, on the intestinal secretory response to ST and on the inhibition of ST by chlorpromazine and quinacrine. Lanthanum (2.5 to 10 mumol per mouse) reduced ST-mediated intestinal fluid secretion in the suckling mouse assay by 40 to 56%, respectively, but did not reduce basal fluid accumulation or ST activation of particulate guanylate cyclase. Intestinal fluid secretion in suckling mice induced by 8-bromocyclic GMP was also reduced by lanthanum. When subeffective doses of lanthanum and chlorpromazine were combined, they blocked both ST- and 8-bromocyclic GMP-mediated gut secretion in suckling mice. Likewise, the combination of subeffective doses of lanthanum and quinacrine reduced ST-mediated gut secretion in suckling mice. However, 8-bromocyclic GMP-induced secretion was not synergistically inhibited by lanthanum and quinacrine. These results suggest that lanthanum blocks ST-induced secretion after ST activation of guanylate cyclase. Additionally, lanthanum potentiates the inhibitory effects of quinacrine and chlorpromazine on ST and suggests that combination antisecretory therapy deserves further exploration.

Animals↗

Comparison of paired whole milk and dried filter paper samples for anti-enterotoxin and anti-rotavirus activities.

Milk specimens, 75 from cows immunized against cholera toxin and 35 from a human population in which enterotoxigenic Escherichia coli and rotaviral infections are endemic, were collected as paired filter paper and frozen whole milk samples. Each pair was tested for antibody activity against heat-labile E. coli and Vibrio cholerae enterotoxins. Additionally, 12 of the 35 paired human milk samples stored as frozen whole milk and dried on filter paper were tested for anti-rotavirus immunoglobulin A. Anti-enterotoxin and anti-rotavirus immunoglobulin A titers in milk dried on filter paper compared favorably with those of their frozen whole milk pairs. Filter paper samples offered considerable advantages for field collection, transportation, and storage over frozen liquid samples.

Animals↗