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Cryptosporidium parvum infection represents a significant cause of diarrhea in humans and animals. We studied the effect of luminally applied glutamine and the PG synthesis inhibitor indomethacin on NaCl absorption from infected calf ileum in Ussing chambers. Infected ileum displayed a decrease in both mucosal surface area and NaCl absorption. Indomethacin and glutamine or its stable derivative alanyl-glutamine increased the net absorption of Na(+) in infected tissue in an additive manner and to a greater degree than in controls. Immunohistochemical and Western blot studies showed that in control animals neutral amino acid transport system ASC was present in villus and crypts, whereas in infected animals, ASC was strongly present only on the apical border of crypts. These results are consistent with PGs mediating the altered NaCl and water absorption in this infection. Our findings further illustrate that the combined use of a PG synthesis inhibitor and glutamine can fully stimulate Na(+) and Cl(-) absorption despite the severe villous atrophy, an effect associated with increased expression of a Na(+)-dependent amino acid transporter in infected crypts.

Cryptosporidium parvum produces a prolonged watery diarrhea unresponsive to conventional antimicrobials. Because of reported efficacy of antibody-based immunotherapy, we studied the effect of inexpensive, commercially available oral bovine serum concentrate (BSC) in experimental cryptosporidiosis. Twenty-four calves were treated with 57 g/d BSC (n ϭ 12) or soy protein (n ϭ 12) added to their standard whey protein-based milk replacer (227 g/2 L twice daily). Of the 24, 9 were also treated with L-glutamine (GLN), 8 g/L (50 mM) in the milk (5 calves in the BSC group and 4 in the soy group). Animals were inoculated with 10 8 cryptosporidium oocysts per os on d 8 of life and received oral rehydration on d 12-14. Eight uninfected controls were treated with BSC or soy protein. Fecal and urine volume and urinary Cr-EDTA excretion were measured. Animals were killed on d 18 of life. Cryptosporidiosis induced severe watery diarrhea lasting Ͼ9 d and produced a 25% increase in intestinal permeability, a 33% decrease in villous surface area, and a 40% reduction in mucosal lactase specific activity. Glutamine treatment had no effect on the diarrhea or any of the intestinal tests; and therefore pooled data were used to compare the 12 calves treated with BSC with the 12 treated with soy. In animals receiving BSC, peak diarrheal volume and intestinal permeability were reduced 33%, fewer oocysts were shed, intestinal crypts were significantly deeper, and villous surface area returned to normal by 9 d after infection (all p Յ 0.05). BSC should be studied as a treatment for human cryptosporidiosis. Cryptosporidiosis is a major enteric pathogen found globally in infants with acute and chronic diarrhea, and is a cause of persistent diarrhea in 10%-20% of patients with AIDS. Cryptosporidium parvum is also the most widespread enteropathogen identified in neonatal calves. Ninety percent of American dairy farms harbor this coccidian, and 92% of asymptomatic adult cows have specific anti-C. parvum IgG, IgG1, IgG2, and IgM antibodies (1). Neonatal calves experience high morbidity, but low mortality with monoinfections, although mixed infections result in a much greater rate of mortality (2). The epidemic potential of this organism was realized in Milwaukee in 1993, when over 400,000 residents contracted the infection from contaminated municipal water sources (3). Presently, there is no available antimicrobial to kill cryptosporidium; in fact, there is no treatment to stimulate bowel repair from any infectious agent in infants with serious or chronic diarrhea.We have shown that cryptosporidial diarrhea is both malabsorptive and secretory in nature, produced by partial mucosal destruction as well as elevated levels of prostaglandin E 2 and prostacyclin, the latter of which activate enteric secretomotor neurons (4). We have also found beneficial effects of growth factors (present in serum and colostrum) in enhancing bowel repair in rotavirus diarrhea and after intestinal ischemic injury (5, 6). Recently, Lembcke (7) showed in Peruvian children...

Acute mastitis was induced in lactating cows by intramammary challenge with 10 micrograms of Escherichia coli lipopolysaccharide. The cows were monitored clinically prior to and for 96 hours after challenge. Milk production, complete blood counts, serum enzyme activities and milk indicators of inflammation were evaluated. Endotoxin challenge was in 7 groups of 3 cows each. Within the groups, cows were randomly assigned to 3 intravenous treatments: saline controls, steroid (one dose of dexamethasone at 0.44 mg/kg) and non-steroidal agent (two doses of flunixin meglumine at 1.1 mg/kg, 8 h apart). Anti-inflammatory therapy reduced rectal and mammary gland surface temperatures. Milk production was significantly reduced (p less than 0.05) in cows treated with dexamethasone. Although dexamethasone treatment produced significant increases (p less than 0.05) in blood leukocytes and segmented neutrophils, milk somatic cell concentrations were not significantly altered. Flunixin meglumine did not alter milk production or blood or milk leukocytes.

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Coliform mastitis in dairy cattle frequently results in systemic disease with occasional deaths in association with endotoxic shock. Systemic anti-inflammatory therapy has been used to alter the course of endotoxic shock in severe cases. Use of anti-inflammatory therapy has been questioned on the basis that such treatment may compromise immune function and decrease clearance of bacteria from infected mammary glands. The purpose of this investigation was to determine whether anti-inflammatory therapy influenced bacterial clearance following intramammary challenge of lactating goats with Escherichia coli. Standardized quantities of a pathogenic coliform culture were infused through the teat canal into one half of the mammary gland in 18 goat does. The does were then randomly assigned to receive one of three intravenous treatments: saline (controls), one dose of steroid (dexamethasone), or two doses of a non-steroidal anti-inflammatory agent (flunixin meglumine). The clinical signs, milk production, complete blood counts, serum clinical chemistry values, milk bacterial cultures and milk somatic cell concentrations were monitored sequentially. Goats treated with anti-inflammatory agents exhibited some improvement in clinical response to challenge with E. coli (e.g. rectal temperature, degree of appetite suppression) as compared to saline controls. There were no significant differences between treatments in the degree of inflammation present in the mammary glands or supramammary lymph nodes examined at necropsy. The most important finding was that anti-inflammatory therapy did not adversely influence the clearance of E. coli from challenged glands.

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