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Biomedical subjects

M J Coyne

Publications and source records attributed to M J Coyne.

At least 19 recordsLinked to original sources

The development and mortality of the free-living stages of Haemonchus contortus in laboratory culture.

Haemonchus contortus eggs were cultured in intact fecal pellets at various temperatures (5-35 degrees C) for 22 days. Temperature and relative humidity were kept constant throughout the incubation period. Nl larval development occurred at 5 degrees C; peak third-stage larval recovery occurred at 20 degrees C. Egg mortality was an age-dependent phenomenon, whereas larval mortality remained constant irrespective of larval age. Development was characterized by a minimum development time followed by a transition to the next stage which occurred at a constant rate. All rates were temperature dependent. The minimum development times reported here are much less than those previously reported. Based on these results a mathematical model was used to describe the demography of the free-living stages of H. contortus at various temperatures.

Animals

The mortality and fecundity of Haemonchus contortus in parasite-naive and parasite-exposed sheep following single experimental infections.

Parasite-exposed lambs and their parasite-naive controls were experimentally infected once only with 30,000 H. contortus larvae at 3, 9, 12, and 20 weeks following termination of a moderate immunizing infection of 30,000 H. contortus larvae. Previously exposed lambs, challenged at 3 weeks, had a significant reduction in the total H. contortus worm burden as compared to parasite-naive controls. No difference in the total H. contortus worm burden was found between parasite-exposed or parasite-naive lambs challenged at 9 weeks or thereafter. Female worms were found to be significantly smaller in lambs previously exposed to the parasite as compared to those found in parasite-naive lambs. The average parasite fecundity was 4700 eggs per female worm per day. Previous exposure of the lambs to the parasite had no effect on parasite fecundity. Various mathematical models were used to examine parasite fecundity. Parasite fecundity was found to increase in the initial post-challenge period reaching a constant value approximately 58 days after challenge infection. No density-dependent constraints on fecundity were observed.

Animals

A study of the mortality and fecundity of Haemonchus contortus in sheep following experimental infections.

The regulation of the fecundity and mortality of H. contortus in sheep was examined using a series of mathematical models. Six-month-old Dorset crossbred lambs were infected once only with various doses of infective H. contortus larvae (500-20,000 larvae). Parasite mortality was found to be an increasing linear function of the magnitude of the initial infection over the range of doses examined. Parasite fecundity was found to remain constant over the intensity and duration of the infection. The average fecundity for H. contortus at the time of slaughter was found to be 7037 eggs per female worm per day. There was no evidence of time-dependent changes in fecundity or density-dependent regulation of fecundity.

Animals

The regulation of mortality and fecundity in Schistosoma mattheei following a single experimental infection in sheep.

The regulation of mortality and fecundity of Schistosoma mattheei in sheep was examined using a series of mathematical models applied to data culled from the literature. Parasite mortality (mu) was found to be an increasing linear function of the magnitude of the initial infection over the ranges of doses examined (200-91,000 cercariae) where mu = 9.78 x 10(-3) + 3.476 x 10(-7) infection dose. Parasite fecundity (lambda) was found to be inversely related to the duration of the infection. The best fit model for parasite fecundity was one in which fecundity decreased exponentially with time since initial infection, lambda = lambda 0e-delta(t-tau). There was no evidence for density-dependent regulation of fecundity.

Animals

Fecundity of gastrointestinal trichostrongylid nematodes of sheep in the field.

Twenty-two Dorset Rambouillet lambs were moved to contaminated pasture on Apr 1, 1987. At regular intervals thereafter, pairs of lambs were withdrawn and euthanatized. Gastrointestinal parasites in the abomasum, small intestine, cecum, and large intestine were removed and counted. The last pair of lambs was euthanatized 8 months after original placement on the contaminated pasture. Fecal samples were taken at 3- to 4-week intervals throughout the grazing season and the fecal egg counts were used to estimate parasite fecundity (output of eggs per female parasite per day). The principal parasite genera found included Haemonchus spp, Trichostrongylus spp, and Nematodirus spp. In each of the genera examined, parasite fecundity remained the same irrespective of the intensity or duration of infection. Estimated average fecundities (eggs/female/day) were as follows: Haemonchus contortus, 6,582; Trichostrongylus spp, 262; Nematodirus spp, 40; and Oesophagostomum venulosum, 11,098.

Abomasum

Mathematic model for the population biology of rabies in raccoons in the mid-Atlantic states.

A series of coupled differential equations was used to model the temporal dynamics of rabies in raccoons in the mid-Atlantic region of the United States. The model takes explicit account of the development of natural immunity to rabies and was used to evaluate culling and vaccination elimination strategies. For habitats typical of the mid-Atlantic states, and given the assumptions of the model, it was estimated that elimination of rabies in raccoons by culling may involve the annual removal of over 32% of the raccoon population or the yearly vaccination of up to 99% of the susceptible fraction. Assuming a constant marginal cost for both culling and vaccination, the model suggests that, whatever the actual cost of each method, the cheapest strategy will always involve either culling or vaccination alone. A combined strategy of culling and vaccination will be cheaper than culling alone only when the per capita cost of vaccination is around one-fifth or less the per capita cost of culling.

Animals

Carbohydrate malabsorption in black and Hispanic dialysis patients.

Patients on chronic hemodialysis have decreased food intake and decreased fat stores. Malabsorption of carbohydrates such as lactose, sorbitol, or fructose cause functional bowel symptoms. The aim of this study was to assess the role of carbohydrate malabsorption in the nutritional abnormalities of chronic hemodialysis (CHD). Eleven patients on dialysis (six Hispanic, five black Americans) were studied, compared to 11 healthy volunteers age-, race-, and sex-matched. Lactulose 10 g (transit time), lactose 12.5 g, sorbitol 5 g, and fructose 37.5 g were tested fasting. Breath [H2] was measured 4 h postprandially by gas chromatograph analysis. Positive test was defined as 20 ppm [H2] above baseline. Weight, height, and triceps skinfold were measured. One hundred percent of CHD patients were below the 50th percentile for triceps skinfold measurement and 55% were below the 10th percentile. No biochemical abnormalities were noted. Breath [H2] tests: lactulose: all patients in both groups responded with positive tests. No difference in transit time was noted. Lactose: 73% of CHD had positive test compared to 36% control. Sorbitol: 73% of CHD had positive test compared to 27% control (p less than 0.05). Fructose: 27% CHD compared to 0% control. This study confirmed that CHD patients have decreased fat stores. It demonstrates for the first time that CHD patients have increased incidence of malabsorption of sorbitol. This carbohydrate malabsorption may contribute to the nutritional abnormalities of CHD.

Adult

Inhibition by propranolol of bile acid- and PGE1-stimulated camp and intestinal secretion.

Three colonic and three ileal loops were prepared in six rabbits pretreated with propranolol (PR) 4 mg./kg. I.V. and in five untreated rabbits. In random order, 1 ml. of either deoxycholic acid (DCA) 6 mM., prostaglandin E1 (PGE1) 20 microgram./ml., or saline was placed in each colonic loop and 1 ml. of either cholera enterotoxin (CE) 10 microgram./ml., PGE1 20 microgram./ml., or saline was placed in each ileal loop. In untreated animals, DCA and PGE1 in the colon and CE and PGE1 in the ileum stimulated (P less than 0.01) adenylate cyclase (AC) and net secretion. In the colon, PR abolished DCA-stimulation of AC and net secretion and decreased PGE1-stimulated AC (P less than 0.01) and net secretion. In conclusion, at the doses and times studied, colonic-AC and net secretion stimulated by PGE1 or DCA was distinguished from small bowel-AC and net secretion stimulated by PGE1 or CE.

Adenylyl Cyclases

Gallstone dissolution by chenodeoxycholic acid and phenobarbital.

Gallstone dissolution and biliary lipids were determined and compared in patients receiving either chenodeoxycholic acid (CDC), or CDC and phenobarbital (PB) for 11/2 to 2 years. Among patients with radiolucent gallstones, dissolution occurred in 53% of those receiving CDC alone and in only 25% of those receiving both CDC and PB. No dissolution occurred in 13 other patients with calcified gallstones. Patients with dissolution had a significantly greater molar percentage of CDC and a significantly lower saturation index in bile than those without dissolution. Diarrhea and transiently abnormal liver function tests were the most frequently observed side-effects but only diarrhea necessitated a reduction of the CDC dose. Gallstones recurred following dissolution in one of six patients followed for six months after discontinuation of CDC. In conclusion, PB did not enhance CDC-induced desaturation of bile or gallstone dissolution.

Chenodeoxycholic Acid

Estrogen enhances dietary cholesterol induction of saturated bile in the hamster.

The influence of ethinyl estradiol (EE) on the effects of dietary cholesterol on the biliary saturation index and on the rate-limiting hepatic enzymes of cholesterol synthesis, hydroxymethylglutaryl-CoA-reductase, and bile acid synthesis, 7 alpha-hydroxylase, were determined. Four groups of 12 male hamsters were treated for 1 month with EE, 15 micrograms per kg per day, or placebo vehicle administered intraperitoneally and fed either a standard diet, 0.8 mg of cholesterol per g of food, or high cholesterol diet, 2.4 mg of cholesterol per g. The high cholesterol diet increased the saturation index to 1.00 +/- 0.03 (P less than 0.01) from 0.65 +/- 0.02 in untreated hamsters on the standard diet. EE treatment on the high cholesterol diet further increased (P less than 0.01) the saturation index to 1.15 +/- 0.02. The high cholesterol diet decreased (P less than 0.01) hydroxymethylglutaryl-CoA-reductase activity from 308 +/- 16 pmoles per mg per min in untreated hamsters on the standard diet. The addition of EE treatment had no effect on hydroxymethylglutaryl-CoA-reductase activity. The high cholesterol diet increased (P less than 0.01) 7 alpha-hydroxylase activity from 23 +/- 1.0 pmoles per mg per min in untreated hamsters on the standard diet. The addition of EE decreased (P less than 0.01) 7 alpha-hydroxylase activity from that in untreated hamsters on the standard diet. The conclusions are as follows: (1) EE prevented dietary cholesterol-induced stimulation of cholesterol 7 alpha-hydroxylase activity; (2) EE enhanced the ability of dietary cholesterol to induce saturated bile; and (3) gallstone formation in estrogen-treated women may result from impaired metabolism of dietary cholesterol.

Animals

Gallstone prevalence and biliary lipid composition in inflammatory bowel disease.

Biliary cholesterol saturation has been correlated with disease variables that might effect bile acid loss in ileitis patients with (N = 9) or without (N = 8) intestinal resection having a defined prevalence of gallstones. In addition, cholesterol saturation was determined in ulcerative colitis patients (N = 7) and gallstone patients (N = 18) as well as in 5 normal controls. Biliary cholesterol saturation in ileitis patients both with and without resection was similar to that in gallstone patients yet the prevalence of gallstones was only 12%. Cholesterol saturation did not correlate with ileal resection nor the extent, duration, or activity of ileitis. Biliary cholesterol saturation was not different in ulcerative colitis patients from that in normal subjects. It is concluded that cholesterol saturation of bile alone does not account for the high prevalence of cholesterol gallstones that has been reported in ileitis patients.

Adult

Feasibility of low-dose and intermittent chenodeoxycholic acid therapy of gallstones.

Chenodeoxycholic acid, by reducing the concentration of biliary cholesterol relative to that of bile acid and phospholipid, dissolves cholesterol gallstones. This bile acid, however, has potential dose-related hepatotoxicity and causes dose-related diarrhea. Therefore, the feasibility of low-dose and intermittent therapy was assessed by studying the induction and persistence of chenodeoxycholic acid-induced biliary lipid changes. Biliary lipid composition with each of 3 doses of chenodeoxycholic acid was determined in bile samples obtained by cholecystokinin-stimulated duodenal drainage before, after one week and one month of treatment, and up to 9 weeks after discontinuation of treatment. The lowest dose that significantly reduced the relative concentration of biliary cholesterol was 250 mg/day. A significant reduction occurred one week after initiation of treatment and was maintained for 9 weeks following discontinuation of treatment. Thus, clinical trials on low-dose and intermittent chenodeoxycholic acid therapy for gallstone prophylaxis or dissolution are warranted.

Adult

Effect of propranolol on bile acid- and cholera enterotoxin-stimulated cAMP and secretion in rabbit intestine.

Stimulation of net secretion by deoxycholic acid (DCA) in the colon and by cholera enterotoxin (CE) in the jejunum is mediated by cAMP. Propranolol (Pr) inhibits adenylate cyclase (AC) activity and net secretion induced by bile acid in the colon. The aim of this study was to assess the organ specificity of DCA and CE as well as the selectivity of Pr inhibition. Three colonic and three jejunal loops were prepared in each of 8 rabbits treated intravenously with Pr, 4 mg per kg, 1/2 hr before loop construction and in each of 10 untreated control rabbits. One milliliter of DCA, 6 mM, CE, 10 mug per ml, or heat-inactivated CE or 0.9% NaCl, as basal controls were injected in random order into each of the loops. The volume of luminal fluid and mucosal AC were measured in each intestinal loop 5 hr later. DCA in the colon stimulated AC 2-fold (P less than 0.01) and luminal fluid 15-fold (P less than 0.01). CE in the jejunum stimulated AC 2.3-fold (P less than 0.01) and luminal fluid 9-fold (P less that 0.01). No significant effects on volume or AC occurred in response to CE in the colon or to DCA in the jejunum. Pr pretreatment completely prevented the stimulation of AC and luminal fluid by DCA in the colon but did not affect the action of CE in the jejunum of the same animals. Thus, DCA and CE are organ-specific stimulants of cAMP systems, and Pr is a selective inhibitor of certain inducers of cAMP and net secretion.

Adenylyl Cyclases

Dietary cholesterol affects chenodeoxycholic acid action on biliary lipids.

Chenodeoxycholic acid (CDC) decreases biliary saturation and dissolves gallstones in one-half of the treated patients. Dietary cholesterol also affects biliary lipids and is a possible factor explaining unsuccessful CDC therapy. The aim of this investigation was to study the effect of high and low dietary cholesterol on the CDC-induced decrease of biliary saturation and activity of hepatic hydroxymethylglutaryl coenzyme A reductase (HMG-CoAR). Seventy two hamsters in six groups were fed for 1 month one of three diets: 0.8 mg of cholesterol per g of food, 2.4 mg of cholesterol per g, or cholesterol-free. On each diet hamsters received no CDC or CDC 30 mg per kg per day. When animals were killed, biliary lipids were determined and the activity of hepatic HMG-CoAR was assayed. CDC administration decreased the saturation index (SI)(P less than 0.01) in hamsters on the high cholesterol and standard diets but not on the cholesterol-free diet. The SI in CDC-treated hamsters on the high cholesterol (0.78 +/- 0.03) and cholesterol-free (0.68 +/- 0.02) diets were greater (P less than 0.02) than in CDC-treated hamsters on the standard diet (0.48 +/- 0.03). CDC decreased (P less than 0.01) HMG-CoA reductase activity on each diet. In comparison to HMG-CoAR activity (190 +/- 7.6 pmoles per mg per min) in CDC-treated hamsters on the standard diet, the activity in CDC-treated hamsters on the high cholesterol diet (176 +/- 5.8 pmoles per mg per min) was decreased ( less than 0.05), whereas the activity on the cholesterol-free diet (495 +/- 11.5 pmoles per mg per min) was greater (P less than 0.01). It is concluded that: (1) dietary cholesterol is necessary for optimum CDC inhibition of HMG-CoAR; (2) high cholesterol and cholesterol-free diets prevent maximum CDC decrease of the biliary saturation index; (3) dietary cholesterol alterations may therefore be one cause of the failure of CDC dissolution of gallstones.

Animals