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Biomedical subjects

R H Fetterer

Publications and source records attributed to R H Fetterer.

71 records · Page 4Linked to original sources
PubMed1987

Ascaris suum: partial isolation and characterization of hypodermis from the adult female.

A method was developed to remove the muscle from body wall strips of adult female Ascaris suum resulting in a hypodermis cuticle preparation. Optimum treatment for obtaining the hypodermis cuticle was a 15 min incubation with trypsin (2.0 mg/ml) at room temperature, followed by mechanical removal of the muscle. The hypodermis cuticle prepared in this manner incorporated radiolabeled amino acids into cuticular and hypodermal proteins; incorporation was inhibited by protein synthesis inhibitors. Characterization of the hypodermal proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the hypodermis apparently contains proteins that differ from those of the cuticle and that the hypodermis of adult A. suum appears to lack cuticle protein precursors. This result will now allow detailed biochemical and physiological investigations of the hypodermis, a tissue which is critical for cuticle synthesis.

Amino Acids↗
PubMed1986

Transcuticular solute movement in parasitic nematodes: relationship between non-polar solute transport and partition coefficient.

The rate constants (K) for steroid transport across the isolated cuticle of Ascaris suum were, linearly related to partition coefficients (P) of steroids in model solvents. The slope of log P vs log K for an isolated cuticle was closest to unity for the more polar solvents, octanol and ether, suggesting that the barrier to steroid movement across the cuticle has partition properties similar to these solvents. The transcuticular movement of steroids into intact adult A. suum and infective larvae of Haemonchus contortus was predicted by the P in model solvents suggesting that the same barriers for transcuticular solute movement may exist in intact worms as in isolated cuticles.

Animals↗
PubMed1986

Peripheral androgen levels in peripuberal rams infected with Fasciola hepatica.

Three-month-old, Polled Dorset rams infected with Fasciola hepatica and uninfected control rams were monitored throughout the peripuberal phase for peripheral concentrations of testosterone and for body weight. No differences between groups occurred in these measurements from early spring to mid-autumn. However, the infected postpuberal rams demonstrated a reduced ability to remove exogenous testosterone from the circulation. Liver damage induced by moderate infections of flukes apparently impairs hepatic catabolism of this steroid but compensatory mechanisms appear to maintain circulating levels comparable to those of uninfected rams.

Animals↗
PubMed1986

The effect of albendazole and triclabendazole on colchicine binding in the liver fluke Fasciola hepatica.

Albendazole (ABZ) and its sulfoxide (SX) and sulfone (SO) metabolites inhibit the binding of 3H-colchicine, a ligand with high affinity for tubulin to homogenate preparations of the liver fluke Fasciola hepatica. The relative potency of these compounds is SX greater than ABZ greater than SO. The benzimidazoles (cambendazole, parbendazole, oxibendazole and mebendazole), when tested at a concentration of 10 microM, also inhibited colchicine binding to fluke homogenates. However, a potent new benzimidazole flukacide, triclabendazole (TCB), was without effect on colchicine binding to F. hepatica homogenates. When intact flukes were exposed in vitro to 10(-5)M SX for as little as 5 min the subsequent binding of 3H-colchicine to fluke homogenates was significantly reduced. However, flukes recovered from sheep either 12 or 24 h after treatment with ABZ did not have a decreased ability to bind colchicine, although the non-specific binding was higher in flukes from treated sheep, suggesting some interaction of drug with tubulin in vivo. ABZ, SX and SO were effective in preventing embryonation of fluke eggs at doses as low as 0.01 microM, but TCB was without effect at concentrations as high as 10 microM. The results suggest that ABZ exerts at least part of its anthelmintic effect by interaction with fluke tubulin.

Albendazole↗
PubMed1985

Prophylactic efficacy of clorsulon against Fasciola hepatica in calves and sheep.

A daily oral 5 mg kg-1 dose of clorsulon for 28 days in calves given Fasciola hepatica cysts at 3, 5, and 7 days after initiation of treatment was highly effective in reducing worm burdens (98%) and preventing liver pathology. In similarly infected and treated sheep, clorsulon showed little effect as a prophylactic for delaying the onset of liver pathology. The size of flukes recovered from treated sheep was reduced. Although clorsulon prevented development of fascioliasis in treated calves, the host antibody response was qualitatively similar to that of untreated infected calves, but the magnitude of the response was reduced. Blood clorsulon levels in calves rose to 2.90 micrograms ml-1 within the first week of treatment then fluctuated between 2.65 and 2.90 micrograms ml-1 for the next two weeks. Clorsulon levels in sheep were 0.50-0.60 micrograms ml-1 lower than those in calf blood. The difference in bioavailability of clorsulon between sheep and calves may have contributed to differences in efficacy of the drug.

Administration, Oral↗
PubMed1984

Ascaris suum: continuous perfusion of the pseudocoelom and nutrient absorption.

A double-cannulation apparatus was constructed for continuous perfusion of the pseudocoelom of adult Ascaris suum while maintaining the intact parasite in a controlled incubation chamber. Peristaltic pumps maintained a constant flow rate of artificial perienteric fluid through the incubation chamber (1 ml/min) and through the parasite (100 microliters/min). Based on protein determinations, perienteric fluid was removed from the pseudocoelom within 35 min of initiation of perfusion (3.5 ml). A nonabsorbable dye, Blue Dextran, was detected first in the perfusate 4 min (400 microliters) after initiation of infusion into the pseudocoelom, and was maintained at a constant concentration in the perfusate by 8 min after initiation of dye infusion. Removal of the dye from the pseudocoelom was accomplished within 8 min (800 microliters) after the cessation of dye infusion. Occlusion of the digestive tract had no effect (P less than 0.05) on the short-term (3 hr) absorption of 3H-labeled cholesterol, [14C]-3-o-methylglucose or [14C]glucose from the incubation medium into the perienteric cavity. Concentrations of isotopes in the pseudocoelom reached steady-state levels within 60 min of the initiation of incubation, but remained low (greater than 0.5%) when compared to medium concentration. Similarly, the time course of the accumulation of [14C]glucose into individual tissue components did not differ in intact worms with or without patent intestinal tracts. Thus, the cuticular/muscle tissue largely appears to be the primary route of absorption of cholesterol and glucose in adult A. suum.(ABSTRACT TRUNCATED AT 250 WORDS)

3-O-Methylglucose↗
PubMed1984

Effects of diamfenetide on metabolic and excretory functions of Fasciola hepatica in vitro.

The effect of diamfenetide (DFT) on the time course of production of end-products of glucose metabolism, tissue ATP levels and NH3 production by adult Fasciola hepatica in vitro was determined. Products of glucose metabolism are increased between 6 and 24 hr incubation in 10(-4) M DFT. Tissue ATP levels and NH3 production are decreased during this time period. The observed metabolic effects of DFT are manifested at a much later time after drug exposure than previously described membrane-disruptive events indicating that metabolic effects of DFT on F. hepatica may be secondary to the initial effects on surface membranes.

Acetanilides↗
PubMed1984

Interaction of Fasciola hepatica with albendazole and its metabolites.

Adult Fasciola hepatica recovered from sheep 12 and 24 h after a single oral dose of albendazole (20 mg/kg) contained significant amounts of two oxidized metabolites of albendazole (ABZ), a sulphoxide (SX) and a sulphone (SO), but not ABZ. Flukes incubated in vitro with 10 microM SX or SO contained these metabolites at a level two to three times the level observed in flukes recovered from sheep 24 h after a curative oral dose of ABZ. The concentration of ABZ in flukes was 10-fold greater than either SX or SO after a 24 h in vitro incubation in 10 microM of the respective drug. Flukes exposed to ABZ in vitro contained two-fold higher SX levels than SX-treated flukes due to a combination of spontaneous oxidation in media and fluke-mediated oxidation of ABZ. Measurement of end-products of glucose metabolism following 24 h incubation in 10 microM of either ABZ, SX or SO did not show a significant difference between treated and untreated flukes.

Albendazole↗
PubMed1983

Fasciola hepatica: effects of diamfenetide free amine on in vitro physiology, biochemistry, and morphology.

Short-term (1-3 hr) incubations in vitro of immature and adult Fasciola hepatica with 10(-4) to 10(-5) M free amine of diamfenetide (DPT-FA) demonstrated a time/dose-dependent, irreversible paralysis that involved an increase in muscular tension and decrease in contraction amplitude. The following events occurred preceding or concomitant with the paralysis: influx of Na+, decrease in surface membrane potential, increase in wet weight, swellings on the ventral surface, and inhibition of 3-O-methyl glucose transport. These events were all consistent with a disturbance in surface membrane functions. The effects of DPT-FA were more severe in immature flukes (3-5 weeks postinfection) than adults which agrees with observed in vivo efficacy.

3-O-Methylglucose↗
PubMed1983

Eimeria tenella: cecal contraction in infected chickens.

The muscle of ceca from chickens infected with Eimeria tenella had an increased amplitude of contraction when compared to the cecal muscle of uninfected control chickens. The increased amplitude was significant (P less than or equal to 0.05) at 5 days postinoculation (PI) and became nonsignificant at 7 days PI. The amplitude also increased with the severity of the infection. The sensitivity of the muscle from infected ceca to acetylcholine (ACH) was greater than the control. Infection by different strains of E. tenella also increased the sensitivity of the cecal muscle to ACH when compared to the uninfected control. The rate of spontaneous contractions was not different in any group or treatment. The wet weight of infected ceca increased with days PI and severity of infection.

Acetylcholine↗
PubMed1981

Na+-K+ transport, motility and tegumental membrane potential in adult male Schistosoma mansoni.

Ouabain applied to adult male Schistosoma mansoni causes a large, non-reversible tension increase of the parasite's musculature and elimination of spontaneous contractions. The tension increase and the time-course of tension development caused by ouabain are dose dependent with significant effects obtained at 3 x 10(-6) M. Digoxin and digoxigenin act in a similar manner with a relative potency of ouabain approximately or equal to digoxin greater than digoxigenin. Lowered temperature as well as substitution of Li+ for Na+ increases muscle tension. The membrane potential recorded from the ventral tegument is also affected by treatments which interact with Na+-K+ transport systems. Ouabain (0.1 mM) causes a rapid depolarization without a significant effect on membrane resistance. The tegument is depolarized by temperature below 30 degrees C. The effect of temperature is readily reversible and the temperature sensitivity is eliminated by pretreatment with ouabain. Substitution of Li+ for Na+ also causes a depolarization of the tegument. Tracer experiments show both an increase in Na+ and a decrease in K+ in the parasite within 10 min after treatment with ouabain (1 x 10(-5) M). Decreasing temperature of the bathing medium also causes an accumulation of Na+ as well as a K+ decrease in the animals. The above results indicate a significant role for active Na+-K+ transport in muscle contraction and in maintenance of the tegumental membrane potential. The data also suggest that the Na+-K+ transport in S. mansoni may be electrogenic.

Animals↗
PubMed1980

Praziquantel, potassium and 2,4-dinitrophenol: analysis of their action on the musculature of Schistosoma mansoni.

Praziquantel (PZ) (10(-6) M), an antischistosomal drug, 60 mM K+ and 2,4-dinitrophenol (DNP) induce a rapid contracture of the musculature in adult male S. mansoni. This event is accompanied, except for DNP, by an increased accumulation of 45Ca2+ in the parasite. K+-induced contractures had phasic and tonic components while DNP and PZ produced only tonic contracture of the parasites musculature. The Ca2+ antagonist, D-600 (10(-4) M) as well as La3+ (10 mM) and Co2+ (10 mM) prevented the 45Ca2+ accumulation produced by high K+. La3+ and Co2+ blocked the tension increasing effects of high K+; D-600 blocked only the tonic contractures. D-600 and Co2+ did not prevent the 45Ca2+ increase produced by PZ but La3+ did. D-600 did not block the PZ response but Co2+ and La3+ partially attenuated it. La3+ also partially attenuated the DNP response. Co2+ and D-600 prevented sustained contractures in response to DNP. Thus, although K+, PZ and DNP have the same final effect on the musculature of S. mansoni, it appears that their effects are not mediated by the same mechanisms.

2,4-Dinitrophenol↗
PubMedDate not supplied

Biochemical and immunochemical characterization of 125I-labeled cuticle components of Haemonchus contortus.

Live Haemonchus contortus developmental stages were radioiodinated and then subjected to a stepwise extraction procedure consisting of a buffer extract (with or without detergent) to solubilize putative surface-associated antigenic macromolecules, followed by a detergent/beta-mercaptoethanol (BME) extract to solubilize putative cuticle collagen proteins. A buffer-extracted iodinated 100-kDa protein was present in the free-living, infective L3(2M) stage. This labeled protein was released during in vitro exsheathment of L3(2M) and was not present in the ecdysed second molt (2M) cuticle. In addition to the 100-kDa protein, exsheathment fluid contained a 70-kDa labeled protein that was not extracted from iodinated L3(2M) with either detergent or BME. The data suggest that these proteins are components of the specialized ring portion of the 2M cuticle that is enzymatically ruptured during ecdysis. The L3(2M) and the exsheathed third-stage larvae (L3) contained 3 labeled, BME-extracted, collagenase-sensitive proteins of 108, 88 and 53 kDa. In contrast, four detergent-extracted, collagenase-insensitive, iodinated proteins (143, 81, 58 and 30 kDa) were present in adult H. contortus. The 143-kDa protein was both glycosylated and immunogenic. All 4 adult cuticle proteins were released from the cuticle surface into culture fluids. Furthermore, a cysteine protease was secreted by adults which apparently hydrolyzed the released 81-, 58- and 30-kDa surface proteins.

Animals↗
PubMedDate not supplied

Elevation of muscle and plasma 3-methylhistidine as a result of turkey coccidiosis.

To assess muscle breakdown during avian coccidiosis, the level of the non-metabolizable amino acid 3-methylhistidine (3MH) was determined in muscle and plasma from turkey poults that received an infection with a field isolate containing a mixture of Eimeria species. The effect of increased levels of parasitism was evaluated at 6 days postinoculation (DPI) in birds receiving 2.5 x 10(4), 1 x 10(5), or 2 x 10(5) oocysts each. The changes in 3MH levels during recovery from acute infection were assessed at 6-29 DPI in animals given 1.9 x 10(5) oocysts per bird. In some experiments, uninoculated birds given the same amount of feed as infected birds (pair fed) were used to determine the impact of feed deprivation on weight loss and 3MH levels. Infected birds had significantly elevated plasma and muscle 3MH at 6 DPI after a single dose of Eimeria oocysts. The plasma and muscle 3MH returned to control levels after 14 DPI. The 3MH levels increased with increased dose of oocysts. Plasma and muscle 3MH levels were well correlated, and an inverse curvilinear relationship between weight gain and plasma 3MH concentrations levels was observed. Plasma and muscle 3MH levels were significantly elevated in pair-fed birds, but 3MH levels in infected birds were increased by 30% over pair-fed birds. The results suggested that muscle breakdown, as assessed by plasma and muscle levels of 3MH, increased during the acute stage of Eimeria infection in turkey poults.

Acute Disease↗