PubMed Health⌕ Search

Biomedical subjects

J W McCall

Publications and source records attributed to J W McCall.

At least 55 records · Page 3Linked to original sources
PubMed1990

In vitro killing of microfilariae of Brugia pahangi and Brugia malayi by eosinophil granule proteins.

Eosinophil infiltration and degranulation around the tissue-invasive stages of several species of helminths have been observed. Release of eosinophil granule contents upon the worms is supported by localization of two of the major granule proteins, major basic protein (MBP) and eosinophil peroxidase (EPO), on and around species of trematodes, nematodes, and cestodes. In the case of filarial worms, MBP is deposited on degenerating microfilariae (mf) of Onchocerca volvulus. Here, we performed in vitro assays of the toxicity of four purified eosinophil granule proteins, namely, MBP, EPO, eosinophil cationic protein (ECP), and eosinophil-derived neurotoxin (EDN), for the mf of Brugia pahangi and Brugia malayi. MBP, ECP, and EDN killed these worms in a dose-related manner although relatively high concentrations of EDN were necessary. EPO, in the presence of a H2O2-generating system and a halide, was the most potent toxin on a molar basis; here, the most potent halide was I- followed by Br- and Cl-. Surprisingly, EPO in the absence of H2O2 killed mf at concentrations comparable to those required for MBP and ECP. The toxicity of EPO + H2O2 + halide was inhibited by heparin, catalase, or 1% BSA, whereas the toxicity of EPO alone was inhibited only by heparin. Heparin also inhibited killing by both MBP and ECP. Despite the homology of ECP with certain RNases, placental RNasin, an RNase inhibitor, was unable to inhibit ECP-mediated toxicity. These results indicate that all of the eosinophil granule proteins are toxic to mf and they support the hypothesis that eosinophil degranulation causes death of mf in vivo.

Animals↗
PubMed1989

Studies on the biosynthesis and fate of ecdysteroids in filarial nematodes.

Experiments were performed to investigate whether adult Dirofilaria immitis and Brugia pahangi were capable of synthesising ecdysteroids from cholesterol or various intermediates from the biosynthetic pathway functioning in insects. Metabolites of radioactively-labelled cholesterol and 5 beta-ketodiol (2,22,25-trideoxy-ecdysone) were detected in the filarial nematodes, but there was no radioactivity corresponding to ecdysteroid. Uptake of tritiated 2-deoxyecdysone was poor and metabolism was not observed. [3H]Ecdysone was absorbed sparingly by adult D. immitis, but was metabolised efficiently to several less polar products. There was no evidence of C-20 hydroxylation capability.

Animals↗
PubMed1988

Comparative effects of anthelmintics on motility in vitro of Onchocerca gutturosa, Brugia pahangi and Acanthocheilonema viteae.

The effects of standard anthelmintics on the motor activity in vitro of adult Onchocerca gutturosa, Brugia pahangi and Acanthocheilonema viteae were determined using a micromotility meter. Fresh adult males dissected from bovine tissues were the best source for observations on O. gutturosa. Parasites liber-ated by collagenase digestion showed poor viability and motility. Only segments of O. gutturosa females were obtainable by dissection and these were not able to sustain motility in vitro. Adult males and females of O. volvulus were active after collagenase digestion of human nodular tissue, but behaved so irregularly that satisfactory monitoring of their movements with the meter was not possible on a regular enough basis to permit quantitation of drug-induced changes. Inhibitory effects on motility of O. gutturosa, B. pahangi and A. viteae were produced by anthelmintics which showed macrofilaricidal effects in vivo in a laboratory rodent model, with the exception of the benzimidazoles. O. gutturosa was, however, much more sensitive than B. pahangi or A. viteae to the temporary paralyzing effects of levamisole and pyrantel. The utility of in vitro screening against O. gutturosa and B. pahangi was evaluated by determining the discriminatory capacity of the tests in detecting novel compounds with reproducible in vivo activity in the jird-B. pahangi/A. viteae model. The results suggested that this would be a valuable selective screening procedure. Although false positives were detected at the rate of 15-17% of the novel anthelmintic chemical series tested, no false negatives were allowed through the screen provided both O. gutturosa and B. pahangi were included.2=

Animals↗
PubMed1986

Induction of protection against Brugia malayi infection in jirds by microfilarial antigens.

The development of immunologic methods to reduce transmission of human lymphatic filariasis depends on measures that will enhance the host's ability to eliminate infective larvae, adult worms, or blood-borne microfilariae (mf). The present study was designed to assess the capacity of a crude extract of Brugia malayi mf to decrease the level of microfilaremia and adult worm burden in jirds inoculated with infective larvae, and to identify the filarial antigens that elicit antibody responses in these animals. Thirty weeks after subcutaneous inoculation with 75 infective larvae, 100% of control jirds were patent (i.e., had microfilaremia) compared with 60% of the group immunized with 10 micrograms of crude microfilarial extract (p less than 0.05). In addition, microfilaremia was lower in patent immunized animals compared with controls (p less than 0.05). The mean total number of adult female B. malayi per jird recovered at necropsy in control animals was 16.0 vs 7.0 in immunized jirds (p less than 0.05). Serum of immunized jirds contained anti-mf antibodies with an end titer of 1:8000, a value similar to that of animals with chronic B. malayi infection. Microfilarial antigens of Mr approximately 150,000, 75,000, 42,000, and 25,000 were identified in immunoblotting studies by reactivity with antibodies in sera of immunized jirds. Antibodies induced by immunization with microfilarial extract were not specific for this stage of the parasite life cycle, as jird anti-mf antibodies reacted with a Mr approximately 150,000 and several Mr 50,000 to 110,000 antigens derived from immature and mature adult parasites of both sexes. These data indicate that immunization of jirds with a water soluble microfilarial extract enhances the host's ability to eliminate adult worms and blood-borne mf. The filarial antigens that induce antibodies in immunized jirds have been identified.

Animals↗
PubMed1986

Electronic spreadsheet program for estimating two-compartment intravenous pharmacokinetic parameters by least squares linear regression analysis.

A microcomputer program using an electronic spreadsheet program was developed to calculate pharmacokinetic values of thiacetarsamide sodium, a drug used to kill the adult heartworm (Dirofilaria immitis) parasite of the dog. A least squares, semilogarithmic regression analysis was done on data using a two compartment intravenous model. The data entered includes the time after injection and the drug concentration at that time. A graph of the points can be viewed or plotted, with the time on the x-axis, and the natural log of the drug concentration on the y-axis. The program was developed on a Televideo (512 kbytes) microcomputer. The spreadsheet used was Lotus 123 with the pharmacokinetics program occupying 16 kbytes of memory (720 cells) out of the 400 kbytes available with Lotus.

Animals↗
PubMed1986

Thiacetarsamide in dogs: disposition kinetics and correlations with selected indocyanine green kinetic values.

The pharmacokinetic values of thiacetarsamide (2.2 mg/kg) were determined in 6 healthy dogs after IV injection. A semilogarithmic plot of serum concentration vs time indicated that the 2-compartment open model best described thiacetarsamide disposition. A least-squares log linear regression microcomputer program was used to calculate the pharmacokinetic values. The mean elimination-phase half-life and clearance rate were 43 minutes and 200 ml/kg/min, respectively. Wide ranges in values were seen for the half-life (20.5 to 83.4 minutes) and the clearance rate (80.0 to 350.0 ml/kg/min). Before thiacetarsamide was given to the dogs, indocyanine green (ICG), an anionic dye that is eliminated almost entirely by hepatobiliary excretion, was administered IV at a dosage of 0.5 mg/kg of body weight. The half-life of ICG was 7.4 minutes, and the clearance rate was 8.43 ml/kg/min. There was a significant (P less than 0.01) correlation between the half-lives of thiacetarsamide and ICG, but not between the clearance rates. The variations in ICG half-lives and clearance rates were less than those seen for thiacetarsamide.

Animals↗
PubMed1986

Thiacetarsamide in dogs with Dirofilaria immitis: influence of decreased liver function on drug efficacy.

The influence that decreased functional hepatic mass had on blood arsenic concentrations in dogs after they were treated with thiacetarsamide, on the clearance of indocyanine green (ICG), on arsenic concentrations in the heartworm (Dirofilaria immitis), and on drug efficacy was studied. Dogs which were partially hepatectomized and treated with thiacetarsamide (1.76 mg/kg, 2 times a day for 2 days) had a significantly (P less than 0.01) reduced ICG clearance, significantly (P less than 0.01) higher arsenic levels in heartworms, and a significantly (P less than 0.01) higher proportion of heartworms killed than did dogs that were sham operated and treated with thiacetarsamide or sham operated and untreated. There were no significant differences in blood arsenic (thiacetarsamide) concentrations 2 minutes after injection between hepatectomized and nonhepatectomized groups. More male heartworms were killed than were female worms in the thiacetarsamide-treated groups. Indocyanine green half-life was longer (12.43 minutes) in the hepatectomized group than it was in the nonhepatectomized sham-operated groups (5.09 and 4.94 minutes). Indocyanine green clearance rate was lower in the hepatectomized group (0.54 ml/min/kg) than that in the nonhepatectomized groups (1.36 and 1.56 ml/min/kg). A parallel seemed to exist between ICG and thiacetarsamide removal from the blood by the liver. This parallel also was suggested in the higher worm arsenic (thiacetarsamide) concentrations for the hepatectomized group vs that for nonhepatectomized groups. Apparently, the slower the removal of thiacetarsamide from the blood by the liver, the higher the worm arsenic level and, consequently, the higher the worm kill.

Animals↗
PubMed1986

Efficacy of ivermectin against Dirofilaria immitis larvae in dogs 30 and 45 days after induced infection.

Forty-two Beagles, 14 to 15 weeks of age, were injected subcutaneously with 50 infective larvae of Dirofilaria immitis and were allotted by weight, within sex, to 6 treatment groups. Group 1 served as nonmedicated vehicle-treated controls; groups 2 through 5 were given an oral tablet form of ivermectin at dosages of 0.3 micrograms/kg, 1.0 micrograms/kg, 2.0 micrograms/kg, and 3.3 micrograms/kg at 30 days after inoculation; group 6 was given the 2.0 micrograms/kg dosage at 45 days after inoculation. Dogs were euthanatized and necropsied 154 days after treatment (day 139 for dogs in group 6) and examined for heartworms. On the numerical bases of helminths recovered in the groups, the efficacies for preventing heartworm maturation were 0% (group 2), 53.2% (group 3), 97.2% (group 4), 98.1% (group 5), and 63.8% (group 6). Drug-related adverse reactions were not detected.

Animals↗
PubMed1985

Surgical transplantation of adult Dirofilaria immitis to study heartworm infection and disease in dogs.

Heartworm infections were established in dogs by surgical transplantation of adult heartworms into the external jugular vein. The heartworms were obtained from donor dogs that had been infected with large numbers of infective larvae. This heartworm model standardized the infection with a known number of heartworms of a known age and sex. This paper presents the methods for obtaining heartworms from donor dogs, for selection of recipient dogs, and for transplantation of heartworms.

Animals↗
PubMed1983

Aspirin and prednisolone modification of radiographic changes caused by adulticide treatment in dogs with heartworm infection.

The effects of aspirin and prednisolone in modifying the radiographic changes following adulticide treatment were studied in 3 groups of 6 dogs each. The dogs were radiographed and then 9 Dirofilaria immitis adults were surgically transplanted in each dog. All dogs were treated with thiacetarsamide 4 weeks later. One group received no additional treatment, the 2nd group received aspirin (10 mg/kg, daily for 4 weeks), and the 3rd group received prednisolone (1 mg/kg, daily for 4 weeks). Radiographs were taken at 1, 2, and 3 weeks after adulticide treatment, and the dogs were euthanatized at 4 weeks. The most consistent radiographic sign of pulmonary disease was a perivascular alveolar pattern in the caudal and accessory lung lobes. The right caudal lobe was the one most frequently affected. These parenchymal lesions were more frequent and more severe in the dogs given only adulticide treatment than in those given aspirin after adulticide treatment; the latter group in turn was more severely affected than the dogs given prednisolone after adulticide treatment. The radiographic evidence of pulmonary disease was resolving in most dogs at 3 weeks. The alveolar pattern on radiographs was distributed similarly to that observed at necropsy, using parenchymal uptake of Evan's blue as an indication of increased vascular permeability. Dissection of the perfusion-fixed lungs revealed that heartworms in 3 of the 6 dogs given prednisolone appeared to survive adulticide treatment.

Animals↗
PubMed1983

Synthesis and antifilarial activity of N-[4-[[4-alkoxy-3-[(dialkylamino)methyl]phenyl]amino]- 2-pyrimidinyl]-N'-phenylguanidines.

A series of N-[4-[[4-alkoxy-3-[(dialkylamino)methyl]phenyl]amino]- 2-pyrimidinyl]-N'-phenylguanidines have been synthesized for antifilarial evaluation. Reaction of the appropriate benzenamines with N-cyanoguanidine, followed by condensation of the resultant N-phenylimidodicarbonimidic diamides (V) with ethyl 4,4,4-trifluoro-3-oxobutanoate provided the intermediate N-(4-hydroxy-2-pyrimidinyl)-N'-phenylguanidines VIa. Alternatively, compounds VIa were synthesized by reaction of the requisite beta-keto esters (VII) with N-cyanoguanidine to give the (4-hydroxy-2-pyrimidinyl)cyanamides (VIII), followed by treatment with the desired benzenamines. Chlorination with POCl3 and condensation with the appropriate benzenamines (IX) generated the desired guanidines (X). Antifilarial activity was confined to adult Litomosoides carinii infections, and a structure-activity relationship for this activity is discussed. Lack of activity against L. carinii microfilaria and adult Brugia pahangi infections preclude further work in this area pending evaluation in additional experimental models.

Animals↗
PubMed1983

Activity of flubendazole against developing stages of Dirofilaria immitis in dogs.

A formulation of flubendazole was studied to determine the activity against developing stages of Dirofilaria immitis in artificially infected pups. Flubendazole suspension was administered subcutaneously at a dose rate of 50 mg/kg of body weight once a day for 1, 3, or 5 consecutive days at various times during the experimental period. The pups were necropsied 6 months after the experimental infection, and the heart and pulmonary arteries were examined for adult worms. Optimal activity was obtained when flubendazole suspension was administered subcutaneously for 5 consecutive days, either 1 or 2 months after infection. The formation of encapsulated deposits, containing white viscous fluid, was observed at the injection sites of all treated pups.

Animals↗
PubMed1983

Clinical responses of dogs to experimentally induced Dipetalonema reconditum infection.

Six male and 6 female Beagles, 6 to 7 months old, were allotted to 2 groups: group I--inoculated subcutaneously with 30 Dipetalonema reconditum infective larvae/dog, and group II--noninoculated controls. Group comparisons were made in regard to hematologic values, Knott test results, body weights, blood urea nitrogen, total serum protein, serum albumin and alanine aminotransferase and creatine kinase activities. Routine urinalysis data were compared at 1 week before and at 28 weeks after the inoculations. Mean total leukocyte counts were significantly (P less than 0.05) greater in group I dogs than in group II dogs at postinoculation weeks (PIW) 4, 5, and 7 to 12, and mean eosinophil counts were significantly greater in group I dogs at PIW 3 to 11, 13 to 15, 20, and 23 to 24. Microfilariae were detected as early as the 10th week and sporadically thereafter. Only 1 D reconditum adult worm was recovered from all of the inoculated dogs. Five other dogs (group III) with chronic, patient experimentally induced dipetalonemiasis, were evaluated with the same tests at PIW 70 to 89. Eosinophilia (greater than 750 cells/microliter) was present in 4 of 5 dogs; lymphocytosis (greater than 4,800 cells/microliter) was evident in 1 dog. Proteinuria (greater than or equal to 30 mg/dl) was detected in 3 of 4 dogs with chronic dipetalonemiasis.

Animals↗