Physiological changes in the pallidum in a progressive model of Parkinson's disease: Are oscillations enough?

Neurophysiological changes in the basal ganglia thalamo-cortical circuit associated with the development of parkinsonian motor signs remain poorly understood. Theoretical models have ranged from those emphasizing changes in mean discharge rate to increased oscillatory activity within the beta range. The present study characterized neuronal activity within and across the internal and external segments of the globus pallidus as a function of motor severity using a staged, progressively severe 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinsonism in three rhesus monkeys. An increase in coherence between neuronal pairs across the external and internal globus pallidus was present in multiple frequency bands in the parkinsonian state; both the peak frequency of oscillatory coherence and the variability were reduced in the parkinsonian state. The incidence of 8-20Hz oscillatory activity in the internal globus pallidus increased with the progression of the disease when pooling the data across the three animals; however it did not correlate with motor severity when assessed individually and increased progressively in only one of three animals. No systematic relationship between mean discharge rates or the incidence or structure of bursting activity and motor severity was observed. These data suggest that exaggerated coupling across pallidal segments contribute to the development of the parkinsonian state by inducing an exaggerated level of synchrony and loss of focusing within the basal ganglia. These data further point to the lack of a defined relationship between rate changes, the mere presence of oscillatory activity in the beta range and bursting activity in the basal ganglia to the motor signs of Parkinson's disease.

Large-scale screening assay to measure epidermal growth factor internalization.

Recently, we showed that the internalization of the epidermal growth factor (EGF) receptor is inhibited by hydrogen peroxide (H(2)O(2)) in human fibroblasts. In order to test the effect of various stress conditions on receptor internalization and to test a variety of antioxidants in their capacity to prevent or reduce the H(2)O(2)-induced inhibition of internalization, a screening assay was developed to measure the internalization in 96-well plates. In this assay, cells are exposed to biotin-conjugated EGF and the amount of internalized EGF is detected with horseradish peroxidase-conjugated streptavidin. We show that the results obtained by this new assay are comparable with those from internalization studies performed with radioactive labeled EGF. Therefore, the cellular internalization assay as presented here is a reliable method to measure EGF receptor internalization. Moreover, because elaborate processing of the cells is not required, the assay is a relatively fast and inexpensive method to study ligand-induced internalization in 96-well plates and thereby is suitable for large-scale screening of compounds or conditions interfering with this internalization.

Natural transmission of Dirofilaria immitis by Aedes vexans.

Aedes vexans mosquitoes were reared in the laboratory from field-collected fourth instar larvae. Mosquitoes were allowed to feed on dogs which were infected with Dirofilaria immitis and then the mosquitoes were housed in an environmental chamber with an ambient air temperature of approximately 26 C and a relative humidity of approximately 80%. Incandescent lighting was used to simulate daylight. On the 17th, 19th, 21st, and 28th day after their infected blood meal, the mosquitoes were allowed to feed on five microfilaria-negative dogs which had been reared in mosquito-free environments. Blood from four of the five exposed dogs became positive for microfilariae of D immitis in an average of 272 days after the feeding. The local strain of A vexans was established as a vector of canine heartworm disease in the Minneapolis-St. Paul metropolitan area.

Efficacy of lufenuron against developmental stages of fleas (Ctenocephalides felis felis) in dogs housed in simulated home environments.

Twenty-four, adult, female Beagles were arranged by body weight from greatest to least and allocated to 2 groups of 12 dogs, using random numbers. Dogs were housed collectively in 2 adjacent metal buildings, each divided into 4 rooms measuring 2.1 x 3.7 m. Each room was paneled and carpeted and had an access door to the outside with a connecting run that measured 2.1 x 9.1 m. Each run had a surface consisting of 5 cm of pea gravel overlaying 5 cm of sand, and was partially covered by an awning that provided shade at its proximal end. For placement in room/run units, dogs in each of the treated and control groups were alloted to 4 subgroups of 3 dogs each. Each subgroup of dogs was placed in a separate room/run unit. Units containing treatment or control subgroups were alternated to avoid placing identically treated subgroups adjacent to each other. Dogs of subgroups A, C, E, and G were treated with lufenuron monthly at a minimal target dosage of 10 mg/kg of body weight; those of subgroups B, D, F, and H were treated with excipient tablets. Dogs were treated on study days 7, 37, 68, and 98. Each dog was infested with 100 newly emerged, unfed, insectary-reared, adult Ctenocephalides felis on each of study days 0 and 2. Thereafter, infestations on all dogs were dependent on continued development of fleas either in the indoor or outdoor environment. Numbers of fleas on each of the treated and control dogs were determined, using a nondestructive counting technique on days 6, 14, 21, 28, 35, 56, 70, 84, 98, 112, and 119.(ABSTRACT TRUNCATED AT 250 WORDS)

Anthelmintic efficacy of ivermectin in naturally parasitized cats.

Ivermectin was administered per os [( PO]; n = 15) or subcutaneously [( SC]; n = 3) to naturally parasitized cats at 10 (n = 6), 100 (n = 6), or 300 (n = 6) micrograms/kg of body weight. Nontreated control cats were given sterile isotonic saline solution PO (n = 5) or SC (n = 1). Qualitative fecal examinations were performed on each cat 1 day before treatment and 14 days after treatment. Cats were euthanatized 14 days after treatment, at which time parasites from the gastrointestinal tracts were recovered, identified, and enumerated. Lungs and urinary bladders were examined histologically or by digestion (lungs only) for Capillaria spp and/or Aelurostrongylus abstrusus. Ivermectin was effective in removing Ancylostoma spp at all doses, but removal of Toxocara cati required 300 micrograms of ivermectin/kg. Efficacies against A abstrusus, Capillaria spp, and Physaloptera spp could not be determined definitively. Ivermectin had no effect on Dipylidium caninum, Hydatigera taeniaeformis, Spirometra mansonoides, or Isospora spp. Adverse reactions were not observed in cats given ivermectin PO; however, 3 cats given ivermectin SC reacted as though they experienced pain at the injection site.

Efficacy of fenbendazole-medicated feed blocks against gastrointestinal nematode infections in calves.

An anthelmintic trial was conducted to determine the efficacy of fenbendazole (FBZ) incorporated into two types of feed blocks given daily for 3 or 10 days to calves naturally parasitized with gastrointestinal nematodes. Each treated calf consumed 5 mg of FBZ/kg of body weight. The FBZ was greater than 99% effective in removing adults of Haemonchus contortus, Ostertagia ostertagi, O lyrata, Cooperia punctata, C pectinata, C onchophora, Trichostrongylus axei, Bunostomum phlebotomum, and Oesophagostomum radiatum. Fenbendazole was also greater than 99% effective against immature nematodes recovered from the small intestine, which were thought to be mainly Cooperia spp. Efficacy was similar for FBZ in each of the two types of feed block carriers and for the 3- and 10-day regimens. Calves readily consumed feed blocks containing FBZ and did not have adverse reactions to FBZ.

Evaluation of three formulations of fenbendazole (10% suspension, 0.5% pellets, and 20% premix) against nematode infections in cattle.

Anthelmintic efficacies of 3 formulations of fenbendazole were evaluated in cattle naturally parasitized with nematodes: a 10% oral suspension, 0.5% pellets as a top dressing on feed, and a 20% premix. All formulations of fenbendazole were greater than 99% effective in removing adults of Haemonchus contortus, Ostertagia spp, Cooperia spp, and Oesophagostomum radiatum. Fenbendazole was greater than 96% effective in removing adults of Strongyloides papillosus and greater than 85% effective in the removal of Trichuris sp. Fenbendazole was greater than 96% effective against immature nematodes, which were thought to be primarily Cooperia spp. Adverse reactions were not observed in calves treated with the 3 formulations of fenbendazole.

Efficacy of milbemycin oxime against naturally acquired or experimentally induced Ancylostoma spp and Trichuris vulpis infections in dogs.

The efficacy of milbemycin oxime was evaluated at dosages of 0.25, 0.50, and 0.75 mg/kg of body weight in dogs naturally infected with mature Ancylostoma spp, at a dosage of 0.50 mg/kg in dogs with experimentally induced immature and mature A caninum, and at dosages of 0.55 to 0.86 mg/kg in dogs naturally infected with mature Trichuris vulpis. Milbemycin oxime was 95 and 99% effective against mature Ancylostoma spp at dosages of 0.50 and 0.75 mg/kg, respectively, but only 49% effective at a dosage of 0.25 mg/kg. Efficacy was 49% against pulmonary L3-L4 stages of A caninum (36 hours after inoculation), greater than 80% against L4 (120 hours after inoculation) and early L5 stages (216 hours after inoculation), and greater than 90% against experimentally induced mature stages (360 hours after inoculation). Milbemycin oxime was also 97% effective in the removal of mature Tr vulpis from naturally infected dogs. Adverse reactions were not observed following treatment in any of the dogs.

Controlled dosage titration of febantel paste in naturally parasitized cattle.

A controlled anthelmintic trial was conducted to determine the efficacy of febantel paste (45.5%) at dosages of 2.5, 5.0, 7.5, and 10.0 mg/kg in calves harboring natural gastrointestinal nematode infections. Dosages of 5.0, 7.5 and 10.0 mg of febantel/kg of body weight were greater than 96% effective in removing adults of Haemonchus contortus, Ostertagia spp, Cooperia spp, and Oesophagostomum radiatum. The 2.5 mg/kg dosage was considered suboptimal because of low efficacy against Ostertagia and Cooperia spp. Efficacies against Trichostronglylus axei, Trichuris spp, Bunostomum phlebotomum, and Stronglyloides papillosus were difficult to determine because fewer numbers of these nematodes were recovered. Efficacies of febantel paste against immature bovine parasites ranged from 83.62% to 97.72%.

Visceral and subcutaneous acariasis caused by hypopi of Hypodectes propus bulbuci in the cattle egret.

Twenty-one of 24 adult male and female cattle egrets (Bubulcus ibis ibis) collected in Geneva County, Alabama had numerous white cyst-like structures (1,466 microns X 354 microns) found within the loose connective tissues of the skeletal muscles of the inguinal region, beneath the serosa of the proventriculus and in the heart beneath the epicardium (one adult male bird). These were identified as hypopi of Hypodectes (Hypodectoides) propus bulbuci. Histologic sections were prepared from the subcutis, proventriculus and heart. The histopathologic changes consisted of cross sections of mites surrounded by macrophages often containing basophilic or clear intracytoplasmic vacuoles and by plasma cells. A minimal fibrous encapsulation was rarely seen surrounding the mites.

Experimental Cryptosporidium parvum infections in opossums (Didelphis virginiana).

Five nursing opossums (Didelphis virginiana) were each inoculated with 5 x 10(6) Cryptosporidium parvum oocysts of calf origin. Following inoculation, endogenous stages of C. parvum were observed in the ileum, cecum, and colon of these opossums. Two of three noninoculated pouch mates acquired infections during the study based on examinations of feces and tissue sections of all eight opossums. Mild diarrhea was observed in four of seven opossums harboring C. parvum, although none died as a result of the infection. Under the conditions of this study, C. parvum appeared to be only mildly pathogenic for opossums.

Cerebral cuterebrosis in a dog.

A second instar Cuterebra larva was found in the thickened meninges of a 6-week-old female Doberman Pinscher at necropsy. The dog appeared blind and had chewing fits before death. Cerebral cuterebrosis in the dog is uncommon. This report briefly discusses the pathogenesis of the condition.

Macracanthorhynchus ingens infection in a dog.

A 4-month-old sexually intact female Siberian Husky was examined because of diarrhea and 4 flesh-colored annulated helminths that were recovered from the dog's feces. Infection with Macracanthorhynchus ingens was diagnosed on the basis of morphologic features of the adult parasites and ova. Spindle-shaped eggs (mean length, 91 microm; mean width; 54 microm) were obtained from the body cavity of a gravid female specimen. The dog was treated empirically with epsiprantel (5.5 mg/kg [2.5 mg/lb] of body weight) and ivermectin (250 to 500 microg/kg [114 to 227 microg/lb]), and the diarrhea resolved. Infection with this parasite has been reported in raccoons from the same geographic area. Macracanthorhynchus ingens is typically a parasite of raccoons, wolves, badgers, foxes, skunks, mink, and moles; transmission from wildlife to dogs may occur via ingestion of infected intermediate hosts (millipedes).

Anatrichosoma sp infection in a dog.

Embryonated, double-operculated eggs were observed during routine examination of a fecal specimen from a 5-month-old dog. Similar eggs were found on a skin scraping of a raised, flaking, erythematous nodule on the dorsal midline in the lumbar region. Eggs were identified as being similar to those of Anatrichosoma spp. After surgical excision, histologic examination of the nodule revealed nematodes with morphologic features consistent with those of Anatrichosoma spp.

Comparison of serologic tests for detection of antigen in canine heartworm infections.

In 30 random-source dogs, we determined sensitivity and specificity of 5 serologic tests for detection of canine heartworm antigens. Seventeen of the dogs were infected naturally with adult Dirofilaria immitis, and 4 of the infected dogs were amicrofilaremic. The ability of the serologic tests to predict whether a dog was infected or uninfected (overall test accuracy) ranged from 73 to 97%. Sensitivity was not affected by circulating D immitis microfilariae, but was markedly influenced by the number of adult D immitis present. False-positive reactions were rare and were not associated with intestinal parasites or Dipetalonema reconditum microfilariae. Modifications of some of the test procedures were necessary to maximize test accuracy and reproducibility. These modifications and other technical details might limit the usefulness of some of the tests in a veterinary practice.

Comparative efficacies of ivermectin, febantel, fenbendazole, and mebendazole against helminth parasites of gray foxes.

Anthelmintic efficacies of ivermectin, febantel, fenbendazole, and mebendazole were compared in 45 adult gray foxes (Urocyon cinereoargenteus) naturally infected with helminth parasites. Fecal specimens were examined one week before treatment and one week and 3 weeks after treatment with each anthelmintic, using a sucrose flotation technique. Compared with pretreatment, fewer foxes in all groups were infected with helminths one week and 3 weeks after treatment. Ivermectin, febantel, and fenbendazole more effectively eliminated helminths than did mebendazole. Parasites found were Ancylostoma sp, Capillaria aerophila, and Aelurostrongylus abstrusus and/or Filaroides osleri.

Furunculoid myiasis in a dog caused by Cordylobia anthropophaga.

Two days after returning with its owners from a 60-day visit to Liberia, an 8-year-old 6.5-kg spayed female Miniature Schnauzer was examined by a veterinarian in the United States. A 1.0 x 1.0-cm raised erythematous nodule was noticed on the medial aspect of the right pinna. In the center of the nodule was a 1.0 x 1.0-mm pore from which a 0.5 x 0.5 x 1.0-cm white larva was extracted. The larva was identified as a third-stage larva of Cordylobia anthropophaga, the African Tumbu fly, a fly restricted to sub-Saharan Africa. Cordylobia anthropophaga does have zoonotic potential, but the owners did not have any skin lesions. Detection of C anthropophaga in the United States warranted reports to state and federal authorities and personnel at the Centers for Disease Control and Prevention. The situation described here illustrated the potential of tourists' pets to import foreign diseases.

Whipworms and intestinal threadworms.

Whipworms (genus Trichuris) parasitize the lower bowel of humans, domestic animals, and wild animals. The species of Trichuris that are important in small animal practice are T. vulpis in the dog and T. campanula and T. serrata in the cat. Intestinal threadworms (Strongyloides stercoralis in the dog and S. tumefaciens in the cat) parasitize the small intestine. The identification of whipworms and threadworms, their life cycles, and the diagnosis, treatment, and control of infection are discussed in this article.

Natural transmission of Dirofilaria immitis by Aedes aegypti.

The Liverpool strain of the mosquito Aedes aegypti was infected with microfilariae of the canine heartworm, Dirofilaria immitis, and was used to transmit heartworm larvae to three dogs. Methods of confirming heartworm infection in these dogs included the modified Knott's test, a commercial enzyme-linked-immunosorbent assay (ELISA), an indirect fluorescent antibody (IFA) test, and post-mortem examination.

Determination of homovanillic acid, 5-hydroxyindoleacetic acid and pressure in the cerebrospinal fluid of collie dogs following administration of ivermectin.

Twelve adult Collie dogs were studied to determine the effects of ivermectin on neurotransmitter metabolites released from the brain into the cerebrospinal fluid (CSF) and on CSF pressure. Ten of the 12 Collies were given ivermectin orally at a concentration of 200 micrograms/kg body weight. Three of these 10 Collies showed clinical signs of ivermectin-induced toxicosis which progressed into a state of unresponsive recumbency in 2 dogs. Cerebrospinal fluid pressures and neurotransmitter metabolite concentrations in cisterna magna CSF were analysed 49 to 50 hours after administration of ivermectin in 6 of the 10 treated dogs, and in the 2 untreated control Collies. Cerebrospinal fluid pressures were within normal limits in all dogs. However, compared to the CSF concentrations in the 2 untreated and 3 non-reactive Collies, the 2 ivermectin-reactive Collies still in recumbency had elevated CSF concentrations of homovanillic acid (HVA), a metabolite of dopamine, and 5-hydroxyindoleacetic acid (5-HIAA), a metabolite of serotonin. These findings suggest an association between altered neurotransmission and severe ivermectin-induced neurological abnormalities. No evidence of elevated intracranial pressure was found.