Non-infected Dogs Research Articles

New human herpesviruses; human herpesvirus 6 and 7

Babesia canis and Babesia gibsoni have, until recently, been considered the only piroplasms that parasitise dogs. However, recent reports indicate that “small” Babesia infections in Spanish dogs are surprisingly frequent and molecular phylogenetic analysis indicates that the infecting agent is closely related to Babesia microti. Because the 18SrDNA sequence was not completely identical to that of B. microti, the new name “Theileria annae” was assigned to the canine agent. No information is available regarding the possible vector of the new piroplasm, T. annae. As part of an effort to identify the tick that may transmit T. annae in northwest Spain we asked veterinary surgeons practising in the region to collect and send to our laboratory ticks from dogs visiting their clinics. Seven hundred and twenty ticks collected from dogs of unknown clinical status during 1998 and 636 ticks collected between November 2001 and March 2002 from 38 dogs infected with T. annae and 131 uninfected dogs were identified. Results from the first study indicated that among the Ixodidae, Ixodes hexagonus clearly predominates over Ixodes ricinus (26.11% versus 6.67%). This observation was consistent with results of the second study, in which I. hexagonus was detected in all infected dogs and 71.8% of non-infected dogs and I. ricinus was not detected in either the infected or non-infected dogs. Results from the 2001–2002 study also indicate that the presence of Dermacentor reticulatus adult females is significantly less frequent among infected than non-infected dogs (OR=0.44; 95% CI: 0.21–0.92). On the other hand, I. hexagonus adult females and males are 6.75 and 4.24 times more likely to be detected among infected than non-infected dogs, respectively, with the association being, in both cases, statistically significant (95% CI: 1.97–23.12 and 1.92–9.36, respectively). I. hexagonus emerges as the main candidate as vector of T. annae because it feeds on dogs more frequently than other ticks and because B. microti is transmitted by Ixodes ticks, both in North America and Europe. In the absence of definitive confirmation of this hypothesis, our observations suggest that I. hexagonus might serve the same role as does Ixodes scapularis (=Ixodes dammini), the vector of B. microti in eastern North America.

Of ticks, mice and men: Identification of newly emerging zoonotic agents

Babesia canis and Babesia gibsoni have, until recently, been considered the only piroplasms that parasitise dogs. However, recent reports indicate that “small” Babesia infections in Spanish dogs are surprisingly frequent and molecular phylogenetic analysis indicates that the infecting agent is closely related to Babesia microti. Because the 18SrDNA sequence was not completely identical to that of B. microti, the new name “Theileria annae” was assigned to the canine agent. No information is available regarding the possible vector of the new piroplasm, T. annae. As part of an effort to identify the tick that may transmit T. annae in northwest Spain we asked veterinary surgeons practising in the region to collect and send to our laboratory ticks from dogs visiting their clinics. Seven hundred and twenty ticks collected from dogs of unknown clinical status during 1998 and 636 ticks collected between November 2001 and March 2002 from 38 dogs infected with T. annae and 131 uninfected dogs were identified. Results from the first study indicated that among the Ixodidae, Ixodes hexagonus clearly predominates over Ixodes ricinus (26.11% versus 6.67%). This observation was consistent with results of the second study, in which I. hexagonus was detected in all infected dogs and 71.8% of non-infected dogs and I. ricinus was not detected in either the infected or non-infected dogs. Results from the 2001–2002 study also indicate that the presence of Dermacentor reticulatus adult females is significantly less frequent among infected than non-infected dogs (OR=0.44; 95% CI: 0.21–0.92). On the other hand, I. hexagonus adult females and males are 6.75 and 4.24 times more likely to be detected among infected than non-infected dogs, respectively, with the association being, in both cases, statistically significant (95% CI: 1.97–23.12 and 1.92–9.36, respectively). I. hexagonus emerges as the main candidate as vector of T. annae because it feeds on dogs more frequently than other ticks and because B. microti is transmitted by Ixodes ticks, both in North America and Europe. In the absence of definitive confirmation of this hypothesis, our observations suggest that I. hexagonus might serve the same role as does Ixodes scapularis (=Ixodes dammini), the vector of B. microti in eastern North America.

Enrofloxacin concentrations in dogs with normal prostate and dogs with chronic bacterial prostatitis

SUMMARY Chronic Escherichia coli-associated prostatitis was induced in 16 dogs; 9 noninfected dogs served as controls; and all dogs were vasectomized. Two to 3 weeks after instillation of bacteria directly into the prostate, the urine or prostatic fluid or both from 13 of 16 dogs were culture positive. Enrofloxacin, a fluoroquinolone antimicrobial agent, was administered orally to all dogs during the third or fourth week after surgery, at a dosage of approximately 5 mg/kg of body weight, every 12 hours for 7 days. Serum and prostatic fluid concentrations of enrofloxacin were concurrently measured in all dogs on days 2, 4, and 6 at 2 hours after dosing. Serum and prostatic tissue concentrations of enrofloxacin were concurrently measured in all dogs on day 7, at 1.5, 3, 4.5, and 6 hours after dosing. When values for these samples were compared, using a two-factor anova, significant differences were not found. Use of this dosing regimen of enrofloxacin resulted in prostatic fluid and prostatic tissue concentrations exceeding the minimum inhibitory concentration of most pathogens that cause bacterial prostatitis. In addition, prostatic fluid-to-serum and prostatic tissue-to-serum concentration ratios were greater than 1.0.

Blood coagulopathy in dogs with shock induced by injection of heartworm extract

Summary A crude, whole-body extract of female heartworms was administered iv to 10 dogs with and 13 dogs without heartworm (hw) infection. Shock developed in 8 of 10 infected dogs and 11 of 13 noninfected dogs, and blood coagulopathy was observed in 12 of 19 dogs with shock. Prevalence and severity of blood coagulopathy were proportionate to prevalence and severity of shock. Platelet count decreased in all dogs with shock with or without blood coagulopathy; thus, the decrease in platelet count might be related to shock. In 4 dogs, activated partial thromboplastin time (aptt) was prolonged - 192.0 seconds at 30 minutes after hw injection - and prothrombin time (pt) was increased-13.8 seconds at initial collapse. In 8 dogs, aptt was increased - 200 seconds for 2 hours after hw injection - and pt was increased - 200 seconds at 30 minutes after the injection. The aptt prolongation might have been caused mainly by decreases in activities of factors VIII, IX, XI, and XII of the intrinsic blood coagulation pathway. In dogs with severely prolonged pt plasma fibrinogen concentration and factor II activity decreased slightly. Prolonged pt was corrected in vitro by addition of normal plasma at high concentration (> 80 %), but prolonged aptt could not be corrected in vitro by addition of 80 % normal plasma. Serum fibrin degradation products concentration was < 10 μg/ml, and soluble fibrin monomer complex was negative in all dogs. Thrombi were not found in blood vessels of any organ at necropsy and after histologic study. Therefore, it was suggested that blood coagulopathy resulting from inhibition of coagulation factor activities might develop in shock induced by hw extract.

Dirofilaria immitis: Depression of Endothelium-Dependent Relaxation of Canine Femoral Artery Seen in Vivo Does Not Persist in Vitro

In heartworm-infected dogs, circulating filarial factors appear to be responsible for the seasonal depression of endothelium-dependent responses seen in the in vivo femoral artery. The effect of heartworm infection on vascular responses of the femoral artery in vitro, when the vessel is not constantly exposed to circulating factors, is unknown. Experiments were designed to test the hypothesis that in vivo exposure to circulating filarial factors leads to changes in the magnitude and mechanism of endothelium-dependent relaxation that are demonstrable in vitro. Rings of femoral artery from heartworm-infected and noninfected control dogs were suspended in muscle baths, and dose-response relationships to endothelium-dependent (methacholine) and -independent (sodium nitroprusside) vasodilators were done. To determine the mechanism of relaxation, dose-response relationships were also done in the presence of an inhibitor of nitric oxide synthase (L-NAME), an inhibitor of guanylate cyclase (methylene blue), or an inhibitor of cyclooxygenase (mefenamic acid). Heartworm infection did not depress endothelium-dependent relaxation of the femoral artery in vitro. Furthermore, the mechanism of relaxation in heartworm and control femoral artery is identical. These data suggest that the effect of circulating filarial factors that alter the magnitude and mechanism of relaxation in systemic vessels in heartworm-infected dogs rapidly disappears in their absence. This result has important bearing on the dynamics of heartworm-induced pathophysiological changes during infection and could influence the nature and chronology of responses to therapy.

Cardiopulmonary effects of medetomidine in heartworm-infected and noninfected dogs

Summary Medetomidine, an investigational drug indicated for clinical use as a short-term chemical restraint in dogs, was evaluated for its cardiopulmonary effects, in 10 naturally heartworm-infected (HW+) and 10 noninfected (hw−) Beagles. The drug was randomly administered IV (30 μg/kg of body weight) and IM (40 μg/kg) in single injections to all dogs. Heart rate, respiratory rate, ecg, blood gas tensions, blood pH, central venous and arterial pressures were measured at 0, 15, 30, 60, 90, 120, and 180 minutes. Medetomidine induced an immediate significant (P ≤ 0.001) increase in mean arterial blood pressure followed by decreased blood pressure that remained below normal throughout the study in both groups, irrespective of route of administration. Medetomidine increased central venous pressure, over time, for both groups and both routes of administration. Heart and respiratory rates were significantly (P ≤ 0.001) decreased after medetomidine administration and remained reduced for the duration of the study in all dogs. The ecg variables were not significantly different between groups or between routes of administration. The HW+ dogs tended to have higher mean Pao2 than did HW− dogs at several postinjection determination times, particularly when the drug was administered IM. The Pao2; decreased during the first 30 minutes in both groups and tended to increase gradually thereafter. The pH decreased over time for both groups and both routes. A significant (P ≤ 0.05) decrease in pH was seen in the HW− dogs, compared with HW+ dogs at each measuring time for both routes. The Paco2 did not significantly change for groups or routes. In general, bradycardia was the predominant cardiovascular effect seen after medetomidine administration in all dogs, irrespective of route. Lowering of blood pressure and heart rate (after a transient blood pressure increase) was synchronized with sedation in these dogs. The overall clinical response with regard to cardiopulmonary effects in HW+ dogs was similar to that in HW− dogs.

Canine leishmaniasis: clinical, parasitological and entomological follow-up after chemotherapy.

Six naturally infected dogs [two with no signs of leishmaniasis ('asymptomatic'), two with a few signs ('oligosymptomatic') and two with many signs ('polysymptomatic')] were studied before and after chemotherapy. Another two, non-infected dogs were kept as controls. The dogs were studied clinically, haematologically and parasitologically five times over 11 months and their infectivity to sandflies was evaluated before and after the treatment. The 'asymptomatic' dogs were as infective to sandflies as the 'symptomatic' before treatment but all dogs were un-infective for at least a few months following chemotherapy. Treatment led to a temporary improvement in the clinical and biochemical condition of most of the dogs, the symptomatic dogs becoming asymptomatic, but parasitological cure was uncommon after 10 months' follow-up. There was often no correlation between clinical condition, parasitological condition and infectivity to sandflies. Some dogs from both the 'asymptomatic' and 'symptomatic' groups became infective to sandflies several months post-treatment.

<I>Hepatozoon canis</I>感染犬における好中球のNitroblue Tetrazolium還元能の検討

Investigation of nitroblue tetrazolium (NBT) reduction of neutrophils was performed in the dog infected with Hepatozoon canis. No positive reactions were observed in the parasitized neutrophils by the resting and the stimulated NBT reduction tests. However, results of resting and stimulated NBT reduction tests apparently made no differences between non-parasitized neutrophils of the infected dogs and neutrophils of the non-infected dogs. These findings show that the parasitized neutrophil has no oxidative bactericidal capacity and the infected dogs had no-change in the host protective mechanism.

Effect of serum from dogs infected with Dirofilaria immitis on endothelium-dependent relaxation of rat aorta in vitro

Summary Endothelium-dependent relaxation of canine femoral artery in vivo is depressed in dogs infected with Dirofilaria immitis (heartworms). In vitro, endothelium-dependent relaxation of aorta from rat is depressed in the presence of adult heartworms or heartworm-conditioned media. The depression of relaxation is attributable, in part, to a low molecular weight, biologically active product that is released by the adult parasites. Because heartworms reside in the right heart and pulmonary arteries, biologically active factors produced by the parasites could circulate and alter endothelial cell function. The hypothesis that filarial factors in serum from heartworm-infected dogs depress endothelium-dependent relaxation was tested. Rings of thoracic aorta from rats were constricted by use of norepinephrine, and cumulative dose-response relationships to methacholine and nitroglycerin were evaluated in the presence of serum from heartworm-infected dogs or serum from noninfected (control) dogs. Nitroglycerin relaxation was not different; however, methacholine relaxation was significantly depressed in rings exposed to serum from heartworm-infected dogs when compared with that of controls. These results supported the hypothesis and suggested that circulating filarial factors have the potential to influence the behavior of any endothelial cell surface.

Standardization of serological tests for detecting anti-Trypanosoma cruzi antibodies in dogs.

This paper reports on the standardization of four serological reactions currently used in human serodiagnosis for the detection of anti-Trypanosoma cruzi antibodies in naturally and experimentally infected dogs. Indirect immunofluorescence test (IFAT) and hemagglutination test (IHAT) were standardized, and complement fixation test (CFT) and direct agglutination test (DAT) were used for diagnostic confirmation. Four hundred and eighty one mongrel dogs that were studied by xenodiagnosis were used: (1) parasitemic dogs of two localities of endemic area (EA) of Santiago del Estero province in Argentina (n = 134); (2) non-parasitemic dogs of the same area (n = 285); (3) dogs experimentally infected with T. cruzi in the patent period (n = 6); (4) non-infected dogs (n = 56) which were born in the city of Buenos Aires (BA), one non-EA for Chagas' disease. For IFAT, parasitemic dogs EA showed 95% of reactive sera. Non parasitemic dogs EA showed 77% of non reactive sera. None sera from BA were reactive for dilutions higher than four. For IHAT, 84% of sera of parasitemic dogs EA showed serological reactivity and among non parasitemic dogs BA, 61% were non reactive, while the remainder showed at most titres of 1/16. The cut-off titres for IFAT and IHAT were 1/16 and 1/32 respectively, and for CFT and DAT 1/1 and 1/128 respectively. Sensitivity for IFAT, IHAT, CF and DAT were 95%, 84%, 97% and 95% respectively.

Immunohistological observations on pulmonary tissues from dogs infected with Dirofilaria immitis.

Pulmonary tissues from non-infected dogs, naturally Dirofilaria immitis-infected dogs and experimentally infected puppies, selectively necropsied after infection, were assessed using peroxidase-antiperoxidase (PAP) staining technology. Sequential sections of pulmonary tissue were PAP stained with anti-fresh D. immitis serum, anti-paraffin processed D. immitis serum, anti-dog immunoglobulin (IgG, IgG Fc, IgM) sera and anti-dog complement (C3) serum, and examined for antibody, complement and for D. immitis antigen. The extent of alveolar septal thickening was positively correlated with infection status. Cellular infiltration was most evident surrounding obstructed areas where D. immitis were in situ. Antigenic material (microfilariae, eggs, fragmented filariae) labelled by PAP was identified in the pulmonary arteries, alveolar capillaries and alveolar septa. Deposits of complement and IgG, presumably associated with immune complex formation, were also observed in some of the infected dogs. Identification of antigen, antibodies and complement associated with alveolar septal pathology suggested that immune mechanisms were active in its development.

Prophylactic oral antibiotics for low-risk dog bite wounds

The use of prophylactic antibiotics in the initial treatment of noninfected dog bite wounds is controversial. All patients with noninfected dog bite wounds who presented to our emergency department (ED) over a two-year period were considered for entry into a randomized prospective study. Patients were excluded from the study if they had any high-risk criteria for infection: puncture wounds, hand or foot wounds, wounds greater than 12 hours old, a history of immunocompromising disorders, or the use of immunosuppressive drugs. Patients in the antibiotic group (n = 89) were treated with local wound care and given either dicloxacillin, cephalexin, or erythromycin orally for seven days. Patients in the control group (n = 96) received local wound care only. All patients had their wounds irrigated with a 1% povidone-iodine solution and debrided and sutured if clinically indicated. All patients were subsequently reevaluated for clinical signs of wound infection. The groups were similar in age, sex, time of delay in seeking treatment, anatomic sites of wounds, depths and types of wounds, and number of wounds requiring suturing. The wound infection rates for the antibiotic and control groups were 1.1 and 5.1%, respectively. This difference was not significant (P = 0.212). There were 36 wounds in the antibiotic group and 37 wounds in the control group that were full thickness. The infection rates for these wounds were 2.8 and 13.5%, respectively. This was not statistically significant (P = 0.132). This study suggests that prophylactic oral antibiotics in low-risk dog bite wounds are not indicated.

Detection of antibody responses and delayed dermal hypersensitivity with Blastomyces dermatitidis yeast and mycelial lysate antigens

Yeast cell lysate and mycelial lysate antigens prepared from one strain (T-58) of Blastomyces dermatitidis were evaluated with respect to the detection of antibodies and delayed dermal hypersensitivity. Comparable ELISA sensitivity values were evidenced with the two antigens when assayed against serum specimens from dogs with blastomycosis, sera from non-infected dogs residing in endemic and non-endemic areas for blastomycosis and sera from rabbits that were hyperimmunized with B. dermatitidis antigens. Specificity determinations with anti-Histoplasma capsulatum rabbit sera indicated that both reagents exhibited only minimal cross-reactivity; the mycelial antigen was slightly more specific than the yeast phase reagent. Similar sensitivity and specificity results were experienced when the two antigens were used to detect delayed dermal hypersensitivity in guinea pigs previously sensitized with B. dermatitidis or H. capsulatum.

Enzyme immunoassay detection of antibodies in canine blastomycosis using Blastomyces dermatitidis lysate antigens

A Blastomyces dermatitidis yeast phase lysate antigen (T-58) prepared in our laboratory was used in an enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies in 201 serum specimens from dogs with blastomycosis. In addition 36 sera from non-infected dogs from an endemic area for blastomycosis and 36 sera from non-infected dogs residing in a blastomycosis non-endemic area were assayed. Sensitivity values ranged from 96.2% (53 pre-treatment sera) to 88.5% (148 post-treatment sera) with the specimens from dogs with confirmed blastomycosis. Minimal reactivity was experienced with the sera from non-infected dogs. Positive reactions were obtained with 8.3% of the endemic area sera and with 5.6% of the sera from the non-endemic area. Mean ELISA index values ranged from 7.66 with the pretreatment sera to 1.11 and 1.03 with the endemic area sera and non-endemic area specimens respectively.

Helicobacter pylori gastric infection in gnotobiotic beagle dogs

Establishment of infection with Helicobacter pylori and gastritis in nonhuman species is currently only successful in gnotobiotic piglets. This study was designed to determine whether H. pylori will colonize the gastrointestinal tract of gnotobiotic dogs. Gnotobiotic beagle pups were derived by standard methods. Group A (five dogs) was orally challenged with 3 x 10(8) H. pylori at 7 days of age. Group B (two dogs) received only peptone water but was contact-exposed beginning on day 23 postinfection (p.i.). Necropsy was performed on dogs on day 30 p.i. H. pylori colonized the stomach of all dogs (groups A and B). Urease map analysis correlated with the microbiologic findings and indicated that the density of colonization was less than that observed in human tissue. Organisms were also recovered from the pharynx, esophagus, duodenum, and rectum of 1, 2, 2, and 1 dog, respectively. All group A and one group B dog developed serum immunoglobulin G specific for H. pylori by day 30 p.i. Gross lesions were restricted to the stomach and consisted of small (less than 1 mm) lymphoid follicles. Microscopically, there were focal to diffuse lymphoplasmacytic infiltrates with follicle formation and mild to moderate infiltration of neutrophils and eosinophils in the gastric lamina propria. With the Warthin-Starry silver stain, organisms were seen on the surface of the gastric epithelial cells, beneath the mucus layer. We conclude that H. pylori colonizes the stomachs of gnotobiotic dogs for at least 1 month and the lesions resemble those seen in humans. H. pylori is transmissible by contact from infected to noninfected dogs.

The prevalence ofTrypanosoma cruziand the demography of dog populations after insecticidal spraying of houses: a predictive model

A three-year demographic and seroparasitological follow-up of the canine population of a rural area of Argentina endemic for Chagas' disease was carried out in order to (a) describe the population dynamics of domestic dogs, and (b) predict the decrease in the prevalence of Trypanosoma cruzi among these reservoirs after indoor spraying of houses with residual insecticides. For the latter project we designed an age-structured model with a discrete time scale. We assumed a time-dependent exponential decay in the frequency of infected hosts proportional to the host mortality rate, and also assumed and that no differential mortality existed between infected and non-infected dogs. Validation of the model was carried out, and yielded an extremely close fit between observed and theoretical values. The relevance of the model as an aid to designing strategies for the control of animal domestic reservoirs of T. cruzi, and the role of dogs as efficient sentinels of re-infestation of an area, are discussed.

Increased erythrophagocytic activity of macrophages in dogs with Babesia gibsoni infection.

To elucidate the mechanism of anemia caused by Babesia gibsoni infection in dogs, the erythrophagocytic activity of macrophages in infected dogs was investigated in vitro. In the present study, macrophages obtained from peripheral blood (PB-macrophages) and bone marrow (BM-macrophages) of splenectomized dogs with chronic B. gibsoni infection were examined. The BM-macrophages in the splenectomized dogs with chronic babesiosis exhibited an increased erythrophagocytic activity compared with those from splenectomized, non-infected dogs. In the infected dogs, erythrophagocytic activities of macrophages against both auto- and iso-erythorcytes from normal dogs were almost the same. Administration of an anti-protozoal drug, diminazene diaceturate, resulted in a decrease of the erythrophagocytic activity of BM-macrophages associated with an increase of the hematocrit value in splenectomized dogs with chronic babesiosis. In splenectomized dogs with acute babesiosis, erythrophagocytic activity of BM-macrophages was also elevated. Such a phenomenon was not, however, observed in splenectomized dogs with onion-induced hemolytic anemia. These results suggest that the erythrophagocytic ability of macrophages in the infected dogs might be accelerated by parasites per se through an unknown mechanism, resulting in severe anemia in spite of low parasitemia.

Histopathological and immunohistochemical study of the brain in the acute and chronic phases of experimental trypanosomiasis cruzi in dogs

A histopathological and immunohistochemical study was undertaken of the brains of 12 young purebred Pinscher dogs, eight of which were inoculated intraperitoneally with the Colombiana strain of Trypanosoma cruzi. The four non-infected dogs formed the control group. An immunoperoxidase method was employed for demonstrating amastigotes of T. cruzi in tissue sections. Three infected dogs died in the acute phase; the other five were sacrificed at different stages of the chronic phase, one of them having survived for almost three years after the inoculation. Histopathological and immunohistochemical examination of the brains showed changes only in the infected group. Three of the eight inoculated dogs showed encephalitis in multiple foci. In one of the dogs the lesion was recent, in activity, containing parasites. In the other two dogs the lesions were milder, without parasites, suggesting a process of regression. These three were the dogs which died in the acute phase. The other five infected dogs did not show brain changes, and these were the dogs which were sacrificed at different stages of the chronic phase. Based on these findings, the authors conclude that, in the experimental model used, central nervous system involvement in the acute phase of the infection is not very frequent. In the chronic phase the inflammatory changes and parasites would not have been still observable, firstly because most of these dogs would not have had central nervous system involvement in the acute phase, and secondly because in some dogs there would have been total regression of any mild inflammatory changes which had been present in the acute phase as the infection progressed to the chronic phase.

Increase in luminal mast cell and epithelial damage may account for increased airway responsiveness after viral infection in dogs.

To elucidate the mechanisms of airway hyperresponsiveness induced by viral infection, we examined histologically and analyzed bronchoalveolar lavage (BAL) fluid using dogs infected with influenza C and noninfected control dogs. Airway responsiveness was assessed as inhaled acetylcholine concentration required to increase pulmonary resistance by 5 cm H2O/L/s (ACh PC). Airway responsiveness was determined before and 2 wk after virus or vehicle inoculation in infected and control dogs, and BAL and histologic studies were performed after the final challenge. Differential cell numbers and histamine concentration were determined in the BAL fluids of both groups. The ACh PC of control dogs did not change with the vehicle inoculation. However, that of infected dogs decreased two to five times as much as their initial value with viral infection. Histologic studies revealed diffuse epithelial damage in the central airways of infected dogs, but infiltrated cell counts within the airway tissue of both groups were not significantly different. From BAL analysis, mast cell number and the histamine concentration of infected dogs increased significantly compared with those of control dogs (3.1 +/- 0.4 x 10(5) versus 0.9 +/- 0.3 x 10(5) cells/ml and 7.3 +/- 1.7 versus 1.9 +/- 0.5 ng/ml, respectively). Luminal mast cell number and epithelial damage score in each dog was correlated with the increase in airway responsiveness. These findings indicate that airway inflammation in virus-induced hyperreactive dogs is characterized by epithelial damage and luminal increase in mast cells and related mediators, and these changes may be related to the appearance of virus-induced airway hyperreactivity.

Dirofilaria immitis: Alteration of endothelium-dependent relaxation in the in vivo canine femoral artery

Pathogenic mechanisms in filarial diseases are complex and poorly understood. While examining endothelium-dependent vasodilatory responses in the in vivo canine femoral artery, we noticed that dogs with Dirofilaria immitis infection had altered vascular responsiveness. The results reported here extend our original observations on vascular reactivity in dogs with D. immitis infection ( L. Kaiser, J. F. Williams, E. A. Meade, and H. V. Sparks, 1987, American Journal of Physiology, 253, H1325–H1329). In noninfected dogs, acetylcholine binds to the luminal endothelial cell muscarinic receptor. This results in release of a nonprostaglandin endothelium-derived relaxing factor. The relaxing factor causes an increase in vascular smooth muscle guanylate cyclase and relaxation. However, in dogs with D. immitis infection the mechanism of relaxation to acetylcholine is different. At least two endothelium derived relaxing factors are involved: the major factor is a prostaglandin; the second factor works through vascular smooth muscle cGMP. These data suggest that adult D. immitis release pharmacologically active factors that can alter distal endothelial cell function. The notion that filarial products may alter the physiological function of endothelial cells should be considered in the pursuit of improved understanding of pathogenic mechanisms of filariasis.