Effect of inhaled nitric oxide on experimentally induced pulmonary hypertension in neonatal foals

OBJECTIVE: To evaluate the efficacy of inhaled nitric oxide (NO) in anesthetized healthy newborn foals with experimentally induced pulmonary hypertension. ANIMALS: Five 1- to 3-day-old foals. PROCEDURE: Anesthesia was induced and maintained with propofol, and foals were intubated and mechanically ventilated. Systemic pressure and pulmonary arterial pressure (P(PA)) were recorded every 30 seconds. Hypertension was induced via a hypoxic gas mixture or chemical vasoconstriction, using the thromboxane mimetic U46619. Nitric oxide was added at a concentration of 80 parts per million (ppm) for 6 minutes under baseline conditions and during pulmonary hypertension-induced alveolar hypoxia (inspired oxygen concentration = 0.08). Nitric oxide (20, 40, 80, and 160 ppm) was evaluated during U46619-induced hypertension. Samples for determination of arterial blood gas tensions were collected before and after each NO treatment. RESULTS: Inhaled NO (approx 80 ppm) did not have an effect on baseline variables. Infusion of U46619 (0.35 +/- 0.04 microg/kg of body weight/min) or alveolar hypoxia resulted in increased P(PA) and decreased arterial oxygenation (PaO2) and hemoglobin saturation (HbSat). The increase in P(PA) was attenuated, in a dose-dependent manner, by NO during U46619 infusion and reversed by NO during induced hypoxemia. The PaO2 and HbSat were significantly improved at all NO doses during U44619 infusion but not during alveolar hypoxia. For all inhaled NO concentrations, nitrogen dioxide and methoglobin values were < 5 ppm and 3%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Nitric oxide is a potent, selective vasodilator of the pulmonary circulation in healthy newborn foals. Inhaled NO may have value as a therapeutic agent in foals with pulmonary hypertension.     

Immunohistochemical detection of canine distemper virus in haired skin, nasal mucosa, and footpad epithelium: a method for antemortem diagnosis of infection.

A reliable antemortem diagnostic method is needed for determining infection with canine distemper virus (CDV). The utility of immunohistochemical detection of CDV antigen was examined was examined for samples of nasal and footpad epithelium and haired skin in dogs with and without detectable CDV antigen in the lung and/or brain. Tissues from 57 dogs at risk of CDV infection were tested. Viral antigen was found in the lung and/or brain of 28 dogs. Among these dogs, viral antigen was demonstrated in the epithelial cells of the nasal mucosa in 24 of 27 dogs, in the footpad epithelium in 24 of 26 dogs, and in the haired skin of the dorsal neck in 26 of 27 dogs. Among the 29 dogs without CDV antigen in either the lung or brain, 1 dog had positive staining for viral antigen in the skin and nasal mucosa. Biopsies of haired skin of the dorsal neck, which is relatively simple to sample, can be used for immunohistochemical testing for acute and subacute infection with CDV.     

Matrix metalloproteinase-2 and -9 are activated in joint diseases.

A study was performed to identify the activation status of the gelatinase MMPs, MMP-2 and -9, in both normal and diseased equine articular tissues. In addition, the production and activation status of equine MMP-2 and -9 by equine articular cells and tissues in response to increasing IL-1beta concentrations was assessed. The study was performed to test the hypothesis that activation of MMPs is a fundamental step in the pathogenesis of joint diseases; and that this activation is mediated by the cytokine IL-1. Using purified equine MMP-2 and -9, the molecular weights of the zymogen and activated form of equine MMP-2 and -9 were identified by a combination of gelatin zymography and a gelatin degradation assay using aminophenylmercuric acetate as a chemical activator of the molecules. Normal equine articular tissues (cartilage and synovial membrane) maintained in short-term tissue culture produced MMP-2 zymogen alone, while similar tissues obtained from a variety of pathological conditions produce both zymogen and active MMP-2, as well as MMP-9 monomer and dimer. Activated MMP-9 was an inconsistent finding. Normal equine synovial fibroblasts in monolayer culture produced zymogen MMP-2 alone under basal conditions. A mild increase in active and zymogen MMP-2 levels occurred with IL-1beta treatment. Equine synovial membrane explants demonstrated a dose-dependent increase in active and zymogen MMP-2 and MMP-9 levels following IL-1beta treatment. Monolayer chondrocyte cell cultures demonstrated a dose-dependent mild increase in active and zymogen MMP-2 following IL-1beta treatment. Explant cartilage cultures demonstrated a dose-dependent mild increase in zymogen MMP-2 alone following IL-1beta treatment. This study supports the hypothesis that activation of MMPs is occurring in joint disease, and that in vitro stimulation of equine articular cells and tissues causes not only an increase in MMP production, but also an increase in amount of activated enzyme released. Further research is required to investigate the role of MMP activation in joint diseases, and to investigate the potential use of therapeutic agents, which inhibit MMP activation, in the treatment and prevention of joint diseases.     

Surgical management of bifid sternum in two African grey parrots

Transposition of the pectoral muscles for treatment of caudal bifid (cleft) sternum in 2 unrelated African Grey Parrots is described. The birds did not have clinical signs of ventilatory compromise prior to surgery; however, both had cutaneous ulcers over the defects. The pectoral muscles provided a thick pad over the heart, minimizing the risk of trauma to the heart.     

Update on vaccination of cattle and wildlife populations against tuberculosis

A recombinant bovine herpesvirus 5 lacking thymidine kinase and glycoprotein E genes (BoHV-5gEΔTKΔ) was evaluated as a live experimental vaccine. In a first experiment, ten-months-old calves were vaccinated intramuscularly (n=9) or remained as controls (n=8) and 42 days later were challenged with BoHV-5 or BoHV-1 intranasally. The four control calves challenged with BoHV-5 developed severe depression and neurological signs and were euthanized in extremis at days 13 and 14 pos-infection (pi); the five vaccinated animals challenged with BoHV-5 remained healthy. The titers of virus shedding were reduced (p<0.01) from days 3 to 7 post-infection (pi) in vaccinated animals. Control and vaccinated calves challenged with BoHV-1 presented mild transient respiratory signs; yet the magnitude of virus shedding was reduced (p<0.05) in vaccinated animals (days 5, 9 and 11pi). In a second experiment, young calves (100-120 days-old) were vaccinated (n=15) or kept as controls (n=5) and subsequently challenged with a BoHV-1 isolate. Control calves developed moderate to severe rhinitis and respiratory distress; two were euthanized in extremis at days 5 and 9 pi, respectively. In contrast, vaccinated animals were protected from challenge and only a few developed mild and transient nasal signs. The duration and titers of virus shedding after challenge were reduced (p<0.05) in vaccinated animals comparing to controls. In both experiments, vaccinated animals developed antibodies to gE only after challenge. These results demonstrate homologous and heterologous protection and are promising towards the use of the recombinant BoHV-5gEΔTKΔ in vaccine formulations to control BoHV-5 and BoHV-1 infections.     

Serum and bronchoalveolar lavage fluid endothelin-1 concentrations as diagnostic biomarkers of canine idiopathic pulmonary fibrosis

Background: Diagnosis of canine idiopathic pulmonary fibrosis (IPF) is challenging. Endothelin‐1 (ET1) is a biomarker of IPF in humans, but whether ET1 can detect and differentiate IPF from other canine respiratory diseases is unknown. Objective: To evaluate whether measurement of the concentration of ET1 in serum and bronchoalveolar lavage fluid (BALF) can be used to distinguish canine IPF from chronic bronchitis (CB) and eosinophilic bronchopneumopathy (EBP). Animals: Twelve dogs with IPF, 10 dogs with CB, 6 dogs with EBP, 13 privately owned healthy West Highland White Terriers (WHWT), and 9 healthy Beagle dogs. Methods: Prospective, case control study. ET1 concentration was determined by ELISA in serum and in BALF. Results: No significant difference in serum ET1 concentration was detected between healthy Beagle dogs and WHWT. Serum ET1 concentration was higher in dogs with IPF (median interquartile range; 2.32 pg/mL, 2.05–3.38) than healthy Beagle dogs (1.28, 1.07–1.53; P < .001), healthy WHWT (1.56, 1.25–1.85; P < .001), dogs with EBP (0.94 0.68–1.01; P = .001), and dogs with CB (1.54 0.74–1.82; P = .005). BALF ET1 concentration was below the detection limit in healthy WHWT and in dogs with CB, whereas it was measurable in all dogs with IPF. A cut‐off serum concentration of 1.8 pg/mL had a sensitivity of 100% and a specificity of 81.2% for detection of IPF, with an area under the receiver operating characteristic curve of 0.818. Conclusions and Clinical Importance: Serum ET1 can differentiate dogs with IPF from dogs with EBP or CB. ET1 can be detected in BALF of dogs with IPF.     

Additivity of effects from dietary copper and zinc on growth performance and fecal microbiota of pigs after weaning

Four experiments were conducted to determine the interactive effects of pharmacological amounts of Zn from ZnO and Cu from organic (Cu-AA complex; Cu-AA) or inorganic (CuSO(4)) sources on growth performance of weanling pigs. The Cu was fed for 4 (Exp. 1) or 6 (Exp. 2, 3, and 4) wk after weaning, and Zn was fed for 4 (Exp. 1) or 2 (Exp. 2, 3, and 4) wk after weaning. Treatments were replicated with 7 pens of 5 or 6 pigs per pen (19.0 ± 1.4 d of age and 5.8 ± 0.4 kg of BW, Exp. 1), 12 pens of 21 pigs per pen (about 21 d of age and 5.3 kg of BW, Exp. 2), 5 pens of 4 pigs per pen (20.3 ± 0.5 d of age and 7.0 ± 0.5 kg of BW, Exp. 3), and 16 pens of 21 pigs per pen (about 21 d of age and 5.7 kg of BW, Exp. 4). In Exp. 1 and 2, Cu-AA (0 vs. 100 mg/kg of Cu) and ZnO (0 vs. 3,000 mg/kg of Zn) were used in a 2 × 2 factorial arrangement. Only Exp. 1 used in-feed antibiotic (165 mg of oxytetracycline and 116 mg of neomycin per kilogram feed), and Exp. 2 was conducted at a commercial farm. In Exp. 3, sources of Cu (none; CuSO(4) at 250 mg/kg of Cu; and Cu-AA at 100 mg/kg of Cu) and ZnO (0 vs. 3,000 mg/kg of Zn) were used in a 3 × 2 factorial arrangement. In Exp. 4, treatments were no additional Cu, CuSO(4) at 315 mg/kg of Cu, or Cu-AA at 100 mg/kg of Cu to a diet supplemented with 3,000 mg/kg of Zn from ZnO and in-feed antibiotic (55 mg of carbadox per kilogram of feed). In Exp. 1 and 2, both Zn and Cu-AA improved (P < 0.001 to P = 0.03) ADG and ADFI. No interactions were observed, except in wk 1 of Exp. 2, where Zn increased the G:F only in the absence of Cu-AA (Cu-AA × Zn, P = 0.04). A naturally occurring colibacillosis diarrhea outbreak occurred during this experiment. The ZnO addition reduced (P < 0.001) the number of pigs removed and pig-days on antibiotic therapy. In Exp 3, ADFI in wk 2 was improved by Zn and Cu (P < 0.001 and P = 0.09, respectively) with no interactions. In wk 1, G:F was reduced by ZnO only in the absence of Cu (Cu × Zn, P = 0.03). Feeding Zn decreased fecal microbiota diversity in the presence of CuSO(4) but increased it in the presence of Cu-AA (Cu source × Zn, P = 0.06). In Exp. 4, Cu supplementation improved the overall ADG (P = 0.002) and G:F (P < 0.001). The CuSO(4) effect on G:F was greater (P < 0.001) than the Cu-AA effect. Our results indicate that pharmacological amounts of ZnO and Cu (Cu-AA or CuSO(4)) are additive in promoting growth of pigs after weaning.     

Prevalence of Bartonella species, haemoplasmas and Toxoplasma gondii in cats in Scotland

The objective of this study was to determine the prevalence rates for select infectious agents of cats presented to the Royal (Dick) School of Veterinary Studies at the University of Edinburgh, Scotland. Whole blood, serum, and oral mucosal and nail bed swabs were collected. While Ehrlichia species, Anaplasma species or Rickettsia felis DNA were not amplified from any cat, 44.2% of the cats had evidence of infection or exposure to either a Bartonella species (15.3% were seropositive and 5.8% polymerase chain reaction (PCR) positive), a haemoplasma (28.6% PCR positive), and/or Toxoplasma gondii (19.2% seropositive). No Bartonella species DNA was amplified from the nail or oral mucosal swabs despite a 5.8% amplification rate from the blood samples. This finding likely reflects the absence of Ctenocephalides felis infection from our study population, as this organism is a key component for Bartonella species translocation in cats. The results from this study support the use of flea control products to lessen exposure of cats (and people) to Bartonella species and support discouraging the feeding of raw meat to cats and preventing them from hunting to lessen T gondii infection.     

Vaccine development for the prevention of staphylococcal mastitis in dairy cows

Staphylococci are the most common and costly mammary disease of dairy cattle worldwide. Target of RNAIII Activating Protein (TRAP), a membrane associated 167AA protein, is highly conserved among staphylococci and was shown in Staphylococcus aureus to be involved in bacterial stress response. The aims of this study were to test the safety and efficacy of recombinant TRAP (rTRAP) vaccine in dairy animals. The vaccine was safe as 2-3 subcutaneous injections of rTRAP (54-100 μg) with adjuvant ISA 206 to cows and goats did not lead to any abnormal symptoms of sensitivity to the vaccine. The rTRAP vaccine was immunogenic and caused the induction of a humoral immune response that remained high for at least 160 d post second immunization. The rTRAP vaccine was efficacious; at parturition only 13.5% (5/37) heifers in the immunized group were infected with Staphylococcus chromogenes as compared to 42.9% (18/42) in the non-immunized group. Additionally, when cows were immunized in mid-lactation, the difference between somatic cell count (SCC) in immunized and control animals was profound (45 ± 7 vs. 470 ± 194, respectively). At the same time, the difference in milk yield was also evident (48.3 ± 1.4 L d(-1)vs. 44.3 ± 0.9 L d(-1), respectively). Put together, these studies indicate the value of the rTRAP vaccine in preventing new udder infections by staphylococci, which significantly lead to lowered SCC and some increase in milk yield. TRAP is conserved among all strains and species and is constitutively expressed in any strain of S. aureus or CNS tested so far, including those isolated from cows. TRAP may thus serve as a universal anti-staphylococcus vaccine.     

Pre-pubertal measurements of the somatotrophic axis as predictors of milk production in Holstein-Friesian dairy cows

This study investigated possible relationships between measurements of the somatotrophic axis in pre-pubertal dairy calves and subsequent milk yields. Endogenous growth hormone (GH) release was measured through a fed and fasted period in fifty 6-month-old Holstein-Friesian heifers and they were then challenged with growth hormone-releasing factor (GRF) to assess their GH release pattern. Insulin-like growth factor-I (IGF-I), insulin and glucose concentrations were measured in relation to time of feeding. Cows were subsequently monitored through their first three lactations to record peak and 305-day milk yields. In the first lactation, milk energy output for the first 120 days of lactation was also calculated. The mean 305-day milk yield increased from 7417 +/- 191 kg in the first lactation (n=37) to 8749 +/- 252 kg in the third (n=25). There were no significant relationships between any measures of GH secretion and peak or 305-day yield in any lactation. A highly significant positive relationship was established between the GH peak measured 10 min post-GRF challenge and 120-day milk energy values in the first lactation. This relationship was, however, only present in the sub-population of 12 cows culled after one or two lactations and was absent in the 25 animals remaining for the third lactation. There were no significant relationships between pre-pubertal IGF-I and fed or fasted insulin or glucose concentrations and any subsequent measurement of yield. The usefulness of GH secretagogue challenges in calves as a predictive test for future milk production is thus limited but may have some bearing on nutrient partitioning and longevity.