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PubMed1998

Regio- and stereoselectivity in propranolol metabolism by dog liver microsomes and the expressed dog CYP2D15.

We have studied the regio- and stereoselectivity of ring-hydroxylation and N-desisopropylation of S(-)- and R(+)-propranolol, using dog liver microsomes and the expressed dog CYP2D15 in insect cells. In dog liver microsomes, 4-hydroxylation was the preferred pathway in S(-)-propranolol oxidation, while N-desisopropylation was the preferred pathway in R(+)-propranolol oxidation. S(-)-Propranolol was preferred over R(+)-propranolol as substrate for 4- and 5-hydroxylations, while R(+)-propranolol was the preferred substrate for N-desisopropylation at higher substrate concentrations. The expressed CYP2D15 had high catalytic activities toward 4-, 5-hydroxylation, as well as N-desisopropylation of both enantiomers. At the substrate concentrations used, 4-hydroxylation was the preferred pathway for the metabolism of both enantiomers, and S(-)-propranolol was the preferred substrate over R(+)-propranolol for all three monooxygenations catalyzed by CYP2D15. Anti-CYP2D15 peptide antibody strongly inhibited 4- and 5-hydroxylation of both enantiomers in dog liver microsomes, while it did not inhibit their N-desisopropylation. These findings suggest that CYP2D15 is highly responsible for the stereoselective 4- and 5-hydroxylations of propranolol in dog liver microsomes.

Animals↗

PubMed1988

Similarity between active and trypsin-activated inactive renin in dog plasma by means of renin inhibition: the dog as an animal model for studies of inactive renin.

A method for trypsin-activation of dog plasma inactive renin is described. Liquid phase trypsin (final concentration 6.7 mg/ml) was used and the reaction was stopped after 2 min at 4 degrees C by soybean trypsin inhibitor (13 mg/ml). Renin was measured as angiotensin I (Ang I) generation in trypsin-treated and untreated plasma using the antibody-trapping method, in the presence of excess ox renin substrate. The renin-like activity after trypsin was indeed due to renin, since Ang I generation in dog plasma before and after trypsin treatment was completely inhibited by H-77 at 10(-6) mol/l, and the two IC50 values were very similar (2.7 +/- 0.7 and 2.9 +/- 0.7 at 10(-8) mol/l, respectively). Dog plasma inactive renin was effectively separated from active renin by chromatography on Affigel Blue. Like human prorenin, dog plasma inactive renin rose in response to sodium depletion (furosemide 5 mg/kg, i.v.) followed by a low-salt diet (1 mmol Na+/day) for 4 days, (from 29.6 +/- 8 to 162 +/- 22 microU/ml; P less than 0.01, n = 10). Active renin also increased as expected. Intravenous captopril (6 mg/kg per h), for 3 h, led to a sharp increase in dog plasma active renin (from 53 +/- 8 to 360 +/- 60 microU/ml; P less than 0.01, n = 6), whereas inactive renin remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1999

Effects of multisite ventricular pacing on cardiac function in normal dogs and dogs with heart failure.

INTRODUCTION: We studied the effects on cardiac function of pacing two right and two left ventricular sites in normal and failing hearts with a normal QRS duration. METHODS AND RESULTS: Hemodynamic parameters were studied in isoflurane-anesthetized dogs with normal hearts and dogs with heart failure induced by rapid ventricular pacing. Unipolar intramyocardial electrodes were placed at the high right atrium and the apex (A) and base (B) of the left (L) and right (R) ventricles (V). Data were collected after pacing for 5 to 20 minutes. In normal dogs, without bundle branch block (BBB), pacing at either the apex or the base of the left ventricle increased cardiac output by approximately 10% compared with right ventricular apex (RVA) pacing with an AV delay of 0 msec. Positive dP/dt increased approximately 10% during four-site left and right ventricular apex and base (LRVAB) pacing compared with RVA pacing. In dogs with heart failure but without BBB, cardiac output increased by 8.5% (P < 0.01) during four-site ventricular pacing with AV delays of 0 and 60 msec compared with RVA pacing. Positive dp/dt increased by 23.5% (P < 0.001) with an AV delay of 0 msec and 9.6% (P < 0.001) with an AV delay of 60 msec during LRVAB pacing compared with RVA pacing. His-bundle pacing was associated with increased cardiac output compared with RVA pacing. CONCLUSIONS: We conclude that pacing simultaneously at two right and two left ventricular sites significantly improves cardiac function compared with single RVA pacing, with or without sequential AV synchrony, in dogs with rapid ventricular pacing-induced heart failure and no BBB.

Animals↗

PubMedDate not supplied

Helical computed tomographic portography in ten normal dogs and ten dogs with a portosystemic shunt.

Contrast enhanced helical computed tomography (CT) of the liver and portal system is routinely performed in human patients. The purpose of this project is to develop a practical protocol for helical CT portography in the dog. Ten clinically normal dogs were initially evaluated to develop a protocol. Using this protocol, ten dogs with confirmed portosystemic shunts (PSS) were then evaluated. Each patient was anesthetized, and a test dose of sodium iothalamate (400 mg I/ml) at 0.55 ml/kg was injected. Serial images were acquired at the level of T12-13 or T13-L1. The time to maximum enhancement of the portal vein was determined. This time period was used as the period between the second injection (2.2 ml/kg) and the start of the helical examination of the cranial abdomen. Delay times for normal dogs ranged from 34.5 s-66.0 s (median: 43.5 s) or 1.41 s/kg-4.12 s/kg (median: 2.09 s/kg). For patients with a PSS, the delay times were 16.5-70.5 s (median: 34.5 s) or 1.47-19.17 s/kg (median: 3.39 s/kg). The aorta, caudal vena cava, portal vein, shunt vessels, and their respective branches were well visualized on the CT images. Clinical case results were surgically confirmed. The surgeons reported that the information gained from the CT portography resulted in a subjective decrease in surgical time and degree of dissection necessary compared with similar surgeries performed without angiographic information. We believe that helical CT portography in the dog will be a useful adjunct in the diagnosis of PSS. The use of helical CT portography may allow clinicians to give clients a more accurate prognosis prior to surgery and will allow patients with lesions that are not surgically correctable to avoid a costly and invasive procedure.

Animals↗

PubMed1983

Effect of acute changes in the PaCO2 on acid-base parameters in normal dogs and dogs with metabolic acidosis or alkalosis.

There is a linear relationship between the PaCO2 and blood hydrogen ion concentration in normal dogs, but for theoretical reasons to be discussed, we questioned whether this relationship would apply in animals with metabolic acidosis or alkalosis. To study this in more detail, animals were divided into three groups: normal, metabolically acidotic, and metabolically alkalotic. Following anesthesia and bilateral ureteral ligation, dogs were intubated and ventilated to produce acute steady state PaCO2 values corresponding to the range observed during disease states. Changes in the volume and electrolyte composition of the gastrointestinal fluid and urine as well as the concentration and distribution of lactate were evaluated in all experiments. We observed the previously described linear relationship between the PaCO2 and blood hydrogen ion concentration in normal dogs, but the slope of the regression line differed significantly from those of dogs with metabolic acidosis and metabolic alkalosis. On the other hand, there was a consistent relationship between the ratio of the PaCO2 values, but not the absolute PaCO2, and the change in the plasma bicarbonate concentration over a wide range of PaCO2 values in all groups of dogs. The chemical basis for these observations will be discussed.

Acid-Base Equilibrium↗

PubMed1989

Histochemical comparison of mast cells obtained from the airways of mongrel dogs and Basenji-Greyhound dogs by bronchoalveolar lavage.

An abnormally large number of mast cells in the airway lumen may be an important factor in the pathogenesis of bronchial hyperreactivity. However, it is unclear just how many mast cells are present in the lumen of normal or hyperreactive airways, in part because of differences in the histochemical techniques that have been used to identify mast cells and questions about the heterogeneity of mast cells. The present study was done (1) to compare the effectiveness of six techniques in the identification of mast cells obtained from dogs by bronchoalveolar lavage (BAL), (2) to compare the mast cells in the airways of normal mongrel dogs with those from a breed of dog (Basenji-Greyhound) known to have bronchial hyperreactivity, and (3) to determine whether the two-type histochemical classification used for rodent mast cells (formaldehyde-resistant or typical and formaldehyde-sensitive or atypical) applies meaningfully to the mast cells in BAL fluid from dogs. Cells obtained by BAL were fixed with Mota's basic lead acetate or formaldehyde. Mast cells were identified by metachromatic staining with toluidine blue or methylene blue, staining of highly sulfated proteoglycans with Alcian blue or berberine sulfate, and a histochemical reaction for chloroacetate esterase (mast cell chymase). After Mota's fixation, the methods were relatively similar in their effectiveness in determining the number of mast cells in lavage fluid from the mongrel dogs, in that all of the values fell within a narrow range: 0.53 to 0.96% of the total number of cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2001

Hematopoietic responses to stress conditions in young dogs compared with elderly dogs.

Clinical observations show that older patients do not tolerate high-dose chemoradiotherapy as well as younger patients. It is unclear whether this is due to age-related differences in their responses to hematopoietic injury or to differential toxicities to other organs. In the present study, 6 young (0.5 years) and 6 elderly (8 years) dogs were challenged with 7 repeated nonlethal doses of 50 or 100 cGy total body irradiation (TBI) each (total 550 cGy), and 21 days of recombinant canine granulocyte-colony stimulating factor (rcG-CSF) after the last TBI dose. Recoveries of absolute neutrophil, platelet, and lymphocyte counts after each TBI dose, responses to rcG-CSF treatment, and telomere lengths in neutrophils were compared before and after the study. No differences were found in recoveries of neutrophils, platelets, or in responses to rcG-CSF among young and old dogs. In contrast, recoveries were suggestively worse in younger dogs. After rcG-CSF, platelet recoveries were poor in both groups compared with previous platelet recoveries (P <.01). Consequently, 2 old and 3 young dogs were euthanized because of persistent thrombocytopenia and bleeding. At the study's completion, marrow cellularities and peripheral blood counts of the remaining young and elderly dogs were equivalent. The telomere lengths in both groups were significantly reduced after the study versus beforehand (P =.03), but the median attritions of telomeres were not different. It was concluded that aging does not appear to affect hematopoietic cell recoveries after repeated low-dose TBI, suggesting that poor tolerance of radiochemotherapy regimens in older patients may be due to nonhematopoietic organ toxicities rather than age-related changes in hematopoietic stem cells reserves.

Aging↗

PubMed1976

Effect of coronary vasodilators on cardiac dynamics of the normal dog and the dog with experimental coronary sclerosis.

Observations are presented about the effects of four kinds of coronary vasodilators (dipyridamole, oxyfedrine, prenylamine and trimetazidine) on coronary circulation in the heart with coronary sclerosis which has been induced by intravenous injection of allylamine in the dog. Following results are obtained: 1) All of the drugs examined increase coronary blood flow and decrease coronary vascular resistance in the dogs with coronary sclerosis as well as in normal dogs. 2) An amplitude of response of coronary circulation to the coronary vasodilators is significantly less in the dogs with coronary sclerosis than in the normal dogs. 3) The clinical value of coronary vasodilator has been discussed.

Allylamine↗

PubMed2001

Transferable residues from dog fur and plasma cholinesterase inhibition in dogs treated with a flea control dip containing chlorpyrifos.

We studied chlorpyrifos, an insecticide present in a commercial dip for treating ectoparasites in dogs, to estimate the amount of transferable residues that children could obtain from their treated pets. Although the chlorpyrifos dip is no longer supported by the manufacturer, the methodology described herein can help determine transferable residues from other flea control insecticide formulations. Twelve dogs of different breeds and weights were dipped using the recommended guidelines with a commercial, nonprescription chlorpyrifos flea dip for 4 consecutive treatments at 3-week intervals (nonshampoo protocol) and another 12 dogs were dipped with shampooing between dips (shampoo protocol). The samples collected at 4 hr and 7, 14, and 21 days after treatment in the nonshampoo protocol averaged 971, 157, 70, and 26 microg chlorpyrifos, respectively; in the shampoo protocol the samples averaged 459, 49, 15, and 10 microg, respectively. The highest single sample was about 7,000 microg collected at 4 hr. The pretreatment specific activities in the plasma of the dogs were about 75 nmol/min/mg protein for butyrylcholinesterase (BChE), and 9 nmol/min/mg protein for acetylcholinesterase (AChE). BChE was inhibited 50-75% throughout the study, and AChE was inhibited 11-18% in the nonshampoo protocol; inhibition was not as great in the shampoo protocol. There was no correlation (p<or= 0.05) between length of hair and residues measured that would explain the residue differences among dogs. Transferable residues had largely dissipated during the three weeks after treatment, with the largest decrease occurring during the first week. Greater plasma ChE inhibition was observed at 7 days than at 4 hr, probably reflecting the bioactivation of chlorpyrifos to chlorpyrifos-oxon. Plasma cholinesterase activity did not return to control levels during the 3-week period. The differences between the shampoo and nonshampoo protocols were explained by differences in the techniques of the dip applicators.

Acetylcholinesterase↗

PubMed1982

Cardiovascular effects of aminophylline and pentoxifylline on intact dogs and isolated dog atria.

The effects of aminophylline and pentoxifylline were investigated on the blood pressure and heart rate in the intact dog and on the atrial rate and contractile force in isolated atrial muscle which was perfused with arterial blood of the donor dog. Firstly, each drug was intravenously administered to the donor dog. Both compounds produced a dose-dependent hypotension. Aminophylline frequently caused bradycardia in intact dogs and positive chrono- and inotropic effects in isolated atria. However, pentoxifylline usually produced only tachycardia in the donor dog and positive chrono- and inotropic effects on the isolated atrium. When the compounds were administered into the sinus node artery, positive chrono- and inotropic effects were induced, with aminophylline being approximately 3--10 times more potent than pentoxifylline. Larger doses of aminophylline or pentoxifylline when administered intravenously might cause a release of catecholamine, because increased sinus rate and developed tension in isolated atria which was perfused with donor's blood were partially, but significantly, suppressed by propranolol treatment. In the isolated atrium, aminophylline, but not pentoxifylline, significantly inhibited the negative chronotropic and inotropic effects of adenosine.

Adenosine↗

PubMed2006

Comparison of variability in cardiorespiratory measurements following desflurane anesthesia at a multiple of the minimum alveolar concentration for each dog versus a multiple of a single predetermined minimum alveolar concentration for all dogs in a group.

OBJECTIVE: To determine whether the variability of cardiorespiratory measurements is smaller when administering desflurane at a multiple of the individual's minimum alveolar concentration (MAC) or at a predetermined, identical concentration in all subjects. ANIMALS: 10 dogs. PROCEDURES: Desflurane was administered at 1.5 times the individual's MAC (iMAC) and 1.5 times the group's MAC (gMAC). The order of concentrations was randomly selected. Heart rate, respiratory rate, arterial blood pressure, central venous pressure, mean pulmonary artery pressure, pulmonary artery occlusion pressure, arterial and mixed-venous blood gas tensions and pH, and cardiac output were measured. The desflurane concentration required to achieve a mean arterial pressure (MAP) of 60 mm Hg was then determined. Finally, the desflurane concentration required to achieve an end-tidal PCO(2) of 55 mm Hg was measured. RESULTS: Variances when administering 1.5 iMAC or 1.5 gMAC were not significantly different for any variable studied. Differences between the MAC multiples needed to reach an MAP of 60 mm Hg and the mean of the sample were significantly larger when gMAC was used, compared with iMAC, indicating that a multiple of iMAC better predicted the concentration resulting in a MAP of 60 mm Hg. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that, in a small group of dogs, variability in cardiorespiratory measurements among dogs is unlikely to differ whether an inhalant anesthetic is administered at a multiple of the iMAC in each dog or at an identical gMAC in all dogs.

Anesthetics, Inhalation↗

PubMed1999

Pharmacokinetics of new calcium channel antagonist clevidipine in the rat, rabbit, and dog and pharmacokinetic/pharmacodynamic relationship in anesthetized dogs.

Clevidipine is a new vascular selective calcium channel antagonist of the dihydropyridine type, structurally related to felodipine. Clinical trials have shown that the drug can be used to effectively control the blood pressure in connection with cardiac surgical procedures. The compound is tailored to be a short-acting drug and, due to incorporation of an ester linkage into the drug molecule, clevidipine is rapidly metabolized by ester hydrolysis. The pharmacokinetics of clevidipine and its primary metabolite, H 152/81, were studied in rats, rabbits, and dogs. In addition, the influence of the pharmacokinetics on the effect on mean arterial blood pressure was evaluated in anesthetized dogs. Compartmental nonlinear mixed effect regression analysis was used to calculate the population mean and individual pharmacokinetics of clevidipine, whereas nonlinear regression analysis of individual data was used to determine the pharmacokinetics of the primary metabolite. A linked Emax model was fitted to the individual pharmacodynamic/pharmacokinetic data in dogs. According to the results, clevidipine is a high-clearance drug with a relatively small volume of distribution, resulting in an extremely short half-life in all species studied. The median initial half-life of the individual value (Bayesian estimates) is 12, 20, and 22 s in the rabbit, rat, and dog, respectively. The primary metabolite is a high-clearance compound in the dog, whereas it is a low-clearance compound in the rat. A significant gender difference in the clearance of the metabolite was observed in the rat. The mean maximum reduction in arterial blood pressure is 38 +/- 12% (Emax) and is achieved at 85 +/- 46 nM (EC50). The half-life for reaching equilibrium between the central and the effect compartment (T1/2ke0) is 47 +/- 49 s.

Anesthesia↗

PubMed2000

[Combat dogs--dangerous dogs].

The claim that the so-called "Kampfhunde" are becoming increasingly dangerous to humans has been the subject of much discussion in Germany. A critical analyses of canine breeds that have been classified as "Kampfhunde" convinces that breed is not an useful possibility for avoiding accidents with dogs: 1. Zoologically no particular breed of dog can be classified as being more dangerous than others and 2. so-called "Kampfhunde" are statistically unimportend as a vector in dog accidents. It would be more productive in the future to substitute the term "Kampfhund" with "dangerous dog" without reference to the breed and to emphasize the role of the owner in the human danger posed by a dog.

Accidents↗

PubMed2001

[Fighting dogs--dangerous dogs: legal situation in Bavaria].

A report is given on eight years of experience with the Bavarian legal regulation for the protection against dangerous dogs of 10.7.1992. The implementation of the regulation was a success. Since then only two cases of biting accidents are reported. In one case the dogs were euthanatized, in the other case they were taken away and given to other owners. The advantages of the regulation are seen in the increased responsibility of the dog owner who has to give proof of the peaceful character of his dog in form of an expert testimony. This lowers the administration costs and has revealed a preventive effect, the dog owners are looking more carefully after their animals to avoid any security problems.

Aggression↗

PubMed2006

A comparative LM and SEM study of the structure of the mucosal glands of the gallbladder in two species of canids: the dog and the Chinese raccoon dog.

The studies were performed on the mucosa of the body of the gallbladder in the dog and Chinese raccoon dog, species belonging to the Canidae family. The mucosal glands in both species mostly have the form of alveolar or short tubular secretory units without excretory ducts and are situated in the middle part at the bottom of the crypts surrounded by folds of the mucosa. Sporadically we observed the mucous intraepithelial glands. The results of the light and scanning electron microscopic observations indicate interspecies differences in the density, type and size of secretory units and also their openings. In the raccoon dog the number of secretory units is 30 times greater than in the dog and the units are predominantly simple glands with small openings. In the dog mostly 2 or 3 secretory units with common wide openings were observed. The SEM images of the NaOH macerated mucosa of the gallbladders showed a connective tissue framework around the glands composed of flat lamina with an irregular pattern of fine collagen fibres and numerous fenestrations. The collagen network around the openings of the glands is more compact and provides mechanical support for the glands of the gallbladder.

Animals↗

PubMed1989

Immunotherapy with dog and cat allergen preparations in dog-sensitive and cat-sensitive asthmatics.

Standardized dog and cat allergen preparations with defined allergen composition were used for immunotherapy (IT) in dog-sensitive and/or cat-sensitive adult patients. Seventeen patients completed 1 year of IT. Eleven patients were treated with dog allergen, five with cat allergen, and one with both dog and cat allergen. The treatment was well tolerated, with increased subjective tolerance. After 3 months of IT there was a significant decrease in conjunctival (p less than .05) and skin sensitivity (p less than .05). Specific IgE decreased significantly within 1 year as assayed by RAST and IgE-crossed radioimmunoelectrophoresis. Specific IgG increased in all patients. The results indicate that IT with potent and standardized dog and cat allergens influence the sensitivity to these allergens.

Allergens↗

PubMed1984

Investigation of the haemolytic effects of Ancylostoma ceylanicum: observations on infected dogs in vivo and human and dog blood in vitro.

Investigations into the probable role of haemolysins in the causation of hookworm anaemia have been undertaken in living infected dogs. Secondly, the effects of living hookworms and various worm products on erythrocytes in vitro have been assessed. In dogs infected with varying numbers of A. ceylanicum, severe microcytic anaemia developed in the most heavily infected animals six weeks after infection. Erythrocytes from the latter animals showed significantly greater autohaemolysis in the presence of added glucose. When serum bilirubin and methaemalbumin, plasma haemoglobin, urinary urobilinogin and osmotic fragility of their red cells were measured, however, no evidence of haemolysis was detected. Erythrocytes from these animals appeared normal under scanning electron microscopy. In in vitro studies varying concentrations of adult worm extract had no effect on the haemolysis of either dog or human erythrocytes in the presence or absence of glucose nor on their mechanical fragility. There was no increase in 51Cr release from dog or human labelled red cells when incubated with either adult worm extract or excretory/secretory products of worms. Living adult worms caused an increase in 51Cr release from human but not dog labelled erythrocytes. Thus, the role of haemolysins in the genesis of hookworm anaemia is minimal.

Ancylostoma↗

PubMed1995

Kidney structure and function of obligate and facultative hibernators: the white-tailed prairie dog (Cynomys leucurus) and the black-tailed prairie dog (Cynomys ludovicianus).

The white-tailed prairie dog is an obligate hibernator that enters a heterothermic phase when maintained in the cold with low intensity light and ad libitum food and water. The black-tailed prairie dog (a facultative hibernator) will not hibernate under similar conditions. It has been suggested that the black tailed prairie dog remains active during the winter because it can conserve water more effectively due to a more efficient kidney. The present study revealed no significant differences between the species in renal morphology: relative medullary thickness, nephron heterogeneity, renal vasculature, or fornix dimensions, all of which are structures associated with the urinary concentrating mechanism. In addition, there was no difference in number of nephrons between the two species. The black-tailed prairie dog does produce a more concentrated urine when food and water deprived. However, this difference was not observed when the animals were salt loaded. The water-deprivation and salt-loading experiments suggest that the higher urine osmolality produced by the back-tailed prairie dog during fasting is a result of a higher urea load due to a greater protein catabolism and not because of a differential capacity to concentrate urine.

Adaptation, Physiological↗