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An experimental kidney disease in dogs produced by injection of heterologous antisera to dog tubular fraction 3 antigen.

Glomerular disease characterised by morphological alterations of the glomerular basement membrane and the mesangium was produced in dogs by injections of heterologous anti-dog renal tubular fraction 3 antibody. The renal lesion was characterised by irregular thickening of the glomerular basement membrane, with electron-dense deposits and loose granular material within it.

Animals↗

Urinary protein excretion rates in experimentally diabetic dogs and experimentally galactosaemic dogs.

The relationship between urinary protein excretion and control of diabetes was evaluated in alloxan-diabetic dogs prospectively assigned to poor, moderate, or good glycaemic control. Protein excretion rate increased with the duration of insulin deficiency, and was significantly greater than normal in the poor control group by the fourth year of diabetes. Appreciable differences in the severity of the proteinuria were observed among animals of the poor and moderate glycaemic control groups; some of the animals excreted in excess of 500 mg protein/24 h while others excreted no more than normal throughout the 5 years of study. Differences in glycaemic control among these insulin-deficient animals seem not sufficient to account for the observed differences in protein excretion. Immunoassay for albumin indicated that the defect resulting in supranormal protein excretion was at least partly glomerular in origin. Good glycaemic control prevented the protein loss from exceeding normal. A potential role of hyperglycaemia in the development of proteinuria was examined in nondiabetic dogs made experimentally hyperglycaemic with galactose. Consumption of a 30% galactose diet for up to 5 years duration had little influence on protein excretion.

Animals↗

Glucagon-like peptide-1(7-37) has a larger volume of distribution than glucagon-like peptide-1(7-36)amide in dogs and is degraded more quickly in vitro by dog plasma.

The pharmacokinetic properties of glucagon-like peptide-1(7-36)amide (GLP-1(7-37) were compared. Four beagle dogs received on 4 separate occasions s.c. bolus doses of 50 micrograms/kg, and 2 min i.v. infusions of 50 micrograms/kg of each peptide. The plasma immunoreactivity of GLP-1 (P-GLP-1-IR) was measured by a sandwich enzyme-linked immunosorbent assay (ELISA). After i.v. infusion, the plasma half-life in the first-phase was 2.1 +/- 0.1 and 2.4 +/- 0.3 min, in the final-phase 68 +/- 6 and 81 +/- 3 min, the total plasma clearance 25 +/- 3 and 22 +/- 4 ml/kg.min, the volume of distribution at steady state 0.16 +/- 0.02 and 0.84 +/- 0.24 l/kg, and the mean residence time 6.2 +/- 0.3 and 36 +/- 5 min for GLP-1(7-36)amide and GLP-1(7-37), respectively. After s.c. administration, the maximum plasma concentration was reached after 15 +/- 5 and 19 +/- 4 min and the absolute bioavailability was 48 +/- 7 and 49 +/- 13% for GLP-1(7-36)amide and GLP-1(7-37), respectively. P-GLP-1-IR, measured by a radioimmunoassay (RIA), was considerably higher than when measured by ELISA. This discrepancy was due to cross-reactivity with metabolites of the parent peptide. The plasma degradation was studied in vitro in dog plasma at 37 degrees C, and the half-lives were found to be 61 +/- 9 and 132 +/- 16 min for GLP-1(7-36)amide and GLP-1(7-37), respectively (n = 6). Bacitracin inhibited the degradation of both peptides.

Animals↗

Allergens in school dust. I. The amount of the major cat (Fel d I) and dog (Can f I) allergens in dust from Swedish schools is high enough to probably cause perennial symptoms in most children with asthma who are sensitized to cat and dog.

BACKGROUND: We investigated the levels of Fel d I and Can f I in dust from tables, chairs, and floors in 29 classrooms in four Swedish schools. METHODS: School authorities were questioned about building characteristics, students were interviewed about their health and exposure to animals, and cleaning personnel were asked about methods and frequency of cleaning. Dust samples were taken from floors and horizontal surfaces of chairs and tables in all classrooms during a 6-week period. RESULTS: Higher amounts of Fel d I were found on chairs (geometric mean, 953 ng per gram of dust) than on tables (525 ng/gm) and floors (134 ng/gm). The concentration of Can f I (5.3 ng/gm) on chairs was 2 to 20 times higher than Fel d I. The concentration of Can f I (200 ng/gm) in dust from floors was twice as high as that of Fel d I. The concentration of Can f I on chairs was within the range previously found by other investigators in houses with dogs. CONCLUSIONS: Since the levels of both Fel d I and Can f I were much higher on chairs than on floors, we hypothesize that allergen is brought to schools on the clothes of students and teachers. We conclude that the levels of the two major allergens from furred pets (i.e., Fel d I and Can f I) in Swedish schools are probably high enough to sensitize children and to induce asthma in most children who are allergic to cats or dogs.

Adult↗

Elevated blood viscosity in alloxan diabetic dogs and experimentally galactosemic dogs.

Blood viscosity was investigated in alloxan-diabetic dogs and in dogs made experimentally hyperglycemic by a galactose-rich diet. The diabetics were prospectively assigned to levels of glycemic control ranging from poor to good. After up to 5 years of study, the blood viscosity of hyperglycemic diabetic animals was significantly greater than normal at both high (100 sec-1) and low (0.1 sec-1) shear rates. Blood viscosity at the low shear rate correlated closely with fibrinogen concentration, (r = 0.75; p less than 0.02) but not with HbA1 concentration (r = 0.14) in the diabetics. Galactosemic animals likewise had elevated blood viscosity at the low shear rate, but the correlation of viscosity with fibrinogen concentration in those animals was not statistically significant (r = 0.42). Plasma viscosity tended to be elevated in both diabetes and galactosemia, but not to a statistically significant degree.

Animals↗

Determination of ibuprofen in dog plasma by liquid chromatography and application in pharmacokinetic studies of an ibuprofen prodrug in dogs.

A liquid chromatography (LC) method for the determination of ibuprofen in dog plasma is described. Chromatographic separation was performed on a Diamonsil C18 column with a C18 guard column using a binary mixture of acetonitrile and 0.02 mol/l phosphate buffer (pH 6.5) (35:65, v/v) delivered at a flow rate of 1.2 ml/min. The linear range for ibuprofen was from 1.0 to 40.0 microg/ml with a limit of quantitation of 1.0 microg/ml. Within-run accuracy and precision ranged from -0.1% to 4.0% and from 1.1% to 5.5% and between-run accuracy and precision ranged from -1.1% to 4.7% and from 1.3% to 7.0%, respectively. The mean extraction recoveries of ibuprofen determined over the concentrations of 1.0, 10.0, and 40.0 microg/ml were (100.5+/-1.8)%, (99.8+/-1.0)%, and (99.2+/-2.3)%. The developed LC method greatly simplified the sample preparation and adopted mild conditions to prevent the possible hydrolysis of the prodrug and was successfully applied to the pharmacokinetic studies of an ibuprofen prodrug in dogs.

Animals↗

Electrocardiographic effects of myocardial ischemia induced by atrial pacing in dogs with coronary stenosis. II. Comparison of S-T segment and QRS changes in dogs with left circumflex arterial narrowing.

The effects of tachycardia on the QRS complex in the absence and in the presence of coronary arterial constriction are of possible clinical significance. To study the spatial and temporal distributions of these effects, a canine model simulating progressive coronary occlusion was studied. Tachycardia was induced by atrial pacing, coronary narrowing was produced by implantation of an ameroid constrictor about the left circumflex coronary artery and electrocardiographic effects were studied by isopotential mapping techniques at rates of up to 250 beats per minute, one to three weeks after constrictor implant. In five dogs. pacing without coronary constriction demonstrated the spatial and temporal dependence of QRS changes; tachycardia-induced changes varied from one torso site to another at any instant, and from one moment to another at any one torso location. Patterns in ten dogs with constrictors were dependent upon time after ameroid placement. Resting QRS and S-T segment distributions remained unchanged. One week after surgery, QRS and S-T segment patterns during pacing were as in controls. Two weeks after surgery, QRS patterns were as in controls but flat S-T segment depression resulted at high rates. After three weeks, QRS patterns during pacing were abnormal and S-T segment depression was observed. At each of the later times, the QRS response was similar at rates which did and which did not cause S-T depression. Thus, the effects of tachycardia on excitation and recovery forces in the presence of restricted coronary flow are independent of one another. This suggests that the two responses to ischemia may be due to different basic mechanisms and, hence, that their detection may reflect different myocardial abnormalities.

Animals↗

High-performance liquid chromatographic method for the simultaneous determination of nalbuphine and its prodrug, sebacoyl dinalbuphine ester, in dog plasma and application to pharmacokinetic studies in dogs.

For the determination of nalbuphine and its long acting prodrug, sebacoyl dinalbuphine ester (SDN), in biological samples, a reversed-phase high-performance liquid chromatographic method using dual detectors was established. Ultraviolet and fluorescence detectors were connected in series for determining SDN and nalbuphine, respectively. The two analytes and internal standard were extracted from plasma by alkaline liquid-liquid extraction using n-hexane-isoamyl alcohol (9:1, v/v). The calibration curve for nalbuphine was linear over the range from 10 to 2,500 ng/ml, while the range was 25 to 2,500 ng/ml for SDN. The within- and between-day precision and accuracy were all within 10% for both nalbuphine and SDN over these concentrations. The method was applied successfully to a pharmacokinetic study of SDN administered at 20 mg/kg to two beagle dogs. Pharmacokinetic analysis revealed that SDN followed a linear one-compartment model with an elimination half-life of 74.7 min. Formation of nalbuphine after intravenous administration of SDN was observed in the first time point sample (5 min). These results indicate that SDN is rapidly metabolized to its active moiety, nalbuphine, in dogs and no other metabolites are detected in plasma.

Analgesics↗

The isolation and identification of leishmanial parasites from domestic dogs in the Machakos District of Kenya, and the possible role of dogs as reservoirs of kala-azar in East Africa.

Two out of 288 sick and emaciated dogs from homesteads in the Machakos District of Kenya, where human kala-azar cases existed, were found to be infected with leishmaniasis. The leishmanial strain isolated from one of the dogs was characterized enzymologically and serologically and found to be identical with strains isolated from human kala-azar cases and Phlebotomus martini. The significance of these findings is discussed in terms of the general epidemiology of visceral leishmaniasis in Kenya.

Animals↗

Pulmonary lymphatic mapping in dogs: use of technetium sulfur colloid and isosulfan blue for pulmonary sentinel lymph node mapping in dogs.

Lung cancer is the most frequent cause of cancer death in the United States. The pattern of regional lymph node involvement is a major prognostic factor in a patient with nonsmall cell lung cancer. The accuracy of information obtained about the lymph node status of lung cancer patients can be potentially increased by sentinel node lymphatic mapping. This technique has been well studied in melanoma and breast cancer. It may be useful in increasing the detection of micrometastases and in decreasing the morbidity from complete mediastinal lymphadenectomy. We report an animal pilot study of pulmonary lymphatic mapping. The aim of our study was to gain experience in the surgical techniques for pulmonary sentinel node lymphatic mapping in an animal model prior to its application in humans. Technetium sulfur colloid and isosulfan blue dye were injected into different lobes of the lung followed by attempts to identify the sentinel node draining that specific portion of the lung. Technetium sulfur colloid identified the sentinel node in five of six dogs within 20 min after the radiotracer was injected into the lung parenchyma. Isosulfan blue dye identified the sentinel node in three of six dogs within 5 min. Both the agents are potentially useful, but we found greater technical ease in identifying the sentinel node with technetium sulfur colloid. Two single-institution pilot studies in humans have been performed. A multicentered study to validate and further refine this technique is necessary. Advanced pathologic techniques such as immunohistochemistry and reverse transcriptase-polymerase chain reaction can be used to enhance the accuracy of staging. This may facilitate proper application of novel therapeutic strategies to improve the current dismal prognosis of this disease.

Animals↗

Effects of IV and ICV hypocretin-1 (orexin A) in hypocretin receptor-2 gene mutated narcoleptic dogs and IV hypocretin-1 replacement therapy in a hypocretin-ligand-deficient narcoleptic dog.

STUDY OBJECTIVES: Using two different canine models of narcolepsy, we evaluated the therapeutic effects of hypocretin-1 on cataplexy and sleep. MEASUREMENTS AND RESULTS: Intracerebroventricular administration of hypocretin-1 (10 and 30 nmol per dog) but not intravenous administration (up to 6 microg/kg) induced significant wakefulness in control dogs. However, hypocretin-1 had no effect on cataplexy or wakefulness in hypocretin receptor-2 gene (Hcrtr2) mutated narcoleptic Dobermans. Only very high intravenously doses of hypocretin-1 (96-384 microg/kg) penetrated the brain, to produce a short-lasting anticataplectic effect in a hypocretin-ligand-deficient animal. CONCLUSIONS: Hypocretin-1 administration, by central and systemic routes, does not improve narcoleptic symptoms in Hcrtr2 mutated Dobermans. Systemic hypocretin-1 hardly crosses the blood-brain barrier to produce therapeutic effects. The development of more centrally penetrable and longer lasting hypocretin analogs will be needed to further explore this therapeutic pathway in humans.

Animals↗

Tragic case of a dog bite in a young child: the dog stands trial.

The authors present the tragic case of an 18-month-old child who was bitten by a dog, causing amputation of the forearm and substantial damage to the cutaneous muscle on his back, shoulder, thorax, and neck. A free latissimus dorsi flap was performed to preserve the humerus from which the periosteum had been torn away. A series of cutaneous expansions were then undertaken to graft skin back onto the back, the armpit, and the shoulder stump, to allow for a mechanical prosthesis. A study of the literature on this subject proves that dog bites are more frequent and serious (sometimes even fatal) in young children than in adults. In view of the current legislation, it would seem that the public health authorities are doing little to resolve this distressing problem.

Amputation, Traumatic↗

Comparison of diatrizoate, iopamidol, and ioxaglate for arterial portography. An experimental study in normal dogs and dogs with portal hypertension.

Diatrizoate, iopamidol and ioxaglate were compared in five normal dogs and in five dogs with presinusoidal cirrhosis and portal hypertension for arterial portography. After selective injection of 40 ml of each contrast agent in iodine concentrations of 320 mg per ml into the superior mesenteric artery, portal vein blood samples were collected in 2-second intervals and the iodine concentrations determined using x-ray energy spectrometry. The highest iodine concentrations in the portal blood were found in both normal portal pressure and portal hypertension with ioxaglate, followed by iopamidol and diatrizoate in this order. Compared with diatrizoate, ioxaglate and iopamidol increased the peak portal blood iodine concentrations 45% and 22%, respectively. The use of ioxaglate in arterial portography should show the portal system at least as well as when a conventional contrast agent is used together with a vasodilator such as tolazoline.

Animals↗

The role of cyclic AMP and phosphodiesterase activity in the mechanism of action of tetramethylpyrazine on human and dog cardiac and dog coronary arterial tissues.

The aim of the present experiments was to explore the underlying cellular mechanisms responsible for the actions of tetramethylpyrazine (TMP) on atrial, ventricular and coronary arterial tissues. Transmembrane potentials of cardiac tissues were detected by means of the glass microelectrode technique and contractile tension by a force transducer. Tissue cyclic (c) AMP level was determined by protein binding assay. Results show that in human atrial and dog Purkinje fibres, high concentration of TMP (3 mM) induced a persistent positive inotropic effect only in the presence of adrenaline. Also, 3 mM TMP increased the cAMP level of the atrial muscle fibres, especially in the presence of adrenaline. Determination of the activity of cAMP-phosphodiesterase revealed that 0.3 and 3 mM TMP inhibited the phosphodiesterase activity of dog coronary artery and human atrial tissues in a concentration-dependent manner. When compared at the lower concentration (0.3 mM), the inhibitory effect of TMP was about 60% that of theophylline. The above findings indicate that the cardiovascular effects of TMP are related to the inhibition of phosphodiesterase activity and the subsequent elevation of the cAMP concentration.

3',5'-Cyclic-AMP Phosphodiesterases↗

Diffusion of metioprim, tetroxoprim and sulphadiazine in the cerebrospinal fluid of dogs with healthy meninges and dogs with experimental meningitis.

The diffusion of metioprim (MTP), tetroxoprim (TXP) and sulphadiazine (SDZ) in cerebrospinal fluid (CSF), following single intravenous doses and continuous infusions, was studied in dogs. The drugs penetrated well into the CSF of animals with and without experimental Staphylococcus aureus meningitis. In dogs with healthy meninges, the CSF bioavailability - expressed as the ratio of CSF/plasma area under the curve 0-5-hour values - following continuous infusion was determined to be 86.7% for MTP, 58.2% for TXP and 38.8% for SDZ. In infected animals, CSF availability following continuous infusion increases slightly to ratios of 96% (MTP), 70% (TXP) and 50% (SDZ). For all drugs, the concentrations reached in CSF were above the minimum inhibition concentrations for the majority of Enterobacteriaceae, indicating their potential value in treatment of gram-negative bacillary meningitis.

Animals↗

Papillary muscle shortening in the intact dog; a cinderadiographic study of tranquilized dogs in the upright position.

Shortening of the anterior papillary muscle of the left ventricle was demonstrated in six intact, tranquilized dogs. Two small metal markers that had been surgically implanted 3-50 months earlier were cineradiographically photographed during approximately ten sequential cardiac cycles in each of two orthogonal positions. Distances between markers were plotted for successive frames. The resulting curves were used to obtain maximum velocities of papillary muscle shortening and lengthening: 1.08 plus or minus 0.29 muscle lengths/sec and 1.39 plus or minus 0.48 muscle lengths/sec, respectively. From the two orthogonal planes, the average maximum spatial distance and the average minimum spatial distance between the markers were calculated. The mean percent shortening of 22.8 plus or minus 6.5% was surprisingly large: it approximated the distance from the foot to the peak of the ascending limb of the myocardial length-tension curve derived from isolated muscle studies. Mechanical studies on isolated papillary muscle have consistently shown reduced shortening with increasing loads. Since the in vivo dog papillary muscle has been reported to be under considerable tension during systole, there appears to be some contradiction between the degree of shortening found in the present study and the shortening observed in isolated papillary muscle studies.

Animals↗

Effects of an inotropic agent, RO 2-2985 (X-537A), on regional blood flow and myocardial function in chronically instrumented conscious dogs and anesthetized dogs.

RO 2-2985 produced a marked positive inotropic effect in unanesthetized, chronically instrumented dogs, measured as an increase in left ventricular dP/ dt and an increase in maximum velocity of myocardial fiber shortening. Similar changes produced in dogs in hemorrhagic shock lasted for 2-3 hours. RO 2-2985 increased peripheral blood flow and caused marked increases in both coronary and renal blood flows. The drug altered the response of the renal vascular bed to subsequent norepinephrine administration. After administration of a single dose of RO 2-2985, norepinephrine produced sustained increases in renal blood flow, and this altered responsiveness to norepinephrine persisted for periods ranging from 1 to 3 weeks.

Anesthesia↗

[Hypertension by nerve section in adrenalectomized, hypophysectomized, thyroidectomized and splanchnectomized dogs or in dogs with diabetes insipidus].

In the dog under anesthesia by pentobarbital, the acute hypertension by depressor buffer nerves section does not develop after adrenalectomy, hypophysectomy or thyroïdectomy. But this type of acute pressor response does appear normal in the dog parathyroïdectomized, splanchnicectomized or with hypothalamic diabetes insipidus.

Adrenalectomy↗