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1.
Hereditary methemoglobinemia associated with nicotinamide adenine dinucleotide-cytochrome b5 reductase (b5R) deficiency is a rare autosomal recessive disorder in animals. Recently, nonsynonymous b5R gene (CYB5R3) variants have been reported to be associated with canine and feline hereditary methemoglobinemia. However, the underlying molecular mechanisms of canine and feline methemoglobinemia caused by these nonsynonymous variants have not yet been reported. Previously, we reported a Pomeranian dog family with hereditary methemoglobinemia, carrying CYB5R3 mutation of an A>C transition at codon 194 in exon 7, replacing an isoleucine residue with leucine (p.Ile194Leu). In this study, we investigated the enzymatic and structural properties of the soluble form of wild-type and Ile194Leu canine b5Rs to characterize the effects of this missense mutation. Our results showed that the kinetic properties of the mutant enzyme were not affected by this amino acid substitution. The secondary structure of the wild-type and Ile194Leu b5Rs detected by circular dichroism showed a similar pattern. However, the mutant enzyme exhibited decreased heat stability and increased susceptibility to trypsin hydrolysis. Moreover, the thermostability and unfolding measurements indicated that the mutant enzyme was more sensitive to temperature-dependent denaturation than the wild-type b5R. We concluded from these results that unstable mutant enzyme properties with normal enzymatic activity would be associated with hereditary methemoglobinemia in the Pomeranian dog family.  相似文献   

2.
Little is known about genetic causes of congenital methemoglobinemia in dogs. Here, we report a CYB5R3 mutation in a Pomeranian dog with congenital methemoglobinemia. A 6‐year‐old neutered female Pomeranian dog was investigated for cyanosis noticed during anesthesia for an orthopedic procedure. The history included lifelong mild exercise intolerance and bluish tongue. Methemoglobinemia was diagnosed using co‐oximetry. The CYB5R3 gene was analyzed by comparing the patient's genomic DNA with the reference canine sequence. Mutation functional significance was investigated using snpEff and multispecies protein homology analyses. A homozygous missense single nucleotide CYB5R3 mutation (ATC ? CTC at codon 194) caused a p.Ile194Leu substitution. The pIle194 residue is highly conserved in other mammals, supporting the likely pathogenicity of the substitution. The mutation described here is identical to that associated with familial methemoglobinemia in a family of Japanese Pomeranian dogs. This observation, together with the homozygous mutation found in our case, indicates that the mutant allele may be widespread within the Pomeranian breed internationally.  相似文献   

3.
Two non‐pedigreed male castrated cats had persistent cyanosis over a 3‐year observation period. Clinical cardiopulmonary evaluations did not reveal abnormalities, but the blood remained dark after exposure to air. Erythrocytic methemoglobin concentrations were high (~40% of hemoglobin) and cytochrome b5 reductase (CYB5R) activities in erythrocytes were low (≤15% of control). One cat remained intolerant of exertion, and the other cat developed anemia and died due to an unidentified comorbidity. Whole‐genome sequencing revealed a homozygous c.625G>A missense variant (B4:137967506) and a c.232‐1G>C splice acceptor variant (B4:137970815) in CYB5R3, respectively, which were absent in 193 unaffected additional cats. The p.Gly209Ser missense variant likely disrupts a nicotinamide adenine dinucleotide (NADH)‐binding domain, while the splicing error occurs at the acceptor site for exon 4, which likely affects downstream translation of the protein. The 2 novel CYB5R3 variants were associated with methemoglobinemia using clinical, biochemical, genomics, and in silico protein studies. The variant prevalence is unknown in the cat population.  相似文献   

4.
A juvenile male mixed breed dog was presented for lethargy, exercise intolerance, and aggression when touched on the head. Cyanosis, tachycardia, and tachypnea were observed and persisted during oxygen supplementation. Arterial blood gas analysis by co‐oximetry identified an increased methemoglobin concentration (27%; normal, <2%) with normal arterial oxygen tension. The methemoglobinemia and associated clinical signs resolved after administration of methylene blue (1 mg/kg) IV, and the dog was discharged. The affected dog's whole‐genome sequence contained 2 potentially causal heterozygous CYB5R3 missense mutations suggesting that cytochrome b5 reductase deficiency was responsible for the methemoglobinemia. This hypothesis was confirmed by enzyme analysis that identified cytochrome b5 reductase activity in the affected dog's erythrocytes to only approximately 6% of that in a control sample. Clinical signs recurred 11 days after discharge but normalized and the methemoglobin concentration decreased with methylene blue administration PO (1.5 mg/kg, initially daily and then every other day).  相似文献   

5.
Canine sulfonamide hypersensitivity (HS) has been associated with a variant in the cytochrome b5 reductase gene (CYB5R3 729A>G), which encodes a drug‐detoxifying enzyme. Study objectives were to determine variant allele frequency in Doberman Pinschers (DOBE), a breed which may be predisposed to sulfonamide HS, and to characterize the effects of CYB5R3 729G on gene expression and function. CYB5R3 729A>G allele frequencies were compared between DOBE (n = 24) vs. non‐Doberman (non‐DOBE; n = 60) dogs. CYB5R3mRNA expression, protein expression, and reduction of sulfamethoxazole hydroxylamine were compared between banked canine liver samples of 729AA vs. GG genotype. The 729G allele was overrepresented in DOBE (1.00) vs. non‐DOBE dogs (0.567, p < .0001). mRNA and protein expressions as well as cyt b5 reductase activity were similar between livers of AA and GG genotype. All Doberman Pinschers in this study were homozygous for CYB5R3 729G, which could contribute to this breed's apparent predisposition to sulfonamide HS. However, CYB5R3 729G does not alter sulfamethoxazole detoxification capacity, so a direct role could not be demonstrated. It is possible that this marker is linked to another contributing variant.  相似文献   

6.

Objectives

Glutathione‐S‐transferases (GSTs) detoxify reactive xenobiotics, and defective GST gene polymorphisms increase cancer risk in humans. A low activity GST‐theta variant was previously found in research beagles. The purpose of our study was to determine the molecular basis for this phenotype and its allele frequency in pet dogs.

Methods

Banked livers from 45 dogs of various breeds were screened for low GST‐theta activity by the substrate 1,2‐dichloro‐4‐nitrobenzene (DCNB), and were genotyped for variants in a novel canine GST gene, GSTT5. Whole‐genome sequences from 266 dogs were genotyped at one discovered variant GSTT5 locus.

Results

Canine livers ranged 190‐fold in GST‐theta activities, and a GSTT5 exon coding variant 385_390delGACCAG (Asp129_Gln130del) was significantly associated with low activity (P < 0.0001) and a marked decrease in hepatic protein expression (P = 0.0026). Recombinant expression of variant GSTT5 led to a 92% decrease in Vmax for DCNB (P = 0.0095). The minor allele frequency (MAF) for 385_390delGACCAG was 0.144 in 45 dog livers, but was significantly higher in beagles (0.444) versus nonbeagles (0.007; P = 0.0004). The homozygous genotype was significantly over‐represented in Pembroke Welsh corgis (P < 0.0001) based on available whole‐genome sequence data.

Conclusions

An Asp129_Gln130del variant in canine GSTT5 is responsible for marked loss of GST‐theta enzyme activity. This variant is significantly over‐represented in purpose‐bred laboratory beagles and in Pembroke Welsh corgis. Additional work will determine the prevalence of this variant among other purebred dogs, and will establish the substrate range of this polymorphic canine enzyme with respect to common environmental carcinogens.  相似文献   

7.
Methemoglobinemia developed in three dogs after the owners' use of benzocaine-containing products for topical treatment of the dogs' pruritic skin conditions. The products were intended for use in man. In two of the dogs, clinical signs of shock were observed within a few hours after the application of a skin lotion containing 5% benzocaine. Methemoglobin was assayed in one case and found to be 51% of total hemoglobin. Both dogs recovered after whole blood transfusions were given. The third dog, which had been treated for several weeks with small amounts of an anesthetic aerosol containing 20% benzocaine, was anorectic and lethargic when examined. Methemoglobin content was 30%, and Heinz bodies were observed in 20% of the erythrocytes. The methemoglobin content and proportion of Heinz bodies decreased rapidly after use of the spray was discontinued. The two benzocaine-containing products incriminated in development of the methemoglobinemia did not induce measurable increases in methemoglobin content in clinically normal dogs, when applied to unbroken skin. Small increases in methemoglobin content were measured, however, when these products were given orally to clinically normal dogs. It was concluded that the skin lesions in the three clinically affected dogs enhanced absorption of the drug, resulting in methemoglobin formation.  相似文献   

8.

Objective

Variants in the MC1R gene have been associated with red hair color and sensitivity to pain in humans. The study objective was to determine if a relationship exists between MC1R genotype and physiological thermal or mechanical nociceptive thresholds in Labrador Retriever dogs.

Study design

Prospective experimental study.

Animals

Thirty-four Labrador Retriever dogs were included in the study following public requests for volunteers. Owner consent was obtained and owners verified that their dog was apparently not experiencing pain and had not been treated for pain during the previous 14 days. The study was approved by the Institutional Animal Care and Use Committee.

Methods

Nociceptive thresholds were determined from a mean of three thermal and five mechanical replications using commercially available algometers. Each dog was genotyped for the previously described MC1R variant (R306ter). Data were analyzed using one-way anova with post hoc comparisons using Tukey’s test (p < 0.05).

Results

Thirteen dogs were homozygous wild-type (WT/WT), nine were heterozygous (WT/R306ter), and eight were homozygous variant (R306ter/R306ter) genotype. Four dogs could not be genotyped. A significant difference (p = 0.04) in mechanical nociceptive thresholds was identified between dogs with the WT/WT genotype (12.1 ± 2.1 N) and those with the WT/R306ter genotype (9.2 ± 2.4 N).

Conclusion

A difference in mechanical, but not thermal, nociceptive threshold was observed between wild-type and heterozygous MC1R variants. Differences in nociceptive thresholds between homozygous R306ter variants and other genotypes for MC1R were not observed.

Clinical relevance

Compared with the wild-type MC1R genotype, nociceptive sensitivity to mechanical force in dogs with a single variant R306ter allele may be greater. However, in contrast to the reported association between homozygous MC1R variants (associated with red hair color) and nociception in humans, we found no evidence of a similar relationship in dogs with the homozygous variant genotype.  相似文献   

9.
Background – The melanocortin 1 receptor (MC1R) gene plays a key role in determining coat colour in mammals by controlling the proportion of eumelanin and pheomelanin granules. Wild raccoon dogs have a mixed coat colour, with black to brown and grey hairs. Hypothesis/Objectives – The study was performed to identify the cause of the variant yellow coat colour in a wild raccoon dog. Animals – A wild raccoon dog that showed coat colour change to yellow and four wild‐type raccoon dogs that showed normal coat colour were included. Methods – To identify the cause of the variant yellow coat colour, we examined the sequence of the MC1R gene and its expression at the mRNA and protein levels. Results – The coding region of the MC1R gene of this raccoon dog comprised 954 bp, the same as for wild‐type raccoon dogs and domestic dogs. By comparing the gene with that in the wild‐type raccoon dog, a 2 bp deletion was detected in the 5′‐untranslated region, positioned 152 bp upstream of the start codon. However, there was no significant difference in the mRNA expression level. The yellow raccoon dog revealed a significantly decreased MC1R protein level compared with the wild‐type raccoon dogs, indicating an increase in pheomelanin synthesis. Conclusions and clinical importance – These results suggest that the variant coat colour in the yellow raccoon dog was associated with decreased MC1R function.  相似文献   

10.

Objectives

To describe an ultrasound-guided thoracic paravertebral block and determine the distribution after injection of two volumes of methylene blue in dog cadavers.

Study design

Prospective experimental cadaveric study.

Animals

Twelve dog cadavers weighing 11 ± 3 kg.

Methods

Ultrasound-guided injections aimed at the fifth thoracic (T5) paravertebral space were performed in randomized order using 0.1 or 0.3 mL kg–1 dye solution (six dogs for each volume). Anatomic dissections determined dye spread characteristics, including the presence and degree of staining of spinal nerves, and the presence of intercostal and sympathetic trunk spread. Staining of mediastinum, epidural, intrapleural and contralateral thoracic paravertebral space was recorded.

Results

There was no significant difference in dye distribution between groups. The use of anatomic landmarks resulted in the inaccurate identification of the T5 paravertebral space. The T4, T5 and T6 paravertebral spaces were injected in four, five and three of 12 dogs, respectively. Complete staining of the spinal nerve of the thoracic paravertebral space injected was observed in 11 of 12 dogs, and partial staining in one dog in the low-volume group. Multisegmental distribution was demonstrated with staining of contiguous spinal nerves in one dog in the high-volume group, and multiple segments of intercostal (three dogs) and sympathetic trunk (four dogs) spread in both groups. No mediastinal, epidural, intrapleural or contralateral thoracic paravertebral space staining was observed.

Conclusions and clinical relevance

Ultrasound-guided injection at the thoracic paravertebral space resulted in staining of the spinal nerve in all dogs. However, T5 paravertebral space was not accurately identified using anatomic landmarks. Dye distribution was not significantly different between the two groups; therefore, the use of the lower-volume and multiple-site injections would be potentially necessary in clinical cases to achieve ipsilateral blockade of the thoracic wall.  相似文献   

11.

Background

Bacteria belonging to the family Chlamydiaceae cause a broad spectrum of diseases in a wide range of hosts, including man, other mammals, and birds. Upper respiratory and genital diseases are common clinical problems caused by Chlamydiaceae. Very little is known about chlamydial infections in dogs. Few clinical reports on natural disease in dogs describe mainly conjunctival and upper respiratory signs, and the role of Chlamydiaceae in genital disease is unclear. The present study aimed at studying the prevalence of Chlamydiaceae in healthy dogs and in dogs with genital or upper respiratory disease, including conjunctivitis.

Methods

A real-time polymerase chain reaction (PCR) for Chlamydiaceae was used to detect any chlamydial species within this family. Swab samples from the conjunctiva and the mucosal membranes of the oropharynx, rectum and genital tract were taken from 79 dogs: 27 clinically healthy dogs, 25 dogs with clinical signs from the genital tract and 28 dogs with conjunctivitis. There were 52 female and 27 male dogs. From 7 of the male dogs, additional semen samples were analysed.

Results

No Chlamydiaceae were detected from any dog.

Conclusions

Although the number of dogs that was included is limited, the results suggest that cases of Chlamydiaceae in dogs probably are related to infection from other species, and that dogs in general do not harbour Chlamydiaceae. Bacteria belonging to the family Chlamydiaceae do not seem to be of major importance for genital or ocular disease in Swedish dogs.  相似文献   

12.
  相似文献   

13.

Background

Cholangitis in dogs appears to be more common than previously thought, but understanding of the disease remains incomplete.

Objective

To describe a population of dogs with cholangitis or cholangiohepatitis.

Animals

Fifty‐four client‐owned dogs with cholangitis or cholangiohepatitis.

Methods

Medical records of dogs with cholangitis or cholangiohepatitis confirmed by histopathology between January 2004 and December 2014 were identified using a computer‐based search and retrospectively reviewed.

Results

Clinical signs included vomiting (72.2%), lethargy (70.4%), and inappetence (64.8%). Most dogs (49/50) had increased liver enzyme activities, hyperbilirubinemia (32/50), and hypercholesterolemia (24/43). Ultrasonographic abnormalities of the hepatobiliary system were seen in 84% of cases. On histopathology, 53 of 54 affected dogs had neutrophilic cholangitis (NC) or cholangiohepatitis, whereas 1 dog had lymphocytic cholangitis. Most cases (42/54) were chronic. Evidence of concurrent biliary disease (46.2%) and biliary tract obstruction (42.6%) was common. Seventeen of 36 biliary and 11 of 25 liver cultures were positive for bacterial growth; Escherichia coli and Enterococcus spp. were most common. Median patient survival was 671 days (95% confidence interval [CI]: 114–1,426). On Cox regression, dogs that did not have a cholecystectomy performed had a 2.1 greater hazard for death (P = 0.037; 95% CI: 1.0–4.3) compared to cholecystectomized dogs. Dogs >13 years old had a 5.0 greater hazard for death (P = 0.001; 95% CI: 1.9–13.2) compared to younger dogs.

Conclusions and Clinical Significance

Chronic NC or cholangiohepatitis was most common. Cholecystitis and biliary tract obstruction often occurred in conjunction with cholangitis. Cholecystectomized dogs had decreased risk of death; thus, cholecystectomy may improve patient outcome.  相似文献   

14.

Objective

Mitral valve (MV) regurgitation due to degenerative MV disease is the leading cause of cardiac death in dogs. We carried out preliminary experiments to determine the feasibility and short-term effects of beating-heart MV repair using an expanded polytetrafluorethylene (ePTFE) chordal implantation device (Harpoon TSD-5) in dogs.

Animals

This study involved six healthy purpose-bred Beagles (weight range 8.9–11.4 kg).

Material and methods

Following a mini-thoracotomy performed under general anesthesia, the TSD-5 was used to place 1 or 2 artificial ePTFE cords on the anterior MV leaflet or the posterior MV leaflet via a left-ventricular transapical approach. The procedure was guided and monitored by transesophageal echocardiography. Postoperative antithrombotic treatment consisted of clopidogrel or a combination of clopidogrel and apixaban. Dogs were serially evaluated by transthoracic echocardiography at day 1, 7, 14, 21, and 30. The hearts were then examined for evaluation of tissues reactions and to detect signs of endothelialization.

Results

One or two chords were successfully implanted in five dogs. Four dogs completed the 30 days follow-up. One dog died intra-operatively because of aortic perforation. One dog died early post-operatively from a hemorrhagic pleural effusion attributed to overly aggressive antithrombotic treatment. One dog developed a thrombus surrounding both the knot and the synthetic cord. Postmortem exam confirmed secure placement of ePTFE knots in the mitral leaflets in all dogs and the presence of endothelialization of the knots and chords.

Conclusions

These preliminary results demonstrate the feasibility of artificial chordal placement using an ePTFE cordal implantation device in dogs.  相似文献   

15.
Deficiencies of enzymes involved in erythrocyte metabolism can have significant effects on erythrocyte function and survival. Animals with pyruvate kinase (PK) or phosphofructokinase (PFK) deficiencies have shortened erythrocyte life spans and regenerative anemia. PK-deficient dogs (but not PK-deficient cats) develop progressive myelofibrosis and osteosclerosis of bone marrow and hemochromatosis and cirrhosis of the liver. PFK-deficient dogs have sporadic episodes of hyperventilation-induced intravascular hemolysis and hemoglobinuria. Cytochrome b5 reductase (Cb5R) deficiency in dogs and cats results in persistent methemoglobinemia and cyanotic mucous membranes. Severe deficiency of glucose-6-phosphate dehydrogenase, the rate-controlling enzyme in the pentose phosphate pathway, resulted in anemia with eccentrocytosis in an American saddlebred colt. Horses with erythrocyte flavin adenine dinucleotide (FAD) deficiency have both eccentrocytosis (attributable to severe deficiency in glutathione reductase activity) and methemoglobinemia (attributable to Cb5R deficiency); the dual enzyme deficiency occurs because FAD is a required cofactor for both enzymes. Erythrocyte enzyme deficiencies do not usually shorten life expectancy, except for PK-deficient dogs and potentially PFK-deficient dogs during a hemolytic crisis. Although enzyme deficiencies are rare causes of anemia and methemoglobinemia, the ability to diagnose deficient animals allows for the possibility of eliminating these undesirable traits in future breeding. DNA-based assays are available for PK and PFK deficiencies; whereas, biochemical tests of enzyme activity are required for other deficiencies. Continued research is needed to document additional enzyme deficiencies that likely occur and to develop additional DNA-based assays to detect heterozygous animals.  相似文献   

16.

Background

Bacterin‐based canine Leptospira vaccines could present a challenge for the use of whole blood real‐time polymerase chain reaction (PCR) as a diagnostic tool. Recent vaccination could induce positive results if the targeted DNA fragment is present within the vaccine and in the blood of the recently vaccinated dog.

Objectives

The objective of this study was to assess whether 2 available 4‐serovar vaccines induce a positive real‐time PCR reaction in the blood of healthy recently vaccinated dogs.

Animals

Twenty healthy dogs.

Methods

This was a prospective study. Dogs were assigned to 1 of 2 vaccine groups. Both vaccines were culture‐based and include Leptospira interrogans serovars Pomona, Canicola, and Icterohaemorrhagiae and Leptospira kirschneri serovar Grippotyphosa. Whole blood for real‐time PCR and serum for the microscopic agglutination test (MAT) were collected prior to and 3 and 7 days after vaccination and weekly thereafter for 8 weeks. Two real‐time PCR tests targeting 2 different genes were performed independently in a blinded fashion.

Results

Both Leptospira vaccines produced positive real‐time PCR reactions when assayed undiluted or diluted 1 : 100 in canine blood. However, blood samples drawn from all dogs at all time points after vaccination were negative on PCR. All dogs developed MAT titers.

Conclusions and Clinical Importance

Recent vaccination with 2 commercially available vaccines does not interfere with the use of real‐time PCR for the identification of acute Leptospira infection in dogs.  相似文献   

17.

Background

Oral levothyroxine (l‐T4) supplementation is commonly used to treat hypothyroid dogs.

Objectives

Investigate the plasma profile and pharmacokinetics of total thyroxine (tT4) after PO administration of a l‐T4 solution and its clinical efficacy in hypothyroid dogs.

Animals

Ten dogs with naturally occurring hypothyroidism.

Methods

After hypothyroidism diagnosis and supplementation with l‐T4 solution PO q24h at 20 μg/kg BW for minimum 4 weeks, the plasma profile and pharmacokinetics of tT4 were determined over 34 hours and the clinical condition of the dogs was evaluated.

Results

Before dosing for pharmacokinetic evaluation, mean tT4 concentration was 23 ± 9 nmol/L. l‐T4 was absorbed rapidly (t max, 5 hours), reaching a mean maximal tT4 concentration of 56 ± 11 nmol/L. The apparent terminal half‐life was 11.8 hours. Clinical signs of hypothyroidism improved or resolved in all dogs after 4 weeks of treatment. The dosage of 20 μg/kg PO q24h was judged appropriate in 5 dogs, and 4 dogs required slight increases (9–16%). Twice daily treatment, with a 30% increase in dosage, was necessary for 1 dog.

Conclusions and Clinical Importance

The pharmacokinetics of l‐T4 in hypothyroid dogs was similar to that reported in healthy euthyroid dogs. Clinical and hormonal responses to l‐T4 solution were rapid in all dogs. The starting dosage of 20 μg/kg PO q24h was suitable for maintenance supplementation in 50% of the dogs, minor dosage modification was required in 4 other dogs, and treatment q12h was required in 1 dog.  相似文献   

18.

Background

Diagnosing canine immune-mediated haemolytic anaemia (IMHA) is often challenging because all currently available tests have their limitations. Dogs with IMHA often have an increased erythrocyte osmotic fragility (OF), a characteristic that is sometimes used in the diagnosis of IMHA. Since the classic osmotic fragility test (COFT) is time-consuming and requires specialized equipment, an easy and less labour-intensive rapid osmotic fragility test (ROFT) has been used in some countries, but its diagnostic value has not yet been investigated.This study aimed to evaluate erythrocyte osmotic fragility in dogs with and without IMHA, to compare results of the classic (COFT) and rapid (ROFT) test and to assess the value of the ROFT as diagnostic test for canine IMHA.Nineteen dogs with IMHA (group 1a), 21 anaemic dogs without IMHA (group 1b), 8 dogs with microcytosis (group 2), 13 hyperlipemic dogs (group 3), 10 dogs with lymphoma (group 4), 8 dogs with an infection (group 5) and 13 healthy dogs (group 6) were included.In all dogs, blood smear examination, in-saline auto-agglutination test, Coombs’ test, COFT and ROFT were performed. In the COFT, OF5, OF50 and OF90 were defined as the NaCl concentrations at which respectively 5, 50 and 90% of erythrocytes were haemolysed.

Results

Compared with healthy dogs, OF5 and OF50 were significantly higher in group 1a (P < 0.001) and OF5 was significantly higher in group 3 (P = 0.0266). The ROFT was positive in 17 dogs with IMHA, 10 hyperlipemic dogs, one anaemic dog without IMHA and one healthy dog.

Conclusions

Osmotic fragility was increased in the majority of dogs with IMHA and in dogs with hyperlipidemia, but not in dogs with microcytosis, lymphoma or an infection. Although more detailed information was obtained about the osmotic fragility by using the COFT, the COFT and ROFT gave similar results. The ROFT does not require specialized equipment, is rapid and easy to perform and can be used easily in daily practice. Although, the ROFT cannot replace other diagnostic tests, it may be a valuable additional tool to diagnose canine IMHA.  相似文献   

19.

Background

Immune system involvement is suggested as an underlying cause for Doberman hepatitis (DH) based on female predisposition, lymphocyte infiltration, abnormal hepatocyte expression of major histocompatibility complex class II antigens, and homozygosity for dog leukocyte antigen DRB1*00601.

Objective

To measure serum antinuclear antibodies (ANA) and serum antihistone antibodies (AHA) in Dobermans with hepatitis. To determine whether increased serum ANA or serum AHA could be used to support the diagnosis of Doberman hepatitis (DH).

Animals

Privately owned 25 subclinically and 13 clinically affected DH Dobermans and 17 healthy control Dobermans.

Methods

Case–control study. Indirect immunofluorescence (IIF) microscopy and line blot tests were employed for the ANA pilot studies and an enzyme‐linked immunosorbent assay (ELISA) assay for detection of IgG AHA.

Results

Indirect immunofluorescence revealed ANA‐positive cases, and line blot showed AHA reactivity. In ELISA, importantly increased concentrations of AHA were found in 92% (23/25) of dogs in the subclinical stage and 84.6% (11 of 13) of dogs in the clinical stage of DH compared with no control dogs (0/17) (P < 0.0005). The mean AHA absorbance values of the blood samples obtained from the 25 subclinical DH dogs (1.36 ± 0.60, mean ± SD) and the 13 clinically affected dogs (1.46 ± 0.49) were significantly higher than in 17 control dogs (0.51 ± 0.18; P < 0.0001).

Conclusions and Clinical Importance

As the presence of AHA indicates autoimmune activity, our results favor an autoimmune background as one cause for DH. Antihistone antibody could represent a novel means for screening Dobermans with increased serum alanine transaminase concentrations and suspicion of DH.  相似文献   

20.

Background

Gastroesophageal reflux (GER) is common in anesthetized dogs and can cause esophagitis, esophageal stricture, and aspiration pneumonia.

Objective

To determine whether preanesthetic IV administration of esomeprazole alone or esomeprazole and cisapride increases esophageal pH and decreases the frequency of GER in anesthetized dogs using combined multichannel impedance and pH monitoring.

Animals

Sixty‐one healthy dogs undergoing elective orthopedic surgery procedures.

Methods

Prospective, randomized, placebo‐controlled study. Dogs were randomized to receive IV saline (0.9% NaCl), esomeprazole (1 mg/kg) alone, or a combination of esomeprazole (1 mg/kg) and cisapride (1 mg/kg) 12–18 hours and 1–1.5 hours before anesthetic induction. An esophageal pH/impedance probe was utilized to measure esophageal pH and detect GER.

Results

Eight of 21 dogs in the placebo group (38.1%), 8 of 22 dogs in the esomeprazole group (36%), and 2 of 18 dogs in the combined esomeprazole and cisapride group (11%) had ≥1 episode of GER on impedance testing during anesthesia (P < .05). Esomeprazole was associated with a significant increase in gastric and esophageal pH (P = .001), but the drug did not significantly decrease the frequency of GER (P = .955). Concurrent administration of cisapride was associated with a significant decrease in the number of reflux events (RE) compared to the placebo and esomeprazole groups (P < .05).

Conclusions and Clinical Relevance

Preanesthetic administration of cisapride and esomeprazole decreases the number of RE in anesthetized dogs, but administration of esomeprazole alone was associated with nonacid and weakly acidic reflux in all but 1 dog.  相似文献   

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