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61.

Background

In veterinary medicine, congenital methemoglobinemia associated with nicotinamide adenine dinucleotide (NADH)‐cytochrome b5 reductase (b5R) deficiency is rare. It has been reported in several breeds of dogs, but little information is available about its etiology.

Objectives

To analyze the NADH‐cytochrome b5 reductase gene, CYB5R3, in a Pomeranian dog family with methemoglobinemia suspected to be caused by congenital b5R deficiency.

Animals

Three Pomeranian dogs from a family with methemoglobinemia were analyzed. Five healthy beagles and 5 nonrelated Pomeranian dogs without methemoglobinemia were used as controls.

Methods

Methemoglobin concentration, b5R activity, and reduced glutathione (GSH) concentration were measured, and a turbidity index was used to evaluate Heinz body formation. The CYB5R3 genes of the affected dog and healthy dogs were analyzed by direct sequencing.

Results

Methemoglobin concentrations in erythrocytes of the affected dogs were remarkably higher than those of the control dogs. The b5R activity of the affected dogs was notably lower than that of the control dogs. DNA sequencing indicated that this Pomeranian family carried a CYB5R3 gene missense variant (ATC→CTC at codon 194) that resulted in the replacement of isoleucine (Ile) by leucine (Leu).

Conclusions and Clinical Importance

This dog family had familial congenital methemoglobinemia caused by b5R deficiency, which resulted from a nonsynonymous variant in the CYB5R3 gene. This variation (c.580A>C) led to an amino acid substitution (p.Ile194Leu), and Ile194 was located in the proximal region of the NADH‐binding motif. Our data suggested that this variant in the canine CYB5R3 gene would affect function of the b5R in erythrocytes.  相似文献   
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Objectives

To develop a provisional immunohistochemistry panel for distinguishing reactive pericardium, atypical mesothelial proliferation and mesothelioma in dogs.

Materials and Methods

Archived pericardial biopsies were subject to haematoxylin and eosin staining, immunohistochemistry for cytokeratin, vimentin, insulin‐like growth factor II mRNA‐binding protein 3, glucose transporter 1 and desmin. Samples were scored for intensity and number of cells stained.

Results

Ten biopsies of reactive mesothelium, 17 of atypical mesothelial proliferation, 26 of mesothelioma and five of normal pericardium were identified on the basis of haematoxylin and eosin staining. Cytokeratin and vimentin were expressed in all biopsies, confirming mesothelial origin. Normal pericardial samples had the lowest scores for insulin‐like growth factor II mRNA‐binding protein 3, glucose transporter 1 and desmin. Mesothelioma and atypical proliferative samples were similar to each other, with higher scores for insulin‐like growth factor II mRNA‐binding protein 3 and glucose transporter 1 than the reactive samples. Desmin staining was variable. Insulin‐like growth factor II mRNA‐binding protein 3 was the best to distinguish between disease groups.

Clinical Significance

An immunohistochemistry panel of cytokeratin, vimentin, insulin‐like growth factor II mRNA‐binding protein 3 and glucose transporter 1 could provide superior information compared with haematoxylin and eosin staining alone in the diagnosis of cases of mesothelial proliferation in canine pericardium, but further validation is warranted.  相似文献   
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The aim of this study was to assess the influence of growth on the pharmacokinetics of sodium salicylate (SS) in male turkeys. SS was administered intravenously at a dose of 50 mg/kg. Plasma drug concentrations were assessed by high‐performance liquid chromatography, and pharmacokinetic parameters were calculated by noncompartmental analysis. As the age increased from 6 to 13 weeks (body weight increase from 2.35 to 9.43 kg), median body clearance decreased from 1.34 to 0.87 ml/min/kg. This caused a significant increase in the median mean residence time from 3.42 to 4.44 hr. Elimination phase proved to be biphasic and two elimination half‐lives (T1/2el) were distinguished. Whereas T1/2el1 was found to increase with age by 128%, T1/2el2 represented a later but faster and less age‐dependent phase of elimination (increase by 56% in the respective groups). Volume of distribution decreased with age. These effects may lead to different therapeutic response to SS in turkeys of different age and body weights.  相似文献   
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Peste des petits ruminants virus (PPRV) causes highly contagious diseases in domestic and particular wild small ruminants, leading to substantial economic loss. The development of effective and cheap antiviral medications shall help to circumvent this emerging burden. In this study, we found that ribavirin, a competitive inosine-5’-monophosphate dehydrogenase (IMPDH) inhibitor, significantly inhibits the replication of PPRV. As IMPDH is a key enzyme in purine nucleotide synthesis, supplementation of exogenous guanosine attenuate the anti-PPRV effect of ribavirin. Interestingly, an uncompetitive IMPDH inhibitor, mycophenolic acid (MPA), exerted more potent antiviral effect again PPRV. Similarly, this effect was largely restored upon supplementation of guanosine. Thus, we have demonstrated that the IMPDH inhibitors ribavirin and MPA combat PPRV infection through purine nucleotide depletion. Because both regimens have been widely used in the clinic for treating viral infection or organ rejection in transplantation patients for decades, respectively, repurposing these existing safe and cheap medications may provide a new avenue for combating PPRV infection.  相似文献   
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