A pig–human comparative RH map comprising 20 genes on pig chromosome 13q41 that harbours the ETEC F4ac receptor locus

The enterotoxigenic Escherichia coli (ETEC) F4ac is a major cause of diarrhoea in newborn and young pigs. The locus for the intestinal ETEC F4ac receptor (F4acR) has been mapped to pig chromosome (SSC) 13q41 with known homology to human chromosome (HSA) 3q21 and q29. However, the causative gene and mutation(s) remain unknown. The aim of this study was to characterize gene-derived markers on SSC13q41 for fine mapping of the F4acR locus, and construct a high-resolution pig–human comparative map to select positional candidate genes for F4acR. Pig-specific sequence-tagged site markers were developed for 20 genes that are located in a 6.8-Mb region on HSA3q21 and q29, and a total of 34 single-nucleotide polymorphisms (SNPs) were identified in 14 of 20 markers developed. Eighteen markers were mapped to SSC13q41, while the other two markers ( PLXNA1 and KLF15 ) were assigned to SSC13q32 and SSC7q13, respectively, by radiation hybrid mapping. This result showed that there was a small conserved segment on SSC7 corresponding to HSA3q21. A framework map comprising 18 markers on SSC13q41 was established, refining the synteny breakpoint on SSC13q41 to a region of 12.3 centiRay. The comparative radiation hybrid (RH) map revealed three interesting candidate genes for F4acR from the human genome, viz. MUC4 , MUC13 and MUC20 . Linkage analysis with six marker polymorphisms revealed that MUC4 had the most significant linkage with the F4acR locus.     

Two cases of reciprocal chromosomal translocation (4; 7)(p+; q-) (2; 8)(q-; q+) in piglets produced by ICSI

In this study, the karyotypes of 14 piglets from four different litters produced by intracytoplasmic sperm injection (ICSI) and embryo transfer were analysed. The chromosome analysis was based on a classical cytogenetic examination following the standard protocols of lymphocyte cultures. Two cases of reciprocal translocation [(4; 7)(p+; q-) and (2; 8)(q-; q+)] were detected in two female transgenic piglets. These animals showed neither anatomical nor physiological alterations and had normal growth. To our knowledge, this is the first karyotype study of piglets produced by ICSI.     

Purification and characterization of the 1q subcomponent of canine complement and its use in the 125I-C1q binding assay for detection of immune complexes

The complement subcomponent, C1q, was isolated from serum obtained from clinically normal dogs, using a rapid 2-step process involving affinity chromatography. Yield of C1q ranged from 8 to 10 mg/L of serum. Hemolytically active C1q had 3 protein bands after sodium dodecyl sulfate polyacrylamide gel electrophoresis under reducing conditions and formed a single line of identity with rabbit anti-canine C1q. The amino acid composition of canine C1q was similar to that of human C1q and contained a high percentage of glycine. Isolated canine C1q was iodinated, and the fluid-phase binding assay was used to detect circulating immune complexes in dogs with systemic lupus erythematosus and rheumatoid arthritis.     

A de novo reciprocal chromosomal translocation t(3;6)(p14;q26) in the black Lucano pig

In the past two decades, several cytogenetic screening programmes identified different chromosome rearrangements in pig, most of which represented by reciprocal translocation (rcp). This chromosome abnormality does not involve the variation in the number of chromosomes, but only the rearrangement of genetic material, resulting in phenotypically normal carriers with fertility problems. During an occasional cytogenetic screening, a new reciprocal translocation was detected in the black Lucano pig native breed. We analysed 15 animals reared by a family-run piggery in Basilicata region (Southern Italy). After karyotyping, four pigs (two boars and two sows) revealed two unpaired chromosomes. Analysis of the RBA karyotype and the dual-colour FISH technique confirmed that these pigs showed the same reciprocal translocation involving the chromosomes SSC3 and SSC6. The precise location of breakpoints was identified by RBH-FISH t(3;6)(p14;q26), whereas the analysis of the pedigree showed a case of Mendelian inheritance within a family, after the de novo occurrence of the new rcp. Considering the consequences of the rcp on the fertility, this study points out the importance of the cytogenetic screening in the native breeds for the safeguard of the genetic biodiversity and the sustainability of the rural areas.     

A Non‐Reciprocal Autosomal Translocation 64,XX,t(4;10)(q21;p15) in an Arabian Mare with Repeated Early Embryonic Loss

Balanced autosomal translocations are a known cause for repeated early embryonic loss (REEL) in horses. In most cases, carriers of such translocations are phenotypically normal, but the chromosomal aberration negatively affects gametogenesis giving rise to both genetically balanced and unbalanced gametes. The latter, if involved in fertilization, result in REEL, whereas gametes with the balanced form of translocation will pass the defect into next generation. Therefore, in order to reduce the incidence of REEL, identification of translocation carriers is critical. Here, we report about a phenotypically normal 3‐year‐old Arabian mare that had repeated resorption of conceptuses prior to day 45 of gestation and was diagnosed with REEL. Conventional and molecular cytogenetic analyses revealed that the mare had normal chromosome number 64,XX but carried a non‐mosaic and non‐reciprocal autosomal translocation t(4;10)(q21;p15). This is a novel translocation described in horses with REEL and the first such report in Arabians. Previous cases of REEL due to autosomal translocations have exclusively involved Thoroughbreds. The findings underscore the importance of routine cytogenetic screening of breeding animals.     

多房棘球绦虫钙网蛋白的表达及其与补体组分C1q的相互作用分析

为表达多房棘球绦虫钙网蛋白EmCRT,并对其进行初步鉴定及结构与补体结合功能分析.本研究以多房棘球绦虫囊cDNA为模板,通过PCR扩增目的基因,克隆至pcDNA3.3-Myc载体,构建重组质粒pcDNA3.3-Myc-EmCRT;PCR、酶切及测序鉴定其正确后,以脂质体转染法转染Hela细胞,运用Western blo...     

Molecular cloning,chromosomal localization and expression pattern of porcine ADP‐ribosylation factor(Arf) gene family

Adenosine diphosphate‐ribosylation factors (Arfs) are a family of guanosine triphosphate‐binding proteins involved in fundamental biological processes including secretion, endocytosis, phagocytosis, cytokinesis, cell adhesion and tumor cell invasion. We report here the molecular cloning, chromosome localization and expression analysis of porcine Arf1–6, of which Arf1–3 (Class I) have >93% similarity to each other and encode nearly similar proteins with 181 amino acids in length. Arf4 and Arf5 (Class II) are 78–81% homologous to Class I Arfs and both encode a protein of 180 amino acids, Arf6 (Class III) shows 64–68% homology to the other Arfs and encodes 175 amino acids. With radiation hybrid mapping, porcine Arf1–6 are assigned to chromosomes 14q21‐q22, 12p14, 5p12‐q11, 13q21.1, 18q24, 1q21‐q27, respectively. Moreover, real‐time quantitative RT‐PCR assays show that porcine Arf1‐6 are ubiquitous in all tissues examined, with the highest levels in the kidney and stomach and the lowest in muscle and the heart. This is the first report of molecular characterization of the Arf gene family in pigs.     

Safety evaluation of combination CCNU and continuous toceranib phosphate (Palladia®) in tumour‐bearing dogs: a phase I dose‐finding study

While maintaining a standard toceranib dosage [2.75 mg kg^?1, PO, every other day (EOD)], three dose‐escalating CCNU cohorts up to and including 60 mg m^?2, PO, q3wk, were completed. The dose‐limiting toxicities (DLT) for the combination were neutropenia and the maximum tolerated dose (MTD) for CCNU when given with continuous toceranib was determined to be 50 mg m^?2, q3wk. While activity is not a primary objective of phase I trials, we observed one complete (lymphoma) and four partial responses (lymphoma, sarcoma, undifferentiated carcinoma and prostatic carcinoma) and two dogs experienced stable disease for >6 weeks [gastric adenocarcinoma and metastatic multilobulated osteochondrosarcoma (MLO)] for an objective response rate of 38.4% and a biological response rate of 53.8%. Concurrent continuous toceranib (2.75 mg kg^?1, EOD) and pulse dose CCNU (50 mg m^?2, q3wk) was well tolerated. Phase II effectiveness and phase III prospective randomized trials should further interrogate the potential activity of this combination.     

Phase II open‐label study of single‐agent hydroxyurea for treatment of mast cell tumours in dogs*

This prospective study evaluated the efficacy and safety of hydroxyurea (HU) in dogs with measurable mast cell tumours (MCTs). Dogs were treated with HU at 60 mg kg^?1per os q24h for 14 days then 30 mg kg^?1 q24h thereafter or until MCT recurrence. Forty‐six dogs were enrolled. The overall response rate was 28%. Two dogs had a complete response (CR) for 256 and 448 days, respectively. Eleven dogs had a partial response for a median duration of 46 days (range, 28–189 days). Grade 2 to 4 neutropenia occurred in eight dogs and grade 4 thrombocytopenia in two. Grade 3–4 anaemia occurred in seven dogs; overall, there was a significant decrease in haematocrit after treatment with HU. The median drop in haematocrit was 10%. This study demonstrated that HU has activity in the treatment of MCTs with mild anaemia being the primary adverse event.     

Efficacy of Omeprazole versus High‐Dose Famotidine for Prevention of Exercise‐Induced Gastritis in Racing Alaskan Sled Dogs

Background: Omeprazole and famotidine both reduce severity of exercise‐induced gastritis, but administering famotidine is easier than administering omeprazole during racing competition. Hypothesis: Famotidine is more efficacious than no treatment in reducing severity of exercise‐induced gastritis; and high‐dose famotidine is more efficacious than omeprazole in reducing severity of exercise‐induced gastritis. Animals: Experiment 1: Randomized placebo‐controlled study, 36 sled dogs (3–8 years); Experiment 2: Randomized positive‐control study, 52 sled dogs (2–8 years). Methods: Experiment 1: Equal numbers of dogs randomly assigned to famotidine (20 mg q24h) or no treatment groups. Gastroscopy was performed 24 hours after the dogs ran 330 miles. Mucosal appearance was blindly scored by previously described scoring system. Experiment 2: Equal numbers of dogs randomly assigned to omeprazole (20 mg q24h) or high‐dose famotidine (40 mg q12h) groups. Gastroscopy was performed 48 hours before and 24 hours after the dogs ran 300 miles. Mucosal appearance was blindly scored by previously described scoring system. Results: Famotidine reduced the prevalence of clinically relevant, exercise‐induced gastric lesions compared with no treatment (7/16 versus 11/16, P= .031). Compared with high‐dose famotidine, omeprazole significantly decreased the severity (0.4 versus 1.2, P= .0002) and prevalence (2/23 versus 7/21, P= .049) of gastric lesions. Conclusions and Clinical Relevance: Although famotidine provides some benefit in the prevention of exercise‐induced gastric lesions, omeprazole is superior to famotidine in preventing gastritis in dogs running 300 miles. Routine administration of omeprazole is recommended to prevent stress‐associated gastric disease in exercising and racing Alaskan sled dogs.     

SNP identification, linkage and radiation hybrid mapping of the porcine lamin A/C (LMNA) gene to chromosome 4q

The lamins are components of nuclear lamina and they have a profound influence on nuclear structure and functions. They are encoded by three genes, LMNA, LMNB1 and LMNB2. A genomic fragment of the porcine LMNA gene (822 bp; from exons 7 to 9) was amplified by polymerase chain reaction and comparatively sequenced. Four single nucleotide polymorphisms (SNPs) were identified in intronic sequences: G162A, G208A, T367G and C618T. The SNPs are within the restriction sites for enzymes Bsh1236I, HpaII, AluI and Bsh1236I respectively. Allele frequencies at SNPs G208A, T367G and C618T were determined by using eight pig breeds. Linkage analysis in the Hohenheim Meishan × Piétrain family placed the LMNA gene in the chromosome 4q linkage group, between MEF2D and GBA (MEF2D– 3.0 cM –LMNA– 0.2 cM –GBA). In radiation hybrid mapping LMNA was most significantly linked to SW270 on chromosome 4 (39 cR; LOD = 7.86). The LMNA gene is located in the quantitative trait loci region for some carcass traits on chromosome 4q.     

Two cases of reciprocal translocations in domestic pigs producing small litters

SUMMARY: Two boars of Finnish Yorkshire breed were selected for chromosomal analysis because of their small litters. One had a complex three breakpoint reciprocal translocation where the small distal chromosome segments were fused in new combinations between autosomes 2,9 and 14. This boar with a 2n = 38,XY,t(2;9;14)(q23;q22;q25) karyotype had produced approximately 3.3 piglets per litter and its fertility was reduced by 70% compared to average of litter size in Finnish Yorkshire breed pigs. In another Finnish Yorkshire breed boar, the long arm of autosome 7 had broken and attached to the terminal end of autosome 15. The boar had a 2n = 38,XY, rcp(7q-;15q+)(q24;q26) karyotype. The average of piglets per litter sired by this boar was 5.2 and the litter size was reduced by approximately 50%. The chromosomal rearrangements t(2;9;14) was inherited by four of the boar's offspring studied from two whole litters having seven piglets altogether. Meiotic chromosomes were analysed conventionally from one male translocation carrier offspring of the t(2;9;14) boar. Total sperm count and progressive motility of spermatozoa were within normal limits in one male translocation carrier offspring of the t(2;9;14) boar and in the rcp(7q-;15q+) boar. The two reciprocal translocations seem to have arisen spontaneously in these two boars. ZUSAMMENFASSUNG: Zwei F?lle reziproker Translokationen bei Ebern mit kleinen Nachkommen Würfen Von zwei Finnischen Yorkshire Ebern hatte einer drei komplexe reziproke Translokationen, wo kurze distale Chromosomensegmente zu neuen Kombinatioenen zwischen Autosomen 2, 9 und 14 fusioniert waren. Der Eber mit 2n = 38,XY,t(2;9;14)(q23;q22;q25) Karyotyp hatte Nachkommenwürfe mit etwa 3.3 Ferkel weniger und 70% Fruchtbarkeit der bei dieser Rasse normalen. In einem anderen Eber war der lange Arm von Chromosom 7 gebrochen und am Ende von Chromosom 15: 2n = 38,XY, rcp(7q-; 15q+)(q24;q26) Karyotyp. Nachkommenwurfgr??e war 5.2. Das chromosomale Rearrangement t(2;9;14) wurde an 4 Nachkommen in zwei Würfen mit zusammen 7 Ferkel vererbt. Meiotische Chromosomen wurden bei einem m?nnlichen Translokationstr?ger dieser Nachkommen analysiert. Gesamtspermienenzahl und ihre Vorw?rtsbewegung waren in normalen Grenzen bei diesem Nahkommen ebenso wie beim rcp(7q-;15q+) Eber. Die zwei reciproken Translokationen scheinen spontan entstanden zu sein.     

The effect of enalapril on furosemide‐activated renin–angiotensin–aldosterone system in healthy dogs

Studies in our laboratory have revealed that furosemide‐induced RAAS activation, evaluated via the urine aldosterone‐to‐creatinine ratio (UAldo:C), was not attenuated by the coadministration of benazepril, while enalapril successfully suppressed amlodipine‐induced urinary aldosterone excretion. This study was designed to evaluate the efficacy of enalapril in suppressing ACE activity and furosemide‐induced circulating RAAS activation. Failure to do so would suggest that this failure may be a drug class effect. We hypothesized that enalapril would suppress ACE activity and furosemide‐induced circulating RAAS activation. Sixteen healthy hound dogs. The effect of furosemide (2 mg/kg PO, q12 h; Group F) and furosemide plus enalapril (0.5 mg/kg PO, q12 h; Group FE) on circulating RAAS was determined by plasma ACE activity, 4–6 h post‐treatment, and urinary A:C on days ?1, ?2, 1, 4, and 7. There was a significant increase in the average urine aldosterone‐to‐creatinine ratio (UAldo:C) after administration of furosemide (P < 0.05). Enalapril inhibited ACE activity (P < 0.0001) but did not significantly reduce aldosterone excretion. A significant (P < 0.05) increase in the UAldo:C was maintained for the 7 days of the study in both groups. Enalapril decreased plasma ACE activity; however, it did not suppress furosemide‐induced RAAS activation, as determined by the UAldo:C. While enalapril blunts ACE activity, the absence of circulating RAAS suppression may be due to angiotensin II reactivation, alternative RAAS pathways, and furosemide overriding concurrent ACE inhibition, all indicating the existence of aldosterone breakthrough (ABT). Along with similar findings with benazepril, it appears that failure to suppress aldosterone suppression with furosemide stimulation may be a drug class effect. The discrepancy between the current data and the documented benefits of enalapril likely reflects the efficacy of this ACE inhibitor in suppressing tissue RAAS, variable population responsiveness to ACE‐inhibition, and/or providing additional survival benefits, possibly through as yet unknown mechanisms.     

First identification of reciprocal translocations in Polish pigs

SUMMARY: Two different reciprocal translocations, rcp (8;14) (p21;q25) and rcp (7;13) (q13;q46), were described for the first time in Poland in the Polish Landrace and Duroc pigs. Observation of synaptonemal complexes showed the presence of a quadrivalent composed of translocational chromosomes and their homologues. Individuals carrying translocations were characterized by normal external appearance and correct semen parameters. Analysis of fertility made on the basis of litter size demonstrated that fertility decreased by 25% in the carrier of translocation rcp (8;14) and by 52% in the carrier of translocation rcp (7;13). ZUSAMMENFASSUNG: Zum erste mal festgestelte gegenseitige Translokationen bei Schweine in Polen Bein Polnischen Landras und Duroc Schweinen wurden zum erstenmal in Polen, zwei verschiedene reciproke Translokationen-rcp (8;14) (p21;q25) und rcp (7;13) (q13;q46)-festgestellt. Anhand der Beobachtungen des Synaptonemal Complex wurde die Anwesenheit eines Tetravalent nachgewiesen, welches aus Translokationschromosomen und seinen Homologen zusammengesetzt ist. Die Translokationstiere hatten normale Exterieur und Spermaparameter. Aufgrund der Fortpflanzungsergebmissen wurden verminderte Fruchtbarkeit bei Translokationstieren rcp (8;14)-um 25% und bei Translokationstieren rcp (7;13)-um 52% festgestellt. RéSUMé: Les translocations réciproques identifiées pour la prèmière fois chez les porcs levés en Pologne Chez les porcs des races Landrace et Duroc on a constaté, pour la première fois en Pologne deux translocations réciproques différentes-rcp (8;14) (p21;q25) ainsi que rcp (7;13) (q13;q46). L'observation des complexes synaptonémals a manifesté la présence du quadrivalent composé de chromosomes de translocation et de leurs homologes. Les animaux-les porteurs de la translocation ont se caractérisé par l'extérieur normal et par les paramètres réguliers du sperme. L'analyse de la fertilité expérimenté selon de la taille des portées a démontré la réduction de la fertilité pour le porteur de la translocation rcp (8;14) à 25% cependant pour les porteurs de la translocation rcp (7;13) à 52%.     

Aldosterone breakthrough with benazepril in furosemide‐activated renin‐angiotensin‐aldosterone system in normal dogs

Pilot studies in our laboratory revealed that furosemide‐induced renin‐angiotensin‐aldosterone system (RAAS) activation was not attenuated by the subsequent co‐administration of benazepril. This study was designed to evaluate the effect of benazepril on angiotensin‐converting enzyme (ACE) activity and furosemide‐induced circulating RAAS activation. Our hypothesis was that benazepril suppression of ACE activity would not suppress furosemide‐induced circulating RAAS activation, indicated by urinary aldosterone concentration. Ten healthy hound dogs were used in this study. The effect of furosemide (2 mg/kg p.o., q12h; Group F; n = 5) and furosemide plus benazepril (1 mg/kg p.o., q24h; Group FB; n = 5) on circulating RAAS was determined by plasma ACE activity, 4–6 h posttreatment, and urinary aldosterone to creatinine ratio (UAldo:C) on days ?1, ?2, 1, 3, and 7. There was a significant increase in the average UAldo:C (μg/g) after the administration of furosemide (Group F baseline [average of days ?1 and ?2] UAldo:C = 0.41, SD 0.15; day 1 UAldo:C = 1.1, SD 0.56; day 3 UAldo:C = 0.85, SD 0.50; day 7 UAldo:C = 1.1, SD 0.80, P < 0.05). Benazepril suppressed ACE activity (U/L) in Group FB (Group FB baseline ACE = 16.4, SD 4.2; day 1 ACE = 3.5, SD 1.4; day 3 ACE = 1.6, SD 1.3; day 7 ACE = 1.4, SD 1.4, P < 0.05) but did not significantly reduce aldosterone excretion (Group FB baseline UAldo:C = 0.35, SD 0.16; day 1 UAldo:C = 0.79, SD 0.39; day 3 UAldo:C 0.92, SD 0.48, day 7 UAldo:C = 0.99, SD 0.48, P < 0.05). Benazepril decreased plasma ACE activity but did not prevent furosemide‐induced RAAS activation, indicating aldosterone breakthrough (escape). This is particularly noteworthy in that breakthrough is observed at the time of initiation of RAAS suppression, as opposed to developing after months of therapy.     

家蚕五种幼虫斑纹浓淡型间的遗传

以本研究室家蚕基因库保存遗传系统的幼虫斑纹为观察对象，发现暗色斑（P^M）．黑缟斑（P^S）．杲蚕（U）鹑斑（q)．褐圆斑（L）均存在斑纹浓淡程度不同且表型稳定的多型系统。根据杂交后能够识别浓淡型性状分离，将暗色斑分成浓型（P^M3)．中型（P^M2)和淡型（P^M1)，黑缟斑分成浓型（P^S2)．淡型（P^S1)，杲蚕分成浓型（U^2)和淡型（U^1）,鹑斑分成浓型（q^3)．中型(q^2)和淡型（q^1)，褐圆斑分成浓型（L^2)和淡型（L^1)。同种斑纹内浓淡型间相互杂交，整体上均表现为等位基因的遗传模式，相对的浓型对淡型为显性，即：P^M3＞P^M2＞P^M1,P^S2＞PS1,U^2＞U^1,q^3＞q^2＞q^1,L^2＞L^1。     

The effect of dosing interval on the efficacy of misoprostol in the prevention of aspirin-induced gastric injury

The effect of twice-daily administration of misoprostol on aspirin-induced gastric injury was evaluated. Twenty-four random-source dogs were divided into groups that received aspirin and misoprostol as follows: group I, aspirin 25 mg/kg PO q8h and placebo PO q8h; group II, aspirin 25 mg/kg PO q8h and misoprostol 3 microg/kg PO q8h; group III, aspirin 25 mg/kg PO q8h, misoprostol 3 microg/kg PO q12h, and placebo PO q24h; and group IV, aspirin 25 mg/kg PO q8h, misoprostol 3 microg/kg PO q24h, and placebo PO q12h for 28 days. Gastroscopy was performed on days -9, 5, 14, and 28. Visible lesions were scored on a scale of 1 (mucosal hemorrhage) to 11 (perforating ulcer). No difference in total score was identified between groups I and IV on any day. Median total scores for groups II and III were significantly (P < or = .05) lower compared to groups I and IV on day 5. Group III had a significantly lower score (P < or = .05) than groups I, II, and IV on day 28. This study suggests that misoprostol 3 microg/kg PO q12h is as effective as misoprostol 3 microg/kg PO q8h in preventing aspirin-induced gastric injury in this model. However, misoprostol 3 microg/ kg PO q8h was less effective in preventing aspirin-induced gastric injury on days 14 and 28 than in previous studies. No difference among numbers of dog-days of vomiting, diarrhea, or anorexia was detected among groups.     

Evaluation of topical nalbuphine or oral tramadol as analgesics for corneal pain in dogs: a pilot study

Objective To evaluate the effectiveness of topical nalbuphine or oral tramadol in the treatment of corneal pain in dogs. Animals studied Fourteen male Beagle dogs. Procedures Dogs were divided into three treatment groups and sedated with dexmedetomidine (5 μ/kg IV). A 4 mm corneal epithelial wound was created in the right eye (OD) of all dogs. Sedation was reversed with atipamazole IM. All dogs received pre/post ophthalmic examinations. Post operatively, Group NB (n = 5) received topical 1% preservative‐free nalbuphine OD q8 h and an oral placebo PO q8 h. Group TR (n = 5) received tramadol (4 mg/kg) PO q8 h and topical sterile saline OD q8 h. Group CNTRL (n = 4) received topical sterile saline OD q8 h and an oral placebo q8 h. All dogs received topical 0.3% gentamicin OD TID until healed. Dogs were pain scored using a pain scoring system modified from the University of Melbourne pain scale at 0, 1, 2, 4, and 6 h, then every 6 h by observers masked to treatment, until corneal wounds were healed. Treatment failure was recorded if cumulative pain scores were above a minimum threshold of acceptable pain and rescue analgesia of morphine (1.0 mg/kg IM) was administered subsequently. Result Four dogs in Group NB, one dog in Group TR, and two dogs in Group CNTRL required rescue analgesia. There was no significant difference in the incidence of treatment failure between groups (P = 0.184). Mean time to rescue was 9.16 h. All corneal wounds were healed by 84 h. Conclusions The results of this study suggest tramadol rather than nalbuphine should be further investigated for the treatment of corneal pain.     

Phase I Dose Escalation of Single‐Agent Vinblastine in Dogs

Background: Vinblastine (VBL) is commonly used in dogs at a dosage of 2.0 mg/m². The minimal toxicity observed at this dosage indicates that higher dosages might be well tolerated. Hypothesis: The maximum tolerated dosage (MTD) for a single VBL treatment is higher than the previously published dosage of 2.0 mg/m². Animals: Twenty‐three dogs with lymphoma or cutaneous mast cell tumors. Methods: Dogs received 1 single‐agent VBL treatment IV. The starting dosage was 3.0 mg/m², and dosages were increased in increments of 0.5 mg/m² in cohorts of 3 dogs. Hematologic toxicity was assessed with weekly CBCs. Gastrointestinal toxicity was assessed from medical histories from owners. Once the MTD was determined, additional dogs were treated with VBL at that dosage. Dogs whose cancers responded to VBL continued to receive treatments q2–3 weeks. Results: VBL dosages ranged from 3.0 to 4.0 mg/m². Neutropenia was the dose‐limiting toxicity, with the nadir identified 7 days after treatment and resolving by 14 days after treatment. The MTD was 3.5 mg/m². Sixteen dogs were treated at this dosage, and 3 experienced severe toxicity characterized by asymptomatic grade 4 neutropenia, febrile grade 4 neutropenia, and death. Gastrointestinal toxicity was mild and self‐limiting. Preliminary evidence of antitumor activity was identified in 2 of 12 dogs with lymphoma treated at the MTD. Conclusions and Clinical Importance: In dogs, single‐agent VBL is well tolerated at a dosage of 3.5 mg/m² IV. At this dosage, the minimum safe treatment interval is q2 weeks, and adjunct treatment with prophylactic antibiotics should be considered.     

Fluticasone Propionate Aerosol is More Effective for Prevention than Treatment of Recurrent Airway Obstruction

Background: Efficacy of inhaled fluticasone propionate (FP) for management of recurrent airway obstruction (RAO) has only been evaluated after several weeks' treatment.
Objectives: To compare efficacy of (1) 3-day treatments with FP to dexamethasone (DEX) for management of RAO; and (2) FP and DEX to no treatment in prevention of acute RAO exacerbations.
Animals: Nine RAO affected horses.
Methods: Crossover studies in RAO-affected horses compared (a) 3-day treatment of RAO exacerbation with FP (3 and 6 mg q12h) and DEX (0.1 mg/kg q24h) and (b) FP (6 mg q12h) and DEX (0.1 mg/kg q24h) to no treatment for prevention of acute exacerbations of RAO. Treatment efficacy and unwanted effects were judged from maximal change in pleural pressure (ΔPpl_max), serum cortisol (COR), bronchoalveolar lavage (BAL) cytology, and subjective scores for respiratory distress and lameness.
Results: In treatment trial, DEX and FP (6 mg) significantly decreased ΔPpl_max by 48 and 72 hours, respectively; FP (3 mg) had no significant effect. DEX decreased COR more than did FP. In prevention trial, both DEX and FP (6 mg) prevented the increase in ΔPpl_max that occurred in untreated horses. Both treatments decreased COR to the same degree. FP and DEX had no effects on bronchoalveolar lavage fluid (BALF) cytology and there was no evidence of laminitis.
Conclusions and Clinical Importance: FP (6 mg q12h) is as effective as DEX for prevention of acute exacerbations of RAO and lower doses should be evaluated. High-dose FP is not as effective as DEX for treatment of RAO exacerbations.