Effects of genetic and environmental factors on chronic lower airway disease in horses

Background : Environment and genetics influence the manifestation of recurrent airway obstruction (RAO), but the associations of specific factors with mild, moderate, and severe clinical signs are unknown.
Hypothesis : We hypothesized that sire, feed, bedding, time outdoors, sex, and age are associated with clinical manifestations of mild, moderate, and severe lower airway disease.
Animals : Direct offspring of 2 RAO-affected Warmblood stallions (F1S1, n = 172; F1S2, n = 135); maternal half-siblings of F1S1 (mHSS1, n = 66); and an age-matched, randomly chosen control group (CG, n = 33).
Methods : A standardized questionnaire was used to assess potential risk factors and to establish a horse owner assessed respiratory signs index (HOARSI 1–4, from healthy to severe) according to clinical signs of lower airway disease.
Results : More F1S1 and F1S2 horses showed moderate to severe clinical signs (HOARSI 3 and HOARSI 4 combined, 29.6 and 27.3%, respectively) compared with CG and mHSS1 horses (9.1 and 6.2%, respectively; contingency table overall test, P < .001). Sire, hay feeding, and age (in decreasing order of strength) were associated with more severe clinical signs (higher HOARSI), more frequent coughing, and nasal discharge.
Conclusions and Clinical Relevance : There is a genetic predisposition and lesser but also marked effects of hay feeding and age on the manifestation of moderate to severe clinical signs, most markedly on coughing frequency. In contrast, mild clinical signs were not associated with sire or hay feeding in our populations.     

柞蚕全茧量的主基因-多基因混合遗传分析

全茧量性状是柞蚕育种的重要指标之一。选择全茧量有显著差异的2个柞蚕品系582(P1)、宽青(P2)为亲本,通过对P1、P2及F1和F2作4家系世代联合分析,研究柞蚕全茧量遗传规律。结果表明:柞蚕全茧量由2对主基因控制,同时存在多基因的修饰作用和性别上的差异,雌性个体符合2对等加性主基因+加显多基因模型,雄性个体符合2对等显性主基因+加显多基因模型;雌、雄个体主基因遗传力分别为49.01%和24.35%,多基因遗传力分别为0.53%和26.47%。柞蚕育种对全茧量的选择应依据性别采用不同的选择方案:雌个体应强化早期选择;雄个体需多代连续选择,并强化后续世代选择。     

A comprehensive search for quantitative trait loci affecting growth and carcass composition of cattle segregating alternative forms of the myostatin gene

The objective of this study was to identify quantitative trait loci for economically important traits in two families segregating an inactive copy of the myostatin gene. Two half-sib families were developed from a Belgian Blue x MARC III (n = 246) and a Piedmontese x Angus (n = 209) sire. Traits analyzed were birth, weaning, and yearling weight (kg); preweaning average daily gain (kg/d); postweaning average daily gain (kg/d); hot carcass weight (kg); fat depth (cm); marbling score; longissimus muscle area (cm2); estimated kidney, pelvic, and heart fat (%); USDA yield grade; retail product yield (%); fat yield (%); and wholesale rib-fat yield (%). Meat tenderness was measured as Warner-Bratzler shear force at 3 and 14 d postmortem. The effect of the myostatin gene was removed using phase information from six microsatellite markers flanking the locus. Interactions of the myostatin gene with other loci throughout the genome were also evaluated: The objective was to use markers in each family, scanning the genome approximately every 25 to 30 centimorgans (cM) on 18 autosomal chromosomes, excluding 11 autosomal chromosomes previously analyzed. A total of 89 markers, informative in both families, were used to identify genomic regions potentially associated with each trait. In the family of Belgian Blue inheritance, a significant QTL (expected number of false-positives = 0.025) was identified for marbling score on chromosome 3. Suggestive QTL for the same family (expected number of false-positives = 0.5) were identified for retail product yield on chromosome 3, for hot carcass weight and postweaning average daily gain on chromosome 4, for fat depth and marbling score on chromosome 8, for 14-d Warner-Bratzler shear force on chromosome 9, and for marbling score on chromosome 10. Evidence suggesting the presence of an interaction for 3-d Warner-Bratzler shear force between the myostatin gene and a QTL on chromosome 4 was detected. In the family of Piedmontese and Angus inheritance, evidence indicates the presence of an interaction for fat depth between the myostatin gene and chromosome 8, in a similar position where the evidence suggests the presence of a QTL for fat depth in the family with Belgian Blue inheritance. Regions identified underlying QTL need to be assessed in other populations. Although the myostatin gene has a considerable effect, other loci with more subtle effects are involved in the expression of the phenotype.     

Idiopathic thrombocytopenia in Cavalier King Charles Spaniels

OBJECTIVE: To determine the prevalence of asymptomatic idiopathic macrothrombocytopenia in the population of Cavalier King Charles Spaniels (CKCS) in New South Wales (NSW) and to determine if it exhibits an autosomal recessive inheritance pattern. We also aimed to determine if significant differences existed when counting platelets manually, by auto analyser or by blood smear estimation in CKCS and mixed breed dogs. METHODS: Blood was collected from 172 dogs (152 CKCS and 20 mixed breed) and placed into sodium-citrate anticoagulant. Platelet counts were performed manually, by auto analyser and by blood smear estimates in CKCS and mixed breed dogs. Blood smears were also examined for platelet clumping and erythrocyte, leukocyte and platelet morphology. Pedigree analysis was performed to determine if an autosomal recessive inheritance pattern was supported. RESULTS: A statistically significant difference was found in platelet counts between CKCS and mixed breed dogs (P < 0.0001). CKCS had a platelet count that was 32% that of the controls (95% confidence interval, 28 to 37%). There was no significant difference between methods used to count platelets. Thirty percent of CKCS had macrothrombocytes. Pedigree analysis and examination of obtained and expected segregation ratios from 17 CKCS families supported an autosomal recessive pattern of Mendelian inheritance. CONCLUSIONS: A high prevalence of idiopathic macrothrombocytopenia exists in CKCS in NSW and automated or blood smear estimates are sufficient to count platelet numbers. Data supports an autosomal recessive inheritance pattern.     

TP53 gene mutations in canine osteosarcoma

Objective— To investigate mutations of the TP53 gene in canine osteosarcoma (OS).
Study Design— Clinical historic cohort study.
Animals— Client-owned dogs.
Methods— OS (n=59) were screened for mutations of the complete TP53 gene using polymerase chain reaction and the mutation was analyzed by single-strand conformational polymorphism. Clinical outcome of dogs with TP53-mutated OS were compared with dogs with OS without a mutation after complete surgical excision of the primary tumor.
Results— TP53 gene mutations were observed in 24 of 59 (40.7%) OS; 3 mutated OS had 2 mutations. The alterations consisted mainly of point mutations (74%). Dogs with mutated OS had a significantly shorter survival time (ST) after surgery than dogs with normal tumor TP53 gene expression ( P =.03). Other significant prognosticators for ST and disease-free interval included elevated serum alkaline phosphatase ( P <.01) and tumor grade ( P =.01).
Conclusion— TP53 genetic mutations are common in canine OS and may have a prognostic value.
Clinical Relevance— Mutations of the TP53 gene may influence survival and should be considered when evaluating canine OS.     

高丹草株高与叶片数主基因+多基因的遗传分析

于200年采用主基因+多基因混合遗传模型,对高丹草(Sorghum×Sudan grass)2002 GZ-1和2002 GB-1杂交组合的个世代(P₁,P₂,F₁,F₂,F_2:3)群体的株高和叶片数进行联合分析.结果表明:株高遗传受2对加性-显性主基因+加性-显性多基因(E-2)控制;叶片数遗传受2对加性-显性-上位性主基因+加性-显性多基因(E-1)控制,两性状的遗传符合2对主基因+多基因混合遗传模型,主基因对株高、叶片数的表现起主要作用.株高中主基因加性和显性效应分别为26.98、10.02和2.36、1.61,而多基因分别为-6.9和-.06,F₂和F_2:3的主基因遗传率分别为77.94%和82.9%.叶片数主基因的加性和显性效应分别为6.11、1.04和0.63、-0.09,多基因分别为-0.16、-0.11,F₂和F(_2:3)的主基因遗传率分别为89.30%和91.60%.表明2个性状是以主基因遗传为主,应在早期世代进行选择.该性状所属遗传模型的研究,旨在为高丹草的遗传改良和杂种优势利用提供理论依据.     

A region on equine chromosome 13 is linked to recurrent airway obstruction in horses

REASONS FOR STUDY: Equine recurrent airway obstruction (RAO) is probably dependent on a complex interaction of genetic and environmental factors and shares many characteristic features with human asthma. Interleukin 4 receptor a chain (IL4RA) is a candidate gene because of its role in the development of human asthma, confirmation of this association is therefore required. METHODS: The equine BAC clone containing the IL4RA gene was localised to ECA13q13 by the FISH method. Microsatellite markers in this region were investigated for possible association and linkage with RAO in 2 large Warmblood halfsib families. Based on a history of clinical signs (coughing, nasal discharge, abnormal breathing and poor performance), horses were classified in a horse owner assessed respiratory signs index (HOARSI 1-4: from healthy, mild, moderate to severe signs). Four microsatellite markers (AHT133, LEX041, VHL47, ASB037) were analysed in the offspring of Sire 1 (48 unaffected HOARSI 1 vs. 59 affected HOARSI 2-4) and Sire 2 (35 HOARSI 1 vs. 50 HOARSI 2-4), age 07 years. RESULTS: For both sires haplotypes could be established in the order AHT133-LEXO47-VHL47-ASB37. The distances in this order were estimated to be 2.9, 0.9 and 2.3 centiMorgans, respectively. Haplotype association with mild to severe clinical signs of chronic lower airway disease (HOARSI 2-4) was significant in the offspring of Sire 1 (P = 0.026) but not significant for the offspring of Sire 2 (P = 0.32). Linkage analysis showed the ECA13q13 region containing IL4RA to be linked to equine chronic lower airway disease in one family (P<0.01), but not in the second family. CONCLUSIONS: This supports a genetic background for equine RAO and indicates that IL4RA is a candidate gene with possible locus heterogeneity for this disease. POTENTIAL RELEVANCE: Identification of major genes for RAO may provide a basis for breeding and individual prevention for this important disease.     

Lung function and airway cytologic profiles in horses with recurrent airway obstruction maintained in low-dust environments

BACKGROUND: The effects of long-term environmental management on airway obstruction and inflammation in horses with recurrent airway obstruction (RAO) are unknown. HYPOTHESIS: Horses with RAO maintained in low-dust environments have persistent airway obstruction and neutrophilic inflammation. ANIMALS: Study horses were treated for RAO and then maintained in low-dust environments with no medical management. Horses were classified into 3 groups by years after diagnosis: 1 year (time 1, n = 9), 2-3 years (time 2, n = 7), and 5-6 years (time 3, n = 8). The comparison groups were age-matched healthy horses. METHODS: In this cross-sectional study, a clinical examination was performed, and the clinical score was calculated. Standard lung function, forced expiratory maneuvers, and the cytology of bronchoalveolar lavage fluid (BALF) were evaluated. RESULTS: The clinical scores of the RAO horses were higher than those of the non-RAO horses at time 2 (P = .018). Standard lung function data were not different between the groups at any time point. The forced expiratory flow between 75-95% of exhaled vital capacity was lower in RAO horses than in non-RAO horses at all time points (P < .02), indicating persistent peripheral airway obstruction. Cytologic evaluation of BALF revealed no difference in total nucleated cell numbers or differential cell counts between RAO and non-RAO horses at any time point. CONCLUSIONS AND CLINICAL IMPORTANCE: The peripheral airway obstruction detected in horses with RAO maintained in low-dust environments likely is due to irreversible airway remodeling but is not associated with cytologic evidence of airway inflammation.     

Clinical characteristics and inheritance of idiopathic epilepsy in Vizslas

Medical record, seizure survey, and telephone interview information was obtained for 29 Vizslas with idiopathic epilepsy (IE), 74 unaffected siblings, and 41 parents to determine the common clinical characteristics and most likely mode of inheritance. IE was diagnosed on the basis of the age of seizure onset, laboratory results, and neurologic examination findings. Computerized tomography (CT) or magnetic resonance imaging (MRI) scan with cerebrospinal fluid (CSF) analysis was required for the inclusion of dogs with an age of seizure onset of < 6 months or > 5 years. Simple segregation analysis was performed with an ascertainment correction and chi-square analysis. IE appeared to be familial in these pedigrees, with 79% of affected Vizslas exhibiting partial onset seizures. Partial seizure signs included a combination of limb tremors, staring, pupillary dilatation, or salivation without loss of consciousness in > 50% of the dogs with partial signs. The estimated segregation frequency of P = .22 (95% CI, P = .08 to .36) was consistent with autosomal recessive inheritance; however, polygenic inheritance could not be excluded as a possibility. Simulated linkage with FASTSLINK estimated that the average logarithm of odds (LOD) score would be 3.23 with a 10-centimorgan (cM) whole-genome scan for these families, indicating that these families would be useful for a whole-genome scan to potentially find the chromosomal segment(s) containing the epilepsy gene or genes. We conclude that IE in Vizslas appears to be primarily a partial onset seizure disorder that may be inherited as an autosomal recessive trait.     

Characteristics of somatotropin and prolactin profiles in young dairy sires before and after a 72-hour fast during different seasons.

Serial blood samples were collected from young (mean = 275 d of age) AI sires at 20-min intervals for an 8-h period before and after a 72-h fast. Samples were collected from four different groups of young sires in January (n = 23), April (n = 31), July (n = 27), and October (n = 24). Samples were collected for only 6 h for the July group. Plasma somatotropin (ST) and prolactin (PRL) data were analyzed by PULSAR, a computerized peak detection program. The PULSAR parameters, except for number of peaks detected, were not different (P greater than .05) when calculated using data from the entire 8-h period or just the first 6 h. Because some endocrine characteristics as defined by PULSAR were influenced by season, deviated values were calculated for those characteristics within seasonal groups by subtracting the mean of that group from each individual observation for all PULSAR parameters. Number of ST peaks was correlated (P less than .01, r = .26) with USDA pedigree index (PI) for fat yield (PIF), sire predicted transmitting ability for fat (PTAF; P less than .01, r = .30), Northeast AI Sire Comparison (NEAISC) PIF (P less than .05, r = 24), and sire PTAF (P less than .01, r = .33). No ST pulsatile characteristics after fasting were correlated (P greater than .05) with PI. Prolactin peak length was negatively related to USDA PIF (P less than .05, r = -.23) before fasting and positively correlated (P less than .05, r = .26) after fasting.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fetal growth of beef calves. II. Effect of sire on prenatal development of the calf and related placental characteristics

Fifteen Hereford and 47 crossbred heifers were allotted by breed and body weight to be artificially inseminated to one of two Angus sires selected for progeny birth weights (L = low; H = high). Forty-two of the heifers were randomly assigned to be slaughtered at 200, 215, 230, 245 or 260 d of gestation for measurement of fetal and placental characteristics. Twenty heifers were allowed to go to term and five calves from each sire group were randomly assigned to be euthanized and dissected within 24 h after birth. Sire differences in birth weight (BW) and dystocia score (32.9 vs 35.4 kg; 1.8 vs 3.1, L vs H sires, respectively) existed (P less than .01), and there was a sire effect (P less than .01) for fetal calf weights (FW) and eviscerated calf weights (EW). However, there was a sire X calf sex interaction for BW (P less than .05), EW (P less than .01), FW (P less than .01), femur length (P less than .05), heart weight (P less than .05), kidney weight (P less than .01) and pituitary weight (P less than .01). Weight differences suggested these interactions were a result of the relationship of the organ weights to fetal body weights and the interaction effects on calf weights resulted from limitations in the maternal environment which restricted growth of H-sired male calves in utero. Sire X fetal age interaction effects were all nonsignificant (P greater than .10) except for cerebrum weight. This finding indicates that fetus and calf growth rates were parallel for the L and H sires. A sire effect was found for biceps (P less than .01) and liver weights (P less than .01), but not for cerebrum weights (P greater than .10). Increasing weight due to fetal age was attributed to hypertrophy for the cerebrum (P less than .05) and liver (P approximately equal to .01), while the biceps increased (P less than .05) by both hypertrophy and hyperplasia, as determined from deoxyribonucleic acid and protein analyses. All measured fetal organ weights except heart, when expressed as a ratio with EW, decreased (P less than .05) with increasing fetal age. Brain (cerebrum + cerebellum):liver weight ratios were higher (P less than .01) in L-sired calves (.32 vs. .28) than in H-sired calves. Total placentome weight (b' = 91; P less than .01) and placental fluid volume (b' = .32; P less than .01) were highly associated with FW, accounting for 84% of the variation in FW.(ABSTRACT TRUNCATED AT 400 WORDS)     

Initial results of genomic scans for ovulation rate in a cattle population selected for increased twinning rate

Genomic scans were conducted with 273 markers on 181 sires from a cattle population selected for increased twinning rate to identify chromosomal regions containing genes that influence ovulation rate. Criteria used for selecting markers were number of alleles, ease of scoring, and relative position within linkage group. Markers were multiplexed or multiple-loaded on the gels to reduce the costs and labor required to obtain genotypic data. This approach reduced the number of gels by 45% when compared with running each marker independently. Male animals selected for the genomic scan sired the majority of the population. A modified interval analysis was used in a granddaughter design to compare effects of each allele within sire for 10 different sire families. The midparent deviation of the son's estimated breeding value for ovulation rate was used as the phenotype. Forty-one potential peaks were identified with a nominal significance level < or = 0.05. The 10 peaks with the highest significance levels (P < 0.02) were selected for further analysis. Markers were genotyped across daughters of the sire where nominal significance was found for each of the 10 peaks. One peak (BTA5, relative position 40 cM) was found to be nominally significant in the daughters. The nominal significance levels were P = 0.01 for the sons (n = 32) and P = 0.02 for the daughters (n = 94) of sire 784403. A combined genomewide significance value (P = 0.07) was calculated that accounted for the 10 analyses with sons and the 10 analyses with daughters. These results strongly suggest that this region contains a gene(s) that is involved in the follicular recruitment and development process.     

Effect of tropically adapted sire breeds on preweaning growth of F1 Angus calves and reproductive performance of their Angus dams

The objective of this study was to determine the effect of tropically adapted sire breeds on preweaning growth performance of F1 calves and on reproductive performance of their Angus dams. Angus (A) cows were bred in two consecutive years (1992 and 1993) by AI using semen from Brahman (B; Bos indicus; n = 10), Senepol (S; Bos taurus; n = 10), and Tuli (T; Sanga; n = 9) bulls. A total of 82 B x A, 85 S x A, and 91 T x A calves were born. The statistical model included the fixed effects of year, sire breed, calf sex, sire breed x calf sex, and cow parity and the random effect of sire within sire breed. Birth weight, weaning weight, 205-d adjusted weaning weight, ADG from birth to weaning, and hip height at weaning were greater (P < .001) for B x A calves than for S x A or T x A calves. Greater differences were detected between sexes for B x A than for S x A and T x A (for all traits sire breed x calf sex, P < .05). Sire breed affected (P < .01) the percentage of unassisted calvings (B x A, 87%; S x A, 98%; and T x A, 100%) and tended (P < .10) to affect the percentage of calves that survived until weaning (B x A, 90%; S x A, 94%; and T x A, 98%). Sire breed of calf did not affect (P > .10) length of gestation, and sire breed did not affect the interval from calving to first observed estrus or pregnancy in Angus dams. These results demonstrate that preweaning growth performance of B x A calves was greater than that of either S x A or T x A calves. However, use of Brahman sires on Angus dams led to calving problems and tended to reduce the percentage of calves that survived until weaning. Thus, heavier weaning weights of B x A calves would be an advantage for cow-calf producers marketing calves, but heavier birth weights and calving difficulty attributed to Brahman sires would be a disadvantage.     

Effects of Body Positioning on Swallowing and Esophageal Transit in Healthy Dogs

Background: Contrast videofluoroscopy is the imaging technique of choice for evaluating dysphagic dogs. In people, body position alters the outcome of videofluoroscopic assessment of swallowing.
Hypothesis/Objective: That esophageal transit in dogs, as measured by a barium esophagram, is not affected by body position.
Animals: Healthy dogs ( n = 15).
Methods: Interventional, experimental study. A restraint device was built to facilitate imaging of dogs in sternal recumbancy. Each dog underwent videofluoroscopy during swallowing of liquid barium and barium-soaked kibble in sternal and lateral recumbancy. Timing of swallowing, pharyngeal constriction ratio, esophageal transit time, and number of esophageal peristaltic waves were compared among body positions.
Results: Transit time in the cervical esophagus (cm/s) was significantly delayed when dogs were in lateral recumbency for both liquid (2.58 ± 1.98 versus 7.23 ± 3.11; P = .001) and kibble (4.44 ± 2.02 versus 8.92 ± 4.80; P = .002). In lateral recumbency, 52 ± 22% of liquid and 73 ± 23% of kibble swallows stimulated primary esophageal peristalsis. In sternal recumbency, 77 ± 24% of liquid ( P = .01 versus lateral) and 89 ± 16% of kibble ( P = .01 versus lateral) swallows stimulated primary esophageal peristalsis. Other variables were not significantly different.
Conclusions and Clinical Importance: Lateral body positioning significantly increases cervical esophageal transit time and affects the type of peristaltic wave generated by a swallow.     

Plasma Atrial Natriuretic Peptide in Healthy Calves and Calves with Congenital Heart Disease

Background: The basic and clinical implications of evaluating plasma atrial natriuretic peptide (ANP) concentration in calves are unknown.
Objective: To investigate the relationship between the plasma ANP concentration and left ventricular end-diastolic pressure (LVEDP) in healthy calves subjected to volume overload (Study 1), and to compare the plasma ANP concentration in calves with or without heart disease (Study 2).
Animals: Six healthy calves were used in Study 1; disease calves and sick calves with (n = 9) and without congenital heart disease (CHD) (n = 9) were used in Study 2.
Methods: In Study 1, LVEDP in anesthetized calves was manipulated by IV administration of acetated Ringer's solution (rate of 100 mL/kg/h for 20 minutes) and furosemide. In Study 2, disease calves were identified by blood examination and echocardiography or pathological examination. The plasma ANP concentration was determined by a chemiluminescence enzyme immunoassay for human α-ANP.
Results: In Study 1, preloading significantly increased the plasma ANP concentration (36 ± 20–185 ± 156, P < .01) and LVEDP (−11 ± 7–2 ± 12, P < .01) from the baseline. Furthermore, plasma ANP concentrations were strongly correlated with LVEDP ( r = 0.61). In Study 2, the plasma ANP concentration was significantly higher in the calves with CHD than in the calves without heart disease (220 [67–970] versus 31 [10–86]; mean [range], P < .001).
Conclusions and Clinical Importance: Measurement of plasma ANP concentrations in calves can provide additional information useful for predicting hemodynamic abnormalities.     

Hereditary and clinical characteristics of lateral luxation of the superficial digital flexor tendon in Shetland sheepdogs

A study was conducted to define the mode of inheritance of lateral luxation of the superficial digital flexor (SDF) tendon in different lines of Shetland sheepdogs by examination of pedigree data. This pedigree analysis included affected and unaffected dams, sires, and offspring; common clinical signs; and age at onset. The clinical, histopathologic, and radiographic features of the disease were also studied. Of the 14 offspring from five matings of an affected sire to unrelated affected females, 100% were affected with lateral luxation of the SDF tendon. Of the 59 offspring from the same affected sire to unrelated, unaffected females, 44% were affected. The mating between normal parents produced 61% unaffected and 39% affected offspring. Application of the phenotypic findings in this study to a Mendelian genetic model of inheritance suggests that lateral luxation of the superficial digital tendon in Shetland sheepdogs is inherited as a simple autosomal recessive trait.     

In Vivo and In Vitro Evidence of the Involvement of CXCL1, a Keratinocyte-Derived Chemokine, in Equine Laminitis

Background: C-X-C motif ligand 1 (CXCL1) is an important chemokine of epithelial origin in rodents and humans.
Objectives: To assess in vivo and in vitro the regulation of CXCL1 in equine laminitis.
Animals: Twenty adult horses.
Methods: Real-time quantitative polymerase chain reaction (PCR) was used to assess expression of CXCL1 in samples of laminae, liver, skin, and lung from the black walnut extract (BWE) model of laminitis, and in cultured equine epithelial cells (EpCs). Tissue was obtained from control animals (CON, n = 5), and at 1.5 hours (early time point [ETP] group, n = 5), at the onset of leukopenia (developmental time point [DTP] group, n = 5), and at the onset of lameness (LAM group, n = 5) after BWE administration. EpCs were exposed to Toll-like/Nod receptor ligands, oxidative stress agents, and reduced atmospheric oxygen (3%). In situ PCR was used to localize the laminar cell types undergoing CXCL1 mRNA expression.
Results: Increases in laminar CXCL1 mRNA concentrations occurred in the ETP (163-fold [ P = .0001]) and DTP groups (21-fold [ P = .005]). Smaller increases in CXCL1 expression occurred in other tissues and organs. In cultured EpCs, increases ( P < .05) in CXCL1 mRNA concentration occurred after exposure to lipopolysaccharide (LPS [28-fold]), xanthine/xanthine oxidase (3.5-fold), and H₂O₂ (2-fold). Hypoxia enhanced the LPS-induced increase in CXCL1 mRNA ( P = .007). CXCL1 gene expression was localized to laminar EpCs, endothelial cells, and emigrating leukocytes.
Conclusion and Clinical Importance: These findings indicate that CXCL1 plays an early and possibly initiating role in neutrophil accumulation in the BWE laminitis model, and that laminar keratinocytes are an important source of this chemokine. New therapies using chemokine receptor antagonists may be indicated.     

Effect of Thyroxine Supplementation on Glomerular Filtration Rate in Hypothyroid Dogs

Background: Glomerular filtration rate (GFR) is decreased in humans with hypothyroidism, but information about kidney function in dogs with hypothyroidism is lacking.
Hypothesis: Hypothyroidism influences GFR in dogs. The objective of this study was to assess GFR in hypothyroid dogs before implementation of thyroxine supplementation and after re-establishing euthyroidism.
Animals: Fourteen hypothyroid dogs without abnormalities on renal ultrasound examination or urinalysis.
Methods: Blood pressure and GFR (measured by exogenous creatinine clearance) were measured before treatment (T0, n = 14) and at 1 month (T1, n = 14) and at 6 months (T6, n = 11) after beginning levothyroxine supplementation therapy (20 μg/kg/d, PO). The response to therapy was monitored at T1 by measuring serum total thyroxine and thyroid stimulating hormone concentrations. If needed, levothyroxine dosage was adjusted and reassessed after 1 month. Statistical analysis was performed using a general linear model. Results are expressed as mean ± standard deviation.
Results: At T0, the average age of dogs in the study group was 6.3 ± 1.4 years. Their average body weight decreased from 35 ± 18 kg at T0 to 27 ± 14 kg at T6 ( P < .05). All dogs remained normotensive throughout the study. GFR increased significantly with levothyroxine supplementation; the corresponding results were 1.6 ± 0.4 mL/min/kg at T0, 2.1 ± 0.4 at T1, and 2.0 ± 0.4 at T6 ( P < .01).
Conclusion: GFR was <2 mL/min/kg in untreated hypothyroid dogs. Re-establishment of a euthyroid state increased GFR significantly.     

Calcium Regulating Hormones and Serum Calcium and Magnesium Concentrations in Septic and Critically Ill Foals and their Association with Survival

Background: Disorders of calcium regulation are frequently found in humans with critical illness, yet limited information exists in foals with similar conditions including septicemia. The purpose of this study was to determine whether disorders of calcium exist in septic foals, and to determine any association with survival.
Hypothesis: Blood concentrations of ionized calcium (Ca²⁺) and magnesium (Mg²⁺) will be lower in septic foals with concomitant increases in parathyroid hormone (PTH), calcitonin (CT), and parathyroid-related peptide (PTHrP) compared with healthy foals. The magnitude of these differences will be negatively associated with survival.
Animals: Eighty-two septic, 40 sick nonseptic, and 24 healthy foals of ≤7 days were included.
Methods: Prospective, observational study. Blood was collected at initial examination for analysis. Foals with positive blood culture or sepsis score ≥14 were considered septic. Foals with disease other than sepsis and healthy foals were used as controls. Hormone concentrations were measured with validated immunoassays.
Results: Septic foals had decreased Ca²⁺ (5.6 versus 6.1 mg/dL, P < .01) and increased serum PTH (16.2 versus 3.2 pmol/L, P < .05), and phosphorus concentrations (7.1 versus 6.3 mg/dL, P < .01). No differences in serum Mg²⁺, PTHrP, and CT concentrations were found. Nonsurviving septic foals (n = 42/82) had higher PTH concentrations (41.1 versus 10.7 pmol/L, P < .01) than survivors (n = 40/82).
Conclusions and Clinical Importance: Septic foals were more likely to have disorders of calcium regulation compared with healthy foals, where hyperparathyroidemia was associated with nonsurvival.     

Prospective Echocardiographic and Tissue Doppler Imaging Screening of a Population of Maine Coon Cats Tested for the A31P Mutation in the Myosin-Binding Protein C Gene: A Specific Analysis of the Heterozygous Status

Background: A mutation in the sarcomeric gene coding for the myosin-binding protein C gene has been identified in a colony of Maine Coon cats with hypertrophic cardiomyopathy (MyBPC3-A31P mutation). However, the close correlation between genotype and phenotype (left ventricular hypertrophy [LVH] and dysfunction) has never been assessed in a large population, particularly in heterozygous (Hetero) cats.
Objectives: To investigate LV morphology and function with echocardiography and tissue Doppler imaging (TDI) in a population of Maine Coon cats tested for the MyBPC3-A31P mutation with focus on Hetero animals.
Animals: Ninety-six Maine Coon cats.
Methods: Prospective observational study. Cats were screened for the MyBPC3-A31P mutation and examined with both echocardiography and 2-dimensional color TDI.
Results: Fifty-two out of 96 cats did not have the mutation (wild-type genotype, Homo WT), 38/96 and 6/96 were Hetero- and homozygous-mutated (Homo M) cats, respectively. Only 11% of Hetero cats (4/38) had LVH and 29% (10/34) of Hetero cats without LVH were >4 years old (4.1–11.5 years). LVH was also detected in 2 Homo WT cats (4%). A significantly decreased ( P < .05) longitudinal E/A (ratio between early and late diastolic myocardial velocities) in the basal segment of the interventricular septum was observed in Hetero cats without LVH (n = 34) compared with Homo WT cats without LVH (n = 50), thus confirming that the Hetero status is associated with regional diastolic dysfunction ( P < .05).
Conclusions: The heterozygous status is not consistently associated with LVH and major myocardial dysfunction. Moreover, Homo WT cats can also develop LVH, suggesting that other genetic causes might be implicated.