We evaluated the long-term effect of early angiotensin-converting enzyme (ACE) inhibition (enalapril maleate) as monotherapy to postpone or prevent congestive heart failure (CHF) in asymptomatic dogs with mitral regurgitation (MR) attributable to myxomatous valvular disease (MVD) in a prospective, randomized, double-blinded, placebo-controlled multicenter trial involving 14 centers in Scandinavia. Two hundred twenty-nine Cavalier King Charles (CKC) Spaniels with MR attributable to MVD but no signs of CHF were randomly allocated to treatment with enalapril 0.25-0.5 mg daily (n 116) or to placebo groups (n 113). Each dog was evaluated by physical examination, electrocardiography, and thoracic radiography at entry and every 12 months (30 days). The number of dogs developing heart failure was similar in the treatment and placebo groups (n 50 [43%] and n 48 [42%], respectively; P .99). The estimated means, adjusted for censored observations, for the period from initiation of therapy to heart failure were 1,150 50 days for dogs in the treatment group and 1,130 50 days for dogs in the placebo group (P .85). When absence or presence of cardiomegaly at the entrance of the trial was considered, there were still no differences between the treatment and placebo groups (P .98 and .51, respectively). Multivariate analysis showed that enalapril had no significant effect on the time from initiation of therapy to heart failure (P .86). Long-term treatment with enalapril in asymptomatic dogs with MVD and MR did not delay the onset of heart failure regardless of whether or not cardiomegaly was present at initiation of the study.

The aim of this study was to investigate effects of dietary levels of histidine (His) and iron (Fe) on cataract development in two strains of Atlantic salmon monitored through parr-smolt transformation. Three experimental diets were fed: (i) a control diet (CD) with 110 mg kg )1 Fe and 11.7 g kg )1 His; (ii) CD supplemented with crystalline His to a level of 18 g kg )1 (HD); and (iii) HD with added iron up to 220 mg kg )1 (HID). A cross-over design, with two feeding periods was used. A 6-week freshwater (FW) period was followed by a 20-week period, of which the first three were in FW and the following 17 weeks in sea water (SW). Fish were sampled for weighing, cataract assessment and tissue analysis at five time points. Cataracts developed in all groups in SW, but scores were lower in those fed high His diets (P < 0.05). This effect was most pronounced when HD or HID was given in SW, but was also observed when these diets were given in FW only. Histidine supplementation had a positive effect on growth performance and feed conversion ratio (P < 0.05), whereas this did not occur when iron was added. Groups fed HD or HID had higher lens levels of His and N-acetyl histidine (NAH), the latter showing a marked increase post-smoltification (P < 0.05). The HD or HID groups also showed higher muscle concentrations of the His dipeptide anserine (P < 0.05). There was a strong genetic influence on cataract development in the CD groups (P < 0.001), not associated with tissue levels of His or NAH. The role of His and Hisrelated compounds in cataractogenesis is discussed in relation to tissue buffering, osmoregulation and antioxidation.

This study demonstrates the positive association between PLD and glaucoma, between narrowing of the iridocorneal angle and glaucoma and the effect of age on the iridocorneal angle. Mating of dogs with normal iridocorneal angles appears to reduce the presence and degree of abnormal appearance of the iridocorneal angle in the offspring. However, breeding only dogs with normal iridocorneal angles without consideration of their relationship to dogs with glaucoma is not a guarantee for preventing glaucoma in the offspring.

No abstract

In the period from winter 1996 to autumn 1999, three feeding trials were conducted to study the possible role of mammalian blood meal in preventing lens opacities in Atlantic salmon. In addition to blood meal supplemented feed, experimental diets were formulated, aiming to mimic the total concentrations of selected elements present in blood meal (BM) enriched diets; the amino acid histidine (His) and the mineral iron (Fe). In addition, these diets were supplemented with Zn. The trials included different rearing conditions, sizes and strains of Atlantic salmon; one small scale feeding experiment with presmolt of Strain A in fresh water (Trial 1) and two semi large trials with sub-yearling (S0s) and yearling (S1s) smolts of Strains A and B in seawater (Trials 2 and 3). The trials included duplicate or triplicate feeding groups and lasted 6-12 months. Standard commercial diets not supplemented with BM were used as controls. High prevalence of cataract developed over time in all three studies, with end point ranges as follows; Trial 1: 40-52 %; Trial 2: 51-83 %; Trial 3: 63-100%. The cataracts normally first appeared in the anterior and/or posterior cortical region and later affected the perinuclear region. In all the experiments, there was a significant cataract preventative effect of both the BM supplemented and experimental diets compared to the respective control diets. To some extent, cataract incidence was reduced, but primarily cataractogenesis was less severe in these groups. A concurrent positive effect on growth of both added BM and experimental diets was observed in the two seawater trials, probably related to maintaining vision and feed uptake ability. In one of the trials, there were significant differences in cataract susceptibility between the two strains, measured both as frequency and severity of cataractous changes. Our data suggest that elevated concentrations of dietary His and/or Fe mitigate cataract formation. KEY WORDS

The development of cataracts in Atlantic salmon, Salmo salar L., was studied in 16 groups of smolts fed diets differing in prooxidant (iron, copper, manganese) and antioxidant (vitamin E, vitamin C, astaxanthin) composition and lipid level for 23 weeks in sea water, using a 2(7-3) reduced factorial design. The seven dietary variables were systematically varied at low (requirement level and 150 g lipid kg(-1)) and high levels (below known toxic levels and 320 g lipid kg(-1)). A mean endpoint cataract incidence of approximately 36% was observed. High dietary levels of vitamin C and astaxanthin reduced cataract frequency, whereas high dietary lipid level, iron and manganese were associated with increased cataract frequencies. Considering the nutritional status of selected organs of the fish, only the status of ascorbic acid correlated negatively to cataract development (P < 0.05). The lens glutathione (GSH) status was not correlated to cataract frequency, nor statistically explained by the dietary variables. However, the study shows that balancing the diet with respect to pro- and antioxidant nutrients may significantly protect Atlantic salmon against development of cataracts. An incidence of reversible osmotic cataract observed at week 14 was positively correlated to plasma glucose concentration.

Cone-rod dystrophy is a retinal degenerative disorder occurring naturally in man and dog. Here we identify a novel gene for early-onset cone-rod dystrophy in the wire-haired dachshund. For the first time, we use genome-wide association-based Sibling Transmission Disequilibrium Test (sibTDT) analysis of only 13 discordant sib-pairs to identify a single significantly associated 6.5-Mb region (PrawTDT = 4.8 × 10−5, PgenomeTDT = 6 × 10−4) on canine chromosome 5, containing more than 70 genes. Segregation studies using microsatellites in the candidate region including additional meiosis supported the sibTDT analysis but could not further reduce the area. Candidate gene resequencing identified a 180-bp deletion in exon/intron 5 of NPHP4 (nephronophthisis 4, also known as nephroretinin). RT-PCR analysis of NPHP4 in cases and controls showed exon skipping of exon 5, resulting in a truncated protein that retains the binding domain interacting with nephronophthisis 1 (also known as nephrocystin-1) in the kidney but lacks the domain interacting with RPGRIP1 in retina. We suggest that this deletion in the canine NPHP4 gene is the cause of cone-rod dystrophy in the standard wire-haired dachshund. In humans, mutations in NPHP4 have been associated with simultaneous eye and kidney disease. Here we describe the first naturally occurring mutation in NPHP4 without additional kidney disease. Further studies will permit elucidation of the complex molecular mechanism of this retinopathy and the development of potential therapies.

This study was conducted to investigate protein synthesis rates and metabolism of histidine (His)-derivatives in lenses of Atlantic salmon (Salmo salar L.) of different dietary His background during parr–smolt transformation. Two populations of Atlantic salmon parr of equal origin were established in freshwater (FW), 3 months prior to transfer to seawater (SW). The populations were fed either a control diet (CD) containing 8.9 g kg-1 His or the same diet added crystalline His to a total level of 14.2 g kg-1 (HD). On the basis of these two populations, 14C His force-feeding studies were performed; in FW 3 weeks prior to sea transfer and in SW 6 weeks after transfer. The studies were conducted by force-feeding the respective diets enriched with 14C labelled His, with subsequent measurements of incorporation of 14C His into lens free amino acid pool, as well as into lens proteins and other free His pool fractions. The latter included the major lens imidazole N-acetylhistidine (NAH). Lens concentrations of His and NAH were clearly influenced by dietary His history, both in parr and smolt. The lens His and NAH concentrations in the CD population were considerably lower in SW than in FW, while in the HD group the His level was equal and the NAH level 50% higher in SW than in FW. Fractional synthesis rate for NAH, KS (NAH), in FW was 8.2 and 4.2 µmol g-1 day-1 for fish in the CD and HD populations, respectively. The corresponding KS (NAH) values in SW were 5.1 and 33.0 µmol g-1 day-1. Our data show that free His is rapidly converted to NAH in the lens, and that NAH seems to have a very high turnover, especially in salmon reared in SW. Fractional synthesis rate for lens proteins, KS (PROTEIN), ranged between 1.8 and 17.3% day-1 (182 and 2791 µg g-1 day-1, respectively), and was generally higher in SW than in FW (P < 0.01). In SW, KS (PROTEIN) was highest in fish in the HD population (P < 0.05), whereas lens protein retention in the HD group was significantly lower than the CD group (P = 0.01). In a second model assuming that His from lens NAH is available for protein synthesis, calculated values of KS (PROTEIN) ranged between 0.17% day-1 (17.6 µg g-1 day-1) and 0.48% day-1 (70.2 µg g-1 day-1). Cataract scores recorded in the His populations at a later point (day 204), showed that the CD fish had significantly higher mean cataract scores than individuals in the HD population (P < 0.01), confirming that low levels of lens His and NAH are associated with cataract development