1. The welfare of male and female male-line turkeys fed ad libitum or food-restricted was determined at 4, 8, 12, 16, 20, 24, 28, 36(38) and 46(48) weeks of age using behavioural and physiological indices of well-being. Traditional turkeys fed ad libitum were kept as a control treatment. Restricted male and female male-line turkeys were fed to 0-5 during rearing and subsequently to 0-8 of sex-specific ad libitum-fed body weight. In another treatment, male-line males were fed ad libitum to 18 weeks and 0.8 of ad libitum thereafter. 2. Traditional turkeys and restricted male-line turkeys were more active than ad libitum-fed birds of both sexes. Restricted turkeys showed a high incidence of wall pecking. In the breeding period, about 0.4 of the observations of male-line males were of strutting behaviour whereas traditional male turkeys showed no strutting behaviour at the end of the breeding period. 3. The heterophil lymphocyte ratio (HLR) and the proportion of basophils were not increased in food-restricted turkeys. The HLR was relatively low in traditional birds, compared with male-line turkeys during the rearing period. 4. Plasma corticosterone concentrations were increased by food restriction during the rearing period. Corticosterone concentrations were relatively high in traditional turkeys at 4 and 8 weeks of age only. 5. Plasma lactate dehydrogenase (LIDH) activity was higher from 12 to 24 weeks of age in ad libitum-fed male-line turkeys and was consistent with mortality from cardiovascular disease in this group of turkeys. The pattern of activity of aspartate transaminase was similar, and alkaline phosphatase was inversely related to that of LDH. 6. It was concluded that turkeys may be better able to adjust physiologically to the demands of food restriction than broiler breeders and that there were few deleterious consequences of restricting male turkeys after 18 weeks of age. Male-line turkeys were less active than traditional turkeys.

Animal Feed↗

PubMed1999

Morphological and physiological characteristics of discontinuous linear atrial ablations during atrial pacing and atrial fibrillation.

INTRODUCTION: Linear atrial ablations are thought to be necessary to accomplish successful catheter ablation of atrial fibrillation. In order to investigate the conduction characteristics of atrial myocardium in regions of linear lesion discontinuity (gaps), we performed activation sequence mapping in gap regions during atrial pacing and atrial fibrillation. METHODS AND RESULTS: In seven dogs, a linear epicardial ablation was created on the right atrial free wall with a discontinuous segment (gap) in the mid-portion of the lesion. A plaque electrode was used to measure conduction across the gap. Conduction was assessed during (1) atrial pacing from the edge of the plaque electrode during sinus rhythm, and (2) during atrial fibrillation. After each series of measurements, the lesion gap was decreased by creating additional radiofrequency ablations and repeat conduction maps were obtained. The process was repeated until conduction block was observed during atrial pacing. Gap lengths ranged from 0 to 25 mm. During atrial pacing, gaps as narrow as 2 mm demonstrated normal conduction and gaps as large as 5 mm demonstrated block during pacing. Although conduction block was never present across gaps greater than 5 mm, the ability to predict conduction block as a function of gap width was difficult for lesions < or = 5 mm due to a significant degree of overlap between normal conduction and conduction block in this gap range. During atrial fibrillation, 1/175 (0.6%) mapped wavelets conducted across gaps that demonstrated block during pacing; whereas, 411/600 (68.5%; P < 0.0001) wavelets conducted across gaps that did not demonstrate block during pacing (P = NS compared to preablation measurements). Histologically normal atrial myocytes were observed within gaps exhibiting conduction block. CONCLUSIONS: Visible gaps > 5 mm rarely demonstrate conduction block during atrial pacing and atrial fibrillation; whereas, gaps < or = 5 mm in length may demonstrate block. Lesion gaps that do not demonstrate conduction block during atrial pacing have no higher rate of functional conduction block during atrial fibrillation than fibrillating atria without ablation lesions.

Animals↗

PubMed1999

Serologic survey for selected infectious disease agents in raccoons from Illinois.

The determination of serologic titers to infectious organisms is a valuable tool for quantitating exposure to disease organisms. Raccoons (Procyon lotor) were live-trapped from September 1989 to October 1993 and samples collected from two distinct locations in west-central Illinois (USA); a state recreational facility (Park) and privately owned farming property (Farm). Sera were submitted for testing Leptospira interrogans (serovars bratislava, canicola, grippotyphosa, hardjo, icterohemmorhagiae, and pomona), canine distemper virus (CDV), pseudorabies virus (PV), and Toxoplasma gondii. Two-hundred and twenty-two (48%) of 459 raccoons were seropositive for L. interrogans. Eighty-five (23%) out of 368 raccoons were seropositive for canine distemper virus. Eighty-two (17%) of 479 raccoons raccoons were seropositive for pseudorabies virus. One hundred and eight-four (49%) of 379 raccoons were seropositive for T. gondii. A significant difference (P < 0.05) in seroprevalence for L. interrogans between the park (43%) and farm (52%) areas was found. A correlation between increasing age and seroprevalence was found for L. interrogans, CDV, PV, and T. gondii. Furthermore, there was a significant difference in seroprevalence for T. gondii during the spring trapping seasons (73%), when compared with the fall (33%). This type of information on exposure to infectious agents is important for developing control programs to manage raccoon-human and raccoon-domestic animals interactions.

Age Distribution↗

PubMed1999

Periodontal and dental lesions in raccoons from a farming and a recreational area in Illinois.

Dental health was evaluated in two populations of raccoons (Procyon lotor) in western Illinois (USA); one was from a rural agricultural area with low human density and the other from a nearby state park heavily used by humans and raccoons. From 1989 through 1993, 300 raccoons were live-trapped in the agricultural area and 246 raccoons were live-trapped in the park. Oral health was assessed using gingival and calculi indices and by measuring loss of attachment and tooth wear. Raccoons from the park were significantly older and smaller, but not thinner, than raccoons from the farmed area. Gingival and periodontal indices, tooth wear, tooth loss, and caries increased significantly from juveniles to yearlings to adults, at both sites. Males had higher levels of gingivitis and loss of periodontal attachment than females, but were similar on other dental measures. There were no seasonal differences between raccoons in dental indices. Animals with high scores for one oral measure tended to have high values for all indices. Dental health was generally good for juveniles and yearlings from both sites. Among adults, periodontal indices and the prevalence of caries were significantly higher in the park, but prevalence of broken or missing teeth was similar for both populations. There was no association between body condition, and a higher dental score or more missing or broken teeth.

Age Factors↗

PubMed1998

Comparative study of fluoroscopy and intracardiac echocardiographic guidance for the creation of linear atrial lesions.

BACKGROUND: Recently, attempts have been made to cure atrial fibrillation by creating multiple linear atrial lesions with radiofrequency energy. Intracardiac echocardiography (ICE) offers imaging of endocardial anatomy and the ablation electrode-tissue interface not available with standard fluoroscopy. This study sought to prospectively compare fluoroscopic with ICE guidance for the creation of linear atrial lesions in a canine model. METHODS AND RESULTS: The creation of 3 linear atrial lesions was attempted in each of 10 dogs, half guided by fluoroscopy alone and half by ICE. Coil-tissue contact was prospectively graded. After ablation, animals were euthanized, and the location and continuity of lesions were evaluated. ICE guidance led to a higher percentage of successful applications (P=0.02) and mean achieved temperature (P=0. 004). The contact scores of excellent, fair, and poor correlated well with successful energy delivery, mean temperature, and efficiency of heating (P<0.0001). In 25% of the blinded energy deliveries, the location, as determined by the ablation operator, differed from that of ICE. Pathological evaluation revealed improved lesion formation in the ICE-guided compared with the ICE-blinded group. Lesions were found outside the target areas in the ICE-blinded but not the ICE-guided group. CONCLUSIONS: Compared with fluoroscopy, ICE guidance improved targeting, energy delivery, and lesion formation in this canine model. This study suggests that ICE guidance improves lesion formation and prevents energy delivery to potentially dangerous sites.

Analysis of Variance↗

PubMed1998

Synthetic matrix metalloproteinase inhibitors and tissue inhibitor of metalloproteinase (TIMP)-2, but not TIMP-1, inhibit shedding of tumor necrosis factor-alpha receptors in a human colon adenocarcinoma (Colo 205) cell line.

The solubilization of plasma membrane receptors through proteolytic cleavage of the ligand binding domain at the cell surface is an important mechanism for regulating cytokine function and receptor signaling. The inhibition of the shedding of a variety of receptors by synthetic inhibitors of the matrix metalloproteinases (MMPs) implicates metalloproteinases in this regulatory event. We examined the effects of two naturally occurring tissue inhibitors of metalloproteinases, TIMP-1 and TIMP-2, and several synthetic MMP inhibitors (MMPIs) on the shedding of both tumor necrosis factor alpha receptor type I (TNFalpha-RI; Mr 55,000) and TNFalpha-RII (Mr 75,000) by the Colo 205 human colon adenocarcinoma cell line. Culture of Colo 205 cells for 48 h resulted in the shedding of both TNFalpha-RI and TNFalpha-RII, as determined by ELISA. The shedding of TNFalpha receptors was not affected by TIMP-1 or protease inhibitors aprotinin, pepstatin, or leupeptin but was inhibited in a dose-dependent manner by the following synthetic MMPIs: batimastat and marimastat (BB-94 and BB-2516, respectively, British Biotech, Inc.); CT1418 (Celltech Therapeutics); CGS27023A (Novartis Pharmaceuticals); and RO31-9790 (Roche), with IC50s ranging from 3.2 to 38.0 microM. Similarly, TIMP-2 from two different sources reproducibly inhibited the shedding of both TNFalpha-RI and TNFalpha-RII in a dose-dependent manner (IC50 = 286 +/- 33 nM for TNFalpha-RI shedding and 462 +/- 52 nM for shedding of TNFalpha-RII). The inhibition of TNFalpha-RI shedding was confirmed in the SW626 human ovarian adenocarcinoma cell line. The synthetic MMPIs and TIMP-2, but not TIMP-1, also caused a dose-dependent increase in the number of TNFalpha receptors retained on the surface of Colo 205 cells, as determined by flow cytometry. Inhibition of TNFalpha receptor shedding with TIMP-2 occurs at molar concentrations 10-100 times less than those required with low molecular weight, synthetic MMPIs but at concentrations greater than those required to inhibit collagen degradation. Modulation of TNFalpha receptor shedding by TIMP-2 could have important implications for the pleiotropic effects of TNFalpha in both normal and malignant cells and for the pharmacological activity of synthetic MMPIs.

Adenocarcinoma↗

PubMed1998

Linear atrial ablations in a canine model of chronic atrial fibrillation: morphological and electrophysiological observations.

BACKGROUND: To test the hypothesis that susceptibility to sustained atrial fibrillation may be decreased by creation of linear atrial ablations, we established a canine model of chronic atrial fibrillation and used a novel catheter design to create atrial ablations. METHODS AND RESULTS: Chronic atrial fibrillation was induced in 16 dogs by creation of mitral regurgitation and rapid pacing of the atria. Temperature-controlled radiofrequency ablations were attempted along empirically derived, preselected atrial target sites in 11 dogs (ablation group), and a sham procedure was performed in 5 dogs (control group). Follow-up electrophysiology study and pathological examination were conducted 13+/-5 days after the initial procedure. Immediately after ablation, sustained atrial fibrillation could be initiated in 1 of 9 surviving ablation dogs and 5 of 5 controls (P=.004). Four dogs died within 24 hours of the procedure. Permanent pacing was required in 4 dogs. At follow-up, 0 of 7 ablation dogs and 5 of 5 controls had atrial fibrillation (P=.001). Furthermore, 2 of 7 ablation dogs had sustained atrial tachycardias, one of which was successfully ablated. Pathological examination demonstrated frequent incomplete lesion sets and discontinuous lesions. CONCLUSIONS: In this model, a reduction in the susceptibility to sustained atrial fibrillation can be achieved by long linear atrial ablations created with specially designed coil electrode catheters. Complete lesion continuity was not required to achieve a therapeutic effect.

Animals↗

PubMed1998

Structural characterizations of nonpeptidic thiadiazole inhibitors of matrix metalloproteinases reveal the basis for stromelysin selectivity.

The binding of two 5-substituted-1,3,4-thiadiazole-2-thione inhibitors to the matrix metalloproteinase stromelysin (MMP-3) have been characterized by protein crystallography. Both inhibitors coordinate to the catalytic zinc cation via an exocyclic sulfur and lay in an unusual position across the unprimed (P1-P3) side of the proteinase active site. Nitrogen atoms in the thiadiazole moiety make specific hydrogen bond interactions with enzyme structural elements that are conserved across all enzymes in the matrix metalloproteinase class. Strong hydrophobic interactions between the inhibitors and the side chain of tyrosine-155 appear to be responsible for the very high selectivity of these inhibitors for stromelysin. In these enzyme/inhibitor complexes, the S1' enzyme subsite is unoccupied. A conformational rearrangement of the catalytic domain occurs that reveals an inherent flexibility of the substrate binding region leading to speculation about a possible mechanism for modulation of stromelysin activity and selectivity.

Animals↗

PubMed1998

Solution structures of stromelysin complexed to thiadiazole inhibitors.

Unregulated or overexpressed matrix metalloproteinases (MMPs), including stromelysin, collagenase, and gelatinase. have been implicated in several pathological conditions including arthritis and cancer. Small-molecule MMP inhibitors may have therapeutic value in the treatment of these diseases. In this regard, the solution structures of two stromelysin/ inhibitor complexes have been investigated using 1H, 13C, and 15N NMR spectroscopy. Both-inhibitors are members of a novel class of matrix metalloproteinase inhibitor that contain a thiadiazole group and that interact with stromelysin in a manner distinct from other classes of inhibitors. The inhibitors coordinate the catalytic zinc atom through their exocyclic sulfur atom, with the remainder of the ligand extending into the S1-S3 side of the active site. The binding of inhibitor containing a protonated or fluorinated aromatic ring was investigated using 1H and 19F NMR spectroscopy. The fluorinated ring was found to have a reduced ring-flip rate compared to the protonated version. A strong, coplanar interaction between the fluorinated ring of the inhibitor and the aromatic ring of Tyr155 is proposed to account for the reduced ring-flip rate and for the increase in binding affinity observed for the fluorinated inhibitor compared to the protonated inhibitor. Binding interactions observed for the thiadiazole class of ligands have implications for the design of matrix metalloproteinase inhibitors.

Binding Sites↗

PubMed1998