The nitroxide 4-methoxy TEMPO inhibits neutrophil-stimulated kinase activation in H9c2 cardiomyocytes.

After acute myocardial infarction (AMI), neutrophils are recruited to the affected myocardium. Hypochlorous acid (HOCl) produced by neutrophil myeloperoxidase (MPO) damages cardiomyocytes and potentially expands the primary infarct. Rat cardiomyocyte-like cells were incubated with isolated human neutrophils treated with chemical activators in the absence or presence of nitroxide 4-methoxy-Tempo (MetT; 25 µM) for 4, 6 or 24 h; studies with reagent HOCl served as positive control. Treating cardiomyocytes with activated neutrophils or reagent HOCl resulted in a marked increase in protein tyrosine chlorination and a decline in protein tyrosine phosphatase (PTP) activity. On balance our data also supported an increase in phosphorylation of MAPK p38 and ERK1/2 suggestive of an intracellular hyperphosphorylation status and this was accompanied by decreases in cell viability, as judged by assessing caspases-3/7 activity. For cells exposed to activated neutrophils receptor-mediated uptake of transferrin decreased although total matrix metalloproteinase (MMP) activity was unaffected. Addition of MetT ameliorated protein tyrosine chlorination, decreased MAPK activity and restored receptor-mediated transferrin uptake and PTP activity in cardiomyocytes. Overall, adverse effects of neutrophil-derived HOCl on cultured cardiomyocytes were ameliorated by MetT suggesting that nitroxides may be beneficial to inflammatory pathologies, where neutrophil recruitment/activation is a prominent and early feature.

Steric, electronic, and secondary effects on the coordination chemistry of ionic phosphine ligands and the catalytic behavior of their metal complexes.

The effects of introducing ionic functionalities in phosphine ligands on the coordination chemistry of these ligands and the catalytic behavior of the corresponding metal complexes are reviewed. The steric and electronic consequences of such functionalizations are discussed. Apart from these steric and electronic effects, the presence of charged groups often leads to additional, supramolecular interactions that occur in the second coordination sphere of the metal complex, such as intramolecular, interligand hydrogen bonding and Coulombic repulsion. These interactions can significantly alter the behavior of the phosphine ligand in question. Such effects have been observed in phosphine-metal association/dissociation equilibria, ligand substitution reactions, and stereoisomerism in phosphine-metal complexes. By drawing general conclusions, this review offers an insight into the coordination and catalytic behavior of phosphine ligands containing ionic functionalities and their corresponding metal complexes.

Hexacationic Dendriphos ligands in the Pd-catalyzed Suzuki-Miyaura cross-coupling reaction: scope and mechanistic studies.

The combination of Pd(2)dba(3) x CHCl(3) and hexacationic triarylphosphine-based Dendriphos ligands (1-3) leads to a highly active catalytic system in the Suzuki-Miyaura cross-coupling reaction. Under relatively mild reaction conditions, nonactivated aryl bromides and activated aryl chlorides can be coupled at a low Pd loading (0.1 mol %). The observed activity of this catalytic system, in particular in coupling reactions of aryl chlorides, is dramatically higher than that of conventional Pd catalysts employing triarylphosphine ligands. Through control and poisoning experiments, it is concluded that a homogeneous Pd(0)-Dendriphos complex is the active species in this catalytic system. Despite their triarylphosphine-based structure, Dendriphos ligands behave as very bulky phosphine ligands and lead to a preferential formation of coordinatively unsaturated and catalytically active Pd(0) species, which explains the observed high catalytic activity for these systems. The presence of six permanent cationic charges in the backbone of this class of ligands is proposed to result in a significant interligand Coulombic repulsion and plays a crucial role in their bulky behavior. In the coupling reactions of activated aryl chlorides, a positive dendritic kinetic effect was observed among the different Dendriphos generations, indicating an increased ability of the higher ligand generations to stabilize the active species due to steric effects. For aryl bromides, no dendritic effect was observed due to a shift in the rate-determining step in the catalytic cycle, from oxidative addition for aryl chlorides to transmetalation for aryl bromides.

Organic transformations on sigma-aryl organometallic complexes.

This work reviews recent developments in the field of organic transformations on sigma-aryl organometallic complexes. The general notion that M--C sigma bonds are kinetically labile, highly reactive, and incompatible with typical reaction conditions met in organic synthesis has limited the use of these synthetic strategies thus far. However, organic transformations on metal-bound sigma-aryl fragments are being used more and more by chemists in both industry and academia. In this Review, emphasis is put on the synthetic methods applied in this field up to now. The simplicity and generally good yields of these methods are very attractive for the construction of functionalized organometallic building blocks that are potentially useful as photochemical molecular devices, biosensors and -conjugates, or molecular switches. Thus, this Review has been tailored for a broader audience with the aim of encouraging the application of these strategies.

Heart rate turbulence after ventricular premature beats in healthy Doberman pinschers and those with dilated cardiomyopathy.

OBJECTIVES: To describe the measurement of heart rate turbulence (HRT) after ventricular premature beats and compare HRT in healthy Doberman pinschers and those with dilated cardiomyopathy (DCM), with and without congestive heart failure (CHF). ANIMALS: Sixty-five client-owned Dobermans: 20 healthy (NORMAL), 31 with preclinical DCM and 14 with DCM and CHF (DCM + CHF). METHODS: A retrospective study of data retrieved from clinical records and ambulatory ECG (Holter) archives, including data collected previously for a large-scale prospective study of Dobermans with preclinical DCM. Holter data were reanalysed quantitatively, including conventional time-domain heart rate variability and the HRT parameters turbulence onset and turbulence slope. RESULTS: Heart rate turbulence could be measured in 58/65 dogs. Six Holter recordings had inadequate ventricular premature contractions (VPCs) and one exhibited VPCs too similar to sinus morphology. Heart rate turbulence parameter, turbulence onset, was significantly reduced in DCM dogs, whereas conventional heart rate variability measures were not. Heart rate variability and HRT markers were reduced in DCM + CHF dogs as expected. CONCLUSIONS: Heart rate turbulence can be measured from the majority of good quality standard canine 24-hour Holter recordings with >5 VPCs. Turbulence onset is significantly reduced in Dobermans with preclinical DCM which indicates vagal withdrawal early in the course of disease. Heart rate turbulence is a powerful prognostic indicator in human cardiac disease which can be measured from standard 24-hour ambulatory ECG (Holter) recordings using appropriate computer software. Further studies are warranted to assess whether HRT may be of prognostic value in dogs with preclinical DCM and in other canine cardiac disease.

The effects of New York state's ban on multiple listing for cadaveric kidney transplantation.

OBJECTIVE: To study the effectiveness of a 1990 ban by New York state on entry to more than one waiting list for a cadaver kidney transplant, and the impact of the ban on equity in access to transplantation. DATA SOURCES: (1) Waiting list files from the Organ Procurement and Transplantation Network, (2) the Health Care Financing Administration's Medicare Program Management and Medical Information System, and (3) U.S. Census Public Use Files. STUDY DESIGN: Multivariate hazard models were used to estimate the impact of the ban of the overall odds of multiple listing and on the odds of multiple listing at in-state and out-of-state transplant centers. After estimating the relationship between multiple listing and subsequent transplantation, we used simulation techniques to estimate the effects of a complete multiple listing ban on group waiting time differentials. Independent variables included demographic/socioeconomic characteristics, measures of ESRD severity, general transplantation suitability, measures that affect the likelihood of finding a good donor organ, and measures of the productivity of the transplant/dialysis center. PRINCIPAL FINDINGS: The ban was associated with a 66 percent reduction in the rate of multiple listing for New York patients, and multiple listing at in-state transplant centers declined by 87 percent. Simulation results suggested that even a completely effective ban would produce only small, mixed equity effects. CONCLUSIONS: While the ban was effective in reducing the proportion of patients who registered at multiple transplant centers, taken together the results suggest that banning multiple listing is not likely to result in large improvements in equity in access to transplantation.

Risk factors associated with early respiratory disease complex in broiler chickens.

Early respiratory disease complex (ERDC) is a term coined to describe an acute disease characterized by depression, respiratory distress, and increased mortality in 2-to-3-wk-old broiler chickens. Postmortem lesions include airsacculitis, fibrinous pericarditis, and perihepatitis. Colisepticemia is the primary cause of death. In order to investigate the association between ERDC and farm management factors, a retrospective case-control study was conducted by collecting data covering a 6-mo period (January-June 1997) from four broiler integrators on the Delmarva peninsula. Univariate and multivariate statistical analyses revealed that flock size was positively associated (P = 0.02) and layout time was negatively associated (P = 0.05) with ERDC.

Luteinizing hormone and growth hormone concentrations in serum of prepubertal gilts treated with N-methyl-D,L-aspartate.

Prepubertal Yorkshire gilts, 189 d of age and 96 kg body weight (BW), were used to determine the effects of intravenous injections of N-methyl-D,L-aspartate (NMA) on circulating concentrations of luteinizing hormone (LH) and growth hormone (GH). In Experiment 1, blood was sampled from four gilts every 15 min for 2 hr on four consecutive days. One hour after the initiation of sampling on each day, gilts received either vehicle (0.9% saline solution) or 1.25, 2.5, or 5 mg of NMA/kg BW as per a 4 x 4 latin square arrangement of treatments. There was no effect of treatment (P > 0.1) on concentrations of LH in serum. However, relative to vehicle-treated animals, gilts administered 2.5 mg of NMA/kg BW had elevated (1,120%; P < 0.05) circulating levels of GH. In Experiment 2, samples were collected from 15 gilts at 15-min intervals for 1 hr before and 1 hr after NMA (10 mg/kg BW; n = 8) or vehicle (n = 7). NMA increased serum concentrations of both LH (by 80%; P < 0.05) and GH (by 700%; P < 0.01). We suggest that LH and GH secretion in gilts was enhanced by treatment with NMA.

Basic hearing tests.

This article contains a discussion of pure-tone and speech audiometry as these measures relate to primary audiologic evaluation of hearing. The scientific foundation underlying the development of stimulus-specific standards for normal hearing, test materials, and methods for basic tests are included. A rationale for test administration, masking, and interpretation of results is presented.

Growth performance and adipose tissue deposition in barrows fed n-methyl-D,L-aspartate.

We previously reported that broilers fed n-methyl-D,L-aspartate (NMA) exhibited enhanced feed conversion efficiency and decreased percentage of fat in carcasses. In this experiment, growth performance and backfat thickness were evaluated in barrows fed NMA. Poland China x Yorkshire barrows weighing 68.8 +/- 1.7 kg (mean +/- SE) were allowed ad libitum access to feed containing NMA at levels of either 0 (n = 7), 100 (n = 6), 200 (n = 8), or 300 (n = 8) mg/kg for 36 d. Barrows were slaughtered at 99.5 +/- 2.3 kg BW. There was no effect (P > 0.1) of NMA on ADG or feed consumption. Gain:feed ratio decreased (P < 0.03) in a linear fashion with increasing level of NMA. There was a cubic effect (P < 0.05) of NMA treatment on first-rib backfat thickness. In response to graded levels of NMA, backfat thickness at the 10th rib (P < 0.08) and last rib (P < 0.03) increased in a linear fashion. The NMA had no effect (P > 0.1) on backfat thickness measured at the lumbar vertebra or longissimus muscle area measured at the 10th rib interface. The percentage of lean in the carcass decreased in a linear fashion (P < 0.05) in response to increasing levels of NMA in the diet. In summary, NMA had an overall negative effect on growth performance and carcass yield characteristics in barrows. The dichotomous effects of NMA on feed efficiency and body composition in poultry and swine warrants further scrutiny.

N-methyl-D,L-aspartate-induced growth hormone secretion in barrows: possible mechanisms of action.

Four experiments were conducted to determine mechanisms by which n-methyl-d,l-aspartate (NMA) increases serum concentrations of growth hormone (GH). Blood samples were collected from barrows every 15 min for 2 h (Exp. 1, 2, and 3) or 3 h (Exp. 4) immediately before and immediately after i.v. treatments. In Exp. 1, barrows (n = 4/treatment) received either .9% saline or 1.25, 2.5, or 5 mg of NMA/kg of BW. The change in circulating GH concentrations was greater (P < .05) for barrows receiving 2.5 mg (by 883%) or 5.0 mg of NMA/kg of BW (by 1,095%) than for those injected with saline. In Exp. 2, barrows (n = 4/treatment) received NMA (2.5 mg/kg of BW) or injections of 1.25 mg of the pure d or pure 1 isomers of NMA/kg of BW. Growth hormone concentrations increased by 177% (P < .025) after NMA treatment and by 245% (P < .01) after injection of the pure d isomer of NMA. The pure 1 isomer of NMA had no effect (P > .1) on GH concentrations. In Exp. 3, barrows received NMA (2.5 mg/kg of BW) 10 min after i.m. injection of saline (n = 7) or ketamine hydrochloride ( n = 8; 19.9 mg/kg of BW), an n-methyl-d-aspartate (NMDA) receptor antagonist. The NMA increased (P < .01) GH concentrations by 289% in saline-pretreated barrows but had no effect (P > .1) on barrows pretreated with ketamine hydrochloride. In Exp. 4, barrows (n = 4/treatment) received NMA 3 h after i.v. pretreatment with antisera to GH-releasing factor (GRF; 154 mL) or no pretreatment. Serum GH concentrations increased by 166% (P < .05) after injection of NMA in barrows receiving no pretreatment. The NMA had no effect (P > .1) on GH concentrations in barrows receiving antisera to GRF. Our results support the concept that NMDA stimulates GRF, and hence GH secretion, by activating an NMDA receptor.

One-year vestibular and balance outcomes of Oklahoma City bombing survivors.

This multisite investigation assessed subjective, behavioral, and objective balance function in 30 blast survivors. Subjects with vertigo, dizziness, or imbalance were screened (n = 6) or evaluated (n = 27) during 1 year. Tests included a questionnaire, electronystagmography (ENG), and computerized dynamic posturography (CDP). Ninety-seven percent of subjects were located inside a building during the blast, and 63 percent of subjects experienced dysequilibrium within 48 hours. Forty-three percent of symptoms could not be attributed to head injury. Sixty percent of subjects had abnormal ENG and/or CDP; ENG abnormalities mostly were peripheral or nonlocalizing, whereas CDP patterns were "vestibular," "surface dependent," and "physiologically inconsistent." At 1-year postblast, 55 percent of initially abnormal CDP results were normal, and 72 percent of subjects said symptoms were unchanged or occurred intermittently. A serial, test battery approach is recommended to assess symptoms. Blast-related dysequilibrium had clinically significant manifestations and should be considered a valid component of aural blast injury.

One-year audiologic monitoring of individuals exposed to the 1995 Oklahoma City bombing.

This longitudinal study evaluated subjective, behavioral, and objective auditory function in 83 explosion survivors. Subjects were evaluated quarterly for 1 year with conventional pure-tone and extended high-frequencies audiometry, otoscopic inspections, immittance and speech audiometry, and questionnaires. There was no obvious relationship between subject location and symptoms or test results. Tinnitus, distorted hearing, loudness sensitivity, and otalgia were common symptoms. On average, 76 percent of subjects had predominantly sensorineural hearing loss at one or more frequencies. Twenty-four percent of subjects required amplification. Extended high frequencies showed evidence of acoustic trauma even when conventional frequencies fell within the normal range. Males had significantly poorer responses than females across frequencies. Auditory status of the group was significantly compromised and unchanged at the end of 1-year postblast.

Effects of ferrous sulfate consumption on the performance of broiler chicks.

Ferrous sulfate is often used as a litter treatment to control ammonia. A series of experiments was conducted to evaluate the effects of single high and multiple low doses of ferrous sulfate (FeSO4-7H2O) on broiler chicks. In Experiment 1, broiler chicks were administered a single oral dose of ferrous sulfate. A direct relationship between mortality and the amount of ferrous sulfate administered was evident. The lethal dose that caused 50% mortality (LD50) for ferrous sulfate was calculated to be 7,010 mg/kg of body weight. In Experiment 2, the addition of ferrous sulfate to the diet at levels from .75 to 12% decreased feed consumption. Ferrous sulfate levels of 3% or greater lowered average daily gain and gain:feed ratios. In a pair-wise comparison preference test in Experiment 3, chicks significantly decreased consumption of a diet containing 3% ferrous sulfate but not of a diet with .375% ferrous sulfate. The results of these experiments indicate that ferrous sulfate can have adverse effects on mortality, weight gain, and feed efficiency of broiler chicks.

Development of a quantitative method for the evaluation of varus-angular bone deformity in chickens.

A quantitative technique was developed to measure the degree of flexion (twisting) and torsion (angulation) of the tibiotarsus bone from chickens affected with varus-angular bone deformity (varus-ABD). A plexiglass device was constructed consisting of X, Y, and Z-axis planes. The Y-axis plane was used to position the tibia in a constant reference position. The distance in millimeters from the (0, 0, 0) coordinate to the (X', 0, 0) coordinate was used to measure medial tibial flexion (TF), and the distance from the (0, 0, 5 cm) coordinate to the (X', 0, 5 cm) coordinate was used to measure lateral TF. The X-axis plane was fitted with a protractor to measure the angle of the proximal head of the tibia as a measure of tibial torsion (TT). The Z-axis plane was used to measure tibial length. Tibias with mild varus-ABD had TF values of greater than 0 but less than or equal to 5 mm, whereas severe varus-ABD tibias had TF values of greater than 5 mm. The TT values ranged from 10 to 60 degrees, with the lower values associated with severe varus-ABD.

The effect of feed restriction and Eimeria maxima infection with or without medication on growth and feed intake in broilers.

Day-old male broiler chicks were raised in floor pens. At 4 days of age, birds in 75% of the pens were inoculated with Eimeria maxima via the feed. There were four dietary treatments: uninoculated, unmedicated control (UUC), infected, unmedicated control (IUC), infected, halofuginone-medicated (3 ppm, HM), or infected, salinomycin-medicated (66 ppm, SM). At 6 days of age, birds in 50% of the pens of each treatment were restricted for 5 days to their maintenance energy intake level. The remainder consumed feed ad libitum. Medication reduced growth from 0 to 6 days of age and feed intake was depressed, irrespective of medication, in infected birds from 0 to 21 days of age. Growth, however, was improved with intake of coccidiostat over IUC from 6 to 11 days of age but did not match UUC until 28 days of age. At 42 and 49 days of age, infected birds were lighter than UUC birds. Dressing percentage for HM and SM birds was greater than that of UUC birds at 49 days of age but HM birds also had a greater percentage of abdominal fat at both 42 and 49 days of age. Feed restriction resulted in some compensatory growth immediately following refeeding. Experimental feed:gain ratio was improved in restricted birds (1.98 versus 2.03 g:g). At 42 and 49 days of age, restricted birds were lighter than birds eating ad libitum and also had a significantly greater percentage abdominal fat. A lower breast yield was observed at 42 days of age in restricted birds.

Nutritional myopathy in a cat.

A case of nutritional myopathy in a cat primarily caused by vitamin E deficiency is described. The animal which had been fed a diet consisting almost entirely of boiled Norwegian coley, was presented with swollen muscles in both the hind and fore legs. Sections of biopsy material revealed chronic, severe myositis, with normal muscle tissue undergoing a series of degenerative changes. Correct dietary management, with multivitamin and mineral supplementation, led to a complete clinical recovery, the cat regaining full use of its legs within 14 days.

Long-term impact on a closed household of pet cats of natural infection with feline coronavirus, feline leukaemia virus and feline immunodeficiency virus.

A closed household of 26 cats in which feline coronavirus (FCoV), feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) were endemic was observed for 10 years. Each cat was seropositive for FCoV on at least one occasion and the infection was maintained by reinfection. After 10 years, three of six surviving cats were still seropositive. Only one cat, which was also infected with FIV, developed feline infectious peritonitis (FIP). Rising anti-FCoV antibody titres did not indicate that the cat would develop FIP. The FeLV infection was self-limiting because all seven of the initially viraemic cats died within five years and the remainder were immune. However, FeLV had the greatest impact on mortality. Nine cats were initially FIV-positive and six more cats became infected during the course of the study, without evidence of having been bitten. The FIV infection did not adversely affect the cats' life expectancy.