Monitoring Mycoplasma gallisepticum and Mycoplasma synoviae infection in breeder chickens after treatment with enrofloxacin.

Three experimental strains of breeder chickens were accidentally exposed to Mycoplasma gallisepticum (MG) and Mycoplasma synoviae (MS), presumably from a newly introduced group of leghorn-type pullets. The experimental strains subsequently became infected and were diagnosed positive for MG and MS by the serum plate agglutination (SPA) test and confirmed by the hemagglutination inhibition (HI) test and the polymerase chain reaction (PCR) of tracheal swabs. Treatment with 10 mg/kg enrofloxacin via drinking water for 14 days was elected.

Diabetes reduces right atrial beta-adrenergic signaling but not agonist stimulation of heart rate in swine.

This study assessed the effects of streptozotocin diabetes in swine on the heart rate response to beta-adrenergic stimulation the adenylyl cyclase signal transduction pathway. Diabetic animals (n = 9) were hyperglycemic compared to the control group (n = 10) (12.6 +/- 1.

Cardiac energetics during ischaemia and the rationale for metabolic interventions.

Cardiac work is supported by high rates of combustion of carbon fuel and oxygen consumption. Fatty acids are the main fuel for the healthy heart, supplying approximately 60-80% of the energy. The balance of the energy comes from the oxidation of glucose and lactate.

In vivo models of myocardial metabolism during ischemia: application to drug discovery and evaluation.

This review examines the in vivo techniques that are available for evaluation of the metabolic effects and efficacy of agents intended for the treatment of myocardial ischemia. Energy substrate metabolism is complex, and requires simultaneous measurement of a variety of processes in order to obtain a thorough understanding of the biochemical mechanisms underlying any functional response. Small animals (from the mouse to the rabbit) are generally not very useful in the study of cardiac metabolism in vivo because it is not possible to sample the coronary venous drainage and measure the rate of substrate uptake or metabolite efflux.

Alterations in enzymes involved in fat metabolism after acute and chronic altitude exposure.

The purpose of this study was to examine the effect of acute (24 h) and chronic (5 wk) hypobaric hypoxic exposure equivalent to a simulated altitude of 4,300 m (446 mmHg) on the enzymes of fat metabolism. Heart, liver, and skeletal muscle were taken from 32 male Sprague-Dawley rats. Altitude exposure did not affect the activity of citrate synthase in any of the tissues, suggesting that mitochondrial content was unchanged.

Partitioning of pyruvate between oxidation and anaplerosis in swine hearts.

The goal of this study was to measure flux through pyruvate carboxylation and decarboxylation in the heart in vivo. These rates were measured in the anterior wall of normal anesthetized swine hearts by infusing [U-(13)C(3)]lactate and/or [U-(13)C(3)] pyruvate into the left anterior descending (LAD) coronary artery. After 1 h, the tissue was freeze-clamped and analyzed by gas chromatography-mass spectrometry for the mass isotopomer distribution of citrate and its oxaloacetate moiety.

Effects of dopamine beta-hydroxylase inhibition with nepicastat on the progression of left ventricular dysfunction and remodeling in dogs with chronic heart failure.

Background: Inhibition of dopamine beta-hydroxylase (DBH) results in a decrease in norepinephrine synthesis. The present study was a randomized, blinded, placebo-controlled investigation of the long-term effects of therapy with the DBH inhibitor nepicastat (NCT) on the progression of left ventricular (LV) dysfunction and remodeling in dogs with chronic heart failure (HF).

Methods And Results: Moderate HF (LV ejection fraction [LVEF] 30% to 40%) was produced in 30 dogs by intracoronary microembolization.

Hypertrophied rat hearts are less responsive to the metabolic and functional effects of insulin.

We determined the effect of insulin on the fate of glucose and contractile function in isolated working hypertrophied hearts from rats with an aortic constriction (n = 27) and control hearts from sham-operated rats (n = 27). Insulin increased glycolysis and glycogen in control and hypertrophied hearts. The change in glycogen was brought about by increased glycogen synthesis and decreased glycogenolysis in both groups.

Characterization and clinical implications of marker chromosomes identified at prenatal diagnosis.

Eighteen fetuses with marker chromosomes were detected at diagnostic amniocentesis in our laboratory among 15 781 amniocentesis samples. Using combined approaches, conventional cytogenetics including special stain techniques and fluorescence in situ hybridization (FISH), we successfully characterized 15 of them, which assisted subsequent genetic counselling. Six marker chromosomes were of sex chromosome origin, each of which substituted a missing sex chromosome, and 12 were supernumerary marker chromosomes (SMCs).

Prenatal diagnosis of Smith-Lemli-Opitz syndrome in a pregnancy with low maternal serum oestriol and a sex-reversed fetus.

A cytogenetically normal male fetus was subsequently found to have female external genitalia, a cardiac malformation and mid-trimester intra-uterine growth retardation by ultrasound examination. The maternal serum oestriol level was low. The combination of low oestriol and sonographic findings suggested Smith Lemli Opitz syndrome (SLO), which was confirmed by a markedly increased amniotic fluid level of 7-dehydrocholesterol.

Beta-receptor blockade decreases carnitine palmitoyl transferase I activity in dogs with heart failure.

Background: Pharmacological inhibition of carnitine palmitoyl transferase I (CPT-I), the enzyme controlling the rate of fatty acid transport into the mitochondria, prevents the contractile dysfunction, myosin isozyme shift and deterioration in sarcoplasmic reticulum Ca2+ handling that occurs in rat models of left ventricular hypertrophy. In this study we examine whether the improved cardiac function with beta blockade therapy in heart failure is associated with an alteration in CPT-I activity.

Methods And Results: We examined dogs with coronary microembolism-induced heart failure treated for 12 weeks with metoprolol (25 mg twice daily).

Cardiovascular effects of nepicastat (RS-25560-197), a novel dopamine beta-hydroxylase inhibitor.

Nepicastat (RS-25560-197) is a novel, selective, and potent inhibitor of dopamine beta-hydroxylase, which modulates catecholamine levels (reduces norepinephrine and elevates dopamine) in cardiovascular tissues. This study was designed to evaluate the cardiovascular effects of nepicastat. Acute oral administration of nepicastat (0.

Ranolazine: a novel metabolic modulator for the treatment of angina.

1. Ranolazine shifts ATP production away from fatty acid oxidation toward glucose oxidation. 2.

Catecholamine modulatory effects of nepicastat (RS-25560-197), a novel, potent and selective inhibitor of dopamine-beta-hydroxylase.

1. Inhibitory modulation of sympathetic nerve function may have a favourable impact on the progression of congestive heart failure. Nepicastat is a novel inhibitor of dopamine-beta-hydroxylase, the enzyme which catalyses the conversion of dopamine to noradrenaline in sympathetic nerves.

Constitutional inversion of chromosome 7 and hematologic cancers.

Nonrandom aberrations of chromosome 7 have been described in various hematopoietic disorders. We describe here two unrelated families with the same constitutional inversion of chromosome 7 [inv(7)(q11.2q22)].

Synthesis and biological evaluation of the enantiomers of the potent and selective A1-adenosine antagonist 1,3-dipropyl-8-[2-(5,6-epoxynorbonyl)]-xanthine.

The individual enantiomers 8 and 12 of the potent and highly selective racemic A1-adenosine antagonist 1,3-dipropyl-8-[2-(5,6-epoxynorbornyl)]xanthine (ENX, 4) were synthesized utilizing asymmetric Diels-Alder cycloadditions for the construction of the norbornane moieties. The absolute configuration of 12 was determined by X-ray crystallography of the 4-bromobenzoate 14, which was derived from the bridged secondary alcohol 13. The latter was obtained from 12 by an acid-catalyzed intramolecular rearrangement.

Regulation of energy substrate metabolism in the diabetic heart.

The effects of diabetes on myocardial metabolism are complex in that they are tied to the systemic metabolic abnormalities of the disease (hyperglycemia and elevated levels of free fatty acid and ketone bodies), and changes in cardiomyocyte phenotype (e.g., down-regulation of glucose transporters and PDH activity).

Regulation of myocardial carbohydrate metabolism under normal and ischaemic conditions. Potential for pharmacological interventions.

It is now clear that the availability of different metabolic substrates can have a profound influence on the extent of damage incurred during episodes of cardiac ischaemia, and on cardiac functional recovery on reperfusion following ischaemia. In particular, increases in fatty acid availability and oxidation, compared to glucose oxidation, under such conditions leads to a worsening of outcome. Therefore metabolic interventions aimed at enhancing glucose utilisation and pyruvate oxidation at the expense of fatty acid oxidation is a valid therapeutic approach to the treatment of myocardial ischaemia.

Decreased myocardial glucose uptake during ischemia in diabetic swine.

The purpose of the study was to assess myocardial glucose uptake in nondiabetic (n = 5) and streptozotocin-diabetic (n = 6) Yucatan miniature swine under matched hyperglycemic and hypoinsulinemic conditions. Fasting conscious diabetic swine had significantly higher plasma glucose levels (20.9 +/- 2.

Loss of the N-myc oncogene in a patient with a small interstitial deletion of the short arm of chromosome 2.

To our knowledge, only four previous cases of distal chromosome 2p deletions exist in the literature. We present a patient with minor facial anomalies who had a distal interstitial deletion of the short arm of chromosome 2, del(2)(p24.2p25.

Impaired pyruvate oxidation but normal glucose uptake in diabetic pig heart during dobutamine-induced work.

We tested the hypothesis that diabetes impairs myocardial glucose uptake and pyruvate oxidation under normal conditions and during a dobutamine-induced increase in work. We also tested the hypothesis that an increase in work would result in a decrease in the levels of malonyl CoA, a potent inhibitor of carnitine palmitoyltransferase I (CPT I). Streptozotocin-diabetic micropigs were compared with a nondiabetic control group (n = 8 per group).

Increased cardiac fatty acid uptake with dobutamine infusion in swine is accompanied by a decrease in malonyl CoA levels.

Objective: Malonyl CoA is an important regulator of fatty acid oxidation in the heart secondary to its ability to inhibit carnitine palmitoyltransferase 1 (CPT 1). Malonyl CoA is produced from acetyl CoA in a reaction catalyzed by acetyl CoA carboxylase (ACC). In this study we determined if alterations in malonyl CoA regulation of fatty acid metabolism are involved in the increase in energy transduction seen following an increase in cardiac work.

Pyruvate dehydrogenase activity and malonyl CoA levels in normal and ischemic swine myocardium: effects of dichloroacetate.

The purposes of this study were to: (1) assess myocardial pyruvate dehydrogenase (PDH) activity and substrate exchange under well-perfused and ischemic conditions; (2) determine the metabolic effects of an intra-coronary infusion of the PDH activator, dichloroacetate (DCA); and (3) measure the effects of ischemia and DCA on malonyl CoA levels. Experiments were performed in anesthetised open-chest swine under non-ischemic conditions, followed by 40 min with a 60% reduction in left anterior descending coronary artery (LAD) blood flow. Myocardial needle biopsies for measurement of PDH activity were taken after an intracoronary infusion of either saline or DCA (1 mM in LAD blood) under aerobic conditions, and after 37 min of ischemia.