The major problems of racing in the United States at the present time are caused by too much racing. This has led to too few horses and small fields. Consequently many owners and trainers are trying to enter their horses too frequently and to race them when they are not really fit to run. The desire to race horses as frequently as possible has led to constant pressure from horsemen through their organizations for so called "permissive medication". Started in the state of Colorado approximately ten years ago this has grown until finally there are only a few states, notably New York and New Jersey that have resisted the pressure. The drug that gave the opening wedge to permissive medication was phenylbutazone, but this in many states has led to the inclusion of other drugs including analgesics and drugs that veterinarians claim are needed for therapeutic purposes. Some states have endeavoured to control phenylbutazone medication by quantitation and while lower limits cause little difficulty, maximum allowable limits have caused problems and are not practical. While there has been no publicity to my knowledge about frusemide (furosemide, lasix) the abuse of this drug for so called "bleeders" is an example that may seriously interfere with drug detection in urine and its use should be confined to proven "bleeders" (i.e. horses suffering from epistaxis). Pre-race blood testing began roughly ten years ago at the harness tracks and has been resisted by our flat tracks rather successfully up to the present time. The blood testing methods and those used by the same laboratories in post-race urine testing is inadequate and will not detect many illegal drugs. (+info)
Formal analysis of electrogenic sodium, potassium, chloride and bicarbonate transport in mouse colon epithelium.
1. The mammalian colonic epithelium carries out a number of different transporting activities simultaneously, of which more than one is increased following activation with a single agonist. These separate activities can be quantified by solving a set of equations describing these activities, provided some of the dependent variables can be eliminated. Using variations in the experimental conditions, blocking drugs and comparing wild type tissues with those from transgenic animals this has been achieved for electrogenic ion transporting activity of the mouse colon. 2. Basal activity and that following activation with forskolin was measured by short circuit current in isolated mouse colonic epithelia from normal and cystic fibrosis (CF) mice. 3. Using amiloride it is shown that CF colons show increased electrogenic sodium absorption compared to wild type tissues. CF mice had elevated plasma aldosterone, which may be responsible for part or all of the increased sodium absorbtion in CF colons. 4. The derived values for electrogenic chloride secretion and for electrogenic potassium secretion were increased by 13 and 3 fold respectively by forskolin, compared to basal state values for these processes. 5. The loop diuretic, frusemide, completely inhibited electrogenic potassium secretion, but apparently only partially inhibited electrogenic chloride secretion. However, use of bicarbonate-free solutions and acetazolamide reduced the frusemide-resistant current, suggesting that electrogenic bicarbonate secretion accounts for the frusemide-resistant current. 6. It is argued that the use of tissues from transgenic animals is an important adjunct to pharmacological analysis, especially where effects in tissues result in the activation of more than one sort of response. (+info)
Postnatal development of hippocampal dentate granule cell gamma-aminobutyric acidA receptor pharmacological properties.
Postnatal development of hippocampal dentate granule cell gamma-aminobutyric acidA (GABAA) receptor pharmacological properties was studied. Granule cells were acutely isolated from hippocampi of 7- to 14- and 45- to 52-day-old rats, and whole cell patch-clamp recordings were obtained. The sensitivity of GABAA receptors to GABA and modulation of GABAA receptor currents by benzodiazepines (BZ), zinc, furosemide, and loreclezole was studied. Multiple changes in the pharmacological properties of dentate granule-cell GABAA receptors occurred during the first 52 days of postnatal development: GABA-evoked maximal current increased with postnatal age; GABAA receptors changed from BZ type 3 in young rats to BZ type 1 in adult rats; furosemide and zinc inhibited GABAA receptor currents in young rats but not in adult rats; the fraction of cells that expressed loreclezole-sensitive GABAA receptors increased with postnatal age. These findings suggest that dentate granule cells in young and adult animals express pharmacologically distinct GABAA receptors and that the postnatal development of these receptors is prolonged, lasting at least 45 days. Comparison with the previously reported pharmacological properties of GABAA receptors on dentate granule cells acutely isolated from hippocampi of 28- to 35-day-old rats suggests that receptors expressed at that age have properties intermediate between young and adult rats. (+info)
A case of eosinophilic myocarditis complicated by Kimura's disease (eosinophilic hyperplastic lymphogranuloma) and erythroderma.
This report describes a patient with eosinophilic myocarditis complicated by Kimura's disease (eosinophilic hyperplastic lymphogranuloma) and erythroderma. A 50-year-old man presented with a complaint of precordial pain. However, the only abnormal finding on examinatioin was eosinophilia (1617 eosinophils/microl). Three years later, the patient developed chronic eczema, and was diagnosed with erythroderma posteczematosa. One year later, a tumor was detected in the right auricule, and a diagnosis of Kimura's disease was made, based on the biopsy findings. The patient developed progressive dyspnea 6 months later and was found to have cardiomegaly and a depressed left ventricular ejection fraction (17%). A diagnosis of eosinophilic myocarditis was made based on the results of a right ventricular endomyocardial biopsy. The eosinophilic myocarditis and erythrodrema were treated with steroids with improvement of both the eosinophilia and left ventricular function. (+info)
Regulation of intracellular chloride by cotransporters in developing lateral superior olive neurons.
The regulatory mechanisms of intracellular Cl- concentration ([Cl-]i) were investigated in the lateral superior olive (LSO) neurons of various developmental stages by taking advantage of gramicidin perforated patch recording mode, which enables neuronal [Cl-]i measurement. Responses to glycine changed from depolarization to hyperpolarization during the second week after birth, resulting from [Cl-]i decrease. Furosemide equally altered the [Cl-]i of both immature and mature LSO neurons, indicating substantial contributions of furosemide-sensitive intracellular Cl- regulators; i.e., K+-Cl- cotransporter (KCC) and Na+-K+-Cl- cotransporter (NKCC), throughout this early development. Increase of extracellular K+ concentration and replacement of intracellular K+ with Cs+ resulted in [Cl-]i elevation at postnatal days 13-15 (P13-P15), but not at P0-P2, indicating that the mechanism of neuronal Cl- extrusion is sensitive to both furosemide and K+-gradient and poorly developed in immature LSO neurons. In addition, removal of extracellular Na+ decreased [Cl-]i at P0-P2, suggesting the existence of extracellular Na+-dependent and furosemide-sensitive Cl- accumulation in immature LSO neurons. These data show clearly that developmental changes of Cl- cotransporters alter [Cl-]i and are responsible for the switch from the neonatal Cl- efflux to the mature Cl- influx in LSO neurons. Such maturational changes in Cl- cotransporters might have the important functional roles for glycinergic and GABAergic synaptic transmission and the broader implications for LSO and auditory development. (+info)
Acute effects of combined administration of kanamycin and furosemide on the stria vascularis studied by distortion product otoacoustic emission and transmission electron microscopy.
Acute effects of kanamycin and/or furosemide administration on the stria vascularis of the guinea pig cochlea were assessed by distortion product otoacoustic emission (DPOAE) and transmission electron microscopy. Kanamycin alone failed to affect the DPOAE levels and ultrastructural changes. Furosemide alone caused a rapid but reversible fall of the DPOAE levels. No remarkable pathological changes in the strial vascularis were observed after a complete recovery of the DPOAEs. On the other hand, furosemide injection following kanamycin with a 2 hour interval resulted in two patterns of significant changes in the DPOAEs, namely, a sudden drop in the DPOAE levels 2 to 3 hours after furosemide injection and a gradual fall in the DPOAE levels immediately after the incomplete recovery from the furosemide-induced decrease of the DPOAE levels. Ultrastructural changes in the stria vascularis included numerous vacuoles in the strial marginal cells and increased electron density of the intermediate and basal cells. These physiological and morphological changes in the stria vascularis may imply new ototoxic features induced by kanamycin potentiated by furosemide. (+info)
Sodium depletion and aldosterone decrease dopamine transporter activity in nucleus accumbens but not striatum.
Motivated behaviors, including sodium (Na) appetite, are correlated with increased dopamine (DA) transmission in the nucleus accumbens (NAc). DA transporter (DAT) modulation affects DA transmission and may play a role in motivated behaviors. In vivo Na depletion, which reliably induces Na appetite, was correlated with robust decreases in DA uptake via the DAT in the rat NAc with rotating disk electrode voltammetry [1,277 +/- 162 vs. 575 +/- 89 pmol. s-1. g-1; Vmax of transport for control vs. Na-depleted tissue]. Plasma aldosterone (Aldo) levels increase after in vivo Na depletion and contribute to Na appetite. Decreased DAT activity in the NAc was observed after in vitro Aldo treatment (428 +/- 28 vs. 300 +/- 25 pmol. s-1. g-1). Neither treatment affected DAT activity in the striatum. These results suggest that a direct action of Aldo is one possible mechanism by which Na depletion induces a reduction in DAT activity in the NAc. Reduced DAT activity may play a role in generating increased NAc DA transmission during Na appetite, which may underlie the motivating properties of Na for the Na-depleted rat. (+info)
Roles of aldosterone and angiotensin in maturation of sodium appetite in furosemide-treated rats.
When rats are treated with furosemide, there is a rapid natriuresis. However, increased sodium appetite does not occur until some time later. One hypothesis to explain this delay is that increased circulating levels of the hormones of sodium depletion prime or sensitize the brain circuits involved in sodium appetite, perhaps by induction of target gene(s). In the present study, we describe the time course of the temporal maturation of sodium appetite after furosemide treatment and the associated changes in plasma levels of ANG II and aldosterone and in plasma volume. Sodium appetite is modest 3 h after furosemide treatment, is increased after 12 h, and is still larger after 24 h. This pattern is evident with repeated testing. Plasma levels of aldosterone and plasma renin activity are substantially increased 3 h after furosemide treatment, and so the NaCl appetite cannot result simply from progressively increasing levels of these hormones. Furthermore, activation of the subfornical organ and the ventral lamina terminalis, assessed with c-Fos immunocytochemistry, did not differ across these three times. Metyrapone, an inhibitor of adrenal steroid synthesis, was used to examine sodium appetite in the absence of elevations in aldosterone after furosemide treatment. Although metyrapone effectively blocked the increase in aldosterone, it was without effect on the appetite 3 or 24 h after furosemide treatment. Furthermore, elevations of plasma aldosterone by the use of minipumps for several days before furosemide treatment did not prime or potentiate but instead tended to inhibit the induced sodium appetite, despite achieving levels of aldosterone and plasma renin activity typically associated with a robust sodium appetite. Infusions of DOCA gave a similar result. Lastly, minipump infusions of ANG II also did not potentiate sodium appetite. Thus neither addition nor subtraction of these hormones alone influenced sodium appetite under these conditions. (+info)