Trends in antifungal susceptibility among Candida sp. Urinary isolates from 1994 and 1998.

Antifungal susceptibilities were determined from 80 urinary isolates of Candida species collected in 1994 and 1998. Our findings demonstrate increasing geometric means of fluconazole MICs and fluconazole resistance in Candida albicans and Candida tropicalis (those for Candida glabrata were unchanged) within the 4-year span. Amphotericin B and voriconazole MICs remained constant.

Reflex effects evoked from the parietal pericardium in the dog: comparison with responses from the visceral pericardium.

Experiments were performed on anaesthetized, open-chest dogs to determine the reflex effects on systemic blood pressure and heart rate produced by stimulation of the parietal pericardium with bradykinin and nicotine, and to compare these effects with those evoked by application of these substances to the visceral pericardium (epicardium) of the left ventricle. Bradykinin (0.01-6.0 micrograms) elicited reflex increases in blood pressure and heart rate when applied either to the parietal pericardium or to the ventricular epicardium; the responses evoked from both sites were dose-dependent from the threshold of 0.01 micrograms to a maximum at 1.0 micrograms of bradykinin. The reflex effects of bradykinin were not affected by either vagotomy or phrenic nerve section, but were suppressed by bilateral sectioning of the upper thoracic (T1-T4) white rami communicantes and stellectomy. In contrast to bradykinin, nicotine (20-100 micrograms) failed to produce any change in blood pressure and heart rate when applied to the parietal pericardium and evoked depressor responses when applied to the epicardium of the left ventricle; these depressor effects of nicotine were abolished by vagotomy. The results indicate that sympathetic, but not vagal, afferent endings innervating the parietal pericardium are susceptible to chemical stimulation. Bradykinin is a powerful algesic agent and is formed and released locally during inflammation. We suggest, therefore, that the pericardial sympathetic pressor reflex is nociceptive in nature and can be activated when kinin formation occurs during pericardial inflammation.

Prostanoids and cardiac reflexes of sympathetic and vagal origin.

Prostaglandins in concentrations too low to stimulate afferent nerve endings in the heart may sensitize them to chemical or mechanical stimuli that activate cardiac reflexes during myocardial ischemia. Bradykinin, which is released from the heart during ischemia, elicits sympathetically mediated reflex pressor effects and tachycardia when applied in low doses (0.1 to 1 microgram) to the epicardium of the left ventricle in open-chest, anesthetized dogs. The reflex pressor effects evoked by bradykinin are reduced after inhibition of prostaglandins biosynthesis with indomethacin and potentiated by concomitant topical application of low doses (0.1 to 0.3 microgram/min) of PGE1 or PGE2 and prostacyclin (PGI2). The pressor and tachycardic responses to bradykinin are also enhanced after temporary (10-minute) coronary occlusion; this potentiation is abolished by indomethacin treatment and can be restored by superfusing the ventricle with prostaglandins. Nicotine is known to excite mechanosensitive vagal receptors with afferent C fibers, which supply the left ventricle, and to elicit reflex hypotension and bradycardia. This depressor vagal reflex evoked by epicardial or intracoronary administration of nicotine (10 to 50 micrograms) was not affected by either indomethacin or by topical application of PGE1, PGE2, or PGI2. Also, intracoronary infusion of PGE2 (0.1 to 0.3 microgram/min), which enhanced the pressor reflex effects of bradykinin, was without effect on nicotine-induced depressor reflex. However, intracoronary infusion of PGI2 (0.1 to 0.3 microgram/min) significantly enhanced the hypotensive and bradycardic responses to nicotine and, at the same time, reduced sympathetically mediated reflex effects of bradykinin. The hypotensive effects induced by epicardial or intracoronary administration of nicotine were also significantly enhanced during intravenous infusion of subdepressor doses of PGI2 (5 to 20 ng/kg/min). Treatment with captopril, which enhances the endogenous production of prostaglandins, greatly enhanced the reflex depressor effects of nicotine; this potentiating effect of captopril was completely abolished by indomethacin treatment. An increase in the magnitude of nicotine-induced reflex depressor effects was also observed after intravenous injection (1 microgram/kg) or infusion (25 to 50 ng/kg/min) of prostaglandin D2. A working hypothesis is proposed to account for the role of prostanoids in activation of cardiac reflexes during myocardial ischemia.

Effects of prostacyclin on cardiovascular reflexes from the ventricular epicardium of the dog: comparison with the effects of prostaglandin E2.

Application of bradykinin to the exposed ventricular surface of the dog's heart produced reflex pressor effects and tachycardia, whereas application of nicotine evoked reflex hypotension and bradycardia. Prostacyclin (PGI2) or prostaglandin E2 (PGE2), when applied epicardially, had no effects by themselves but potentiated the reflex pressor changes to bradykinin; the depressor responses to nicotine were not changed. The potentiating effect of PGI2 was prompt but short-lived, whereas that of PGE2 was slow in onset but prolonged. The results suggest that PGI2, which is present in the pericardial fluid, may contribute to signalling of pain and reflex circulatory changes when kinin formation occurs during myocardial ischaemia or pericardial inflammation.

Participation of the sympathetic and the renin--angiotensin systems in blood pressure control during hypercapnia in the anaesthetized dog.

The effects of hypercapnia on plasma renin concentration and blood pressure were studied in anaesthetized dogs, untreated and after pretreatment with guanethidine, propranolol or prazosin. An increase in plasma renin concentration which accompanied hypercapnia in untreated dogs was completely suppressed by pretreatment with guanethidine or propranolol. Prazosin significantly reduced but did not abolish renin release during hypercapnia. The pressor response normally occurring during hypercapnia was abolished by propranolol and reversed by guanethidine and prazosin.

Role of renal prostaglandins in circulatory homeostasis.

The evidence is reviewed that prostaglandins of renal origin through (i) their local actions on renal blood vessels, and (ii) complex interactions with the nervous adrenergic and the endocrine vasoactive renin-angiotensin-aldosterone and kallikrein-kinin systems, may participate in the regulation of excretory functions of the kidney and thereby contribute to circulatory homeostatic mechanisms.

Sympathetic cardiovascular reflex initiated by bradykinin-induced stimulation of cardiac pain receptors in the dog.

1. Bradykinin (0.02-5 microgram) applied to the epicardium of the left ventricle in the open-chest, anaesthetized dog, elicits dose-related reflex pressor effects and acceleration of the heart rate. 2. Bradykinin-induced reflex tachycardia was suppressed after the blockade of beta-adrenoceptors with propranolol, whereas reflex pressor responses were prevented by blocking the alpha-adrenoceptor sites with phenoxybenzamine. 3. Vagotomy and atropine treatment did not affect reflex hypertension and tachycardia to epicardial bradykinin. 4. After spinal section at C1, the pressor responses to epicardial bradykinin were significantly reduced, but still present in all but one experiment. A small acceleration of the heart occurred in two out of five spinal dogs with intact vagi and was absent in three vagotomized spinal dogs. 5. The results indicate the reflex activation of the sympathetic outflow to the heart and blood vessels, mediated mainly at a supraspinal level as a predominant mechanism for the cardiovascular response initiated by bradykinin-induced stimulation of cardiac pain receptors.

Suppression of the release of prostaglandin-like substances by hydrocortisone in vivo.

Muscular exercise of the dog's hind leg evokes the release of prostaglandin-like substances/PG-like substances/into femoral venous blood. The release of PG-like substances detected by the bioassay method was significantly greater in adrenalectomized as compared to normal dogs. To test the possibility that this difference may be related to the deficiency of adrenocortical secretion in adrenalectomized dogs, the effect of hydrocortisone/HC/and aldosterone/AS/upon the release of PG-like substances induced by muscular work of the dog's hind leg was investigated. The doses of HC and AS infused intravenously or intraarterially were close to the range of physiological secretion rate of these hormones. HC suppressed the release of PG-like material by 30 to 60%, whereas AS had no effect upon the rate and duration of the release. The rate of removal of exogenous PGE2 in the hind limb circulation was not influenced by HC, suggesting that the diminution of PG release by HC results from the suppression of PG generation rather than from the enhancement of degradation. It is suggested that PG-like substances may be related to the membrane-stabilizing properties of this hormone. The difference in the intensity of the release of PG-like substances between normal and adrenalectomized dogs suggests that, at least in some conditions, the release of endogenous PGs from tissues may be influenced by the state of adrenocortical activity.

Humoral response and blood pressure regulation during hypercapnia and haemorrhage in dogs.

1. The blood-bathed organ technique was used to study the release of catecholamines, angiotensin II and prostaglandin-like (PL) substances into the circulation during hypercapnia and after haemorrhage in anaesthetized dogs. 2. Elevated blood concentrations of noradrenaline, angiotensin II and prostaglandin-like substances have been detected during both experimental conditions. 3. The rise of arterial blood pressure during hypercapnia and after haemorrhage was associated with elevated concentrations of angiotensin II in the blood and could be abolished by inhibition of the angiotensin I-converting enzyme with SQ 20881. 4. The compensation of arterial pressure during both stresses was significantly impaired by release of prostaglandin-like substances; it could be restored by inhibition of prostaglandin biosynthesis with indomethacin. 5. The results indicate that activation of the renin-angiotensin system represents the major humoral mechanism for the maintenance of arterial pressure during hypercapnic acidosis and after haemorrhage.

Muscular work and the release of prostaglandin-like substances.

Experimental evidence for the release of prostaglandin-like substances, mainly of the E type, into the venous outflow from working skeletal muscles in the dog is described. Muscular exercise of the hind-leg produced by sciatic nerve stimulation evoked the release of prostaglandin-like substances detected in femoral venous blood by the bioassay method. This release occurred during and after muscular work, was abolished by indomethacin, and was not present in gallamine-treated dogs. The results suggest that endogenous vasodilator prostaglandins released during and after muscular work may contribute to local hyperaemic response during and, mainly, after muscular activity.

An excitatory nociceptive cardiac reflex elicited by bradykinin and potentiated by prostaglandins and myocardial ischaemia.

Application of bradykinin to the exposed ventricular surface of the dog heart elicits a reflex cardiovascular response which includes a rise in blood pressure, tachycardia, renal vasoconstriction and muscular vasodilation. The reflex response depends on the dose of bradykinin and is increased by concomitant application of prostaglandin E1 or E2 and reduced by indomethacin. Temporary occlusion of the coronary artery supplying the area of the ventricle under study also sensitized the heart to topical application of bradykinin. Bradykinin and prostaglandins are released by the heart during ischaemia. We suggest, therefore, that bradykinin and prostaglandins acting in concert are the natural stimulus for excitation of the sensory receptors signalling the pain of myocardial ischaemia. We also suggest that the nervous reflex which arises from activation of sympathetic sensory nerve endings is the mechanism subserving the cardiovascular events which accompany anginal attacks.

Evidence that prostaglandin is responsible for the 'rebound contraction' following stimulation of non-adrenergic, non-cholinergic ('purinergic') inhibitory nerves.

The prostaglandin synthesis inhibitor, indomethacin, blocks the "rebound contractions" which characteristically follow the inhibitory responses of the guinea-pig taenia coli to non-adrenergic, non-cholinergic (purinergic) nerves and to exogenously applied ATP, without affecting the responses to periaterial adrenergic nerves. Since adenine nucleotides are known to induce prostaglandin synthesis, this result is consistent with the purinergic hypothesis and suggests that purinergic nerves may form a link with prostaglandin in the physiological regulation of a variety of organs.