Occlusive gloves and skin conditions: is there a problem? Results of a cross-sectional study in a semiconductor company.

BACKGROUND: Although there is poor scientific evidence that working with occlusive gloves is as damaging as wet work, prolonged glove occlusion is considered to be a risk factor for developing hand eczema similar to wet work. OBJECTIVES: To assess the effects of wearing occlusive gloves during the whole working day, without exposure to any additional hazardous substances, on skin condition and skin barrier function. METHODS: We investigated 323 employees of a semiconductor production company in Germany: 177 clean-room workers wearing occlusive gloves during the whole shift (exposed group) and 146 employees working in administration (control group). A standardized interview was performed, the skin condition of both hands was studied using the quantitative skin score HEROS, and transepidermal water loss (TEWL) and stratum corneum hydration were measured. RESULTS: There was no significant difference in skin condition between the two subgroups. Values for TEWL and corneometry were significantly higher in exposed participants (P < 0·05). However, the TEWL values were similar to control values if participants took off the occlusive gloves at least 30 min before the measurement. Hence, the effect of occlusion on skin barrier function seems to be transient. CONCLUSIONS: Prolonged wearing of occlusive gloves with clean hands and without exposure to additional hazardous substances does not seem to affect the skin negatively.

Intra-operative myocardial ischaemia cannot be detected by analysis of transmitral inflow patterns in patients undergoing off-pump coronary surgery.

BACKGROUND AND OBJECTIVE: Transmitral inflow patterns have been used for detection of myocardial ischaemia. However, its diagnostic value has not been tested in anaesthetized and mechanically ventilated patients undergoing coronary artery bypass graft surgery. METHODS: Transmitral inflow patterns were studied by transoesophageal Doppler echocardiography in 43 patients undergoing coronary artery bypass graft surgery without cardiopulmonary bypass after opening of the sternum (baseline) and during grafting of the left anterior descending artery. Peak early (E) and peak late (A) transmitral velocities and their ratio (E/A) were recorded. Myocardial ischaemia was defined by standard criteria using two-dimensional echocardiography and seven-lead electrocardiogram. RESULTS: Thirty-one patients (64 +/- 8 yr, 9 women) fulfilled the predefined inclusion criteria for analysis. During distal revascularization, 16 patients showed myocardial ischaemia and 15 did not. The use of vasoactive drugs, haemodynamic findings and transmitral inflow patterns were similar in both groups at baseline and during grafting. In the ischaemic group, E was 67.1 +/- 13.9 cm s-1 at baseline and 69.5 +/- 23.2 cm s-1 during grafting, and the E/A ratios were 1.3 +/- 0.3 and 1.4 +/- 0.9, respectively. In the non-ischaemic group, E was 64.0 +/- 17.1 cm s-1 at baseline and 60.9 +/- 14.8 cm s-1 during grafting, and the E/A ratios were 1.4 +/- 0.7 and 1.2 +/- 0.3, respectively. CONCLUSIONS: Analysis of Doppler findings of transmitral inflow patterns did not allow for detection of myocardial ischaemia during surgical revascularization of the myocardium.

Selection bias of elderly patients with chronic angina referred for catheterization.

BACKGROUND: Registry patients are generally older and more sick than patients enrolled in trials questioning the generalizability of trial results. We assessed whether such a selection bias also exists in elderly patients with chronic angina referred for catheterization. METHODS AND RESULTS: All 119 patients age>or=75 years with Trial of Invasive versus Medical Therapy in the Elderly (TIME) inclusion but no major exclusion criteria referred for catheterization during the TIME trial inclusion period in four TIME centers were registered and followed-up for one year. Registry patients differed from the 188 trial patients in the same hospitals in that they were younger, somewhat more frequently male, with less antianginal drugs and studied more often after acute chest pain at rest but with more comorbidities than study patients. Left ventricular ejection fraction and vessel disease were similar. One year mortality was 11.4% in registry and 9.6% in invasive TIME patients but differences disappeared after adjustment for baseline differences. Symptomatic status after one year was similar too. CONCLUSIONS: In elderly patients with chronic angina, a bias in the selection for invasive management exists which seems different from that reported in younger patient settings. After adjustment for these selection factors, however, one-year outcome was remarkably similar in registry and trial patients.

Impact of female gender on the early outcome in off-pump coronary artery bypass surgery.

BACKGROUND/OBJECTIVE: Female gender is an independent risk factor for adverse outcome after conventional coronary bypass surgery (CABG). The objective of this retrospective study was to evaluate the influence of the gender on the early outcome in "off pump" coronary bypass surgery without extracorporeal circulation (OPCAB). PATIENTS AND METHOD: Between January 2001 and December 2003, a total of 225 patients, 49 female and 176 male, underwent OPCAB surgery for multivessel disease at our institution. Operations were performed by the same surgeon. The relationship between OPCAB surgery and clinical outcome with major and minor adverse events was assessed with univariate analysis. RESULTS: The same operative technique was applied for both female and male patient groups. No conversion to conventional CABG with cardiopulmonary bypass was necessary. The overall in-hospital mortality was 1.3% (3 of 225 patients), all of them in the male patient group (p = 0.08). Female patients showed a lower rate of postoperative atrial fibrillation than male patients (6% vs. 15%; p = 0.08). The incidence for further postoperative complications such as rethoracotomy for bleeding, stroke, delirium, pneumonia and wound infection was identical and statistically not different in both groups. CONCLUSIONS: In OPCAB surgery, female gender plays not a predictive role for postoperative adverse events and complications influencing morbidity and mortality. In selected female patients OPCAB surgery has a beneficial effect on early clinical outcome.

Clinical outcome after composite grafting of calcified left anterior descending arteries.

AIM: The treatment of a severely calcified left anterior descending coronary artery (LAD) remains a challenge in cardiac surgery. The objective of this retrospective study was to assess the early clinical outcome obtained from LAD reconstruction, which was performed using a combination of both, saphenous vein and the left internal thoracic artery (LITA) as a composite graft, in order to achieve complete revascularization. METHODS: Between January 1998 and December 2003, 71 patients, 13 female and 58 male, with a mean age of 67+/-9.12 years were retrospectively analyzed. All patients suffered from a severe 3-vessel disease with a diffusely calcified LAD. The design of the reconstruction consisted in a long arteriotomy of the LAD grafted with a matched segment of the saphenous vein using the plaque exclusion technique to avoid endarterectomy. The LITA was then anastomosed to the saphenous vein in an end-to-end configuration. With this design, the saphenous vein was used first as a ''patch'' reconstruction of the LAD and second as an elongation for the LITA. The clinical outcome was assessed by mailed questionnaires or by telephone interview with the responsible cardiologist or general practitioner. RESULTS: The follow-up was 100%, comprising a mean follow-up time of 17+/-11.8 months. Overall mortality was 7% (N=5/71). Four cardiac deaths and 1 non cardiac-related death were registered. The in-hospital mortality was 2.8% (2/71); 2 cardiac-related deaths and one non cardiac-related death were observed after 30 days (4.2%). Postoperative myocardial infarction without heart failure was seen in 4 patients (5.4%). In addition, an episode of transitory cerebral ischemia was observed in 1 patient (1.4%). No further postoperative complications occurred. At the time of evaluation, 67% of the patients were in functional class CCS 0 and 33% in functional class CCS I to II. CONCLUSIONS: Composite graft reconstruction without endarterectomy is an alternative treatment option for severely calcified LADs with a good early clinical outcome.

Morphine-induced stimulation of pituitary-adrenocortical activity is mediated by activation of nitric oxide in the early stages of postnatal life in the rat.

OBJECTIVE: The first aim of the present study was to determine if morphine, a prototypic mu-opioid agonist drug, affects pituitary-adrenocortical activity in developing rat pups (first and second weeks of postnatal life). The second aim of this study was to explore, in vivo, if nitric oxide (NO) could be involved in the neurohormonal response to morphine in the early stages of postnatal life. METHODS: Plasma ACTH and corticosterone concentrations were determined by RIA in rat pups (n=5-14 rats/experimental group) after they had been killed by decapitation. In a first experiment, 1-day and 1- and 2-week-old rats were treated s.c. with morphine (20 mg/kg) or with vehicle (0.9% NaCl) and killed 5-90 min later. In a second experiment, 2-week-old pups were pretreated s.c. with naltrexone (NAL; 0.4 mg/kg or 10 mg/kg), and injected 1 h later with either morphine (20 mg/kg) or vehicle, and killed 30 min later. Some pups injected with only NAL were killed 60 or 90 min later. On the other hand, pups injected with NAL (10 mg/kg) or NAL and morphine were killed 30 min later. In a third experiment, 2-week-old pups were pretreated s.c. with N-omega-nitro l arginine methyl-ester (L-NAME; 30 mg/kg or 100 mg/kg), and injected 1 h later with either morphine (20 mg/kg) or vehicle, and killed 30 min later. Moreover, some pups injected with L-NAME (100 mg/kg) or L-NAME with morphine were killed 30 min later. In a final experiment, pups were injected s.c. with either S-nitroso-N-acetylpenicillamine (SNAP; 5 mg/kg) or vehicle, and killed 60 or 90 min later. RESULTS: Morphine administered to rat pups elicited marked rises in both ACTH and corticosterone secretion. Moreover, these responses increased with advancing postnatal age. In 2-week-old rat pups, NAL, a competitive antagonist at mu-opioid receptors, administered alone increased both plasma ACTH and corticosterone concentrations 30 min later. L-NAME, a specific NO synthase inhibitor, did not affect plasma ACTH and corticosterone concentrations 30 min later when administered alone. NAL, when concomitantly administered with morphine, was unable to block morphine responses. In contrast, morphine responses were blocked by pretreatment (60 min before) with NAL or with L-NAME. Acute injection of SNAP increased both ACTH and corticosterone release. CONCLUSION: Our results suggest that opioids have controversial effects on pituitary-adrenocortical activity in the early postnatal period in the rat, and that endogenous NO is one of the major factors in the response of the pituitary-adrenocortical axis to morphine.

Effects of Estrous Cycle and of in vivo Unilateral or Bilateral Adrenal Demedullation on the Distribution of Norepinephrine and Epinephrine Between Different Zones of the Adrenal.

Abstract The distribution of norepinephrine (NE) and epinephrine (E) between the capsule/glomerular zone and the remainder of the adrenal was studied in the adult female rat. Both catecholamines were present in these two parts of the gland. The concentration of E was higher than that of NE. In the capsule/glomerular zone the catecholamine concentrations were more than twenty to thirty times lower than in the inner part of the gland. The circulating levels of catecholamines were always very low. The present data also support very weak or no changes in catecholamine concentrations in both parts of the adrenal during the different stages of the estrous cycle. The plasma levels of both aldosterone and corticosterone, like those of catecholamines, did not vary significantly throughout the estrous cycle. One week after unilateral or bilateral demedullation, both E content and concentration were reduced in the whole capsule/glomerular zone of the adrenal although the NE content did not change. The reduction of NE concentration could be related to the drastic weight increase of this part of the gland on the operated side. Moreover, unilateral demedullation was unable to significantly modify the plasma levels of both E and NE. In contrast bilateral demedullation suppressed circulating E and induced a significant reduction (about 50%) of NE plasma level. The present data suggest: 1) an extra-adrenal origin for the NE innervation of the capsule/glomerular zone of the adrenal cortex, and 2) a dual origin for E in the capsule/glomerular zone; part of E could arise from the adrenal medulla and part from an extra-adrenal site.

Metyrapone-induced glucocorticoid depletion modulates tyrosine hydroxylase and phenylethanolamine N-methyltransferase gene expression in the rat adrenal gland by a noncholinergic transsynaptic activation.

The hypothalamic corticotropin-releasing hormone system and the sympathetic nervous system are anatomically and functionally interconnected and hormones of the hypothalamic-pituitary-adrenocortical axis contribute to the regulation of catecholaminergic systems. To investigate the role of glucocorticoids on activity of the adrenal gland, we analysed plasma and adrenal catecholamines, tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) mRNA expression in rats injected with metyrapone or dexamethasone. Metyrapone-treated rats had significantly lower epinephrine and higher norepinephrine production than control rats. Metyrapone increased TH protein synthesis and TH mRNA expression whereas its administration did not affect PNMT mRNA expression. Dexamethasone restored plasma and adrenal epinephrine concentrations and increased PNMT mRNA levels, which is consistent with an absolute requirement of glucocorticoids for PNMT expression. Adrenal denervation completely abolished the metyrapone-induced TH mRNA expression. Blockage of cholinergic neurotransmission by nicotinic or muscarinic receptor antagonists did not prevent the metyrapone-induced rise in TH mRNA. Finally, pituitary adenylate cyclase activating polypeptide (PACAP) adrenal content was not affected by metyrapone. These results provide evidence that metyrapone-induced corticosterone depletion elicits transsynaptic TH activation, implying noncholinergic neurotransmission. This may involve neuropeptides other than PACAP.

Consequences of prenatal morphine exposure on the hypothalamo-pituitary-adrenal axis in the newborn rat: effect of maternal adrenalectomy.

The hypothalamo-pituitary-adrenal axis is already functional in rat fetuses in late gestation. We have reported previously that prenatal morphine exposure induced a severe atrophy of the adrenals and a decrease of corticosterone release in newborn rats at birth and during the early postnatal period. The first aim of the present study was to determine the effects of prenatal morphine exposure (1) on corticotrophin releasing factor (CRF) content of the hypothalamus, CRF immunofluorescence in the median eminence, CRF mRNA in the paraventricular nucleus (PVN) and pro-opiomelanocortin (POMC) mRNA in the anterior pituitary gland; (2) on CRF-induced ACTH release from the anterior pituitary gland in vitro; and (3) on ACTH-induced corticosterone release by the adrenals in vitro. Moreover, as morphine is a hepatotoxic factor, we determined the effects of prenatal morphine on liver weight and plasma corticosteroid binding globulin (CBG) binding capacity in newborn rats. Since acute administration of morphine stimulates corticosterone secretion in adult rats and since maternal corticosterone can cross the placental barrier, we also measured both adrenal weight and glucocorticoid activity in newborns from adrenalectomized mothers treated with morphine. The present results show that prenatal morphine given to intact mothers induced adrenal atrophy and hypoactivity in newborns but did not affect the responsiveness of the anterior pituitary gland to CRF or that of the adrenal gland to ACTH. Prenatal morphine reduced both CRF content in the newborn hypothalamus and CRF immunofluorescence in the median eminence without a significant effect on CRF mRNA expression in the PVN. Moreover, morphine induced a significant decrease of POMC mRNA in the anterior pituitary gland. However, morphine did not significantly affect the weight of the liver, or the plasma CBG binding capacity for corticosterone, in rat pups. In contrast, morphine treatment of the adrenalectomized mothers did not induce adrenal atrophy in newborns and did not impair adrenal activation during the early postnatal period. Maternal adrenalectomy also prevented the effects of prenatal morphine on hypothalamic content of CRF, CRF immunofluorescence in the median eminence, and POMC mRNA in the anterior pituitary gland. However, adrenal atrophy was observed at term in newborns of adrenalectomized mothers treated with both morphine and corticosterone or only corticosterone. In conclusion, morphine given to pregnant rats induced inhibition of the hypothalamo-pituitary-adrenal axis in pups at term. As maternal adrenalectomy prevented these effects, we speculate that an adrenal factor of maternal origin, probably corticosterone, mediated these drug effects on newborns.

Perinatal malnutrition programs sympathoadrenal and hypothalamic-pituitary-adrenal axis responsiveness to restraint stress in adult male rats.

In humans, an altered control of cortisol secretion was reported in adult men born with a low birth weight making the hypothalamic-pituitary-adrenal (HPA) axis a possible primary target of early life programming. In rats, we have recently shown that maternal food restriction during late pregnancy induces both an intrauterine growth retardation and an overexposure of fetuses to maternal corticosterone, which disturb the development of the HPA axis in offspring. The first aim of this work was to investigate, in adult male rats, whether perinatal malnutrition has long-lasting effects on the HPA axis activity during both basal and stressful conditions. Moreover, as the HPA axis and sympathetic nervous system are both activated by stress, the second aim of this work was to investigate, in these rats, the adrenomedullary catecholaminergic system under basal and stressful conditions. This study was conducted on 4-month-old male rats malnourished during their perinatal life and on age-matched control animals. Under basal conditions, perinatal malnutrition reduced body weight and plasma corticosteroid-binding globulin (CBG) level but increased mineralocorticoid receptor (MR) gene expression in CA1 hippocampal area. After 30 min of restraint, perinatally malnourished (PM) rats showed increased plasma noradrenaline, adrenocorticotropin hormone (ACTH) and corticosterone concentrations similarly as controls, but calculated plasma-free corticosterone concentration was significantly higher and adrenaline level lower than controls. During the phase of recovery, PM rats showed a rapid return of plasma ACTH and corticosterone concentrations to baseline levels in comparison with controls. These data suggest that in PM rats, an elevation of basal concentrations of corticosterone, in face of reduced CBG and probably increased hippocampal MR lead to a much larger impact of corticosterone on target cells that mediate the negative-feedback mechanism on the activities of both the HPA axis and sympathoadrenal one.

[Emotional reactivity and neurovegetative balance in the rat (author's transl)]. / Réactivité émotionelle et équilibre neurovégégtatif chez le rat.

It has been shown in male rats of two albino strains, Wistar and Sprague-Dawley, that differences in emotional reactivity were related to physiological differences (Bernet and Denimal, 1978). Particularly the resting heart rate was slower in the more emotionally reactive rats. It has been suggested that emotional reactivity is linked with a certain neurovegetative balance. This possibility was investigated in twelve rats of each strain by means of differential blockade of the autonomic nervous system by atropine and propranolol. The heart rate response of the emotionally reactive strain to propranolol was statistically smaller than that of the non reactive strain. On the other hand, the heart rate increase resulting from atropine treatment was more elevated in the same rats. The calculated sympathetic and parasympathetic tones (as % of intrinsic heart rate) were 8% and 30% respectively in the reactive rats. However, both of the tones were 14% in the non reactive rats. In conclusion, the high defecating rats in the open-field exhibit a lower sympathetic tone linked with a higher parasympathetic tone.

Diazepam-like effects of a fish protein hydrolysate (Gabolysat PC60) on stress responsiveness of the rat pituitary-adrenal system and sympathoadrenal activity.

RATIONALE: Gabolysat PC60 is a fish protein hydrolysate with anxiolytic properties commonly used as a nutritional supplement. OBJECTIVE: The diazepam-like effects of PC60 on stress responsiveness of the rat pituitary-adrenal system and on sympathoadrenal activity were studied. METHODS: The activity of the pituitary-adrenal axis, measured by plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone (B) of the sympathoadrenal complex, measured by circulating levels of noradrenaline (NA) and adrenaline (A), and the gamma aminobutyric acid (GABA) content in the hippocampus and the hypothalamus were investigated in male rats which received daily, by an intragastric feeding tube, for 5 days running either diazepam (1 mg/kg) or PC60 (300 or 1,200 mg/kg). Controls received only solvent (carboxymethylcellulose 1%). Six hours after the last force-feeding, the rats were subjected to 3 min ether inhalation or 30 min restraint and killed by decapitation 30 min after ether stress or at the end of restraint. RESULTS: Baseline plasma levels of ACTH, B, NA and A were not affected by either diazepam or PC60. Both ether- and restraint-induced release of ACTH, but not B, were similarly and drastically reduced by diazepam and PC60 (1,200 mg/kg). Both diazepam and PC60 (1,200 mg/kg) deleted restraint-induced NA and A increases. Both treatments also reduced the ether-induced rise of A. Basal levels of GABA were significantly increased in both the hippocampus and the hypothalamus in PC60-treated rats and only in the hippocampus in diazepam-treated ones. In controls, ether inhalation as well as restraint increased GABA content of these two brain structures. In contrast, such stress procedures performed in PC60-treated rats reduced GABA content slightly in the hippocampus but significantly in the hypothalamus. In diazepam-treated rats, GABA content of the hypothalamus was unaffected by stresses but that of the hippocampus was slightly decreased. CONCLUSIONS: Present data suggest diazepam-like effects of PC60 on stress responsiveness of the rat pituitary adrenal axis and the sympathoadrenal activity as well as GABA content of the hippocampus and the hypothalamus under resting and stress conditions. These effects of PC60 agree with anxiolytic properties of this nutritional supplement, previously reported in both rats and humans.

In vitro steroidogenic effects of neuropeptide Y (NPY1-36), Y1 and Y2 receptor agonists (Leu31-Pro34 NPY, NPY18-36) and peptide YY (PYY) on rat adrenal capsule/zona glomerulosa.

The effects of neuropeptide Y (NPY1-36), of two analogs (Leu31-Pro34 NPY and NPY18-36) and of Peptide YY (PYY) on aldosterone and corticosterone secretions by freshly isolated rat adrenal capsule/zona glomerulosa preparations were investigated in vitro. NPY-related peptides (NPY1-36, Leu31-Pro34 NPY, NPY18-36), but not PYY, induced a dose-dependent release of aldosterone at concentrations ranging from 10(-8) to 10(-6) M. All the investigated peptides failed to significantly affect corticosterone secretion in concentrations ranging from 10(-10) to 10(-6) M (NPY1-36, NPY18-36), 10(-11) to 10(-6) M (Leu31-Pro34 NPY) or 10(-9) to 10(-6) M (PYY). Aldosterone secretion by this preparation of isolated adrenal capsule/zona glomerulosa was also significantly stimulated by high potassium levels (55 mEq) or by angiotensin II (AII) in concentrations ranging from 10(-8) to 10(-6) M. Moreover, NPY and Y1 or Y2 receptor agonists were positive aldosterone releasing agents as potent as AII. The present data support the existence of: (1) NPY binding sites of the Y3-like subtype, on rat adrenal capsule/zona glomerulosa. (2) A stimulatory effect of NPY on aldosterone production. So that the NPYergic innervation of the rat adrenal capsule/zona glomerulosa could be implicated in the multifactorial control of aldosterone production.

Long-term remission after resection, chemotherapy, and irradiation of a metastatic myxoma.

Malignant local or metastatic myxomatous tumors of the heart are rare and sometimes present with an unpredictable outcome. The present report demonstrates an unusual case of left atrial myxoma with a rather strange distribution of metastases that had long-term remission after combined surgical resection, chemotherapy, and irradiation of cerebral and pulmonary metastases.

Age does not influence early and late tumor-related outcome for bronchogenic carcinoma.

BACKGROUND: The influence of age on early and late outcome after surgical resection of bronchogenic carcinoma is unknown. In an attempt to clarify this issue, we reviewed the outcome of 212 consecutive patients with primary lung cancer who had surgical treatment for bronchogenic carcinoma. METHODS: Ninety-two patients were younger than 50 years (group 1), and 120 patients were older than 70 years of age (group 2). Squamous cell carcinoma and adenocarcinoma were the most common histologic types in both groups. According to the new international staging classification, a similar proportion of stage I, II, and III were observed in both groups. RESULTS: Only the rate of pneumonectomy was significantly higher in younger patients (41% versus 22%, p = 0.002). The overall operative mortality rate in group 1 was 2.2% and 2.6% after pneumonectomy. In group 2 the overall mortality rate was 2.5% and 3.8% after pneumonectomy. Advanced age did not affect operative mortality. The adjusted (tumor-related) survival rate at 5 years was 56% in group 1 and 53% in group 2 (p = 0.93). The adjusted survival rate for patients with stage I was 61% in group 1 and 65% in group 2 (p = 0.21), and for stage IIIa 39% in group 1 and 48% in group 2 (p = 0.43). The adjusted 5-year survival rate was 56% in group 1 and 59% in group 2 for squamous cell carcinoma (p = 0.53) and 49% in group 1 and 42% in group 2 for adenocarcinoma (p = 0.76). CONCLUSIONS: Perioperative risk and midterm survival were similar in younger and older patients after surgical resection of bronchogenic carcinoma. We believe that this result is because surgical candidates constitute already a highly selected group of patients. From these data it is not possible to conclude that biologic behavior of lung cancer is more aggressive in younger patients.

Autonomic dysreflexia increases plasma adrenaline level in the chronic spinal cord-injured rat.

Autonomic dysreflexia (AD) occurs in up to 80% of quadriplegics and high paraplegics and is characterized by exaggerated sympathetic reflexes which induced paroxysmal hypertension. The aim of this study was to determine if plasma catecholamine levels increased during autonomic dysreflexia in the chronic spinal cord-injured (SCI) rats with special care to adrenaline. Catecholamine samples were collected before, during and 1 h after AD induced hypertension with colorectal distension. Results showed that plasma noradrenaline and adrenaline levels increased respectively 1.5-fold and 5-fold during AD in the chronic SCI rats. This suggests substantial roles for these two hormones in mediating the cardiovascular changes during AD. Knowledge of catecholamine levels during AD may thus aid in determining pathophysiology and potential pharmacologic treatments of this autonomic dysfunction.

Effect of adrenal demedullation on neuropeptide Y content of the capsule/glomerulosa zone of the rat adrenal gland.

The capsule/glomerulosa zone of the adrenal gland is richly innervated by neuropeptide Y (NPY)-containing nerve fibers. The content and concentration of NPY in the capsule/glomerulosa zone of the female rat adrenal were determined by radioimmunoassay both in unoperated females (controls) and in operated ones, a week after in situ unilateral demedullation which excludes both the medulla and the fasciculata/reticularis zones. Demedullation induced a significant weight increase of the capsule/glomerulosa zone of the operated gland (compared to contralateral intact one) as well as of the medulla/fasciculata-reticularis zone of the contralateral intact one (compared to the corresponding part of the gland of controls). Both NPY content and concentration in the capsule/glomerulosa zone of the demedullated adrenal were significantly reduced in comparison with those in the corresponding part of the contralateral intact gland. NPY immunoreactive fibers, revealed by immunofluorescence, were present in the capsule/glomerular zone of both intact and contralateral demedullated adrenal gland. In the former, NPY fibers were regularly distributed in this part of the gland, while in the latter, some areas were devoid of immunoreactive fibers. NPY content, but not concentration, was increased in the medulla/fasciculata-reticularis zone of the contralateral intact gland. Present data support a dual origin for the NPY nerves present in the capsule/glomerulosa zone of the adrenal cortex: one part could arise from extra-adrenal site possibly the suprarenal ganglia while the other part could arise from intra adrenal ganglia cells which also contain NPY.

Neuropeptide Y (NPY)- and vasoactive intestinal peptide (VIP)-induced aldosterone secretion by rat capsule/glomerular zone could be mediated by catecholamines via beta 1 adrenergic receptors.

The effects of two Neuropeptide Y (NPY) analogs (Y1- and Y2-type) and vasoactive intestinal peptide (VIP) on both catecholamine (adrenaline and noradrenaline) release and aldosterone production by rat adrenal capsule/glomerular zone, have been investigated in vitro. The adrenal capsule/glomerular zones, collected from adult male rats, were incubated in a medium (Krebs-Ringer bicarbonate buffer supplemented with glucose and bovine serum albumin) containing or not one of the following synthetic peptides: human Leu31,Pro34-NPY (an agonist of the Y1-type receptors), human/porcine NPY18-36 (an agonist of the Y2-type receptors) and VIP at the concentration of 10(-7) M, associated or not with 10(-7) M atenolol (a beta 1 adrenergic antagonist) or ICI-118,551 hydrochloride (a beta 2 adrenergic antagonist). The two NPY analogs as well as the VIP stimulated the release of catecholamines and of aldosterone. The beta 1 adrenergic antagonist, but not the beta 2 one, which failed to affect basal aldosterone production when given alone, prevented NPY18-36-, Leu31,Pro34-NPY- or VlP-induced aldosterone secretion. Present data support the hypothesis that adrenaline and/or noradrenaline could mediate the effects of both NPY and VIP on aldosterone secretion via beta 1 adrenergic receptors; alternatively, the steroidogenic effect of NPY or VIP could be related to direct interaction between NPY- or VIP-specific binding sites, present on the capsule/glomerular zone of the rat adrenal cortex, and beta 1 adrenergic receptors. Then the NPYergic, VIPergic and catecholaminergic innervation of the adrenal cortex, previously characterized by immunohistochemistry, may be a potent stimulatory element in the nervous control of the aldosterone secretion.

Circulating neuropeptide Y (NPY) and catecholamines in rat under resting and stress conditions. Arguments for extra-adrenal origin of NPY, adrenal and extra-adrenal sources of catecholamines.

Neuropeptide Y (NPY) is found in cell bodies of neurons in the brain and co-localized with noradrenaline (NA) in sympathetic nerves as well as with NA and adrenaline (A) in the adrenal chromaffin cells. The purpose of the present work is to determine whether NPY and catecholamines found in the plasma of the rat under resting and stress conditions (ether inhalation, restraint) arise from the adrenals or from extra-adrenal sites. We used adrenalectomized (adx) rats and sham-adx ones. Adrenalectomy increased plasma adrenocorticotrophic hormone (ACTH) levels but decreased drastically circulating corticosterone (B) and A (-97%). However, resting NA was slightly but not significantly decreased and NPY not affected. Ether inhalation (3 min) increased plasma levels of ACTH, B, NA and A in sham-adx rats, ACTH, NA and, weakly, A in adx ones. Restraint (30 min) increased B, NA and A in sham-adx rats, NA and, poorly, A, in adx ones. In contrast, plasma levels of NPY were not significantly affected by these stress conditions. The present data suggest that NA found in rat plasma at rest and during ether or restraint stress could arise from both adrenal medulla and noradrenergic nerve endings while A arises mainly from the adrenergic chromaffin cells of the adrenals. In contrast, NPY found in the circulation, at rest and under stress conditions, is not derived from the adrenals but emanates mainly from an extra-adrenal source.

Hypothalamic-pituitary-adrenocortical and gonadal axes and sympathoadrenal activity of adult male rats prenatally exposed to morphine.

The present investigation concerns 80-90 day-old male rats born from morphine-exposed mothers (2 x 10 mg/kg per day from days 11 to 18 of gestation which showed at birth reduced size and activity of the adrenals). This prenatal treatment did not significantly disturb under resting conditions: (1) the postnatal body growth up to week 10 after birth, (2) the activity of the pituitary gonadal axis (circulating luteinizing hormone (LH) and testosterone (T), weight of the testicles and seminal vesicles), (3) the activity of the hypothalamo-pituitary-adrenal axis (HPA) (hypothalamic corticoliberin (CRF) content, plasma adrenocorticotrophic hormone (ACTH) level, adrenal weight and corticosterone (B) content, plasma B level) as well as Bmax and Kd of mineralocorticoid (type I) and glucocorticoid (type II) receptors to B in both the hippocampus and the hypothalamus. In contrast these rats showed reduced content of adrenals in noradrenaline (NA) and adrenaline (A) but increased circulating levels of A.