Biomedical subjects

C Clerici

Publications and source records attributed to C Clerici.

At least 19 recordsLinked to original sources

PubMed1992

Effect of intraduodenal administration of 23-methyl-UDCA diastereoisomers on bile flow in hamsters.

3 alpha,7 beta-Dihydroxy-23-methyl-5 beta-cholan-24-oic acid (MUDCA) and its two diastereoisomers, alpha- and beta-MUDCA, were infused intraduodenally in biliary fistula hamsters in order to evaluate the effect on bile flow and their hepatic biotransformation processes compared with the natural analog ursodeoxycholic acid (UDCA). In addition, the corresponding glycine conjugates were compared. The bile acids were administered at different doses (0.7-6 mumol/min/kg) over periods of 90 min. The results indicate that the racemic mixture exhibits a potent choleretic effect at both low and high doses, while the two individual diastereoisomers show this effect only at high doses. The presence of a C-23 methyl group in the side chain prevents hepatic amidation and alternative conjugations occur, such as glucuronidation, in order to facilitate their biliary secretion. Biotransformation of the methyl derivatives of UDCA occurred mainly by conversion to more polar glucuronide conjugates. There was little alteration to the molecule and, unlike UDCA, very little amidation occurred. These data indicate that the presence of a C-23 methyl group prevents the usual side-chain amidation common to the most naturally occurring bile acids and that glucuronidation is a requisite for efficient biliary excretion.

Acute Disease↗

PubMed1992

Impairment of sodium-coupled uptakes by hydrogen peroxide in alveolar type II cells: protective effect of d-alpha-tocopherol.

Hydrogen peroxide (H2O2) is likely to play an important role in oxidant alveolar epithelium injury. We investigated the effect of H2O2 on uptake of phosphate, alanine in cultured rat alveolar type II cells. H2O2 induced inhibition of Na-dependent component of phosphate and alanine uptakes in time- and concentration-dependent manner. Twenty minutes exposure to 2.5 mM H2O2 decreased the maximum velocity (Vmax) of phosphate and alanine uptake by 50 and 62%, respectively, whereas Michaelis constant (Km) values were unchanged. H2O2 also decreased Na-K-ATPase activity, measured by ouabain-sensitive rubidium influx, and this effect was independent of H2O2-induced ATP depletion. A lipid-soluble antioxidant, d-alpha-tocopherol (20 microM, 24 h), prevented H2O2-induced decrease in Na-coupled uptake and Na-K-ATPase activity. These results indicate that H2O2 affects Na-dependent phosphate and alanine uptakes and suggest that this effect may be related at least, in part, to a decrease in Na transmembrane gradient, since H2O2 also affects Na-K-ATPase activity. The protective effect of d-alpha-tocopherol suggests that peroxidation of the membrane lipids is likely to be involved in the observed effects.

Adenosine Triphosphate↗

PubMed1992

Different effects of nasal and bronchial glucocorticosteroid administration on bronchial hyperresponsiveness in patients with allergic rhinitis.

Disorders of the upper respiratory tract, particularly allergic rhinitis, are commonly associated with bronchial hyperresponsiveness. The latter may be due to postnasal drip or to mediator or chemotactic factors into the lower airways that either directly alter airway reactivity or cause airway inflammation. The aim of this study was to compare the effect of an identical dose of nasal or bronchial corticosteroid administration on bronchial hyperresponsiveness in patients with allergic rhinitis. Eleven patients were studied. All of them were judged atopic on the basis of positive skin tests to common allergens. During control, spirometry, flow-volume curves, and specific airway conductance (SGaw) were measured. Bronchial challenges were then performed with increasing concentrations of carbachol, and dose-response curves were constructed. The concentration of carbachol that decreased SGaw by 35% from baseline (PD35) was determined by interpolating from the dose-response curve. Control measurements were repeated at 1-wk intervals to ensure that PD35 was stable in all the patients. Then the patients received for 2 wk, in a double-blind randomized crossover fashion, a topical administration of either an aerosol of 400 micrograms of beclamethasone dipropionate (B) into the nose (100 micrograms four times per day) or into the bronchi. During each trial period, identical sprays of placebo were used, the latter being administered into the nose when B was administered into the bronchi and vice versa. Measurements were then performed after 2 wk of intranasal administration and after 2 wk of intrabronchial administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

PubMed1991

Sodium-dependent phosphate and alanine transports but sodium-independent hexose transport in type II alveolar epithelial cells in primary culture.

Inorganic phosphate, amino acids and sugars are of obvious importance in lung metabolism. We investigated sodium-coupled transports with these organic and inorganic substrates in type II alveolar epithelial cells from adult rat after one day in culture. Alveolar type II cells actively transported inorganic phosphate and alanine, a neutral amino acid, by sodium-dependent processes. Cellular uptakes of phosphate and alanine were decreased by about 80% by external sodium substitution, inhibited by ouabain (30 and 41%, respectively) and displayed saturable kinetics. Two sodium-phosphate cotransport systems were characterized: a high-affinity one (apparent Km = 18 microM) with a Vmax of 13.5 nmol/mg protein per 10 min and a low-affinity one (apparent Km = 126 microM) with a Vmax of 22.5 nmol/mg protein per 10 min. Alanine transport had an apparent Km of 87.9 microM and a Vmax of 43.5 nmol/mg protein per 10 min. By contrast, cultured alveolar type II cells did not express sodium-dependent hexose transport. Increasing time in culture decreased Vmax values of the two phosphate transport systems on day 4 while sodium-dependent alanine uptake was unchanged. This study demonstrated the existence of sodium-dependent phosphate and amino acid transports in alveolar type II cells similar to those documented in other epithelial cell types. These sodium-coupled transports provide a potent mechanism for phosphate and amino acid absorption and are likely to play a role in substrate availability for cellular metabolism and in regulating the composition of the alveolar subphase. The decrease in phosphate uptake with time in culture is parallel to decrease in surfactant synthesis reported in cultured alveolar type II cells, suggesting that phosphate availability for surfactant synthesis may be accomplished by a sodium-dependent phosphate uptake.

Alanine↗

PubMed1991

Protective effect of theophylline on bronchial hyperresponsiveness in patients with allergic rhinitis.

Disorders of the upper respiratory tract, particularly allergic rhinitis are commonly associated with bronchial hyperresponsiveness. The latter may be responsible for chronic cough, a common symptom in patients with allergic rhinitis, which, as previously shown, can be the sole presenting manifestation of bronchial hyperresponsiveness. Theophylline is widely used in patients with asthma for its bronchodilator effect, whereas its action on bronchial reactivity is controversial. The aim of this study was to determine the effect of theophylline administration on bronchial hyperresponsiveness in patients with allergic rhinitis complaining of chronic cough. Fourteen patients were studied. All of them were judged atopic on the basis of positive skin tests to common allergens. During control, spirometry, flow-volume curves and specific airway conductance (SGaw) were measured. Bronchial challenges were then performed with increasing concentrations of carbachol, and dose-response curves were constructed. The concentration of carbachol, which decreased SGaw by 35% from baseline (PD35) was determined by interpolating from the dose-response curve. After control measurements patients received in a randomized, double-blind crossover fashion either theophylline 10 mg/kg/day orally or placebo for 30 days. Measurements were then redone. After a washout period of 8 days the measurements were repeated, and patients received theophylline or placebo for a second period of 30 days. Measurements were again performed at the end of this last study period. During control all patients had normal baseline lung function data and showed marked bronchial hyperresponsiveness, PD35 amounting to 26 +/- 7 micrograms of carbachol (normal value greater than 160 micrograms). No significant changes in PD35 were noted after placebo and washout when compared with control values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Prevention of ursodeoxycholate hepatotoxicity in the rabbit by conjugation with N-methyl amino acids.

The effect of dietary administration of four different amino acid (N-acyl) conjugates of ursodeoxycholic acid on biliary bile acid composition, liver tests and hepatic morphology by light microscopy was examined in the rabbit. Each group of four to five rabbits received a chow diet supplemented with a single conjugate of ursodeoxycholic acid ursodeoxycholyl-glycine, ursodeoxycholyl-sarcosine, ursodeoxycholyl-taurine or ursodeoxycholyl-N-methyltaurine for 3 wks at a dose of 50 mg/kg/day; a control group received chow alone. After 3 wks of feeding, animals receiving ursodeoxycholyl-glycine or ursodeoxycholyl-taurine had hepatotoxicity associated with abnormal liver tests. Lithocholic acid made up 11% +/- 2.7% of biliary bile acids in the ursodeoxycholyl-glycine and 10% +/- 2.2% in the ursodeoxycholyl-taurine group. In contrast, animals receiving ursodeoxycholyl-sarcosine or ursodeoxycholyl-N-methyltaurine had neither hepatotoxicity nor abnormal liver tests and the proportion of lithocholic acid in biliary bile acids increased much less. Complementary studies showed that ursodeoxycholyl-sarcosine and ursodeoxycholyl-N-methyltaurine were not biotransformed during hepatic transport and were resistant to deconjugation and dehydroxylation in the rabbit. These experiments indicate that the N-methyl amino acid conjugates of ursodeoxycholic acid are nontoxic in the rabbit and resist deconjugation and dehydroxylation. Such resistance decreases formation of lithocholic acid in the colon, thus reducing its accumulation and consequent induction of hepatotoxicity.

Amino Acids↗

PubMed1990

Transport, metabolism, and effect of chronic feeding of lagodeoxycholic acid. A new, natural bile acid.

Ursodeoxycholic acid, the 7 beta-hydroxy epimer of chenodeoxycholic acid, is more hydrophilic and less hepatotoxic than chenodeoxycholic acid. Because "lagodeoxycholic acid," the 12 beta-hydroxy epimer of deoxycholic acid, is also more hydrophilic than deoxycholic acid, it was hypothesized that it should also be less hepatotoxic than deoxycholic acid. To test this, lagodeoxycholic acid was synthesized, and its transport and metabolism were examined in the rat, rabbit, and hamster. The taurine conjugate of lagodeoxycholic acid was moderately well transported by the perfused rat ileum (Tmax = 2 mumol/min.kg). In rats and hamsters with biliary fistulas, the taurine conjugate of lagodeoxycholic acid was well transported by the liver with a Tmax greater than 20 mumol/min.kg; for the taurine conjugate of deoxycholic acid, doses infused at a rate greater than 2.5 mumol/min.kg are known to cause cholestasis and death. Hepatic biotransformation of lagodeoxycholic acid in the rabbit was limited to conjugation with glycine; in the hamster, lagodeoxycholic acid was conjugated with glycine or taurine; in addition, 7-hydroxylation occurred to a slight extent (approximately 10%). When lagodeoxycholic acid was instilled in the rabbit colon, it was absorbed as such although within hours it was progressively epimerized by bacteria to deoxycholic acid. When injected intravenously and allowed to circulate enterohepatically, lagodeoxycholic acid was largely epimerized to deoxycholic acid in 24 hours. Surgical creation of a distal ileostomy abolished epimerization in the rabbit, indicating that exposure to colonic bacterial enzymes was required for the epimerization. Lagodeoxycholic acid was administered for 3 weeks at a dose of 180 mumol/day (0.1% by weight of a chow diet; 2-4 times the endogenous bile acid synthesis rate); other groups received identical doses of deoxycholic acid (hamster) or cholyltaurine, a known precursor of deoxycholic acid (rabbit). After 3 weeks of lagodeoxycholic acid ingestion, liver test results and liver appearance were normal. The total bile acid pool expanded by 37% in the rabbit, lagodeoxycholic acid composing 10% of biliary bile acids. In the hamster, the total bile acid pool was expanded by 95%, lagodeoxycholic acid composing 22% of biliary bile acids; biliary lipid secretion remained unchanged. Tracer studies indicated that the fractional turnover rate of lagodeoxycholic acid was high (157%/day, rabbit; 116%/day, hamster) because of its rapid epimerization to deoxycholic acid in the colon. These studies indicate that lagodeoxycholic acid, the more hydrophilic epimer of deoxycholic acid, is transported and metabolized as other dihydroxy bile acids but is much less toxic than deoxycholic acid.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1989

[Chronic idiopathic eosinophilic pneumopathy. Carrington's disease].

Eleven cases of idiopathic chronic eosinophilic pneumonia were studied. Ten of the patients were followed up for more than 3 years and the last one for 15 years. The female predominance observed, the mean age of 51 years, the late manifestations of asthma-like symptoms preceding the systemic signs by 8 1/2 months on average and the scarcity of extra-pulmonary manifestations characterized the clinical data. The most frequent radiological signs were non-systematized, bilateral alveolar opacities in the axillary and apical regions, sometimes migratory and giving in 9 cases a mirror image of pulmonary oedema. Beside this major inflammatory syndrome, blood eosinophilia was present in 10 patients with 4,500 eosinophils on average per cubic millimetre. Eosinophils were also present in the bronchoalveolar lavage fluid of those who underwent this examination. Both clinical and radiological signs responded to corticosteroids in all cases, with return to normal chest radiography within less than 10 days. Subsequently, the possibility of radiological relapse in the same or other territories, together with the development of a steroid-dependent intrinsic asthma accounted for the fact that after a follow-up of about 3 years corticosteroid therapy could not be discontinued in any of our patients.

Adult↗

PubMed1989

[Hypoxemia in liver cirrhosis].

Hypoxaemia is observed in almost 30 per cent of patients with cirrhosis of the liver, irrespective of the cause of cirrhosis. Two main physiopathological mechanisms can be described: hypoxaemia may be secondary to intrapulmonary vascular abnormalities or due to a regional disequilibrium of the ventilation/perfusion ratio. In the first case, the severity of hypoxaemia often requires complex and invasive investigations, while in the second case, by far the most frequent, hypoxaemia is moderate, usually asymptomatic and in practice only needs a few investigations.

Arteriovenous Malformations↗

PubMed1989

Effects of propranolol on pulmonary gas exchange in patients with cirrhosis.

Propranolol, a beta-blocking agent, has been proposed in the prevention of gastro-intestinal bleeding in cirrhotic patients, and is known for its bronchoconstrictive effects. Since hypoxemia is a frequent finding in patients with cirrhosis, this work was undertaken to study the effects of intravenous propranolol on pulmonary function and on gas exchange in these patients. The 10 patients studied had cirrhosis associated with an increase in the alveolar arterial O2 difference, (A-a)DO2, an index of arterial oxygenation impairment. Their 1-s forced expiratory volume/forced vital capacity (FEV1/FVC) was normal, but in most a reduction of the forced expiratory flow of 25-75% of vital capacity was observed (FEF 25-75), suggestive of some degree of small airway obstruction. Although propranolol induced a significant decrease of FEF 25-75 from 67.7 +/- 19.3% to 55.4 +/- 21.5% (P less than 0.01), suggesting a bronchoconstriction of the small airways, there was no significant decrease in mean arterial oxygen partial pressure (PaO2) (74.1 +/- 6.4 mmHg before and 77.0 +/- 6.5 mmHg after propranolol). Indeed, a slight but significant improvement of the (A-a)DO2 was observed, from 39.1 +/- 5.9 mmHg to 34.4 +/- 4.9 mmHg (P less than 0.02). Although the mechanism of this beneficial effect remains to be elucidated, we conclude that in spite of its bronchoconstrictive action, propranolol is not contra-indicated in cirrhotic patients with hypoxemia who have normal expiratory flow.

Adult↗

PubMed1989

Cholinergic component of histamine-induced bronchoconstriction in newborn guinea pigs.

The magnitude of parasympathetic reflex-mediated bronchoconstriction during histamine infusion was compared in anesthetized paralyzed newborn and adult guinea pigs. The animals were ventilated using a constant-flow ventilator, and the conductance and compliance of the respiratory system were continuously monitored. We found that reactivity to histamine infusion was less in newborns than in adults, because newborns required a larger dose of histamine than adults (300 vs. 125 ng.kg-1.s-1) to produce an equivalent decrease in conductance (42 +/- 13 vs. 42 +/- 15%). Vagal interruption by bilateral cervical vagotomy or muscarinic blockade with atropine (3 mg/kg) significantly reduced the bronchoconstrictor response to histamine in adults. By contrast, neither vagotomy nor atropine significantly changed this response in the newborns. These results indicate the lack of a vagal component in the bronchoconstriction that histamine induced in the newborns. Their relative unresponsiveness to histamine might partly be related to the fact that, in the newborn, histamine mainly acts directly via its airway receptors.

Aging↗

PubMed1989

Nonadrenergic bronchodilation in adult and young guinea pigs.

The contribution of the nonadrenergic inhibitory system to airway responses to infusion of 5-hydroxytryptamine (5-HT) was evaluated in anesthetized, tracheotomized, and paralyzed young (13 days) and adult (82 days) guinea pigs. Animals were mechanically ventilated by a constant flow ventilator. Compliance (C) and conductance (G) of the respiratory system were continuously monitored. Three series of experiments were performed involving intravenous pretreatment with 1) atropine (3 mg/kg) and propranolol (1 mg/kg); 2) atropine (3 mg/kg), propranolol (1 mg/kg), and phentolamine (2 mg/kg); and 3) atropine (3 mg/kg) and hexamethonium (2 mg/kg). 5-HT was then intravenously infused for 5 min at a rate of 40 ng.kg-1.s-1 in adults and 60 ng.kg-1.s-1 in young guinea pigs to obtain the same degree of bronchoconstriction in both groups. At the 3rd min of the infusion, bilateral cervical vagotomy was performed and C and G were measured at the maximal response, 1-2 min thereafter. Vagotomy increased bronchoconstriction (P less than 0.01) in both young animals and adults. Phentolamine did not modify this increase, but hexamethonium completely inhibited it. These results indicate that, in adult and young guinea pigs, 5-HT infusion induces reflex activation of the nonadrenergic inhibitory system, which in turn modulates the bronchoconstrictor responses to 5-HT. This neural modulation is not mediated by an alpha-adrenergic pathway.

Animals↗

PubMed1989

The efficacy of an information group intervention on relatives of schizophrenics.

Socio-therapy of schizophrenia cannot fail to consider such an important element as assistance to relatives. This report will review the main treatment methods used today and presents an intervention model which acts on the family of the schizophrenic at different levels. While the schizophrenic patient receives an individual treatment (pharmacological and psychotherapeutic), his/her relatives undergo a two-step group intervention. The first phase concerns an information group. This paper gives an early assessment as to the efficacy of the information groups for relatives. Particularly, it focuses on the actual ability of the group in conveying information to relatives. Such transfer of information is measured by means of a structured interview (Knowledge Interview). Results demonstrate that after an information group family members had a significant statistical increase of their information level (p less than 0.001). Some areas recorded a considerable increase in the knowledge levels, as far as the legitimacy of the illness and the management of symptoms are concerned.

Adult↗

PubMed1988

Effects of rilmenidine on bronchomotor responses in the guinea pig.

This study compares the effects of 2 alpha 2-adrenergic agonists, rilmenidine (S 3341) and clonidine, on histamine-induced bronchoconstriction (HIB) in guinea pigs. Clonidine has previously been shown to potentiate HIB in guinea pigs. The study was conducted in anesthetized, paralyzed and ventilated guinea pigs. Six groups of at least 6 guinea pigs were pretreated with saline, rilmenidine (0.1, 0.3 and 1 mg/kg intravenously) or clonidine (0.01 and 0.03 mg/kg intravenously), respectively. Conductance, dynamic compliance and static compliance of the respiratory system were measured before and during histamine infusion (80 ng/kg/s) and expressed as percent variation. Clonidine potentiated HIB as previously reported. In contrast, rilmenidine potentiated HIB only at the dose of 1 mg/kg. As it is well known that HIB is influenced by adrenergic outflow, these results suggest that rilmenidine has less inhibitory effect than clonidine on adrenal secretion.

Adrenergic alpha-Agonists↗

PubMed1988

Comparative effects of bisoprolol and acebutolol in smokers with airway obstruction.

1. The effects of single oral doses of 10 mg bisoprolol and 400 mg acebutolol on respiratory function were studied in nine smokers with airway obstruction in a double-blind, placebo-controlled experiment. 2. The effects of the drugs were assessed by measuring specific airway conductance (sGaw) for 3 h after their administration and by studying their interaction with the bronchodilator response to inhaled salbutamol. 3. sGaw did not change for 3 h after bisoprolol or acebutolol administration. The bronchodilator response to inhaled salbutamol was not affected by bisoprolol but significantly reduced by acebutolol (P less than 0.05 vs placebo). 4. Under these conditions, bisoprolol behaves like a selective beta 1-adrenoceptor antagonist but acebutolol exhibits less beta 1-adrenoceptor selectivity.

Acebutolol↗

PubMed1988

Smoking and pulmonary sarcoidosis: effect of cigarette smoking on prevalence, clinical manifestations, alveolitis, and evolution of the disease.

Patients with pulmonary sarcoidosis are less likely to smoke than persons of a similar age in the general population. This could be because smoking reduces the likelihood of developing sarcoidosis, or alternatively smoking could reduce the severity of the disease process so that smoking patients are underrepresented among patients with clinically overt disease. To evaluate these possibilities 64 patients with sarcoidosis of recent onset were studied at presentation and after a one year follow up period, clinical, functional, radiographic, and bronchoalveolar lavage fluid criteria being used to identify factors that might account for the lower incidence of sarcoidosis in smokers and to determine whether the disease is less severe in smoking patients. Smoking was less common in the patients with sarcoidosis (30%) than in the control subjects (46%). The study did not support the conclusion that sarcoidosis is less severe in smokers, as clinical, radiographic, and functional abnormalities were similar in smokers and non-smokers at initial evaluation and after a one year follow up period. Nevertheless, smoking did influence various indices used to assess disease "activity." Cigarette smoking was associated with a significant increase in the serum angiotensin converting enzyme activity (SACE), and patients with very high SACE and pulmonary gallium-67 uptake were smokers. Furthermore, more CD8+ (but not CD4+) lymphocytes were recovered by lavage from smoking than from non-smoking patients, giving a lower CD4: CD8 ratio in smokers. Fewer alveolar macrophages were recovered by lavage from smokers with sarcoidosis than from normal subjects with a similar smoking history. These finding support the possibility that smokers, particularly those with a prominent accumulation of alveolar macrophages in the lower respiratory tract, may be less likely to develop sarcoidosis.

Adult↗

PubMed1988

Effects of cardioselective beta blockade on the peripheral lung in guinea pigs.

Impairment of lung function with selective beta-1 blocking drugs has been repeatedly demonstrated in guinea pigs, normal subjects and asthmatic patients. The effects of several beta blockers, propranolol (non-selective), atenolol (beta-1 selective), IPS 339 (beta-2 selective) on histamine-induced bronchoconstriction have been investigated in 30 anaesthetized and mechanically ventilated guinea pigs, measuring changes in conductance and dynamic compliance. Their effects on peripheral lung, where only beta-2 adrenoceptors are present, were more specifically assessed using changes in lung distensibility by means of static pressure-volume curves. Atenolol (1 mg.kg-1), IPS 339 (2 mg.kg-1) and propranolol (2 mg.kg-1) enhanced histamine-induced decrease in lung distensibility, conductance and dynamic compliance. The decrease was of the same order of magnitude for all three parameters. Atenolol (1 mg.kg-1) and propranolol (2 mg.kg-1) decreased lung distensibility to the same extent. By contrast low dose atenolol (0.1 mg.kg-1) did not potentiate histamine-induced bronchoconstriction although this dose did produce a significant cardiac beta blockade. These results demonstrate that 1) beta blockers have a clear effect on the peripheral lung, 2) beta-1 adrenoceptors are not involved in pulmonary effects of cardioselective drugs. They suggest that dose dependent loss of selectivity is the major mechanism behind impairment of lung function following such drugs.

Adrenergic beta-Antagonists↗

PubMed1988

Mechanism of histamine-induced epinephrine release in guinea pig.

The aims of this study were to provide direct evidence that in anesthetized guinea pigs i.v. administration of histamine induces sympathoadrenal activation and to identify the source and mechanism of histamine-induced epinephrine release. Plasma epinephrine measurements were used as the index of sympathoadrenal activity. In intact guinea pigs, histamine infusion caused a 3-fold rise in plasma epinephrine levels. In guinea pigs pretreated with 6-hydroxydopamine to obtain chemical sympathectomy, the rise in plasma epinephrine induced by histamine was distinctly smaller than in controls. This rise was completely inhibited in guinea pigs pretreated with the ganglion blocking agent hexamethonium and in pithed guinea pigs. Pretreatment with the H2-receptor antagonist cimetidine or the H1-receptor antagonist mepyramine reduced the rise in plasma epinephrine. These results demonstrate that in guinea pigs, epinephrine is released not only from the adrenal medulla but also from nerve endings and that histamine releases epinephrine by indirect action through central reflex pathways.

Animals↗