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R Bernardini

Publications and source records attributed to R Bernardini.

At least 19 recordsLinked to original sources
PubMed1992

Plasma beta-endorphin levels and natural-killer cells in two cases of congenital indifference to pain.

We have investigated plasma beta-endorphin (beta-E), ACTH, and cortisol in two cases of congenital indifference to pain (CIP), a rare syndrome characterized by unresponsiveness to painful stimuli. As the two patients had frequent skin infections, we also studied lymphocyte response to mitogens in the absence or presence of beta-E. In addition, we explored a series of lymphocyte membrane antigens related to different aspects of the immune response, such as CD3+, CD4+, CD8+, B, NK Leu 7, Leu 9, and Leu 19, anti-interleukin-2 receptor (anti-TAC). Plasma beta-E levels in the two patients were significantly higher than in controls, whereas plasma ACTH and cortisol levels were normal. Lymphocyte response to the mitogen phytohemagglutinin was normal. The expression of Leu 7, Leu 9, and Leu 19, three antigens related to natural killer cells, was decreased by about 50%. The results indicate that in the two cases of CIP studied, high plasma beta-E levels are associated with a reduction in the expression of natural killer cells. This suggests that the two phenomena are specifically related to each other. These data represent further evidence of the possible pathophysiological relevance of the neuroendocrine-immune feedback.

Adolescent↗
PubMed1992

Neurotransmitter-induced hypothalamic-pituitary-adrenal axis responsiveness is defective in inflammatory disease-susceptible Lewis rats: in vivo and in vitro studies suggesting globally defective hypothalamic secretion of corticotropin-releasing hormone.

The susceptibility of female Lewis (LEW/N) rats to the development of streptococcal cell wall (SCW)-induced arthritis and other autoimmune phenomena is associated with the inability of their hypothalamic-pituitary-adrenal (HPA) axis to adequately respond to inflammatory stimuli. In contrast, resistance to the development of SCW-induced arthritis and other inflammatory autoimmune manifestations in histocompatible female Fischer rats (F344/N) is related to their intact HPA axis response to inflammatory mediators. To evaluate the mechanism and the specificity of the HPA axis defect in LEW/N rats, we examined the ability of three major excitatory neurotransmitter systems to activate the HPA axis in both Lewis and Fisher rats. The responsiveness of plasma ACTH and corticosterone to the cholinergic muscarinic receptor agonist arecoline, the alpha 1-adrenergic receptor agonist methoxamine and the serotonin (5-HT) type 2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane were significantly blunted and/or abolished in LEW/N compared to F344/N rats. To localize the HPA axis defect to the hypothalamic CRH neuron, we evaluated the ability of explanted hypothalami from the two strains to secrete immunoreactive CRH in vitro, in response to acetylcholine (ACh), norepinephrine (NE), 5-HT and the 5-HT agonist quipazine. LEW/N hypothalami released less immunoreactive CRH (iCRH) in response to ACh, NE, 5-HT and quipazine than F344/N hypothalami. The dose-response curves of these compounds in the former were shifted to the right and/or abolished, suggesting decreased sensitivity of LEW/N hypothalami to these neurotransmitters.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1992

Cholecystokinin-octapeptide stimulates hypothalamic-pituitary-adrenal function in rats: role of corticotropin-releasing hormone.

Peripherally-administered cholecystokinin (CCK) is a profound suppressor of food intake, can promote anxiety, and causes the acute release of ACTH into plasma. Centrally administered corticotropin-releasing hormone (CRH), on the other hand, not only represents the principal stimulus to the pituitary corticotroph cell, but also has been shown to suppress appetite and to be profoundly anxiogenic. Because of the overlap in the effects of peripherally administered CCK and of centrally administered CRH, we report here a study to determine whether sulphated CCK octapeptide (CCK-8) could induce the release of CRH within the central nervous system. To accomplish this task, we first assessed the dose-related effects of CCK-8 on ACTH release. Graded doses of CCK-8 (0.1-10 micrograms/kg BW) given in an i.v. bolus to freely moving male rats, resulted in a dose-dependent increase of plasma immunoreactive (IR)-ACTH (ED50: 1-10 micrograms/kg BW). The lowest maximal stimulatory dose of CCK-8 (5 micrograms/kg BW) was used in all subsequent experiments. To evaluate whether CCK-induced ACTH secretion was mediated by a peripheral CCK receptor, an i.v. bolus injection of vehicle or L-364,718 (1 mg/kg BW), a specific, highly potent peripheral CCK receptor antagonist, was given before the i.v. administration of CCK-8 or vehicle. Plasma IR-ACTH response to CCK-8 was significantly attenuated by L-364,718. A role for the vagal afferents that contain CCK receptors in peripherally administered CCK-mediated hypothalamic-pituitary-adrenal (HPA) axis activation was examined in animals that had been pretreated with capsaicin, a potent neurotoxin that destroys vagal afferents. Plasma IR-ACTH and IR-corticosterone responses in capsaicin-treated animals were significantly lower than those in vehicle treated rats. In subsequent in vivo experiments, pituitary stalk-transected and sham-operated animals were used to evaluate whether CCK-8 stimulates the HPA axis via a centrally mediated mechanism. IR-ACTH and IR-corticosterone responses to i.v. CCK-8 were significantly reduced in the pituitary stalk-transected compared to sham-operated animals. In further effort to determine whether the central nervous system was involved in the plasma IR-ACTH response to the peripheral administration of i.v. CCK-8, we compared the effects of the i.v. administration of CRH antisera vs. normal rabbit serum on this parameter. IR-ACTH and IR-corticosterone responses to i.v. CCK-8 were significantly reduced in the context of pretreatment with CRH antisera compared to the administration of normal rabbit serum.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗
PubMed1992

Eel calcitonin induces creatine kinase BB activity in the rat kidney medulla.

We have studied the effect of intravenous injection of eel calcitonin (ECT) on creatine kinase E.C.2.7.3.2. BB isozyme (CKBB) in the kidney of male Wistar rats. CKBB immunoreactivity was detected by the peroxidase-antiperoxidase method. Eel calcitonin increased CKBB immunoreactivity in the renal medulla in a dose-dependent fashion. Its effect peaked at 2 h and lasted up to 24 h. The distribution of activated CKBB in the kidney occurs in the same areas where highly specific CT-binding sites have been previously demonstrated, and is in agreement with the current concepts on renal actions of this hormone.

Animals↗
PubMed1991

Chronic sodium or chloride depletion upregulates angiotensin II receptors in the anterior pituitary lobe of young rats.

The effect of chronic (35 days) and selective sodium or chloride depletion on the regulation of angiotensin II receptors in the anterior pituitary gland of young male rats was studied by quantitative autoradiography. Both chronic sodium or chloride depletion produced significant extracellular fluid volume contraction, stimulation of the circulating renin-angiotensin system and increased the number of angiotensin II receptors in the anterior pituitary gland. Changes in angiotensin II receptors in both sodium- and chloride-depleted animals were associated with increased plasma prolactin levels. Our results suggest a participation of the pituitary renin-angiotensin system in the physiological response and/or possible adaptation to chronic sodium or chloride depletion. Extracellular fluid volume contraction and profound chronic stimulation of the circulating renin-angiotensin system may contribute to regulate anterior pituitary angiotensin II receptors and may influence prolactin release.

Aldosterone↗
PubMed1990

Rat hypothalamic corticotropin-releasing hormone secretion in vitro is stimulated by interleukin-1 in an eicosanoid-dependent manner.

We studied the effect of interleukin-1 alpha (IL-1) on corticotropin-releasing hormone (CRH) secretion by explanted rat hypothalami in vitro. We also assessed possible mediation of arachidonic acid metabolites on IL-1-stimulated CRH secretion, by preincubating hypothalami with the cyclooxygenase inhibitor indomethacin (INDO, 1 microM), the lipoxygenase and cyclooxygenase inhibitor eicosatetraynoic acid (ETYA, 10 microM), or the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA, up to 30 microM). In additional experiments, prostaglandins (PG) E2 and F2 alpha were added to the cultures treated with INDO or ETYA. Finally, we investigated the effect of dexamethasone (DEX) on IL-1-stimulated CRH secretion. IL-1 stimulated immunoreactive CRH (iCRH) secretion by explanted hypothalami in a concentration-dependent fashion. Both INDO and ETYA inhibited IL-1-(10nM)-stimulated iCRH secretion, whereas NDGA did not have any effect. The addition of PGF2 alpha (10 nM) restored the secretion of iCRH inhibited by INDO. DEX treatment significantly inhibited IL-1-stimulated iCRH release. Our results suggest that the stimulatory effect of IL-1 on the hypothalamic CRH neuron is mediated by the cyclooxygenase metabolites of arachidonic acid, and, among others, by PGF2 alpha.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1990

Procaine and lidocaine stimulate corticotropin-releasing hormone secretion by explanted rat hypothalami through a sodium conductance-independent mechanism.

We have previously shown that procaine and lidocaine stimulate corticotropin-releasing hormone (CRH) secretion by explanted rat hypothalami. This effect was of interest in light of the fact that both lidocaine and CRH administration to experimental animals can produce kindled seizures which cross-sensitize with electrically kindled seizures, and of recent data suggesting that limbic hyperexcitability, perhaps mediated through CRH, may be involved in the pathophysiology of affective illness. Because a prominent effect of the local anesthetics is to decrease neuronal firing by blocking sodium conductance, we were surprised by the capacity of these agents to cause CRH secretion and pituitary-adrenal activation and wished to further elucidate the possible mechanism(s) of these effects. To accomplish this, we first explored the effect of the sodium channel blocker tetrodotoxin (TTX) on basal and stimulated immunoreactive CRH (iCRH) secretion by explanted rat hypothalami. In contrast to procaine and lidocaine, TTX inhibited rather than stimulated iCRH secretion. Moreover, TTX inhibited lidocaine-induced iCRH secretion but had no influence on the response of the CRH neuron to procaine. To explore other potential mechanisms of action, we examined the effect of the calcium channels blocker verapamil and of pharmacologic antagonists to serotonergic, alpha-adrenergic and cholinergic receptors. The latter was particularly of interest because of structural similarities between procaine or lidocaine and acetylcholine (ACh) and because it has been shown that these anesthetic agents interact with the ACh receptor. Verapamil and blockade of serotonergic, alpha-adrenergic and cholinergic receptors did not inhibit the effects of procaine or lidocaine on iCRH secretion, whereas both GABA and dexamethasone exerted inhibitory effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Interactions between tumor necrosis factor-alpha, hypothalamic corticotropin-releasing hormone, and adrenocorticotropin secretion in the rat.

We studied the effects of tumor necrosis factor-alpha (TNF alpha), a macrophage-derived pleiotropic cytokine produced during the inflammatory/immune response, on the function of the hypothalamic-pituitary-adrenal (HPA) axis of the rat. Intravenous injections of TNF alpha stimulated plasma ACTH and corticosterone secretion in a dose-dependent fashion. This effect was inhibited by a rat CRH antiserum that was administered to the rats 1 h before the TNF alpha injections. This suggested that CRH is a major mediator of the HPA axis response to TNF alpha. We subsequently evaluated the ability of TNF alpha to influence CRH and ACTH secretion in vitro by explanted rat hypothalami in organ culture and by dispersed rat anterior pituicytes in primary culture respectively. Hypothalami were incubated for 40 min with graded concentrations of TNF alpha (10 pM to 1 microM). This cytokine stimulated CRH secretion in a dose-dependent fashion, with an EC50 of 6.7 x 10 pM (P less than 0.05). Preincubation of hypothalamic explants with dexamethasone, indomethacin (1 microM), eicosatetraynoic acid (10 microM), or nordihydroguaiaretic acid (30 microM) resulted in inhibition of TNF alpha-stimulated CRH secretion (P less than 0.05). Interestingly, 4-h incubation with TNF alpha had no effect on ACTH secretion from rat anterior pituicytes at a concentration of 10 nM. Higher concentrations of TNF alpha (100 nM and 1 microM), however, elicited a dose-dependent increase in the ACTH concentration in the medium. Our results suggest that TNF alpha represents one of the immune response mediators that directly or via stimulation of other cytokines act as activators of the HPA axis during immune/inflammatory reactions. This effect appears to be glucocorticoid suppressible and eicosanoid mediated. The primary site of action of TNF alpha appears to by the hypothalamic CRH-secreting neuron. Some pituitary and adrenal effects of TNF alpha, however, cannot be excluded.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1990

Effects of peripheral benzodiazepine receptor ligands on hypothalamic-pituitary-adrenal axis function in the rat.

High concentrations of the "peripheral" benzodiazepine (pBZD) binding site ("receptor") have been described in the hypothalamus, the pituitary and the adrenal glands. This study was undertaken to examine the effects of ligands of this binding site on the hypothalamic-pituitary-adrenal axis (HPA). To accomplish this we administered graded doses of the pBZD receptor agonist 4-chloro-diazepam (Ro5-4864) i.v. to catheterized, freely moving adult male Sprague-Dawley rats. Serial blood samples for plasma adrenocorticotropin hormone (ACTH) and corticosterone determinations were drawn from the catheter before and after the injection of the drug. Ro5-4864 significantly stimulated ACTH and corticosterone secretion in a dose-dependent fashion. To examine whether this effect could be antagonized by the pBZD binding site antagonist PK 11195, we treated rats with PK 11195 at doses 10- and 50-times higher than Ro5-4864 before administration of a maximally effective dose of Ro5-4864. Neither dose of PK 11195 antagonized Ro5-4864-induced plasma ACTH or corticosterone elevations. However, this agent, given alone, stimulated ACTH and corticosterone release. Similarly, carbamazepine (CBZ), which binds to the pBZD binding site with low affinity, stimulated weakly the HPA in vivo, reaching statistical significance only at the highest dose tested. To examine the site(s) of action of these compounds on the HPA, we evaluated their effects on hypothalamic corticotropin-releasing hormone (CRH) and pituitary ACTH secretion in vitro. Ro5-4864 stimulated hypothalamic CRH, but not pituitary ACTH secretion. Neither PK 11195 nor CBZ had any agonist effect on hypothalamic CRH secretion in vitro, whereas both antagonized Ro5-4864-induced CRH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1977

[Post-amputation dehiscence. A problem resolved].

70 peripheral amputations of the lower extremities in arteriosclerotic and diabetic vasculopathics have been examined. In a number of cases, the postoperative period was complicated by dehiscence of the suture on the stump, with lengthening of hospitalization time, risk of infection in the underlying bone and thus further amputation. To solve this problem, dehiscence was treated with dermo-epidermal autografts to cover the missing tissue area. The dehiscence was cleaned with compresses of 2% amuchina associated with topical instillations of Lincomycin hydrochloride. The cure percentage after grafting was about 80%.

Aged↗
PubMed1975

[Benzogammapirone in the treatment of digestive hemorrhages].

Given the difficulties of treating digestive haemorhages with normal coagulant methods, and considering that most haemorrhages are due to vascular factors, a vasoprotective substance was associated with common coagulant therapies. Benzogammapirone was used orally and by selective arterial infusion. The series is presented and the results discussed.

Administration, Oral↗
PubMedDate not supplied

[Unusual reactions to food additives].

The most important symptoms caused by food additives are urticaria and angioedema, but rhinitis, asthma and gastrointestinal disturbances are also reported. Only seldom food additives have been shown to induce symptoms in other organs such central nervous system or joints and with a sparse objective evidence. In this study, we report two cases of unusual reactions to food additives (tartrazine and benzoates) involving mainly the central nervous system (headache, migraine, overactivity, concentration and learning difficulties, depression) and joints (arthralgias), confirmed with diet and double blind challenge. The possible pathogenetic mechanisms are also discussed.

Adolescent↗
PubMedDate not supplied

[Preventive effect of thymomodulin in recurrent respiratory infections in children].

Recurrent respiratory infections (RRI) are a common occurrence in early childhood. Several investigations report the primary role of environmental factors (as early social mixing and passive smoking) in inducing RRI. In RRI children immunological defects, transient and not typical, have been often observed, but it is reasonable to suppose that they are essentially secondary to infections. Since immune modifications involve essentially cell-mediated immunity, several therapeutical attempts with thymic hormones have been carried out. In the present study the efficacy of thymomodulin was evaluated in a clinical trial in a group of children with RRI. Forty-six children suffering from RRI were enrolled on the basis of RI number in the previous year. Twenty-three children were treated with thymomodulin, twenty-three were not treated and were studied as control group. A significant reduction in the frequency of RI was noted only in treated children. Interleukin-2 production was assayed in all children before and after the trial, but not significant modification was observed in this immunological parameter. This study confirms the effectiveness of treatment with thymomodulin in RRI children, even though immunological background of clinical improvement remains to be elucidated.

Child↗