PubMed Health⌕ Search

Biomedical subjects

M Vacca

Publications and source records attributed to M Vacca.

At least 55 records · Page 3Linked to original sources

Replacement therapy against increased hydroxyurea toxicity in pituitary or adrenal ablated rats.

The main rat adrenocortical hormone, corticosterone, the mineralocorticoid, 11-deoxycorticosterone (DCA) acetate given alone or together (2:1 ratio) twice daily at doses of 2-4 and 1-8 mg/kg, DCA enanthate given in a single injection of 20 mg/kg 0-3 days before the beginning of the experiments and a highly-concentrated injectable extract of the adrenal cortex (4 mg/kg as hydrocortisone twice a day) given by the intramuscular route, delay and partially protect against the increased toxicity following administration of the anticancer drug, hydroxyurea (800 mg/kg/day for 5 days) in adrenalectomized or hypophysectomized animals (80-100% lethality; in control non ablated rats 0-10% lethality). ACTH1-24 (tetracosactide) also proved effective in pituitary ablated rats. The best protection was afforded with the joint administration of corticosterone and DCA (2-4 and 1-2 mg/kg twice a day) or with corticosterone alone at doses (4 mg/kg twice a day) capable of giving plasma levels, six hours after administration on the third day, similar to those observed in non ablated rats receiving HYD in the morning. The adrenocortical hormones may replace a possible unique defense mechanism against drug toxicity, which is lacking in pituitary or adrenal ablated rats.

Adrenalectomy↗

Antitumour drug toxicity in pituitary or adrenal-ablated rats.

Hypophysectomy or adrenalectomy increase the toxicity of the antitumour drug hydroxyurea (HYD) given by the oral route at daily doses/kg over 5 days, 10 times higher (10 Htd) than that employed in daily schedules for humans (100% and 85% lethality against 0% in intact controls). No differences were found between intact or hypophysectomized rats in their ability to tolerate a 5-day treatment with 1 Htd HYD given orally, 1-10 Htd of procarbazine (i.v.) and cisplatinum (i.v.) at a dose per kg/day equivalent to that recommended for protocols providing daily drug schedules in humans. L-asparaginase (10 Htd) induce 45% lethality in adrenalectomized animals. All the above drugs in intact rats induce significant (p less than 0.01) adrenocortical activation after single, and in the case of hydroxyurea after 5-days, treatment at the above dosages. Replacement therapy with corticosterone may reduce HYD toxicity in adrenalectomized (20% lethality) but less so (90% lethality) in hypophysectomized rats.

Adrenalectomy↗

Tolerance to pituitary-adrenal axis activation by anticancer drugs in normal and tumour-bearing rats.

Cisplatinum given intravenously (i.v.), hydroxyurea given orally (os), procarbazine (os) and L-asparaginase (i.v.), on a decreasing scale, produce significant (p less than 0.01) adrenocortical activation over 4-h period at a single dose per kg 10 times higher than those employed in human therapy. Only hydroxyurea retained this activity after a 5-day treatment both in normal and Walker carcinosarcoma-bearing rats. Adrenocortical activation depends on the presence of pituitary ACTH both after single or repeated treatments.

Adrenal Cortex↗

Etomidate inhibits prolactin release but not through a dopaminergic mechanism.

A short-acting non-barbiturate intravenous general anaesthetic, etomidate, when administered i.v. lowered serum prolactin levels in the rat. The effect was evident at rest, after surgical stress or after injection of 5-hydroxytryptophan. Haloperidol-induced hyperprolactinaemia was not modified. Administered via the intracerebroventricular route, etomidate strongly reduced serum prolactin levels in unanesthetized rats. Studies performed on superfused synaptosomes from brain areas rich in dopaminergic nerve endings did not show any influence of the etomidate, 10(-7) M-10(-6) M, on [3H]dopamine release. A peculiar GABA-like mechanism and/or possible interplay with serotonergic control of the prolactin release may be postulated in order to explain the suppressive effects of the drug on secretion of lactotrophs.

5-Hydroxytryptophan↗

Effects of naloxone on the secretion of prolactin and corticosterone induced by 5-hydroxytryptophan and a serotonergic agonist, mCPP.

The effects of naloxone, an opiate "pure" receptor antagonist, on the release of prolactin and corticosterone in the rat were studied following the administration of the serotonin precursor 5-hydroxytryptophan or the serotonin receptor agonist (-) -m-chlorophenylpiperazine. Naloxone clearly antagonizes the release of prolactin induced by 5-hydroxytryptophan administered alone at a dosage of 50 mg/Kg/b.wt. or at dosage of 30 mg/Kg/b.wt. preceded 60 minutes before injection by the administration of the serotonin uptake blocker fluoxetine. The opiate antagonist does not modify the increase in blood level of prolactin induced by (-) -m-chlorophenylpiperazine. Naloxone itself does not reduce the increase in plasma level of corticosterone induced by 5-hydroxytryptophan, 5-hydroxytryptophan+fluoxetine or (-)-m-chlorophenylpiperazine. The results suggest that endogenous opioids may be involved in the increase in serum level of prolactin induced by 5-hydroxytryptophan and also indicate the existence of different serotonergic neurotransmitter circuits capable of modulating the release of prolactin and corticosterone. A mutual interplay between serotonergic and opiate neurons may be involved in controlling the release of prolactin, but such an interplay does not seem to occur in the secretion of corticotrophin-releasing hormone.

5-Hydroxytryptophan↗

Cimetidine and adrenals.

An H2-antagonist, cimetidine, reduces in the rat normal plasma corticosterone levels and strongly antagonizes their increase after cold stress. This latter effect is dose dependent. Plasma corticosterone reduction by cimetidine lasts 4 h both in normal and stress situations. Both a hypophyseal or adrenal site of action of the drug may be involved in the inhibition of adrenocortical secretion.

Adrenal Glands↗

Neuramide stimulates adrenocorticotropin but not prolactin release from rat pituitary.

Neuramide (NMD), a substance found in crude preparations of porcine stomach extract, is a viral inhibitor that also has putative immunostimulatory effects. The effects of NMD on stress-hormone (ACTH and prolactin-PRL) release were assessed in in vivo and in vitro studies. In the former, blood levels of corticosterone and PRL were measured in NMD-treated male rats. In vitro experiments were performed to evaluate the effects of NMD and three of its fractions (obtained with high performance liquid chromatography) on ACTH and PRL release from perfused rat pituitary slices. NMD increased plasma corticosterone levels in vivo and produced dose-dependent increases in in vitro pituitary release of ACTH. No effects on PRL secretion were observed in vivo or in vitro. The stimulatory effects on ACTH release were caused by the NMD fraction with a molecular weight of > 5000 < 10000 Da.

Adrenocorticotropic Hormone↗

The regulation of feeding: a cross talk between peripheral and central signalling.

Feeding and energy expenditures are modulated by the interplay of hormones and neurotransmitters in the central nervous system (CNS), where the hypothalamus plays a pivotal role in the transduction of peripheral afferents into satiety and feeding signals. Aminergic neurotransmitters such as dopamine (DA), norepinephrine (NE) and serotonin (5-hydroxytryptamine, 5-HT) are historically considered to play a key role, but a number of peptides are involved in finely tuning feeding regulation. This review summarizes the current understanding of the CNS mechanisms of orexigenic peptides, such as neuropeptide Y, orexins, and ghrelin, as well as anorectic peptides, such as leptin, neurotensin (NT), cocaine- and amphetamine regulated transcript (CART) peptide, thyrotropin-releasing hormone (TRH), corticotropin-releasing hormone (CRH), urocortin, amylin.

Animals↗

Elevated 8-isoprostane levels in basal cell carcinoma and in UVA irradiated skin.

Isoprostanes are prostaglandin isomers produced from the peroxidation of polyunsaturated fatty acids from the cellular membrane. They have been used as a specific index of cellular lipoperoxidation and as an indirect measure of oxidative stress. However, these molecules also present several biological activities. An oxidative environment measured as the presence of other indirect measurements of reactive oxygen species lipoperoxidation has recently been described in basal cell carcinoma, the most frequent type of non-melanoma skin cancer. This study aims to measure the levels of 8-isoprostaglandin F2alpha, an isoprostane widely studied in other models as a by-product of ROS-induced lipid peroxidation, in basal cell carcinoma and in UVA irradiated healthy skin. We found that 8-iso-PGF2 alpha is present in higher levels in BCC specimens compared to healthy non sun-exposed skin, confirming previous studies on the production of lipoperoxidation in this tumor. Moreover, we demonstrated that topical pre-treatment with a compound containing vitamin E is capable of reducing 8-iso-PGF2 alpha formation in UV irradiated skin suggesting a role for isoprostanes in UV induced inflammation and eventually carcinogenesis and confirming the function of vitamin E as an antioxidant in this model.

Administration, Topical↗

[Substitutive therapies in sepsis and acute renale failure].

Substitutive treatment of sepsis associated acute renal failure is an emergent challenge in the intensive care unit due to the number of cases and to the high mortality rate. Standard hemofiltration is unable to improve survival, since a high mortality rate is sustained by the septic process. New therapeutic approaches currently available are based on the increased clearance of molecules ranging 10-30 kDa considered important in the physiopathology of sepsis and multiorgan failure. Clinical experiences in progress are: (1) adsorption resins able to bind bacterial products, cytokines, anaphylotoxins and several inflammation mediators; (2) the bioartificial kidney, that is the addition to hemofilter of human tubular cell culture grown in devices in order to mimic metabolic tubular function to a traditional hemofilter; (3) increased exchange volumes (high volume hemofiltration), up to 0-100 L/24 hr and; (4) increased membrane permeability associated with either discarded ultrafiltrate (high cut-off membranes) or plasma substitution plasmapheresis with regeneration by sorbents technology (C FA). Generally, by applying these new technologies to septic shock patients, the observed survival was higher than that predicted by the gravity score. While these results are encouraging, they are not conclusive and need further study.

Acute Kidney Injury↗

[Acute pancreatitis: retrospective study on the treatment of 45 cases observed in a general surgery department].

The Authors have developed a retrospective study of 45 patients, suffering from acute pancreatitis and hospitalized at a general surgery Departement during a period of two years. The purpose of the study was to evaluate the validity of the classification of acute pancreatitis in three degrees (slight, moderate, serious), suggested by Hollender to prognostic and therapeutic aims.

Acute Disease↗