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Biomedical subjects

A Bertolini

Publications and source records attributed to A Bertolini.

At least 19 recordsLinked to original sources

Opening of brain potassium-channels inhibits the ACTH-induced behavioral syndrome in the male rat.

In adult male rats, the intracerebroventricular (i.c.v.) injection of pinacidil, a potassium channel opener, at the doses of 100, 200 or 300 micrograms/rat, dose-dependently reduced the display of the most typical behavioral symptoms (excessive grooming, stretching, yawning, penile erections) induced by the i.c.v. administration of ACTH-(1-24) (4 micrograms/rat). These data indicate that the complex mechanism of the melanocortin-induced behavioral syndrome involves closure of potassium channels in target neurons, and provide further experimental support to the idea that melanocortins are functional antagonists of opioids.

Animals

Reperfusion-induced arrhythmias and lethality are reduced by a 2KDa heparin fragment.

The influence of a low molecular weight heparin (Oligo-H, m.w. 2KDa) on ventricular arrhythmias and lethality induced by heart reperfusion following a 5 min coronary occlusion was studied in anesthetized rats. Both intravenous (i.v.) and subcutaneous (s.c.) injection of the compound dose- and time-dependently prevented the reperfusion syndrome: in all saline-pretreated animals post-ischemic reperfusion induced ventricular tachycardia (VT), which degenerated into ventricular fibrillation (VF) in 25 out of 30 rats, with a mortality rate of 73%; on the other hand, in rats i.v. or s.c. pretreated with Oligo-H (20 mg/kg, 30 and 90 min, respectively, before coronary occlusion), VT occurred in 4 out of 10-11 animals and degenerated into VF in 2-3 out of 10-11 animals, with a mortality rate of 18-20%. Even more effective was a low molecular weight dermatan sulfate (Oligo-DS, m.w. 2.1KDa). In rats treated with lidocaine, used as reference compound, at the dose of 5 mg/kg i.v. 10 min before coronary occlusion, VT occurred in 2 out of 10 animals and degenerated into VF in 1 out of 10 animals, with a mortality rate of 10%. It is concluded that low molecular weight glycosaminoglycans significantly reduce the consequences of heart reperfusion.

Animals

Polymodal dose-response curve for oxytocin in the social recognition test.

Available data concerning the effect of oxytocin on memory are often inconsistent. In the present study it was found that oxytocin, intracerebroventricularly injected to adult male rats in a dose range of 1 fg-10 ng/rat immediately after a 5-minute encounter with a juvenile, significantly reduces the social investigation time of the adult rat towards the same juvenile during a second encounter (120 min later) with two peaks of activity, at 10 fg and 1 ng/rat. Larger doses of oxytocin were ineffective. The oxytocin antagonist d(CH2)5Tyr(Me)-Orn8-vasotocin, injected 5 min before oxytocin by the same route and at the same doses, while being ineffective per se, completely abolished the memory-improving effect of a low dose of oxytocin (1 ng/rat) and, on the other hand, turned into memory-improving the effect of a high dose of oxytocin (500 ng/rat).

Animals

The opioid/anti-opioid balance in shock: a new target for therapy in resuscitation.

Teleologically, pain is of paramount importance for survival and induces the organism to cope in an active way with aggressions from a basically hostile environment. While the activation of endogenous analgesic (opioid) systems typically occurs in conditions of surrender (pre-terminal conditions, sustained tortures, etc.), the activation of endogenous anti-analgesic systems triggers mechanisms of active or passive defence (such as camouflage) aimed at survival. The distinctive features of the main anti-analgesic systems (melanocortinergic, cholecystokininergic, thyroliberinergic) and the dramatic results obtained in experimental pre-terminal conditions (hemorrhagic shock, prolonged respiratory arrest) with the administration of their neuropeptide transmitters (ACTH and several ACTH-fragments, including alpha-MSH, CCK peptides and thyrotropin-releasing hormone) are here reviewed. The study of the mechanisms underlying the resuscitating effects of these neuropeptides has led to the discovery of the (often extremely potent) resuscitating effect of other drugs (protoveratrines, nicotine, centrally-acting cholinergic agents, ganglion-stimulating drugs). It is particularly remarkable that in pre-terminal conditions these neuropeptides and drugs have highly impressive effects on cardiocirculatory parameters at doses that are almost or actually inactive under normal conditions, and that their resuscitating effect is obtained without the need for any other supportive treatment and at dose-levels well below toxic ranges. Finally, in hemorrhage-shocked animals, the treatment with anti-analgesic neuropeptides shortly after bleeding considerably extends the time-limit for an effective and definitively curing blood reinfusion. This would be of self-evident importance in clinical practice, because an extremely simple, non-toxic first-aid treatment in the field, shortly after a massive hemorrhage, could resuscitate the patient for a period sufficient to effectively set up the most appropriate in-hospital treatment.

Adrenocorticotropic Hormone

Evidence for a role for the neurosteroid allopregnanolone in the modulation of reproductive function in female rats.

The present study investigated the effect of allopregnanolone (5 alpha-pregnan-3 alpha-ol-20-one) or of passive immunoneutralization of brain allopregnanolone, the most potent steroid produced by neurons, on ovulation rate and sexual behavior in female rats. Allopregnanolone was injected intracerebroventricularly in rats on diestrus and proestrus and tests were done on estrus. The intracerebroventricular injection of allopregnanolone significantly decreased the number of oocytes collected on estrus (p < 0.01). To support a physiological involvement, antiserum to allopregnanolone was injected centrally to block the activity of the endogenous neurosteroid. When administered on diestrus and proestrus or only on proestrus, the antiserum was shown to be correlated with a significant increase (p < 0.01) in oocytes retrieved on estrus. In female rats treated with antiserum to allopregnanolone, the lordosis intensity was augmented significantly as compared to controls. Finally, the possible changes of medial basal hypothalamus concentration of allopregnanolone throughout the estrous cycle and at the time of ovulation were investigated. Hypothalamic extracts were eluted on high-pressure liquid chromatography and allopregnanolone concentration was measured by radioimmunoassay. Brain cortex was used as control tissue. Hypothalamic allopregnanolone concentration on proestrus morning and afternoon was found to be significantly lower than in the remaining phases of the estrous cycle (p < 0.01), while no significant changes were observed in brain cortex concentration of allopregnanolone. The present results suggest that hypothalamic allopregnanolone may be involved in the mechanism of ovulation, affecting hormonal and behavioral events.

Animals

Recombinant interferon-alfa therapy in children with chronic hepatitis C.

The efficacy of recombinant interferon-alfa therapy in children with chronic hepatitis C has been evaluated in a randomized, controlled pilot study including 27 patients, aged 2 to 14 years, without underlying systemic diseases. On entry, all patients had abnormal alanine transaminase (ALT) levels, 22 were hepatitis C virus (HCV) RNA positive, 19 had mild chronic active hepatitis, and 8 had chronic persistent hepatitis on liver biopsy. Fourteen children received 5 MU/m2 of recombinant interferon-alfa2b thrice weekly for 4 months. If at this time ALT had been reduced to at least 50% the baseline level, treatment was continued up to 12 months. The other 13 children remained untreated. The whole follow-up period lasted 24 months. Interferon was stopped at 4 months in 4 children because of an ALT increase (2 cases), unchanged ALT and febrile convulsions (1 case), and slight ALT decrease (1 case). This latter patient, however, had normal ALT at 6 months and throughout further follow-up, and cleared HCV RNA, thus behaving as a sustained responder. All 10 children treated for 12 months had normal levels of ALT, and 9 were HCV RNA negative at the end of treatment. Of the 9 children who could be followed to 24 months, 4 relapsed soon after therapy withdrawal and 5 maintained a sustained biochemical and virologic response. Overall, 6 (43%) of 14 treated children had a sustained ALT normalization associated with HCV RNA clearance as compared with only 1 (7.5%) untreated child who had a sustained ALT normalization but did not clear HCV RNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Old rats are unresponsive to the behavioral effects of adrenocorticotropin.

In 28 month-old male rats, the i.c.v. injection of adrenocorticotropin [ACTH-(1-24)] (4 micrograms/rat) did not induce the typical behavioral syndrome (excessive grooming, stretching, yawning, penile erections). This indicates that the behavioral effects of melanocortins are age-dependent, suggesting either an aging-linked impairment of the nervous circuitries involved or a reduction of the number (or affinity, or both) of the brain melanocortin receptors in the elderly.

Aging

Galantide stimulates sexual behaviour in male rats.

While intracerebroventricular injection of galanin (5 micrograms/rat) inhibited sexual behavior in experienced male rats--without producing any other locomotor or behavioral deficit-, injection of the galanin antagonist, galantide, by the same route (1 or 2 micrograms/rat) stimulated sexual behavior (improving arousal, motivation and performance indexes) and antagonized the effect of galanin. These data further suggest that galanin plays a physiological role in male sexual behavior.

Animals

Comparison of the effects of ACTH-(1-24), methylprednisolone, aprotinin, and norepinephrine in a model of hemorrhagic shock in rats.

Rats bled to a severe condition of volume-controlled hemorrhagic shock were randomly assigned to one of the following treatments: (1) saline, 1 ml/kg i.v.; (2) saline, 0.2 ml/kg per min i.v. for 10 min; (3) ACTH-(1-24), 160 micrograms/kg i.v.; 4) methylprednisolone, 40 mg/kg i.v.; (5) methylprednisolone, 80 mg/kg i.v.; (6) aprotinin, 10,000 KIU/kg i.v.; (7) norepinephrine, 5 micrograms/kg per min i.v. for 10 min; (8) norepinephrine, 10 micrograms/kg per min i.v. for 10 min. All rats treated with saline or with either of the two doses of methylprednisolone, and half of the rats treated with aprotinin, died within the subsequent 2 h. On the other hand, rats treated with norepinephrine, at either dose, or with ACTH-(1-24) were all still alive 2 h later, a similar improvement in cardiovascular and respiratory parameters being obtained with the two treatments. The effect of ACTH on mean arterial pressure was however more sustained throughout the observation period. These results further support the potential usefulness of ACTH-(1-24) as first-aid treatment in cases of severe blood losses.

Animals

Capsaicin prevents the adrenocorticotropin-induced improvement of cardiovascular function and survival in hemorrhage-shocked rats.

A volume-controlled hemorrhagic shock was produced in anesthetized rats by intermittent bleeding from an iliac vein over a period of 20-30 min, until the carotid mean arterial pressure (MAP) stabilized around 20-24 mmHg. In this condition, which caused the death of all saline-treated animals within 25-30 min, the intravenous (i.v.) bolus injection of the adrenocorticotropin fragment 1-24 (ACTH(1-24)) at a dose of 160 micrograms/kg promptly restored MAP, as well as pulse pressure, heart rate and respiratory function, and greatly prolonged the survival time. Capsaicin (125 mg/kg cumulatively, s.c., 1 week before) completely prevented the anti-shock effect of ACTH(1-24), which, on the other hand, was shared by i.v. [Nle11]-substance P (SP) (200-300 micrograms/kg). Finally the SP-antagonist [D-Arg1,D-Pro2,D-Trp7,9,Leu11]-SP prevented the effect of ACTH(1-24). These results suggest that SP-containing nerve fibers are required for the effect of ACTH in hemorrhagic shock.

Adrenocorticotropic Hormone

Reversal of experimental hemorrhagic shock by dimethylphenylpiperazinium (DMPP).

In a rat model of hemorrhagic shock which caused the death of all control rats within 30 min, i.v. injection of the ganglion-stimulating drug dimethylphenylpiperazinium (DMPP) caused a dose-dependent reversal of the shock condition--without the need for reinfusion of the shed blood--starting from the dose of 4 ng/kg i.v. Shock reversal was associated with the mobilization of residual blood and improvement in blood flow, particularly at the carotid level. These results could influence our thinking on pathophysiology and first-aid management of shock.

Animals

Left ventricular function after reversal of myocardial hypertrophy in systemic hypertension, and response to acute increase of afterload by cold pressor test.

Using digitized M-mode echocardiography, the left ventricular (LV) response to acute increase in blood pressure after regression of myocardial hypertrophy due to an effective antihypertensive treatment was evaluated. Fifteen hypertensive patients with basal LV hypertrophy (LV mass greater than 230 g, and normal LV diastolic diameter) and normal LV mass after 3 to 4 months of treatment with angiotensin-converting enzyme inhibitors were selected for study. Subjects performed a cold pressor test before and after therapy. LV systolic function was normal in all subjects. LV diastolic function (impaired at basal evaluation in 13 subjects) improved after therapy in all subjects, with normalization in 10. Before treatment, the cold pressor test induced significant increases in blood pressure and heart rate without changes in LV parameters. After regression of hypertrophy, the cold pressor test induced increases in hemodynamic parameters comparable to those of the basal test, and LV parameters remained unchanged. Our results indicate that regression of myocardial hypertrophy induced by angiotensin-converting enzyme inhibitors does not impair the ability of the left ventricle to face acute increases in afterload. The improvement in LV diastolic function (found at rest after reversal of hypertrophy) persists during the cold pressor test, which confirms that it is primarily due to LV mass reduction and is not simply a consequence of decrease in afterload induced by treatment.

Adult

Galanin inhibits sexual behavior in male rats.

Intracerebroventricular injection of galanin potently inhibited (0.5 micrograms/rat) or completely suppressed (5.0 micrograms/rat) copulatory activity in sexually experienced male rats, without producing any other obvious behavioral deficit. It is suggested that galanin, known to potently stimulate feeding behavior, may be involved in the inverse modulation of feeding and sexual behaviors.

Animals

Sustained AIDS education campaigns and behavioural changes in Italian drug abusers.

In the area of Padua, northern Italy, fear of AIDS along with AIDS educational campaigns had reduced risk behaviours for HIV among intravenous drug abusers (IVDA) as early as 1987, although at that time 38% of seropositive cases still shared needles and only 22% of subjects used condoms. The present study has been conducted in the same area and with similar criteria to evaluate the effectiveness and limits of a sustained education campaign. Drug related and sexual risk behaviours and motivations preventing behavioural changes were investigated by direct interview in 190 IVDA. Fourteen percent of the participants, including 16% of the seropositive, were still sharing needles, mainly because they did not have works available at the time they were needed. Demographic features, drug-related characteristics and anti-HIV seroprevalence did not differ significantly between needlesharers and other drug abusers. Condom use was reported by 46% of subjects, but encouragingly enough this figure included 80% of the seropositives. While knowledge of seropositivity seemed to encourage condom use, a higher selectivity about partners and a negative attitude towards condoms were the most frequent motivations preventing safer sex. These results suggest that sustained AIDS education campaigns are being successful in maintaining and reinforcing the trend to risk reduction previously observed among drug abusers in this area. Nevertheless the persistence of risk behaviours in a consistent proportion of participants emphasizes the urgency of additional prevention strategies, such as syringe exchange or supply to the limited number of sharers and counselling to encourage safer sex.

Acquired Immunodeficiency Syndrome

Pinacidil potentiates morphine analgesia.

The opening of K+ channels in the membrane of target neurons is a key mechanism of the effect of opioids. Here we show that the K+ channel opener, pinacidil, i.c.v. injected at doses of 50, 100 or 150 micrograms/rat, significantly increases and prolongs the effect of morphine on the thermal pain threshold (hot-plate and tail-flick tests). These data may suggest a novel approach to the management of pain.

Analgesia

Repeated administration of triiodothyronine enhances the susceptibility of rats to isoniazid- and picrotoxin-induced seizures.

In an experimental condition of hyperthyroidism, obtained by repeated administration of triiodothyronine in adult rats (100 micrograms/kg/day, sc for 7 consecutive days), there is an increased susceptibility to the convulsant effect of isoniazid (300 mg/kg, ip) and picrotoxin (4 mg/kg, ip). On the other hand, the characteristics of brain [3H] flunitrazepam binding sites are not modified. These data afford further experimental evidence of the influence of thyroid hormones on brain function.

Animals