ABSTRACT
Using a combination of oligonucleotide probes and restriction endonuclease enzymes, we characterize beta-thalassemic mutations in 91 homozygous patients and 86 unrelated carriers. Overall, 268 beta-thalassemic genes were obtained. Eleven beta-globin mutations were identified, confirming the wide molecular heterogeneity of beta-thalassemia in Calabria. Information from the present study represents the mainstay for the development of a program of early prenatal diagnosis by direct detection of mutations in Calabria.
Subject(s)
Mutation , Prenatal Diagnosis , beta-Thalassemia/genetics , Codon , Female , Frameshift Mutation , Heterozygote , Homozygote , Humans , Italy , Pregnancy , beta-Thalassemia/diagnosisABSTRACT
1. The effects of muscimol and bicuculline on mean arterial blood pressure (MAP) and heart rate (HR) were studied after their microinfusion into the nucleus tractus solitarii (NTS) and into the nucleus parabrachialis medialis (NPBmed) in 3 and 24 month old rats. 2. In 3 month old rats a dose of 0.01 microgram of muscimol given into the NTS increased MAP, whereas higher doses (0.05, 0.1 and 0.25 microgram) produced dose-dependent bradycardia with either no change (0.05 and 0.1 microgram) or a decrease (0.25 microgram) in MAP. 3. On the other hand, in 24 month old rats, the same doses of muscimol given into the NTS failed to change MAP, whereas in comparison to 3 month old rats they produced a significantly lesser bradycardia. 4. The cardiovascular changes elicited by infusion of muscimol into the NTS in 3 and 24 month old rats were prevented by prior microinfusion of bicuculline into the same site. 5. Muscimol given into the NPBmed in doses from 0.05 to 0.25 microgram produced, in 3 month old rats dose-dependent decreases in MAP and HR which were prevented by prior administration of bicuculline. These effects were significantly reduced in 24 month old rats. 6. The present experiments show that with aging there is impairment of GABA-ergic mechanisms involved in the regulation of cardiovascular activity in the NTS and NPBmed.
Subject(s)
Aging/physiology , Hemodynamics/drug effects , Medulla Oblongata/physiology , Muscimol/pharmacology , Pons/physiology , Animals , Bicuculline/pharmacology , Blood Pressure/drug effects , Heart Rate/drug effects , Injections , Male , Medulla Oblongata/drug effects , Muscimol/administration & dosage , Pons/drug effects , Rats , Rats, Inbred StrainsABSTRACT
The cardiovascular responses induced by intracerebroventricular or intravenous administration of ketanserin in normotensive rats were evaluated. Ketanserin, which is an antagonist at 5-HT2 receptors, when microinfused into the third cerebral ventricle, did not induce significant cardiovascular effects, except for a slight and transitory hypotensive response after the microinfusion of the highest dose (200 micrograms). However, at doses which were unable to affect directly blood pressure or heart rate, ketanserin, microinfused into the same site, antagonized the pressor response induced by peripheral administration of methoxamine, an alpha 1-adrenoceptor agonist. Furthermore, peripheral administration of ketanserin produced dose-dependent hypotension and bradycardia and antagonized the pressor effect of an intravenous bolus injection of methoxamine. In conclusion, the present experiments confirmed the ability of ketanserin to produce cardiovascular effects when administered peripherally and provides evidence for an involvement of ketanserin-sensitive receptors in the brain in the regulation of phasic responses during experimentally induced hypertension.
Subject(s)
Blood Pressure/drug effects , Heart Rate/drug effects , Ketanserin/antagonists & inhibitors , Ketanserin/pharmacology , Methoxamine/pharmacology , Animals , Brain/drug effects , Dose-Response Relationship, Drug , Injections, Intraventricular , Male , Rats , Rats, Inbred Strains , Receptors, Adrenergic, alpha/drug effects , Receptors, Serotonin/drug effectsABSTRACT
An epidemiologic study was conducted from 1979 through 1984 on subjects presenting transitory ischemic attacks (TIA) and admitted into our Institute. We investigated year, season, month, day, and hour of every attack on 80 patients aged between 51 and 88 years. Time-series analysis showed a seasonal pattern of disease onset in early spring. Peaks occurred in March-April, and isolated peaks were also detected in January and October. Concerning TIA-onset day, we observed a peak distribution in the last 10 days of the month. Data on the hour of onset, according to single cosinor (mesor +/- SE = 2.67 + 1.13; amplitude +/- SE = 2.57 + 1.13), yielded a significant (P less than 0.05) acrophase. The acrophase is at -135 degrees (-93 degrees, -245 degrees) for tau = 48 hr.
Subject(s)
Ischemic Attack, Transient/epidemiology , Periodicity , Aged , Aged, 80 and over , Epidemiologic Methods , Humans , Italy , Middle Aged , SeasonsABSTRACT
The rats systemic administration of tolonidine in rats (0.05-5.0 mumol/Kg) produced behavioural and electrocortical slow-wave sleep lasting between 35 and 200 min depending on the dose. In addition, a dose-dependent fall in deep body temperature was observed. Similar effects were evoked by infusing tolonidine (5-80 nmol) into the third cerebral ventricle. Behavioural, ECoG and body temperature effects were prevented by previous intraventricular or systemic injection of phentolamine, an antagonist at alpha 1- and alpha 2-adrenoceptors, and of yohimbine, an antagonist at alpha 2-adrenoceptors, whereas prazosin, an alpha 1-adrenoceptor antagonist, was ineffective. In conclusion, the present experiments show that tolonidine possesses central effects similar to those evoked by clonidine and provide further evidence in favour of the idea that central alpha 2-adrenoceptors are involved in the control of slow-wave sleep and body temperature.
