Biomedical subjects

E Ongini

Publications and source records attributed to E Ongini.

133 records · Page 8Linked to original sources

PubMed1978

The neuromuscular blocking activity of a new aminoglycoside antibiotic netilmicin sulphate (SCH 20569).

The neuromuscular blocking activity of netilmicin sulphate (Sch 20569), a new aminoglycoside antibiotic, was studied on the rat sciatic nerve-gastrocnemius muscle preparation. The i.v. administration of netilmicin caused a gradual fall, up to complete blockade, of the muscular contraction elicited by nerve stimulation. Conversely, the muscular response to direct stimulation was not affected. The response pattern was similar to that seen with known aminoglycoside antibiotics. The acute toxic effects (LD50 i.p. in mice) of netilmicin were antagonized by pretreatment with neostigmine; this latter partially prevented netilmicin-induced blockade, but was not able to reverse it. Calcium chloride was the only agent effective both to prevent and to reverse the neuromuscular blocking effects of netilmicin.

Animals↗

PubMed1978

Comparison of neuromuscular effects and acute toxicity of some aminoglycoside antibiotics.

The correlation between acute toxicity and the effects occurring at neuromuscular junction level of some aminoglycoside antibiotics was investigated. Netilmicin (Sch 20569), sisomicin, gentamicin and kanamycin were administered i.v. in the rat and the following effects were studied: neuromuscular blocking activity (sciatic-gastrocnemius preparation), and acute toxicity evaluation. Neuromuscular blocking effects were found to be well correlated to acute toxicity data for all test-antibiotics. Comparison of results gave a sequence of relative potency which was as follows: netilmicin = sisomicin greater than gentamicin greater than kanamycin. Our findings confirmed that both respiratory failure, reporter as a side effect of the clinical use of aminoglycosides, and experimental toxicity follow the neuromuscular block.

Aminoglycosides↗

PubMedDate not supplied

The Mongolian gerbil in experimental epilepsy.

The Mongolian gerbil is recognized as a suitable experimental model for studying epileptiform seizures. About 10-20% of the gerbils provided by animal breeders show convulsions when placed in a new laboratory environment or handled for drug administration. In this review, the usefulness of the gerbil is critically evaluated on the basis of the literature available and our experience. Since gerbils often react with seizures in response to external stimuli we utilized a blast of compressed air. Seven gerbils were tested once weekly, for 15 consecutive weeks, and electroencephalographic (EEG) activity was recorded. When the animals were challenged by a blast of compressed air they developed seizures, but with varying intensity and frequency. In the first weeks the majority of gerbils did not show seizures but they began to be susceptible to the stimulus from the 5th or 6th week. Four out of 7 animals proceeded to more severe seizures, characterized by clonic-tonic components. The pattern of behavioral seizures was paralleled by changes in the EEG recording. Altogether, data available indicate that the gerbil model is interesting in ethological studies and may be useful for investigating the mechanisms underlying "spontaneous" seizures. In pharmacology, however, the model has some weaknesses which limit its application in the study of new and established antiepileptic drugs.

Animals↗

PubMedDate not supplied

Selective adenosine A2A receptor antagonists.

In the early 1990s it became clear that the A2A adenosine receptor had characteristics that made it distinct from the other A1, A2B and A3 adenosine receptors. Great progress has been made with the discovery of selective A2A receptor antagonists. A variety of synthetic substitutions on the xanthine moiety led the chemists of Kyowa-Hakko to discover that introduction of the styryl group in the 8 position of xanthines was critical in achieving compounds endowed with selective A2A receptor antagonistic properties. One compound, KW 6002, (E)1,3-diethyl-8-(3,4-dimethoxystyryl)-7-methylxanthine, is currently being developed for treatment of Parkinson's disease. A number of non-xanthine heterocycles have also been synthesized starting from the non-selective adenosine antagonist CGS 15943, a triazoloquinazoline. Thus, replacement of the phenyl ring of CGS 15943 with a heterocyclic ring such as pyrazole or imidazole, led to a series of interesting compounds whose prototype, SCH 58261, 7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine, has become a reference A2A receptor antagonist. Modification of N7 substituents has progressed to optimize A2A receptor selectivity and pharmacokinetic characteristics. A related class of compounds having a bicyclic instead of the tricyclic ring structure is also of interest. The prototype of these triazintriazolo derivatives, ZM 241385, is a potent A2A receptor antagonist; however, it also shows interactions with A2B receptors. The relevance of the A2A receptors in specific disease states, especially in the central nervous system, makes this class of adenosine receptor blockers of interest for treatment of neurodegenerative disorders such as Parkinson's disease.

Animals↗

PubMedDate not supplied

Cardiovascular safety of second-generation antihistamines.

Reports of serious cardiac arrhythmia associated with some second-generation antihistamines have prompted concern for their prescription. This article reviews the nature of the adverse events reported and concludes that the blockade of potassium channels, particularly the subtype responsible for the rapid component of the delayed rectifier current (IKr), is largely responsible for such adverse cardiac events. Consequently, antihistamines with little or no interaction with these channels are expected to have the greatest safety margin. The main cardiac arrhythmia of concern is that of torsades de pointes, a potentially fatal phenomenon characterized by prolonged ventricular depolarization that manifests as a prolonged QT interval and polymorphic ventricular tachycardia, with twisting of the QRS complexes. Based on pre-clinical and clinical evidence, it appears that loratadine, cetirizine, and fexofenadine are safe from cardiac arrhythmia via the IKr channel, whereas astemizole and terfenadine have a propensity to cause ventricular tachyarrhythmias.

Animals↗

PubMedDate not supplied

Vestibulo-ocular reflex (VOR) in guinea pigs. Impairment induced by aminoglycoside antibiotics.

The vestibulo-ocular reflexes (VORs) were studied in guinea pigs receiving daily administration of aminoglycoside antibiotics. The vestibular epithelia were also examined by scanning electron microscope technique (SEM). The treatment with aminoglycosides led to varying degrees of VORs according to (i) the type of aminoglycoside drug; (ii) the duration of the treatment and, (iii) the sensitivity of the various vestibular receptors. Gentamicin caused an earlier and severe reduction of the VOR gain. Dibekacin also caused evident damage, but the onset of its action was delayed. Both drugs affected mainly the vertical responses. Tobramycin and netilmicin altered the VORs slightly. Histological examination revealed damage to the sensory epithelia corresponding to the observed VOR impairments.

Aminoglycosides↗

PubMedDate not supplied

Effect of long-term administration of two beta-blocking agents on myocardial structure in spontaneously hypertensive rats.

Two vasodilating beta-blockers, dilevalol and pindolol, were studied for their effects on the development of hypertension and left ventricular hypertrophy in spontaneously hypertensive rats. Dilevalol has agonist activity at beta 2-, whereas pindolol interacts with both beta 1- and beta 2-receptor subtypes. Groups of 7-week old spontaneously hypertensive rats were given dilevalol (30 mg/kg) or pindolol (3 mg/kg) in the drinking water for 3 months. A control group of spontaneously hypertensive rats and age-matched normotensive Wistar Kyoto rats were also used. Systolic blood pressure and heart rate were recorded weekly. Cardiac structural changes were determined by morphometric analysis. Control spontaneously hypertensive rats developed hypertension and left ventricular hypertrophy as compared with normotensive rats. Dilevalol and pindolol prevented the rise in blood pressure, but only dilevalol lowered heart rate. However, neither of the compounds prevented the development of left ventricular hypertrophy, but they differently influenced myocardial structure as measured by the volume fraction of fibrotic tissue in the left ventricle. Dilevalol markedly prevented the amount of fibrosis to a level comparable to that found in normotensive rats, whereas pindolol had a weaker effect. The data suggest that individual pharmacologic characteristics, such as partial agonist activity of each beta-blocker examined, may account for differential effects on the myocardial structure.

Analysis of Variance↗