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Biomedical subjects

P Nencini

Publications and source records attributed to P Nencini.

At least 19 recordsLinked to original sources

Toxicological aspects of perinatal analgesia.

Perinatal exposure to analgesics and anesthetics is responsible of acute effects which are relatively easy to detect and, accordingly, a large number of clinical and experimental observations has been gathered. On the contrary, the possible long term consequences of perinatal administration of these drugs have recently become the object of great interest. It is possible, infact, that perinatal exposure to neurotropic agents may lead to long term neuropsychopharmacological effects that outlast the effective presence of the drug in the newborn. The conceptual framework of this hypothesis is provided by the modern concept of neuroplasticity, according to which early life experiences that serve to set the operating characteristics of the brain may represent the target of pharmacologically-induced chan-ges. Clinical studies have already provided evidence of the association between labour analgesia and the development of maladaptive behaviour in adult life, while experimental studies suggest that maternal care can actively program differences in gene expression through stable effects on the epigenome. Although they require to be confirmed by further studies possibly performed on wider cohorts, these results suggest caution in the use of obstetric pain relief methods that permit substantial passage of drugs through the placenta.

Adult↗

Thrombophilic risk factors and unusual clinical features in three Italian CADASIL patients.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetically transmitted cerebrovascular disease. Typically, the first clinical manifestation is migraine and the full clinical spectrum of the disease with recurrent strokes of the subcortical type, cognitive, and mood disorders is seen during the fourth and fifth decades of life. Vascular risk factors are usually absent in CADASIL patients and the diagnosis of the disease is particularly suspected in young adults with cerebrovascular events of unknown cause, diffuse leukoencephalopathy on computed tomography or magnetic resonance imaging, and a history of cerebrovascular diseases or dementia in many family members. We describe three Italian CADASIL patients who presented to medical attention for cerebrovascular events occurred after the age of 55 and had, in addition to hypertension and hyperlipidemia, thrombophilic risk factors such as hyperhomocysteinemia, elevated levels of lipoprotein(a), and antiphospholipid antibodies. Symptoms possibly related to cortical involvement, such as dysphasia and visual field deficits, were reported by two of these patients. We conclude that a diagnosis of CADASIL should not be disregarded in patients with vascular risk factors and presenting with symptoms not immediately referable to subcortical damage at ages more advanced than commonly reported.

Aged↗

Artificial neural network assessment of substitutive pharmacological treatments in hospitalised intravenous drug users.

Artificial neural networks (ANNs) provide better solutions than linear discriminant analysis (LDA) to problems of classification and estimation involving a large number of non-homogeneous (categorical and metric) variables. In this study, we compared the ability of traditional LDA and a feed-forward back-propagation (FF-BP) ANN with self-momentum to predict pharmacological treatments received by intravenous drug users (IDUs) hospitalised for coexisting medical illness. When medical staff considered detoxification appropriate they usually suggested methadone (MET) and (or) benzodiazepines (BDZ). Given four different treatment options (MET, BDZ, MET+BDZ, no treatment) as dependent variables and 38 independent variables, the FF-BP ANN provided the best prediction of the consultant's decision (overall accuracy: 62.7%). It achieved the highest level of predictive accuracy for the BDZ option (90.5%), the lowest for no treatment (29.6), often misclassifying no treatment as BDZ. The LDA yielded a lower mean accuracy (50.3%). When the untreated group was excluded, ANN improved its absolute recognition rate by only 1.2% and the BDZ group remained the best predicted. In contrast, LDA improved its absolute recognition rate from 50.3 to 58.9%, maximum 65.7% for the BDZ group. In conclusion, the FF-BP ANN was more accurate than the statistical model (discriminant analysis) in predicting the pharmacological treatment of IDUs.

Adult↗

Analysis of cocaethylene, benzoylecgonine and cocaine in human urine by high-performance thin-layer chromatography with ultraviolet detection: a comparison with high-performance liquid chromatography.

Cocaine and ethanol are frequently used at the same time, resulting in the formation of cocaethylene by transesterification. We studied the capability of high-performance thin-layer chromatography (HPTLC) to simultaneously detect cocaethylene, cocaine and benzoylecgonine in 16 urine specimens of drug addicts, previously tested as positive for benzoylecgonine at immunoenzymatic screening. Accuracy and precision, as well as detection and quantitation limits of the method, were evaluated by comparison with high-performance liquid chromatography (HPLC). HPTLC limit of quantitation was 1.0 microg/ml for the three compounds, whereas HPLC limits were 0.2 microg/ml for benzoylecgonine and cocaine, and 0.1 microg/ml for cocaethylene. The relative standard deviation (RSD) ranged from 1.03 to 12.60% and from 1.56 to 16.6% for intra- and inter-day HPTLC analysis, respectively. In the case of the HPLC method, the RSD for the intra-day precision ranged from 0.79 to 5.05%, whereas it ranged from 1.19 to 10.64% for the inter-day precision. In comparison with HPLC, HPTLC is less expensive and faster, requiring 2-3 h to analyze 10-12 samples on a single plate. In conclusion, HPTLC is suitable for determinations of the three analytes only for samples with high concentrations.

Chromatography, High Pressure Liquid↗

Modulation of food intake by the kappa opioid U-50,488H: evidence for an effect on satiation.

The main goal of the present study was to test the hypothesis that the prophagic effect of the kappa opioid agonist U-50,488H (U50) is primarily due to an effect on satiation. In Experiment 1, the feeding effects of U50 (2.0 and 4.0 mg/kg, i.p.) was tested in animals with ad libitum access to ground food and to three sucrose solutions (1, 4, and 20%). In Experiment 2, a classical "one-bottle" test was utilized to test for the effect of U50 (4.0 mg/kg, i.p.) on the intake of five different sucrose solutions (1, 4, 16, 32, and 40%) over a 30-min period. Finally, in Experiment 3 we evaluated the effect of U50 (2.0, 4.0, and 6.0 mg/kg, i.p.) on extracellular dopamine (DA) concentration in the nucleus accumbens. In Experiment 1, U50 enhanced the intake of ground food but not of sucrose. In Experiment 2, U50 increased the intake of high concentration sucrose solutions whereas it decreased that of low concentration solutions. In Experiment 3, U50 produced a dose-dependent decrease in DA concentrations in the absence but not in the presence of food. The most likely explanation for the present results is that U50 enhances feeding by activating mechanisms that block satiety and satiation. In contrast, we found little evidence for an effect of U50 on palatability.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Cadmium inhibits stimulated amylase secretion from isolated pancreatic lobules of the guinea-pig.

The effect of cadmium chloride on pancreatic exocrine secretion 'in vitro' was examined using guinea-pig isolated lobules. Cadmium (10(-3)M) stimulated amylase release when added alone to the incubation medium and the increase of amylase was unaffected by atropine. Cadmium (10(-4)M) did not significantly modify the basal amylase release. Depolarization of pancreatic nerves with potassium stimulated amylase secretion; the stimulant effect of KCl was completely inhibited by atropine. Cadmium (10(-4)M) inhibited, but did not abolish, the stimulant effect of KCl, indicating a direct effect of the metal on the acinar cell. Cadmium (10(-4)M) also inhibited the amylase release evoked by the secretagogues carbachol and caerulein, which are known to act directly on the acinar cell. Taken together with previous data reporting a large increase of pancreatic cadmium concentration following cadmium ingestion, the strong inhibition of pancreatic secretion observed in our experiments suggests that the exocrine pancreas may be regarded as a possible target organ of cadmium toxicity.

Amylases↗

Ethanol combined with cocaine inhibits amylase release in guinea pig pancreatic lobules.

Concurrent ingestion of alcohol and cocaine is a common occurrence in cocaine-dependent individuals. Cocaethylene is a pharmacologically active metabolite of cocaine that is formed in the liver in the presence of ethanol. The effects of ethanol combined with cocaine on the exocrine pancreas are not known. We studied the effect of ethanol and cocaine, alone or in combination, and cocaethylene on amylase release from isolated lobules of the guinea pig pancreas. Incubation of lobules with ethanol plus cocaine produced a more evident reduction of amylase release than each drug alone. An even larger reduction was observed with cocaethylene. HPLC analysis of incubation medium showed that no cocaethylene was formed in vitro in the presence of ethanol and cocaine. It is concluded that cocaethylene could strongly contribute to inhibition of exocrine pancreatic secretion in individuals who coadminister alcohol with cocaine.

Amylases↗

Abulia and cognitive impairment in two patients with capsular genu infarct.

BACKGROUND: An internal capsule genu infarct has been rarely reported to cause cognitive impairment and behavioral changes. This clinical picture can be explained on anatomical and functional basis because important subcortical-cortical pathways traverse the internal capsule genu. We report 2 previously non-demented patients who developed acute confusional state, abulia, and moderate cognitive decline after the occurrence of an infarct in the capsular genu. METHODS: Clinical, neuropsychological, and MRI evaluation at baseline and 12-month follow-up. RESULTS: Abulia and cognitive impairment were still present 1 year after stroke. In 1 patient there were associated multiple lacunar infarcts and leukoaraiosis. In the other an old small left frontal infarct was also present. In both moderate cortical atrophy co-existed. CONCLUSIONS: We hypothesize that co-existing lesions, possibly associated with a sub-clinical reduction of cognitive functions, facilitate the development of a persistent clinically evident mental deficit after the occurrence of an infarct in the capsular genu.

Aged↗

Stereoselective morphine-like discriminative properties of a new alkylaminonaphthalenic derivative.

The morphine-like properties of a series of aminoalkyl- and cycloalkylamino-naphtalenic derivatives of 17-methyl-17-azaequilenine were studied in rats trained to discriminate morphine (5.6 mg/kg IP) from vehicle in a two-lever operant behavioral procedure reinforced by water access. It was found that one of the compounds tested (i.e., A8; 1-ethyl-1-hydroxy-1-[2-(6-hydroxynaphthyl)]-2-methyl-3- dimethylaminopropane) fully generalized for the morphine stimulus. The discriminative effects of A8 were stereospecific, as indicated by the fact that (+)-(1R,2R)-A8 was three times more potent than the racemic compound and that the (-)-(1S,2S) enantiomer was completely inactive. (+)-(1R,2R)-A8 generalization for the morphine cue was inhibited by naloxone. None of the other five derivatives examined generalized for the morphine stimulus. In conclusion, the naphthalenic structure is a source of compounds with stereospecific and naloxone-reversible morphine-like properties.

Animals↗

Quinpirole- and amphetamine-induced hyperdipsia: influence of fluid palatability and behavioral cost.

Daily administration of moderate doses of amphetamine or of the dopaminergic D2 agonist quinpirole is associated with the development of excessive, non-regulatory drinking. Here we compared the influence of manipulating fluid palatability and behavioral cost on the development of this drinking augmentation. Experiment 1 was based on the phenomenon of contrafreeloading (CFL): animals work for a resource even though the same resource is freely available. The effects of 15 daily injections of amphetamine (1.0 and 1.7 mg/kg i.p. ) or quinpirole (0.1 and 0.56 mg/kg i.p.) were evaluated in mildly water-deprived rats. For the first 6 days the rats obtained water by lever pressing (FR3) only; over the following 9 days water was also freely available (CFL). Initially, 0.56 mg/kg quinpirole reduced lever pressing for water. A complete recover of responding was then obtained, and was followed by a progressive increment in the amount water obtained by lever pressing during the CFL phase (from 10 to 50%). Amphetamine did not affect percent CFL, but at the highest dose (1.7 mg/kg) reduced total water intake during the last 3 days of treatment. In experiment 2 the rats had free access to two bottles, one of which contained tap water, and the other contained either an ethanol (6%) or a sucrose (5%) solution. After habituation to this regimen, the rats received 10 daily i.p. injections of vehicle, amphetamine (1.0 or 3 mg/kg), or quinpirole (0.1 or 0.56 mg/kg). Quinpirole 0.56 mg/kg enhanced daily fluid intake under both sucrose and ethanol conditions, but selectively reduced ethanol preference. The higher amphetamine dose reduced fluid intake and sucrose preference. In conclusion, chronic exposure to a dopaminergic D2 agonist, but not to amphetamine, produced an increment of drinking that was resistant to manipulation of either palatability or the behavioral cost of the fluid.

Alcohol Drinking↗

[Toxicologic approach to the clinical aspects of drug dependence: rational choice of dependence evaluation scales].

Fast but reliable approaches to evaluate the dependence syndrome to psychoactive substances are needed, particularly in those environmental conditions that do not allow a long interview with the drug addict. In this direction, easy to be administered questionnaires have been recently proposed. We used some of these questionnaires, such as SDS (severity of dependence scale) CAGE (cut down, annoyed, guilty, eye-opener) and VAS (visual analogical scales) in association with scales for clinical quantitation of alcohol and opiate withdrawal syndrome, to study a sample of 87 heroin addicts. Answers obtained were compared with clinical examination data and specific laboratory determinations. Our preliminary results demonstrate that the use of fast evaluation scales represents a reliable approach to estimate the dependence syndrome as well as to identify pharmacological therapies to be administered.

Adult↗

Acamprosate does not antagonise the discriminative stimulus properties of amphetamine and morphine in rats.

Acamprosate (calcium acetylhomotaurinate) is a GABA derivative that prevents drinking relapses in a significant number of alcoholics. Since little is known about the interaction of acamprosate with other addictive drugs, we studied the effects of this agent (as sodium salt) in two groups of rats trained to discriminate, respectively, morphine (1.7 mg kg(-1)i.p.) or amphetamine (0.5 mg kg(-1)i.p.) from solvent in a two-lever fixed ratio 30 operant behaviour reinforced by water access. Accordingly to the finding that acamprosate inhibits the action of excitatory aminoacids, its effects were compared with those of dizocilpine (MK-801), an NMDA antagonist. Results show that acamprosate (170 and 320 mg kg(-1)i.p. ) produced a slight, and not significant, shift to the left of generalization curves of both morphine and amphetamine without affecting response rates. In contrast, MK-801 potentiated response rate effects of both morphine and amphetamine without affecting their generalization curves. As far as discriminative stimuli participate in the relapsing process of addiction, our results do not predict a role of acamprosate in the prevention of amphetamine or morphine abuse relapsing.

Acamprosate↗

(-)-Norpseudoephedrine, a metabolite of cathinone with amphetamine-like stimulus properties, enhances the analgesic and rate decreasing effects of morphine, but inhibits its discriminative properties.

Like psychomotor stimulants, a weak amphetamine-like agent, such as phenylpropanolamine, enhances the analgesic effects of morphine (MOR). Thus, it is possible that full psychomotor stimulant potency is not required to increase the analgesic action of opiates. The validity of this assumption is here tested by studying the ability of (-)-norpseudoephedrine (NPE), an enantiomer of phenylpropanolamine and a metabolite of cathinone, to influence both the analgesic effects of MOR and its discriminative stimulus properties. In mice NPE (5.6-10.0-17.0 mg/kg i.p.) did not prolong the latency to lick or to remove paws from a plate warmed at 54 degrees C. However, it significantly potentiated the analgesic effect of 3.2 mg/kg of MOR. These results were replicated in rats by use of the formalin test, which measures the numbers of hind paw flinches produced by injecting 50 microl of formalin into the dorsal surface of the paw. The higher dose of NPE (17 mg/kg) increased the effect of sub-analgesic doses of MOR (0.56 and 1.0 mg/kg). In rats trained to discriminate between 0.5 mg/kg of amphetamine and solvent in a two-lever operant behavior reinforced by water access. NPE induced a dose-dependent increment of drug lever responding from 0% at 1.0 mg/kg to 100% at 32.0 mg/kg. In contrast, NPE did not generalize for the MOR cue up to the dose of 56.0 mg/kg, which produced a substantial reduction of the response rate. However, when given in combination, NPE attenuated the discriminative effects of MOR and potentiated its inhibitory action on the response rate. These results exclude a direct action of NPE on the mu opiate system. In conclusion, NPE preserves amphetamine-like properties and these properties are probably responsible for the interaction of the drug with the analgesic and discriminative effects of MOR. Therefore, this study contradicts the assumption that the analgesic effects of MOR can be enhanced by a sympathomimetic drug that lacks significant psychostimulant actions.

Alkaloids↗

Posterior spinal artery infarct.

Acute medullary syndrome developed in a patient in whom glue had been inadvertently injected into the right posterior radiculomedullary artery during endovascular occlusion of a spinal dural arteriovenous fistula at T-11. MR imaging 40 days after the procedure showed signal changes and contrast enhancement in the posterior and right lateral column at T10-11. Circumscribed signal changes in the same areas without contrast enhancement were seen 4 months later. MR imaging was able to show this posterior spinal artery infarct.

Aged↗

Amphetamine reinstates polydipsia induced by chronic exposure to quinpirole, a dopaminergic D2 agonist, in rats.

The hypothesis that the combined activation of D1 and D2 dopaminergic receptors is instrumental in inducing amphetamine (AMPH)-mediated hyperdipsia was tested in rats. The D1 agonist SKF-38393 (SKF) and the D2 agonist quinpirole (QNP) were i.p. injected, alone or in combination, to male rats for 10 days. After 2 days of wash-out, a single dose of AMPH (3 mg/kg) was administered. Intake of water and food and diuresis were daily measured at 2, 5 and 24 h. In two further experiments the higher dose of QNP (0.56 mg/kg) was given with two different doses of the D1 antagonist SCH-23390 (SCH), or, respectively, of the peripheral D2 antagonist domperidone (DMP). In a fourth experiment, the possibility that QNP, given alone or in combination with SKF, produces an AMPH-like internal state was evaluated by using a drug-discrimination paradigm. Results show that chronic administration of QNP produced a significant increase of 24 h water intake that was reinstated by AMPH. This QNP effect was only partially prevented by DMP, suggesting a main central mechanism of action. By itself D1 receptor manipulation did not affect water intake, but influenced QNP polydipsia that, accordingly, was enhanced by the lower dose of SKF (0.3 mg/kg) and inhibited by the lower dose of SCH (0.01 mg/kg). In rats trained to discriminate AMPH from solvent, QNP partially generalized for the AMPH stimulus, an effect that was potentiated by SKF. In conclusion, a D1-modulated sensitization of D2 dopaminergic mechanisms is probably involved in AMPH-induced hyperdipsia.

Amphetamine↗

The rules of drug taking: wine and poppy derivatives in the ancient world. I. General introduction.

Many believe that the public attitude toward psychotropic drugs is easy to change because it depends upon transient socioeconomic and cultural contingencies. This belief is here tested by analyzing literary sources on the use of wine and poppy derivatives in the Greek and Roman civilizations. As expected, the existence of elaborated myths about the discover of wine supports the view that wine drinking played an important social role in the ancient world. Contingencies in which drinking was considered illicit were carefully selected with the ultimate aim of maintaining sobriety. Rules of drinking were often enforced by law. This first part of the study lists drunkenness outcomes considered particularly harmful by the Ancients.

Alcohol Drinking↗