Alberto Loizzo

Clinical and pharmacological profile in a clenbuterol epidemic poisoning of contaminated beef meat in Italy

Long-acting beta adrenergic agonists, such as clenbuterol accumulate in the liver, but not meat of treated farm animals, and result in epidemic poisonings in consumers. We describe an outbreak of poisoning in 15 people, following the consumption of meat. Clinical symptoms (distal tremors, palpitations, headache, tachipnoea-dyspnoea, and also moderate hyperglycaemia, hypokalemia and leucocytosis) were seen in nine hospitalised patients, starting about 0.5-3 h after poisoning, and disappearing within 3-5 days later. Clenbuterol was found in the urine of all the symptomatic patients, at higher levels than pharmacokinetic computing (mean level 28 ng/ml, 36 h after ingestion), based on the levels found in the meat (1140-1480 ng/g edible tissue). Thus, epidemic poisoning can be produced following the consumption of contaminated meat. The need for a better definition of pharmaco- and toxico-kinetics, not only for drugs ingested as parent drug, but also when ingested as residues with animal tissues, is recommended.

Orphanin FQ reduces morphine-induced dopamine release in the nucleus accumbens: a microdialysis study in rats

The effects induced by orphanin FQ (OFQ) on morphine-induced dopamine (DA), 3,4-dihydroxyphenilacetic acid (DOPAC) and homovanillic acid (HVA) release in the nucleus accumbens were studied in rats by using microdialysis with electrochemical detection. Morphine administered intraperitoneally (i.p., 2, 5 and 10 mg/kg) dose-dependently increased DA and metabolites release in the nucleus accumbens. OFQ intracerebroventricularly (i.c.v.) administered at doses of 2, 5 and 10 nmol did not change DA and metabolites release in the nucleus accumbens. OFQ (10 nmol) administered i.c.v. 15 min before morphine (5 and 10 mg/kg, i.p.) significantly reduced morphine-induced DA and metabolites release in the nucleus accumbens. These effects suggest that OFQ may regulate the stimulant action linked to morphine-induced DA release in the nucleus accumbens.

Taurine supplementation and diabetes mellitus.

Purpose of reviewTaurine is a semi-essential sulphur amino acid derived from methionine and cysteine metabolism. It has been evaluated either in experimental or clinical type 1 and 2 diabetes mellitus and insulin resistance. One form of experiment has included the possibility that perinatal taurine administration could prevent diabetes mellitus and/or insulin resistance. Recent findingsExperimental data suggest strongly that taurine could have beneficial effects in type 1 diabetes mellitus, and could generally reduce organ lipid peroxidation and plasma lipids. Interestingly, retina, lens and nerves seem to respond better to taurine than other organs such as kidneys. It has been shown in some experimental models that in type 2 diabetes mellitus and insulin resistance there is alteration in taurine homeostasis. Taurine could prevent the onset of diabetes mellitus in NOD mice and postnatal taurine modifies the glucose-loading curves in adults. However, the clinical studies are too small and too short to have any real significance. SummaryFurther experimental and clinical studies are required to evaluate taurines possible therapeutic potential. Careful attention has to be paid in the selection of animal species, in standardization of taurine concentrations and patient selection. Moreover, care must also be given to the metabolic state, presence of complications, duration of supplementations and selection of the right end-points.

EEG Responses to Visual Landmarks in Flying Pigeons

BACKGROUND GPS analysis of flight trajectories of pigeons can reveal that topographic features influence their flight paths. Recording electrical brain activity that reflects attentional processing could indicate objects of interest that do not cause changes in the flight path. Therefore, we investigated whether crossing particular visual landmarks when homing from a familiar release site is associated with changes in EEG. RESULTS Birds carried both data-loggers for recording GPS position and EEG during flight. First, we classified characteristic EEG frequencies of caged birds and found five main bands: A: 0-3, B: 3-12, C: 12-60, D: 60-130, and E: 130-200 Hz. We analyzed changes in these activity bands when pigeons were released over sea (a featureless environment) and over land. Passing over the coastline and other prominent landmarks produced a pattern of EEG alterations consisting of two phases: activation of EEG in the high-frequency bands (D and/or E), followed by activation of C. Overlaying the EEG activity with GPS tracks allowed us to identify topographical features of interest for the pigeons that were not recognizable by distinct changes of their flight path. CONCLUSIONS We provide evidence that EEG analysis can identify landmarks and objects of interest during homing. Middle-frequency activity (C) reflects visual perception of prominent landmarks, whereas activation of higher frequencies (D and E) is linked with information processing at a higher level. Activation of E bands is likely to reflect an initial process of orientation and is not necessarily linked with processing of visual information.

Long-term changes induced by developmental handling on pain threshold : effects of morphine and naloxone

Mice pups were exposed daily to a stress-producing procedure (handling and saline injection) during the first 3 weeks of life. At 25 and 45 days of age, they were tested for differences in the tail-flick and hot-plate tests. The results indicate that chronic handling procedures during developmental stages can produce a long-lasting increase of the threshold for painful stimuli. This phenomenon is completely prevented by naloxone pretreatment and has enhancing effects on morphine analgesia, thus suggesting that postnatal handling can exert long-lasting interference on the sensitivity of some opioid receptor populations.

Age and strain differences in rat place learning and hippocampal dentate gyrus frequency-potentiation.

Induction of post-tetanic potentiation (PTP) and long-term potentiation (LTP) was analyzed in hippocampal slices obtained from (i) young (6 months old) rats of different strains (Sprague-Dawley, SD; spontaneously hypertensive rats, SHR; and Wistar-Kyoto, WKY), and (ii) from aged (20-24 months old) SD and Fischer 344 (F 344) rats, each group showing a different performance in the Morris maze test. After the application of an electrical tetanus (1 s, 100 Hz, 50 microA) in the stratum moleculare, a significant difference was found in the percent of induction of the dentate PTP in hippocampal slices obtained from rats of different strains and ages. In particular, the induction of the dentate PTP was significantly (P < 0.01) higher in slices obtained from young SD or spontaneously SHR rats, having the better performance in the Morris maze than in slices obtained from old SD or F 344 rats or young WKY rats which had poorer performances in the Morris maze. On the contrary, no significant differences were found in the percent of induction of the LTP in the dentate area of hippocampal slices obtained from rats of different strains and ages. Moreover, after the application of an electrical tetanus (1 s, 100 Hz, 50 microA) in the stratum radiatum, no significant differences were found in the percent of induction of both PTP and LTP in the CA1 area of hippocampal slices obtained from rats of different strains and ages.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduced hippocampal CA1 Ca2+-induced long-term potentiation is associated with age-dependent impairment of spatial learning

Expression of Ca(2+)-induced CA1 long-term potentiation (LTP) was analysed in hippocampal slices obtained from (1) 3-month-old and (2) 18-20-month-old Sprague-Dawley rats selected for their performances in the Morris water maze task. In all slices, a transient (10 min) increase of extracellular Ca2+ concentration (4 mM) caused a long-lasting enhancement of potentials evoked by electrical stimulation of radiatum fibers. However, a significant difference was found in the degree of potentiation among groups. In particular, increases of the CA1 response amplitudes were significantly lower in old rats impaired in spatial learning than in young at 30 (P < 0.05), 60, 90 and 120 min (P < 0.01) after restoring the normal Ca2+ concentration. On the contrary, no differences were observed between young animals and the old ones with good performances in spatial learning. The data suggest that amplitude of CA1 Ca(2+)-induced LTP in old rats is related to spatial learning abilities.

The interaction of peripherally and centrally administered dexamethasone and RU 38486 on morphine analgesia in mice

1. Dexamethasone or RU 38486 were administered intraperitoneally or intracerebroventricularly to mice 10 or 120 min before morphine administration. The interaction of these drugs with the analgesic effects of morphine was examined using the hot plate test. 2. Dexamethasone i.p. pretreatment reduced analgesic responses to morphine injected 120 min but not 10 min after dexamethasone; i.c.v. injection of dexamethasone 10 and 120 min before morphine administration was effective in reducing morphine analgesia. 3. RU 38486 i.c.v. pretreatment (but not i.p. pretreatment) performed 120 (but not 10) min before morphine administration enhanced morphine analgesic effects. 4. These results, particularly the effects of drug interaction for i.c.v. administration, strongly confirm a central site for dexamethasone and RU 38486 action.

Dexamethasone-induced selective inhibition of the central μ opioid receptor: functional in vivo and in vitro evidence in rodents

1 Endogenous corticosteroids and opioids are involved in many functions of the organism, including analgesia, cerebral excitability, stress and others. Therefore, we considered it important to gain information on the functional interaction between corticosteroids and specific opioid receptor subpopulations. 2 We have found that systemic administration (i.p.) of the potent synthetic corticosteroid, dexamethasone, reduced the antinociception induced by the highly selective μ agonist, DAMGO or by less selective μ agonists morphine and β‐endorphin administered i.e.v., On the contrary dexamethasone exerted little or no influence on the antinociception induced by a δ1 agonist, DPDPE and a δ2 agonist deltorphin II. Dexamethasone potentiated the antinociception induced by the k agonist, U50,488. 3 In experiments performed in an in vitro model of cerebral excitability in the rat hippocampal slice, dexamethasone strongly prevented both the increase of the duration of the field potential recorded in CA1, and the appearance and number of additional population spikes induced by μ receptor agonists. 4 In both models pretreatment with cycloheximide, a protein synthesis inhibitor, prevented the antagonism by dexamethasone of responses to the μ opioid agonists. 5 Our data indicate that in the rodent brain there is an important functional interaction between the corticosteroid and the opioid systems at least at the μ receptor level, while δ and k receptors are modulated in different ways.

Potential Therapeutic Effects of Vitamin E and C on Placental Oxidative Stress Induced by Nicotine: An In Vitro Evidence

There have been a few studies that examined the oxidative stress effects of nicotine during pregnancy and lactation. The adverse effect of prenatal smoking exposure on human fetal development and growth has been a major public health issue. Active or passive smoking during pregnancy can result in a wide variety of adverse outcomes, including intrauterine growth retardation (IUGR), prematurity, stillbirth, and the sudden infant death syndrome. Smoking in pregnancy has also been associated with an increased risk of attention deficit and learning problems in childhood. Some studies argued that as a principal component of tobacco smoke, nicotine alone is responsible for the majority of negative reproductive outcomes. Nicotine and its major metabolite cotinine can cross the placental barrier. The level of nicotine in fetal tissues was found to be equal to or greater than the plasma nicotine level in the mothers. The oxidative stress induce by nicotine has been increasingly postulated as a major contributor to endothelial dysfunction. A large body of research has investigated the potential role of antioxidant nutrients in the prevention of endothelial dysfunction in women. Therefore, the present study was undertaken to assess the potential benefit of antioxidant supplementation on markers of placental oxidative stress in an in vitro model of endothelial dysfunction induced by nicotine, since it was previously found that nicotine is able to trigger the placental secretion of stress molecules. In this regard, we evaluated the effects of vitamin C, vitamin E and N-acetylcysteine (NAC), alone or in combination, in placental villi culture after exposure to nicotine. The effect of antioxidant nutrients on trophoblast cells proliferation and vitality was also evaluated. The results obtained suggest that in a patho-physiological condition, such as endothelial dysfunction induced by nicotine, the deleterious effect of reactive oxygen species may be counteracted by an antioxidant therapy, and there is the need to investigate the optimum dosing and timing of antioxidants administration, since an inappropriate antioxidant treatment in pregnant women may have deleterious consequences, reducing placental cells proliferation until to cell death.