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Biomedical subjects

R Zucchi

Publications and source records attributed to R Zucchi.

At least 19 recordsLinked to original sources
PubMed2006

Trace amine-associated receptors and their ligands.

Classical biogenic amines (adrenaline, noradrenaline, dopamine, serotonin and histamine) interact with specific families of G protein-coupled receptors (GPCRs). The term 'trace amines' is used when referring to p-tyramine, beta-phenylethylamine, tryptamine and octopamine, compounds that are present in mammalian tissues at very low (nanomolar) concentrations. The pharmacological effects of trace amines are usually attributed to their interference with the aminergic pathways, but in 2001 a new gene was identified, that codes for a GPCR responding to p-tyramine and beta-phenylethylamine but not to classical biogenic amines. Several closely related genes were subsequently identified and designated as the trace amine-associated receptors (TAARs). Pharmacological investigations in vitro show that many TAAR subtypes may not respond to p-tyramine, beta-phenylethylamine, tryptamine or octopamine, suggesting the existence of additional endogenous ligands. A novel endogenous thyroid hormone derivative, 3-iodothyronamine, has been found to interact with TAAR1 and possibly other TAAR subtypes. In vivo, micromolar concentrations of 3-iodothyronamine determine functional effects which are opposite to those produced on a longer time scale by thyroid hormones, including reduction in body temperature and decrease in cardiac contractility. Expression of all TAAR subtypes except TAAR1 has been reported in mouse olfactory epithelium, and several volatile amines were shown to interact with specific TAAR subtypes. In addition, there is evidence that TAAR1 is targeted by amphetamines and other psychotropic agents, while genetic linkage studies show a significant association between the TAAR gene family locus and susceptibility to schizophrenia or bipolar affective disorder.

Amino Acids↗
PubMed2006

Ghrelin tissue distribution: comparison between gene and protein expression.

Ghrelin, the natural ligand of the GH secretagogue (GHS) receptor, was originally isolated from the stomach and detected in several tissues, but a systematic study of its tissue distribution has not been performed. In the present investigation, we evaluated ghrelin gene expression (by RT-PCR technique) and ghrelin protein concentration (by enzyme immunoassay technique) in tissues obtained from control rats as well as in rats subjected to 48-h fasting. The ghrelin gene was expressed in stomach, small intestine, brain, cerebellum, pituitary, heart, pancreas, salivary gland, adrenal, ovary and testis, with maximum expression occurring in the stomach, while no significant expression was detected by standard RT-PCR in liver, lung, kidney and skeletal muscle. Ghrelin protein was detected in stomach, small intestine, brain, cerebellum, pituitary, lung, skeletal muscle pancreas, salivary gland, adrenal, ovary and testis, at concentrations ranging from 0.05 to 1.43 ng/mg of homogenate protein (the highest concentration occurred in the lung, followed by the brain). Ghrelin was not detectable in the heart, liver and kidney. Therefore, gene and protein expression were dissociated. Fasting did not produce significant changes in ghrelin gene expression, while the distribution of ghrelin between different tissues was significantly modified: protein concentration increased in the brain, cerebellum, lung and salivary gland, while it decreased in the stomach.

Animals↗
PubMed2004

Thorax vibrations of a stingless bee ( Melipona seminigra). I. No influence of visual flow.

An important question in stingless bee communication is whether the thorax vibrations produced by foragers of the genus Melipona upon their return to the nest contain spatial information about food sources or not. As previously shown M. seminigra is able to use visual flow to estimate flight distances. The present study investigated whether foraging bees encode the visually measured distance in their thorax vibrations. Bees were trained to collect food in flight tunnels lined with a black-and-white pattern on their side walls and floor, which substantially influenced the image motion they experienced. When the bees had collected inside the tunnels the temporal pattern of their vibrations differed significantly from the pattern after collecting in a natural environment. These changes, however, were not associated with the visual flow experienced inside the tunnel. Bees collecting in tunnels offering little visual flow (stripes parallel to flight direction) modified their vibrations similarly to bees collecting in tunnels with high image motion (cross stripes). A higher energy expenditure due to drastically reduced flight velocities inside the tunnel is suggested to be responsible for changes in the thorax vibrations. The bees' vibrations would thus reflect the overall energetic budget of a foraging trip.

Animal Communication↗
PubMed2004

Thorax vibrations of a stingless bee ( Melipona seminigra). II. Dependence on sugar concentration.

Using a laser vibrometer we studied the influence of the food's sugar concentration on different parameters of the thorax vibrations produced by foragers of Melipona seminigra during trophallaxis in the nest. The concentrations tested (20-70% sugar w/w) were within the biologically relevant range. They substantially influenced different parameters of the thorax vibrations. An increase of energy gains at the food source due to an increased sugar concentration was followed by an increase of both the pulse duration and the duty cycle and by a decrease of the pause duration between two subsequent pulses. These findings further support the hypothesis that the temporal pattern of the thorax vibrations reflects the energy budget of a foraging trip rather than food source distance. Likewise, the steep increase of pulse duration variability with sugar concentration is hard to reconcile with the assumption that pulse duration conveys reliable information about food source distance when bees collect at high-quality food sources.

Animal Communication↗
PubMed2004

A stingless bee uses labial gland secretions for scent trail communication ( Trigona recursa Smith 1863).

The pheromones used by several species of stingless bees for scent trail communication are generally assumed to be produced by the mandibular glands. Here we present strong evidence that in Trigona recursa these pheromones originate from the labial glands, which are well developed in the heads of foragers. Analysis of the behavior involved in scent marking shows that a bee extends her proboscis and rubs it over the substrate. A single scent marking event lasts for 0.59+/-0.21 s while the bee runs a stretch of 1.04+/-0.37 cm on a leaf. According to choice experiments the bees are attracted by a feeder baited with labial gland extract (84.2+/-6% of the bees choose this feeder) but repelled from a feeder baited with mandibular gland extract (only 27.5+/-13.1% of the bees choose this feeder). They do not discriminate between two clean feeders (49.6+/-3% of the bees at a feeder). 87+/-5.1% of bees already feeding leave the feeder after the application of mandibular gland extract whereas only 6.2+/-4.9% and 2.6+/-4% do so when labial gland extract or pure solvent was applied.

Animal Communication↗
PubMed2003

A stingless bee (Melipona seminigra) uses optic flow to estimate flight distances.

Foragers of a stingless bee, Melipona seminigra, are able to use the optic flow experienced en route to estimate flight distance. After training the bees to collect food inside a flight tunnel with black-and-white stripes covering the side walls and the floor, their search behavior was observed in tunnels lacking a reward. Like honeybees, the bees accurately estimated the distance to the previously offered food source as seen from the sections of the tunnel where they turned around in search of the food. Changing the visual flow by decreasing the width of the flight tunnel resulted in the underestimation of the distance flown. The removal of image motion cues either in the ventral or lateral field of view reduced the bees' ability to gauge distances. When the feeder inside the tunnel was displaced together with the bees feeding on it while preventing the bee from seeing any image motion during the displacement the bees experienced different distances on their way to the food source and during their return to the nest. In the subsequent test the bees searched for the food predominantly at the distance associated with their return flight.

Animal Communication↗
PubMed2003

Laser-evoked potentials in post-herpetic neuralgia.

OBJECTIVE: We evaluated the reliability of laser-evoked potentials (LEPs) as a diagnostic tool in patients with post-herpetic neuralgia (PHN), i.e. a chronic painful condition that causes small-diameter fibre dysfunction. Furthermore, we sought information on pathophysiology of PHN pain. METHODS: We recorded 'late' LEPs after stimulation of the supraorbital, upper cervical, lower cervical, upper thoracic, mid thoracic, and lower thoracic territories in 12 control subjects and 40 patients with PHN. We also determined the correlation of LEP data with age, duration of disease, and severity and quality of pain. RESULTS: At all stimulation sites, laser pulses invariably evoked high-amplitude brain potentials related to small-myelinated (A-delta) fibre activation. The laser perceptive threshold and LEP latency correlated with the distance of the dermatome from the brain (P<0.001). In patients, the perceptive threshold was higher and the LEP amplitude was lower in the affected dermatome than on the contralateral side (P<0.001). We found no significant LEP-clinical correlation except for a correlation between LEP abnormality and age. CONCLUSIONS: Being sensitive and reliable in assessing sensory function also in proximal dermatomes, LEPs are a promising diagnostic tool in radiculopathies. Although PHN severely impairs small myelinated fibres, the lack of a significant correlation between LEP abnormalities and pain suggests that pain in PHN does not chiefly arise from a dysfunction of small-myelinated afferents.

Adult↗
PubMed2001

A3 adenosine receptor stimulation modulates sarcoplasmic reticulum Ca(2+) release in rat heart.

OBJECTIVE: Stimulation of A3 adenosine receptors has been shown to protect cardiac myocytes from ischemic injury, but the mechanism of this action is unknown. We evaluated the effect of adenosine agonists and antagonists on the sarcoplasmic reticulum (SR) Ca(2+) channels. METHODS: Isolated rat hearts were perfused with control buffer or different adenosine agonists and antagonists. Hearts were then homogenized and used to determine SR Ca(2+)-induced Ca(2+) release, assayed by quick filtration technique after loading with 45Ca(2+), and the binding of [3H]ryanodine, a specific ligand of the SR Ca(2+) release channel. In parallel experiments, hearts were challenged with 30 min of global ischemia and 120 min of reperfusion, and the extent of tissue necrosis was evaluated by triphenyltetrazolium chloride staining. RESULTS: Perfusion with the A1>A3 agonist R-PIA and the A3>A1 agonist IB-MECA was associated with reduced [3H]ryanodine binding, due to reduced B(max) (by about 20%), whereas K(d) and Ca(2+)-dependence of the binding reaction were unaffected. These actions were abolished by the A3 antagonist MRS 1191, while they were not affected by A1 and A2 antagonists. The rate constant of SR Ca(2+) release decreased by 25-30% in hearts perfused with R-PIA or IB-MECA. Tissue necrosis was significantly reduced in the presence of R-PIA or IB-MECA. Protection was removed by MRS 1191, and it was not affected by A1 and A2 antagonists. Hearts were also protected by administration of dantrolene, a ryanodine receptor antagonist. In the presence of dantrolene, no further protection was provided by IB-MECA. CONCLUSION: A3 adenosine receptor stimulation modulates the SR Ca(2+) channel. This action might account for the protective effect of adenosine.

Adenosine↗
PubMed2001

Modulation of sarcoplasmic reticulum function: a new strategy in cardioprotection?

This article reviews the experimental evidence suggesting that cytosolic Ca(2+) overload plays a major role in the development of myocardial injury during ischemia-reperfusion and that Ca(2+) release from the sarcoplasmic reticulum (SR) is of crucial importance in the early phase of ischemia. It is suggested that interventions able to deplete the SR Ca(2+) pool and/or to reduce the rate of SR Ca(2+) release should be cardioprotective. This thesis is supported by the review of experimental studies in which modulators of the SR Ca(2+)-ATPase or SR Ca(2+) release channel (ryanodine receptor) have been used. In addition, the role of the SR in ischemic preconditioning and in some instances of toxic myocardial injury (particularly, anthraquinone-induced injury) is discussed.

Calcium↗
PubMed2000

Protection of ischemic rat heart by dantrolene, an antagonist of the sarcoplasmic reticulum calcium release channel.

Cytosolic Ca2+ overload plays a major role in the development of irreversible injury during myocardial ischemia. Such overload is due at least in part to the release of Ca2+ from the sarcoplasmic reticulum. Therefore, we investigated whether dantrolene, a blocker of the sarcoplasmic reticulum Ca2+ release channel, may protect from ischemic injury. In binding experiments, we determined the effect of dantrolene on [3H]-ryanodine binding in rat cardiac tissue. In perfusion experiments, isolated rat hearts were perfused for 20 min in the working mode, in the presence of 0-45 microM dantrolene. The hearts were then subjected to 30 min of global ischemia and 120 min of retrograde reperfusion. Tissue injury was evaluated on the basis of triphenyltetrazolium chloride (TTC) staining and LDH release. The binding experiments showed that dantrolene displaced 4 nM [3H]-ryanodine with IC50 of 34 microM. In the perfusion experiments, tissue necrosis (i.e., TTC-negative tissue) averaged 28.3 +/- 1.6% of the ventricular mass under control conditions. Dantrolene was protective at micromolar concentrations: tissue necrosis decreased to 21.4 +/- 1.0% and 8.4 +/- 1.4% with 1 microM and 45 microM dantrolene, respectively (P < 0.05 and P < 0.01). Similar results were obtained with regard to LDH release. At low concentrations (up to 4 microM), dantrolene did not produce any significant hemodynamic effect, except for a slight increase in coronary flow, whereas at higher concentration a negative inotropic effect was apparent. In conclusion, dantrolene reduced ischemic injury even at concentrations that did not affect contractile performance. Modulation of sarcoplasmic reticulum Ca2+ release might represent a new cardioprotective strategy.

Animals↗
PubMed2000

Myocardial ischemic preconditioning and mitochondrial F1F0-ATPase activity.

A short period of ischemia followed by reperfusion (ischemic preconditioning) is known to trigger mechanisms that contribute to the prevention of ATP depletion. In ischemic conditions, most of the ATP hydrolysis can be attributed to mitochondrial F1F0-ATPase (ATP synthase). The purpose of the present study was to examine the effect of myocardial ischemic preconditioning on the kinetics of ATP hydrolysis by F1F0-ATPase. Preconditioning was accomplished by three 3-min periods of global ischemia separated by 3 min of reperfusion. Steady state ATP hydrolysis rates in both control and preconditioned mitochondria were not significantly different. This suggests that a large influence of the enzyme on the preconditioning mechanism may be excluded. However, the time required by the reaction to reach the steady state rate was increased in the preconditioned group before sustained ischemia, and it was even more enhanced in the first 5 min of reperfusion (101 +/- 3.0 sec in preconditioned vs. 83.4 +/- 4.4 sec in controls, p < 0.05). These results suggest that this transient increase in activation time may contribute to the cardioprotection by slowing the ATP depletion in the very critical early phase of post-ischemic reperfusion.

Adenosine Triphosphate↗
PubMed2000

Effect of MEN 10755, a new disaccharide analogue of doxorubicin, on sarcoplasmic reticulum Ca(2+) handling and contractile function in rat heart.

1. The use of anthraquinone antineoplastic agents is limited by their cardiac toxicity, which is largely due to activation of the sarcoplasmic reticulum (SR) Ca(2+) release channel (ryanodine receptor). MEN 10755 is a new disaccharide analogue of doxorubicin. We have evaluated its effects on SR function and its toxicity in isolated working rat hearts. 2. In rat SR vesicles, doxorubicin stimulated [(3)H]-ryanodine binding by increasing its Ca(2+)-sensitivity. At 1 microM Ca(2+), ryanodine binding increased by 15.3+/-2.5 fold, with EC(50)=20.6 microM. Epirubicin produced a similar effect, i.e. 9.7+/-0.6 fold stimulation with EC(50)=11.1 microM. MEN 10755 increased ryanodine binding by 1.9+/-0.3 fold (P:<0.01 vs doxorubicin and epirubicin), with EC(50)=38.9 microM. 3. Ca(2+)-induced Ca(2+) release experiments were performed by quick filtration technique, after SR loading with (45)Ca(2+). At 2 microM Ca(2+), doxorubicin (50 microM) increased the rate constant of Ca(2+) release to 82+/-5 s(-1) vs a control value of 22+/-2 s(-1) (P:<0.01), whereas 50 microM MEN 10755 did not produce any significant effect (24+/-3 s(-1)). 4. Ca(2+)-ATPase activity and (45)Ca(2+)-uptake were not significantly affected by doxorubicin, its 13-dihydro-derivative, epirubicin, MEN 10755 and the 13-dihydro-derivative of MEN 10755, at concentrations < or =100 microM. 5. In isolated heart experiments, administration of 30 microM doxorubicin or epirubicin caused serious contractile impairment, whereas 30 microM MEN 10755 produced only minor effects. 6. In conclusion, in acute experiments MEN 10755 was much less cardiotoxic than equimolar doxorubicin or epirubicin. This result might be accounted for by reduced activation of SR Ca(2+) release.

Animals↗
PubMed1998

Sulfhydryl redox state affects susceptibility to ischemia and sarcoplasmic reticulum Ca2+ release in rat heart. Implications for ischemic preconditioning.

We investigated the effect of sulfhydryl and disulfide reagents on ischemic preconditioning and on sarcoplasmic reticulum Ca2+ release. Isolated working rat hearts were subjected to ischemic preconditioning (three 3-minute periods of global ischemia) or to control aerobic perfusion, which was followed by 30 minutes of global ischemia and 120 minutes of retrograde reperfusion. Necrosis was evaluated on the basis of lactate dehydrogenase release and triphenyltetrazolium chloride staining. In parallel experiments, sarcoplasmic reticulum Ca2+ release and [3H]-ryanodine binding were determined before the sustained ischemia. Ischemic preconditioning was associated with protection versus ischemic injury, decreased Ca2+ release and reduced [3H]-ryanodine binding. The disulfide reducing agent dithiothreitol (1 mmol/L) removed the protection provided by ischemic preconditioning, if added to the perfusion buffer either before or after the preconditioning procedure. In preconditioned hearts, dithiothreitol increased sarcoplasmic reticulum Ca2+ release and ryanodine binding, whereas in control hearts it had no effect on either tissue injury or sarcoplasmic reticulum function. Perfusion of control hearts with the sulfhydryl blocking agents 4,4'-dithiodipyridine (25 micromol/L) and N-ethylmaleimide (16 micromol/L) increased the resistance to ischemia and reduced sarcoplasmic reticulum Ca2+ release and [3H]-ryanodine binding. These effects were not additive with those induced by preconditioning. Sulfhydryl and disulfide reagents produced similar effects on Ca2+ release and [3H]-ryanodine binding if added in vitro to preparations obtained from control and preconditioned hearts. We conclude that ischemic preconditioning is associated with the oxidation of sulfhydryl groups involved in the modulation of sarcoplasmic reticulum Ca2+ release.

Animals↗
PubMed1998

Altered autonomic cardiac control in hypertrophic cardiomyopathy. Role of outflow tract obstruction and myocardial hypertrophy.

AIM: The goal of this study was to investigate the role of left ventricular outflow tract obstruction and myocardial hypertrophy on autonomic cardiac function in patients with hypertrophic cardiomyopathy. METHODS AND RESULTS: The sympatho-vagal function was evaluated by spectral analysis of heart rate variability in 28 patients with hypertrophic obstructive cardiomyopathy, 22 patients with hypertrophic non-obstructive cardiomyopathy, 12 with systemic hypertension and left ventricular hypertrophy and 28 healthy subjects. Left ventricular out-flow tract pressure gradient in patients with hypertrophic cardiomyopathy was evaluated by echo-Doppler methods and the quantitative assessment of left ventricular hypertrophy was based on an echocardiographic index. At rest, patients with hypertrophic non-obstructive cardiomyopathy showed normal spectral patterns, while in patients with hypertrophic obstructive cardiomyopathy and in patients with systemic hypertension we observed, respectively, a significant reduction and increase in the low frequency component relative to the control (P < 0.05). During tilt, the physiological increases in the low frequency component and in the low to high frequency ratio were markedly blunted, or even reverted, only in patients with hypertrophic obstructive cardiomyopathy. In these patients, the heart rate increase during tilt was delayed in comparison to the other groups. Finally, in the hypertrophic obstructive cardiomyopathy group, the impairment of sympathetic activation (lack of increase in the low frequency component during tilt) was significantly correlated to the echocardiographic index of left ventricular hypertrophy (r = -0.800, P < 0.001) rather than to the left ventricular outflow tract pressure gradient (r = 0.295, P: ns). CONCLUSION: Among patients with hypertrophic cardiomyopathy, only those with outflow tract obstruction show spectral signs of altered autonomic cardiac control. Within this group, the autonomic dysfunction appears to be correlated to myocardial hypertrophy rather than to left ventricular outflow tract obstruction.

Adult↗