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Biomedical subjects

M Nobile

Publications and source records attributed to M Nobile.

At least 55 records · Page 3Linked to original sources
PubMed1997

Incorrect identification of a military pilot with international implications.

The case is reported of a military pilot shot down in 1986 during a mission whose body was recovered in an advanced state of decomposition and delivered to Italian police in 1989. The first autopsy led to an incorrect identification of the corpse. Because of the advanced decomposed state of the corpse, a correct identification was made only through evaluation of the dental status and radiological examination. The correct evaluation of the specific shape of the amalgam restorations, particularly of those of the first and second inferior right molars, showed agreement with those of the pilot of the plane and not of the co-pilot as was initially stated.

Accidents, Aviation↗
PubMed1997

Inhibition of delayed rectifier K+ channels by phenytoin in rat neuroblastoma cells.

1. The action of the anticonvulsant drug phenytoin on K+ currents was investigated in neuroblastoma cells by whole-cell voltage-clamp recording. 2. Neuroblastoma cells expressed an outward K+ current with a voltage- and time-dependence which resembled the delayed-rectifier K+ current found in other cells. When added to the standard external solution at concentrations ranging between 1 and 200 microM, phenytoin reduced the current (n = 65). Inhibition was concentration-dependent with a half-maximal inhibitory concentration of 30.9 +/- 0.8 microM. 3. The K+ current inhibition by phenytoin was voltage-dependent with block by phenytoin being relieved by depolarization. 4. The times taken to reach steady-state inhibition and complete recovery from inhibition were about 20 s. Neither the activation and inactivation rates of the K+ current nor the K+ channel availability were significantly altered by the blocking drug. A use-dependent block was observed at phenytoin concentrations of 10, 25 and 50 microM. 5. These results suggest that phenytoin affects K+ currents and that this effect might lead to a reduction in neuronal excitability.

Animals↗
PubMed1997

Association study of schizophrenia and the histidase gene.

Previous findings of increased heterozygosity for histidinemia among schizophrenic patients make the histidase gene a plausible candidate for genetic studies in schizophrenia. In the present study, we used a tetranucleotide repeat polymorphism in intron 8 of the histidase gene to examine the possibility that the histidase gene contributes to the genetic component of schizophrenia. In a first sample of 161 patients and 128 controls, we found the 4 repeat allele to be in excess in the patients. In contrast, the 3 repeat allele was less frequent in patients. A second sample of 95 patients and 93 controls was utilized to test these hypotheses. However, both observations were not replicated. We therefore concluded that our results do not support an involvement of the histidase gene in the development of schizophrenia.

Alleles↗
PubMed1997

Bone density and skeletal metabolism in patients with orthotopic ileal neobladder.

The interposition of a bowel segment as a bladder substitute into the urinary tract may result in impaired calcium metabolism. We studied 25 male patients (aged 45 to 77 yr) who had undergone a Vescica Ileale Padovana (VIP) reconstruction following cystectomy 29 to 75 mo before. Bone mineral density of the spine and femur was measured by dual x-ray absorptiometry. Blood and 24-h urine samples were analyzed for the main parameters of bone metabolism. Sixteen healthy men were enrolled as a control group. Although blood pH did not differ between patients and control subjects, VIP subjects showed lower levels of plasma HCO3- (P < 0.005) and higher serum chloride (P < 0.001). Bone alkaline phosphatase was higher (P < 0.001), and urine calcium, phosphate, and creatinine levels were lower in VIP patients (P < 0.01, P < 0.01, and P < 0.05, respectively). Bone mineral density at the femoral neck (P < 0.03) and Ward's triangle (P < 0.05) was decreased in VIP patients. When subdivided according to time since operation, patients who had the ileal neobladder implanted for a shorter period of time showed lower blood pH (P < 0.03) and urine calcium (P < 0.05) levels and higher urinary hydroxyproline (P < 0.02). Duration of the ileal neobladder was positively correlated with PTH (r = 0.46, P < 0.03) and blood pH (r = 0.47, P < 0.02). Furthermore, pH values were positively correlated with urine calcium (r = 0.48, P < 0.02). In conclusion, in patients with ileal neobladder, a mild metabolic acidosis is responsible for an increased bone turnover and lower bone mass. Moreover, a decrease over time in the absorption capacity of the ileal pouch might result in calcium malabsorption, which represents an additional risk factor for reduced bone mass in these patients.

Aged↗
PubMed1996

Helothermine, a lizard venom toxin, inhibits calcium current in cerebellar granules.

Helothermine (HLTx), a 25.5-kDa peptide toxin isolated from the venom of the Mexican beaded lizard (Heloderma horridum horridum), was found to be an inhibitor of Ca2+ channels in cerebellar granule cells of newborn rats. Macroscopic currents, carried by 10 mM Ba2+, were measured in whole-cell configuration. The toxin at the saturating dose of 2.5 microM reversibly produced an approximately 67% block of the voltage-dependent Ca2+ current by a fast mechanism of action. The current inhibition and recovery were reached in less than 1 min. Inhibition was concentration-dependent, with a half-effective dose of 0.25 microM. The current block was practically voltage-independent, whereas the steady-state inactivation h infinity was significantly affected by HLTx (approximately 10 mV). The toxin did not affect the activation and inactivation kinetics of the Ca2+ current. Experiments with other Ca2+ channel blockers showed that HLTx abolished omega-cono-toxin GVIA-sensitive Ca2+ currents, as well as omega-Aga-IVA- and dihydropyridine-sensitive Ca2+ currents. These drugs had virtually no effect when HLTx was applied first. The present results indicate that HLTx produce a high-potency blockage of the three pharmacologically distinct Ca2+ current components.

Animals↗
PubMed1995

Functional aspects of dexamethasone upregulated nicotinic acetylcholine receptors in C2C12 myotubes.

Three days of treatment with the glucocorticoid dexamethasone (1 nM-1 microM) induced a concentration-dependent up-regulation of muscle nicotinic acetylcholine receptor (nAChR) in C2C12 mouse myotubes (EC50 = 10 +/- 7.3 nM), as assessed by [3H]alpha-BuTx binding. The maximum increase in binding amounted 148 +/- 17.6% of control. Parallel electrophysiological measurements employed the patch-clamp technique in cell-attached configuration. The nAChR single channel properties were investigated in the presence of carbachol (1 microM) in the pipette. Treatment with dexamethasone (1 microM, 1-5 days) induced an increase in the number of patches showing channel activity from 30 to 70%. Ion channel characteristics did not differ significantly in control and dexamethasone treated myotubes. Conductance was 32 +/- 3 vs 31 +/- 2 pS, respectively. The time constants of open time events tau 1 and tau 2 were 0.6 +/- 0.1 and 6.6 +/- 1 ms vs 0.6 +/- 0.1 and 6.6 +/- 1 ms, respectively. Closed duration's tau 1 and tau 2 were 1.1 +/- 0.2 and 110 +/- 12 ms vs 1.2 +/- 0.3 and 107 +/- 18 ms. In conclusion, dexamethasone upregulated nAChRs are functional and their electrophysiological parameters are similar to those found in control myotubes.

Animals↗
PubMed1995

Pharmacological types of calcium channels and their modulation by baclofen in cerebellar granules.

Voltage-dependent calcium currents were measured by whole-cell recording technique in cultured cerebellar granule neurons from 8 d old rats, in 10 mM BaCl2 and with a holding potential of -80 mV. A saturating dose (10 microM) of the dihydropyridine nimodipine reversibly inhibited the maximum current by 25% and the dose dependence showed IC50 close to 50 nM. omega-Conotoxin GVIA (cgtx, 5 microM) and omega-agatoxin IVA (agatx, 200 nM) irreversibly inhibited the current by 17% and by 47%, respectively. The effect of nimodipine was additive with that of the toxins. The GABAB agonist (+/-)baclofen, or (-)baclofen (100 microM), reduced the calcium current by 30 +/- 5%, with a IC50 4 microM. The effect was mediated by a pertussis toxin-sensitive G-protein. In cells treated with cgtx during the experiment or preincubated with the toxin for 30 min, the effect of baclofen was significantly reduced. However, the action of baclofen was not confined to cgtx-sensitive channels: application of nimodipine or agatx resulted in a 50% reduction of the baclofen effect as well. In contrast, baclofen inhibited approximately the same amount of current both before and after the increase caused by the dihydropyridine agonist BayK 8644 and did not modify the slow BayK-induced tail current. These results indicate (1) the modulation through GABAB receptors does not clearly discriminate between pharmacologically distinct calcium channels and (2) L-type calcium channels represent an heterogeneous population in these neurons.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1994

Novel K(+)-channel-blocking toxins from the venom of the scorpion Centruroides limpidus limpidus Karsch.

Two novel toxins were purified from the venom of the Mexican scorpion Centruroides limpidus limpidus, using an immunoassay based on antibodies raised against noxiustoxin (NTX), a known K(+)-channel-blocker-peptide. The primary structure of C. l. limpidus toxin 1 was obtained by Edman degradation and was shown to be composed of 38 amino acid residues, containing six half-cystines. The first 36 residues of C. l. limpidus toxin 2 were also determined. Both toxins are capable of displacing the binding of radio-labelled NTX to rat brain synaptosomes with high affinity (about 100 pM). These toxins are capable of inhibiting transient K(+)-currents (resembling IA-type currents), in cultured rat cerebellar granule cells. About 50% of the peak currents are reduced by application of a 1.5 microM solution of toxins 1 and 2 The K+ current reduction is partially reversible, under washing but not voltage-dependent. Comparison of the primary structure of C. l. limpidus toxin 1 with other known toxins shows 74% identity with margatoxin, 64% with NTX, 51% with kaliotoxin, 39% with iberiotoxin, 37% with charybdotoxin and Lq2, and 29% with leirutoxin 1. The only invariant amino acids in all these toxins are the six cysteines, a glycine in position 26 and two lysines at positions 28 and 33, respectively. The relevance of these differences in terms of possible structure-function relationships is discussed.

Amino Acid Sequence↗
PubMed1994

Lack of association between obsessive-compulsive disorder and the dopamine D3 receptor gene: some preliminary considerations.

Controversial results possibly suggesting an association between Tourette's Syndrome (TS) and excess of homozygosity at a Msc I polymorphism in the Dopamine D3 receptor (DRD3) gene have recently been reported. Since a relationship between Obsessive-Compulsive Disorder (OCD) and Tourette's Syndrome (TS) has been suggested, in this study we assessed the frequency of this 2-allele polymorphism in a sample of 97 OCD patients and in 97 control subjects. No statistically significant differences in allele or genotype frequencies were found. Thus this mutation in the coding sequence of the DRD3 gene is unlikely to confer susceptibility to OCD.

Adolescent↗
PubMed1994

The toxin helothermine affects potassium currents in newborn rat cerebellar granule cells.

Helothermine, a recently isolated toxin from the venom of the Mexican beaded lizard Heloderma horridum horridum was tested on K+ currents of newborn rat cerebellar granule cells. In whole-cell voltage-clamp experiments, cerebellar granule neurons exhibited at least two different K+ current components: a first transient component which is similar to an IA-type current, is characterized by fast activating and inactivating kinetics and blocked by 4-aminopyridine; a second component which is characterized by noninactivating kinetics, is blocked by tetraetylammonium ions and resembles the classical delayed-rectifier current. When added to the standard external solution at concentrations ranging between 0.1 and 2 microM, helothermine reduced the pharmacologically isolated IA-type current component in a voltage- and dose-dependent way, with a half-maximal inhibitory concentration (IC50) of 0.52 microM. A comparison between control and helothermine-modified peak transient currents shows a slowdown of activation and inactivation kinetics. The delayed-rectifier component inhibition was concentration dependent (IC50 = 0.86 microM) but not voltage dependent. No frequency- or use-dependent block was observed on both K+ current types. Perfusing the cells with control solution resulted in quite a complete current recovery. We conclude that helothermine acts with different affinities on two types of K+ current present in central nervous system neurons.

4-Aminopyridine↗
PubMed1994

Temperature dependence of multiple high voltage activated Ca2+ channels in chick sensory neurones.

The temperature dependence of high voltage activated Ca2+ channels has been investigated in cultured dorsal root ganglion neurones from chick embryos, using the cell-attached patch-clamp technique. The dihydropyridine sensitive L-type Ca2+ channel had a conductance of 23 pS, with 110 mM Ba2+ as charge carrier and in the presence of 3 microM Bay K 8644. When the temperature was raised from 15 to 30 degrees C, the unitary channel current amplitude increased, with Q10 value equal to 1.4. The rising phase of the averaged single-channel current became faster, with Q10 value 2.7, whereas the decay phase showed a lower temperature sensitivity. Channel open probability decreased according to an exponential distribution of open and closed times. A second type of Ca2+ channel was identified, which was DHP-insensitive and had a lower conductance with a mean value equal to 13 pS. For the current amplitude, the Q10 value was 1.3. Both activation and inactivation kinetics were strongly accelerated by an increase in temperature. The corresponding time constants gave Q10 values equal to 5.9 for activation, and 2.0 for inactivation. Peak channel open probability was highly sensitive to a change in temperature, with a Q10 value of 1.6. Finally, in omega-conotoxin GVIA pre-treated neurones, a non-inactivating DHP-insensitive Ca2+ channel with the lowest unitary conductance (10 pS) and a much lower temperature dependence was recorded. Single-channel current was increased by heating, with Q10 value 1.3, whereas the channel kinetics were almost unaffected by temperature.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1994

Isolation of a toxin from Centruroides infamatus infamatus Koch scorpion venom that modifies Na+ permeability on chick dorsal root ganglion cells.

A novel toxin was isolated and characterized from the venom of the Mexican scorpion Centruroides infamatus infamatus. It has an apparent mol. wt of 7600, compatible with the presence of 66 amino acid residues per molecule. The N-terminal amino acid sequence was determined (up to residue 48) and showed approximately 95% similarity with toxins from other Mexican scorpions of the gnus Centruroides. Experiments conducted with chick dorsal root ganglion cells showed that toxin 1 is a Na+ channel effector, causing a decrease in the peak Na+ permeability, similar to decreases observed for typical beta-scorpion toxins.

Amino Acid Sequence↗
PubMed1994

Bone density and mineral metabolism in thyroidectomized patients treated with long-term L-thyroxine.

1. A decreased bone mass has been reported in patients with endogenous hyperthyroidism, but the effect on bone density and mineral metabolism of thyroxine administration in thyroidectomized patients is still controversial. To further contribute to this debate, we studied 25 women thyroidectomized for thyroid cancer on long-term treatment with thyroid-stimulating hormone-suppressive doses of L-thyroxine. Twenty-one sex- and age-matched normal subjects were also studied as a control group. 2. The bone density of the spine and serum calcitonin, calcitriol and parathyroid hormone concentrations were not different when the whole patient group was compared with the control subjects, nor when the patients and control subjects were compared according to their menopausal status. However, post-menopausal thyroidectomized patients showed significantly lower bone mass (P < 0.001) than premenopausal patients. 3. L-Thyroxine-treated patients showed significantly higher levels of bone alkaline phosphatase and urine hydroxyproline excretion than control subjects (P < 0.003 and P < 0.001, respectively). These differences were still present when patients and control subjects were analysed according to their menopausal status. However, bone alkaline phosphatase was significantly higher in postmenopausal than in premenopausal women only in L-thyroxine-treated patients (P < 0.05). In postmenopausal L-thyroxine-treated patients a negative correlation between time since menopause and bone mass (P < 0.05) and a positive correlation between bone alkaline phosphatase and hydroxyproline excretion (P < 0.03) were also found.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Distribution of the MscI polymorphism of the dopamine D3 receptor in an Italian psychotic population.

The finding of contrasting results regarding an association between schizophrenia and the MscI polymorphism site in the dopamine D3 receptor gene prompted us to study the distribution of this polymorphism in an Italian sample of 52 patients suffering from delusional disorder, 85 schizophrenic patients and 78 control subjects. No significant differences in genotype, allele and homozygosity frequencies between schizophrenics and controls were found, while a significant, albeit modest, association was discovered between delusional disorder and both the 1 allele and the 1-1 genotype. This suggests a contribution of this gene to the liability to develop delusional disorder.

Adult↗
PubMed1994

Extracellular pancuronium affects sodium current in chick embryo sensory neurones.

1. The action of pancuronium on transmembrane sodium conductance was investigated in dorsal root ganglion neurones of chick embryos. The Na+ current was measured by use of the patch-clamp technique in whole-cell configuration. 2. Externally perfused pancuronium (50 microM to 1 mM) reversibly inhibited the current by a fast mechanism of action. Inhibition was concentration-dependent (with a half-effective dose of 170 microM) but not voltage-dependent. 3. The activation and inactivation kinetics of the Na+ current were estimated in pancuronium and in control solution by fitting experimental data with a Hodgkin-Huxley theoretical model. 4. The activation time constant tau m, at negative membrane voltages, was larger in the presence of pancuronium than in the control. In contrast, the inactivation time constant tau h was smaller during drug perfusion at membrane voltages < -10 mV. The steady-state inactivation h infinity was not affected by pancuronium. 5. These results suggest that pancuronium may reduce the sodium current by interacting with the sodium channels in both the resting and open states.

Animals↗
PubMed1994

A molecular investigation suggests no relationship between obsessive-compulsive disorder and the dopamine D2 receptor.

Some studies suggest a relationship between obsessive-compulsive disorder (OCD) and Gilles de la Tourette's syndrome. The pathophysiology of the latter may involve the dopamine system. We screened three important exons of the dopamine D2 receptor (DRD2) gene for mutations in a group of OCD patients with or without tics. No structural changes were found, suggesting no relationship between DRD2 and OCD. Moreover, the frequency of the polymorphism in exon 6 was different from that found in schizophrenics.

Adolescent↗
PubMed1994

The general anesthetic propofol inhibits transmembrane calcium current in chick sensory neurons.

The action of propofol on voltage-gated calcium channels was investigated in cultured dorsal root ganglion neurons from chick embryos. The Ca2+ current was measured by using the patch-clamp technique in whole cell configuration. Low-voltage-activated (LVA) and high-voltage-activated (HVA) Ca2+ currents were selected by means of appropriate stimulation protocols. Propofol (0.3 mM) inhibited the LVA T-type current by 80% (P < 0.001). The same concentration of propofol reduced the HVA Ca2+ current with a high variability (10%-75%). The inactivation time constant of the HVA current was also shortened to 50% by propofol. omega-Conotoxin and nifedipine were used to discriminate between the HVA N- and L-type current components. Only the L-type component was strongly depressed (75%) by propofol (P < 0.001); different effects on the HVA current might, therefore, reflect different percentages of L- and N-type channels in neurons. We conclude that propofol inhibits the T-type and L-type components of the Ca2+ current. This inhibition may play a role in the cardiovascular side effects clinically observed.

Animals↗