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Biomedical subjects

L Volpi

Publications and source records attributed to L Volpi.

34 records · Page 2Linked to original sources

Evidence of an adenosine-dependent mechanism in the hypotensive effect of L-arginine in man.

1. The hypothesis that endogenous adenosine could play a role in the haemodynamic response to L-arginine is investigated. 2. The study has been divided into two parts. The first part was a single blind, randomized, placebo-controlled study in which L-arginine i.v. infusion (0.07 mmol/kg per min) in five healthy volunteers caused a significant fall in systolic (-14.2%, from 129.0 +/- 8.2 to 110.6 +/- 8.5 mmHg; F = 62.89, P < 0.01), diastolic (-16%, from 80.0 +/- 7.9 to 67.2 +/- 7.0 mmHg; F = 18.97, P < 0.01) and mean (-15.5%, from 96.4 +/- 6.7 to 81.4 +/- 6.5 mmHg; F = 28.78, P < 0.01) arterial blood pressure, with a concomitant increase of plasma adenosine concentration (from 244.0 +/- 32.2 to 637.0 +/- 43.4 nmol/L; F = 79.3 P < 0.01). Maximal effects were obtained at the end of L-arginine infusion: haemodynamic parameters returned to basal values in about 30 min while adenosine concentrations normalized in about 15 min. Saline infusion had no effect on these parameters. 3. In the second study the effect of L-arginine i.v. infusion on arterial blood pressure, lower limb blood flow and plasma adenosine, before and after theophylline treatment (1000 mg/day for 3 days, p.o.) was examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

Epileptic negative myoclonus.

ENM is an etiologically heterogeneous disorder clinically evident as brief (less than 500 msec) lapses of tonic muscular contraction which seems to be related to lesions or dysfunction of different anatomofunctional levels of the CNS (Fig. 13). ENM can occur in heterogeneous epileptic disorders, ranging from benign syndromic conditions (such as BECTS) to focal static lesional epilepsy, as in neuronal migration disorders, and even to severe static or progressive myoclonic encephalopathies (PMEs). Neurophysiological studies in patients with ENM lead to the following conclusions: 1. A cortical origin of ENM is supported by EEG mapping and dipole analysis of spikes related to the ENM. In particular, our data suggest that the focal spike is a paroxysmal event involving, primarily or secondarily, the centroparietal and frontal "supplementary" motor areas. 2. A cortical inhibitory active mechanism for the genesis of ENM is supported by the occurrence of a decreased motor response to TMS, with preserved spinal excitability as demonstrated by the persistence of F waves. A "cortical motor outflow inhibition" related to spike-and-wave discharges was suggested by Gloor in his Lennox lecture (34). The cortical reflex negative myoclonus, described by Shibasaki et al. (16) in PME, is also consistent with a cortical active inhibitory mechanism. The spike associated with ENM raises new issues about the definition of "interictal" versus "ictal" EEG paroxysmal activity. A single spike on the EEG can be clinically silent (therefore, "interictal") or clinically evident as ENM (then viewed as "ictal"), depending on whether a given group of muscles is at rest or is showing tonic activity (see Fig. 4). These data, from a more general perspective, imply that the motor manifestation related to EEG paroxysmal events can depend not only on amplitude, topography, or intracortical distribution of seizure activity (35), but also on plasticity (36) and on the functional condition of the motor system (37). The variability of latency between the spike and the onset of the muscular inhibition (ranging from 15 to 50 msec, for the upper limbs), and the variability of duration of the ENM itself (from 50 to 400, or more, msec) indicate that ENM could be the result of inhibitory phenomena arising not only from a single cortical "inhibitory" area, but also from subcortical and pontine structures, as discussed by Mori et al. (this volume). The neurophysiological distinction between ENM and postmyoclonic periods of muscular suppression, mainly related to an EGG slow wave, as described by Lance and Adams (2) in the postanoxic action myoclonus is still a matter of discussion (38, 39). This is also the case for other movement disorders combining action myoclonus and epilepsy-as described in Ramsay Hunt syndrome (30), now better referred to as Unverricht-Lundborg syndrome (40) (Fig. 14). In these conditions, myoclonia and muscular silent periods are inconstantly associated with paroxysmal EEG discharges, suggesting a possible thalamocortical mechanism rather than a purely cortical one. In the most prolonged muscular inhibitions, both cortical and thalamocortical mechanisms might be implicated. Clearly, our knowledge of ENM is still very limited and gaining further insights into this complex phenomenon is a challenging problem.

Brain Mapping↗

Differential induction of the two early genes c-jun and c-fos in weakly and strongly metastatic murine lymphoma cell lines.

Induction of the 2 early-response genes c-jun and c-fos was investigated in the weakly metastatic T-lymphoma Eb line and the related strongly metastatic lymphomacrophage ESb line to find possible correlations with their different in vitro and in vivo phenotypes. The response of c-jun was elicited by the protein kinase-C activators TPA and A23187 in ESb but not in Eb cells. A much lower response of c-fos was also found in Eb than in ESb cells, in this case by means of serum and the cAMP elevator forskolin. However, both TPA and the calcium ionophore A23187 were similarly effective in inducing fos-mRNA in both cell lines. The uncoupling of c-jun and c-fos induction in Eb, but not in ESb cells, as well as the uncoupling of c-fos response to different stimulators, point to a differential activation of these 2 early-response genes by the main signal transduction pathways in the 2 cell types. The coordinate/uncoordinate availability of the fos/jun heterodimer may confer distinct regulatory patterns on different target genes in ESb/Eb cells. Activation of these genes may underlie the distinct differentiation phenotypes and in vivo behavior of Eb/ESb cells.

Animals↗

Pharmacokinetics of exogenous adenosine in man after infusion.

The plasma kinetics of adenosine was investigated in healthy volunteers after a 1 minute infusion of 2.5, 5 and 10 mg (38.79 and 148 micrograms.kg-1 respectively) and after infusion of 200 micrograms.kg-1 in 10 min followed by 400 micrograms.kg-1 in 10 min. As the dose in the 1 min infusion study was increased the mean CL of adenosine decreased (10.7, 4.70 and 4.14 l.min-1, respectively), its mean half-life increased (0.91, 1.24 and 1.86 min, respectively), and the mean volume of distribution did not show any clear trend (8-13 l). After the 20 minute infusion the plasma level of adenosine reached a peak value comparable to that observed after infusion of 5 mg in 1 min (about 0.5 micrograms.ml-1), but the mean clearance and half-life were significantly different (12.1 l.min-1 and 0.63 min respectively). In all the subjects the plasma concentration of adenosine had returned to the baseline value in 5-15 min after the end of the infusion.

Adenosine↗

Activation of c-fos and c-fes in metastatic lympho-macrophage hybrids.

The expression of proto-oncogenes involved in myelomonocytic differentiation was studied in 3 metastatic murine lympho-macrophage hybrids (ESb, EbF1, EbF2-C4) which display several antigenic and functional macrophage properties. Constitutive expressions of fos and fesmRNA, which were not detectable in the weakly metastatic parent lymphoma (Eb), was shown in all the proliferating hybrid lines. By contrast, c-myc and c-myc expressions were shared by the tumor parent and the hybrids. The c-fos transcripts observed in the hybrids were atypical in size, 2.3 kb, but standard 2.2-kb transcripts could be detected in serum-induced cells, even in the non-expressing Eb lymphoma. The kinetics of the induced fos mRNA was found to conform to the features reported in the literature for a large variety of cells. No structural alteration of the c-fos gene was detected by Southern analysis. PCR amplification of the 2.3- and 2.2-kb fos mRNA showed that they are identical in size in both the coding and the 3' untranscribed region. A longer poly A tail is thought to account for the additional 100 bp in the 2.3-kb fos mRNA, as both the 2.3- and 2.2-kb transcripts attain the same size following de-adenylation.

Animals↗

Pharmacodynamics of ticlopidine in man in relation to plasma and blood cell concentration.

In 6 normal volunteers given single oral doses of 250,500 and 1000 mg ticlopidine (T), the peak plasma level of unchanged drug was reached after about 2 h. There was no correlation between the plasma T level and its inhibitory effect on platelet function, expressed as % inhibition of ADP-induced aggregation. By means of HPLC and GC/MS significant concentrations of T were demonstrated in washed red cells, platelets and neutrophils, with a marked difference in the time course of the appearance of cell-associated drug. The time course of platelet-associated T very accurately fitted that of the antiaggregatory activity. After subacute oral administration (250 mg b.d. for 7 days), the maximum effect on platelet function was observed after 3 to 4 days, when a significant concentration of platelet-associated T had been reached. The pharmacological effect persisted as long as drug was detectable in platelet. An in vitro study strongly suggested that the antiaggregating effect was retained by treated washed platelets but not by treated plasma. It is suggested that the platelet compartment represents the pharmacological target of T via a specific uptake system.

Adult↗

Evidence of cell fragility caused by gene kil following lambda induction.

Escherichia coli cells carrying lambda cI857 prophage lyse 40 min after lambda thermoinduction; the lysis depends on the lambda genes Q, R, and S. If chloramphenicol (CAP) is added within 20 min after lambda cI857 induction, an early, unproductive lysis occurs. This lysis is independent of the genes int, rex, O, P, Q, and all late genes. Instead, early lysis depends upon the kil gene. The early lysis is under the positive control of lambda gene N and the negative control of gene cro. One or more events specifically connected with lambda induction appear to be necessary for the occurrence of early lysis, since early lysis cannot be observed after lambda infection. Induced lambda kil+ lysogens are more sensitive to osmotic shock than induced lambda kil- lysogens. CAP-induced early lysis can be prevented in a hypertonic medium. These results suggest that induction of lambda causes an osmotic fragility due to a damage of the cell envelope which requires repair; in the absence of protein synthesis the cell envelope is not repaired and cell lysis ensues.

Bacteriolysis↗

Action of levamisole on E-rosette forming cells and serum adenosine deaminase in Hodgkin's disease.

The interaction of levamisole and/or adenosine in vitro on E-rosette forming cells (RFC) of healthy subjects and on low RFC of patients affected with various diseases was investigated. Levamisole did not enhance normal RFC. The drug enhanced low RFC in some patients (responders) but not in others (non-responders). Adenosine inhibited normal and low RFC and this inhibition could be reversed by levamisole. Further, levamisole 150 mg 2 days a week was given to 12 Hodgkin's disease (HD) responders for 2 weeks, then 150 mg 1 day weekly for 2 1/2 months. After one week of treatment RFC increased and the enhancement could be maintained during the whole treatment period. Lastly levamisole in vitro and in vivo diminished serum adenosine deaminase activity in normal subjects and HD patients.

Adenosine↗

Complement in pemphigus vulgaris and other bullous dermatoses.

The behavior of the complement and of its components C4 and C3 has been studied in serum and in blister fluid both in patients with pemphigus vulgaris and other bullous dermatoses and in healthy subjects with experimentally induced blisters. The results are suggestive of local activation of the complement, in the blister fluid of patients with pemphigus vulgaris, pemphigus erythematosus and bullous pemphigoid according to the classical enzymatic sequence.

Beta-Globulins↗

Determination of plasma concentrations of cyclandelate and mandelic acid in patients with generalized atherosclerotic vasculopathy treated with oral cyclandelate.

Cyclandelate, a vasoactive substance consisting of the mandelic acid ester of 3,3,5-trimethylcyclohexanol, was administered to 10 patients with cerebrovascular and/or peripheral vascular disease. Blood specimens were collected at 1-6 h after oral administration of 1600 mg cyclandelate, and the ester and acid were extracted from plasma in acid medium using n-hexane/isopropyl alcohol. The concentrations were determined by a high-performance liquid chromatography isocratic system. The highest plasma cyclandelate concentrations were detected at the third hour, whereas plasma mandelic acid concentrations were still increasing 6 h after administration.

Administration, Oral↗