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Biomedical subjects

C Forni

Publications and source records attributed to C Forni.

At least 55 records · Page 3Linked to original sources
PubMed1996

[Neoadjuvant chemotherapy in malignant fibrous histiocytoma of the limbs: 10 years of experience (1983-1992) at the Rizzoli Orthopedic Institute].

During the period September 1983 to December 1991, 47 patients with nonmetastatic malignant fibrous histiocytoma (MFH) of the limbs were treated using 3 different protocols of neoadjuvant chemotherapy activated at successive intervals. Surgery consisted of limb salvage in 41 cases and amputation in 6. After a mean follow-up of 6.5 years 33 patients (70%) had been continuously disease-free and 14 had undergone relapses. In the latter group the first sign of recurrence was metastasis in 12 cases and local recurrence in 2 cases. These results are distinctly better than those obtained in 20 patients treated during the same period using surgery alone (24% of disease-free survival and 30% local recurrence), and compared to those obtained in an earlier study in which surgery was associated with postoperative chemotherapy alone (59% of disease-free survival and 25% of local recidivation). The authors conclude that, as already observed in the case of osteosarcoma, neoadjuvant chemotherapy can significantly improve prognosis even in patients with bone MFH localised in the limbs. Moreover, given that, contrary to adjuvant chemotherapy, associated chemotherapy is effective not only in controlling the microscopic disease but also reducing the incidence of local recurrence, it enables amputation to be avoided in the majority of patients.

Adult↗
PubMed1995

Effects of ionotropic excitatory amino acid receptor antagonists on glutamate transport and transport-mediated changes in extracellular excitatory amino acids in the rat striatum.

This study examined the effects of intrastriatal administration of ionotropic excitatory amino acid receptor antagonists on biochemical markers of excitatory amino acid transmission in the rat striatum. High-affinity glutamate uptake was measured ex vivo on striatal homogenates 15 min after the local administration of either 6,7-dinitroquinoxaline-2,3-dione (DNQX), a non-NMDA receptor antagonist, or DL-2-amino-5-phosphonopentanoic acid (AP5), a competitive NMDA antagonist, at various doses (10-500 pmol injected). DNQX induced a dose-dependent increase in glutamate uptake rate, related to an increase in the Vmax of the transport process, whereas no significant change in glutamate uptake was detected after AP5 administration. Similar results were obtained from animals subjected to excitotoxic lesion of striatal neurons by kainate administration 15 days before the injection of DNQX or AP5. In a parallel series of experiments using in vivo microdialysis we showed that DNQX (10(-5) M) in the dialysis probe diminished by approximately 30-40% the increases in the concentrations of glutamate and aspartate elicited by L-trans-pyrrolidine-2,4-dicarboxylic acid (1 mM). These data suggest that presynaptic glutamate transmission in the rat striatum may undergo facilitatory autoregulatory processes involving ionotropic non-NMDA receptors and highlight the view that transporters for glutamate may be potent regulatory sites for glutamatergic transmission.

2-Amino-5-phosphonovalerate↗
PubMed1995

Effects of high pressures of various gas mixtures on rat striatal dopamine detected in vivo by voltammetry.

This work was performed to study the effect of pressure of various gas breathing mixtures on dopaminergic activity in the striatum by in vivo differential pulse voltammetry using carbon multifiber electrodes chronically implanted in 23 freely moving rats. Compression (0.5 bar/min) in a helium-oxygen mixture induced an increase in striatal extracellular dopamine (DA) beginning at 10-20 bars and reaching 32% above precompression levels when arriving at 90 bars (n = 9). To demonstrate that this increase is dopaminergic, nine rats with right nigrostriatal pathway 6-hydroxydopamine lesions were compressed in the same conditions. In this case, the increase in DA did not occur in the right caudate nucleus but was recorded in the intact left caudate nucleus. To study the effects on DA increase of narcotic gases, which are known to reduce some high-pressure nervous syndrome symptoms, eight and six rats were compressed in helium-nitrogen-oxygen and hydrogen-helium-oxygen mixtures, respectively. They produced similar changes in striatal DA level in the same pressure range (23 and 20% increase, respectively, at the end of the compression). Consequently, the increase in striatal DA seems independent of the nature of the breathing mixture and seems related to the increase of pressure. The origin of this increase could be a pressure effect at the pre- or postsynaptic level.

Animals↗
PubMed1995

[Neoadjuvant treatment of Ewing's sarcoma: results obtained in 122 patients treated with a 6-drug chemotherapeutic protocol (vincristine, adriamycin, cyclophosphamide, dactinomycin, ifosfamide and etoposide)].

From January 1988 to October 1991, one hundred and twelve patients with non metastatic Ewing's sarcoma of bone were treated with a 6 drugs neoadjuvant chemotherapy protocol (IOR/Ew2) in which, to the four drugs usually used in the treatment of this tumor (vincristine, adriamycin, cyclophosphamide and dactinomycin), Ifosfamide and VP-16 were added. The local treatment consisted of radiation therapy in 52 cases, a surgical treatment was performed in 27 cases and in the remaining 33 cases both the previous treatments were used. At a mean follow-up of 4.5 years (3-6.5), 62 patients (55.3%) remained continuously free of disease and 50 relapsed: 41 with metastases, 8 with mestastases and local recurrence and 1 with local recurrence alone. These results do not differ from the ones obtained in our Institution in 98 patients treated between 1983 and 1988 with a neoadjuvant protocol (IOR/Ew1) in which only VCR, ADM, CTX and actD were used (3 year CDFS: IOR/Ew2 = 60.7%-IOR/Ew1 = 55.1%). In IOR/Ew2 a higher DFS rate was observed in the patients with tumor located in the axile bones in comparison with that obtained in the previous study (IOR/Ew2 = 48.6%, IOR Ew1 = 25.6%). Despite the fact that these results came from a not-randomized study, the authors conclude that the addition of Ifosfamide and VP-16 to the four drugs standard regimen do not improve the outcome of patients with Ewing's sarcoma of bone, with the possible exception of the patients with tumor located in the axile bones. This data should be confirmed in further and larger studies.

Adolescent↗
PubMed1994

Regulation of dopamine levels in intrastriatal grafts of fetal mesencephalic cell suspension: an in vivo voltammetric approach.

An in vivo voltammetric technique was used to monitor dopamine (DA) release in the 6-hydroxydopamine (6-OHDA)-lesioned rat striatum reinnervated by grafts of ventral mesencephalon containing DA neurons. Extracellular levels of DA were measured during the administration of D1 or D2 DA receptor antagonists. In addition, changes in DA levels induced by agonists and antagonists of excitatory amino acid (EAA) receptors were studied to verify the possible existence of a host glutamatergic control on the grafted DA cells in the 'transplanted' rats. Two months after the grafts were performed, the voltammetric signal measured under baseline conditions in the grafted striata was found to be almost similar to that recorded on the contralateral control side. Likewise, in another group of transplanted rats, the turnover of the amine, as expressed by the DO-PAC/DA tissue level ratio, was found to have become "normalized" after grafting, compared with the lesion-only group. The increase in the voltammetric signal observed after administering the D2 antagonist sulpiride (100 mg/kg i.p.) was lower in the grafted striata than on the contralateral side, however. This suggests that some D2 autoreceptor subsensitivity may have helped to maintain the baseline level of dopaminergic transmission. Adaptive processes of this kind might compensate for the partial DA reinnervation of the host striatum found to occur on the basis of the tyrosine hydroxylase immunostaining patterns. After administration of either the D1 antagonist SCH 23390 (0.1 mg/kg s.c.), or injection of EAA receptor agonists--1-glutamate, quisqualate and N-methyl-D-aspartate (all 10 nmol i.c.v.)--and antagonists--amino-phosphono-valeric acid (10 nmol i.c.v.) and dizocilpine (MK801, 0.2 mg/kg i.p.)--no significant differences between the two striata were detected in the voltammetric signals. These results suggest that, in the grafted rats, neurons belonging to the host population, such as the striatal cells bearing D1 receptors or the corticostriatal afferents presumed to contain glutamate, might modulate the DA levels, as was found to occur under normal conditions.

2-Amino-5-phosphonovalerate↗
PubMed1992

Intracerebroventricular administration of neuropeptide Y affects parameters of dopamine, glutamate and GABA activities in the rat striatum.

The effects of intracerebroventricular (ICV) injection of neuropeptide Y (NPY) on parameters of dopamine (DA), glutamate (Glu) and gamma-aminobutyric acid (GABA) activities were investigated in the rat striatum. NPY (1.17-4.70 nmol) induced a dose-dependent increase in the striatal endogenous DA release monitored in freely moving animals by means of a voltammetric method. Maximal increase was observed about one hour after the peptide injection. This result is consistent with the hypothesis that NPY may influence striatal DA turnover in a facilitatory manner by activating DA release. DA, DOPAC, Glu and GABA endogenous contents as well as 3H-Glu and 3H-GABA synaptosomal high affinity uptakes were examined one hour after NPY ICV administration at the same dose range in chloral hydrate-anesthetized animals. Depending on the NPY dose injected, opposite changes in Glu uptake were observed, suggesting that NPY has a bimodal influence on glutamatergic transmission. The Glu uptake rate increased markedly at 1.17 nmol NPY and decreased at 4.70 nmol, which may reflect an activation and an inhibition of the striatal Glu transmission, respectively. In parallel, the GABA uptake was found to decrease slightly at the higher doses of NPY tested, whereas no significant alteration of the striatal concentrations of either DA, DOPAC, Glu or GABA was observed. These results indicate that NPY may be involved in regulating the activity of nigral dopaminergic and cortical glutamatergic afferent pathways and that of intrinsic GABA neurons in the rat striatum.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Indole-3-acetic acid (IAA) production by Arthrobacter species isolated from Azolla.

Arthrobacter species, isolated from the leaf cavities and the microsporocarps of the aquatic fern species Azolla pinnata and Azolla filiculoides, produced indole-3-acetic acid (IAA) in culture when the precursor tryptophan was added to the medium. No IAA production was detected in the absence of tryptophan. Maximum IAA formation was obtained in the first 2 d of incubation. Part of the tryptophan was transformed to N alpha-acetyl-L-tryptophan.

Arthrobacter↗
PubMed1989

Time-course of recovery of dopamine neuron activity during reinnervation of the denervated striatum by fetal mesencephalic grafts as assessed by in vivo voltammetry.

In vivo voltammetry was used to monitor dopamine (DA) neuron activity during the course of reinnervation of the initially denervated caudate-putamen by grafted mesencephalic neurons. Fetal DA neurons were implanted as a cell suspension into the depth of the caudate-putamen in adult 6-hydroxy-dopamine-lesioned recipient rats. Recordings were performed over a period of 2.5-4 months, starting within a week after transplantation, using chronically implanted surface-treated multifiber carbon electrodes. The voltammetric method used in this study has generated considerable discussion centred on the ability of the multifiber electrodes to measure DA alone in vivo, but the results of previous studies have led to the conclusion that changes in the voltammetric signal most probably reflect dopaminergic terminal activity. It seems therefore possible to follow the time-course of changes in the voltammetric signal amplitude during the process of dopaminergic reinnervation of the host striatum from the grafts. A 6-hydroxydopamine lesion of the mesostriatal dopamine pathway caused a substantial (greater than 80%) reduction of the voltammetric signal within 8-10 days, and the low residual signal remained essentially unchanged for time periods up to at least 5 months in the non-grafted control rats. In 7 of 11 rats with DA-rich grafts there was a recovery of the signal amplitude to levels within, or close to, the range recorded from the striatum of normal intact rats. The increase was observed 6-8 weeks after grafting in the rats which had received the largest transplants, and at about 13-14 weeks after grafting in the rats which had received the smallest ones. The recovery of the signal amplitude, from baseline to maximal response, was quite rapid and typically developed between two or three recording sessions, i.e. over a period of one to two weeks. In contrast to the intact striatum, the recovered signal in the graft-reinnervated striata showed a progressive decline within one hour of sampling time at high sampling frequencies (1 per min to 1 per 3 min). Grafted striata also showed a larger response to systemically administered amphetamine than did intact striata. Since the changes in the voltammetric signal recorded with the multifiber electrode mainly reflect dopaminergic terminal activity, the results provide evidence that the intrastriatal DA-rich grafts are spontaneously active, and that the grafted DA neurons can restore DA neuro-transmission in the reinnervated part of the host caudate-putamen to levels which are within the normal range.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1989

Effect of helium-oxygen pressure on dopamine detected in vivo in the striatum of hamsters.

Free-moving hamsters chronically implanted in the striatum with carbon multifiber electrodes selective to dopamine were compressed in a helium-oxygen breathing mixture to 81 bars. Under these conditions, there was an increase in the electrochemical responses recorded from the carbon electrode by differential pulse voltammetry, which occurred during the compression and disappeared when the animals returned to the surface. This change was related to an increase in extracellular dopamine levels induced by the increase in pressure of the helium-oxygen mixture.

Animals↗
PubMed1987

In vitro and in vivo characterization of the properties of a multifiber carbon electrode allowing long-term electrochemical detection of dopamine in freely moving animals.

We recently developed a multifiber carbon electrode for voltammetric studies which shows an apparent selectivity for dopamine (DA) in vitro and which can be used over very long periods of time after implantation for in vivo recordings in the striatum of rodents. This series of experiments was undertaken to further characterize our voltammetric signal detected in the brain. Comparison of voltammetric signals obtained in vitro after electric pretreatment of the electrode in solutions of various oxidizable endogenous compounds at regularly increasing concentrations showed that the sensitivity of the electrode for DA is 10,000 times higher than for ascorbic acid (AA) and 1000 times higher than for 3,4-dihydroxyphenylacetic acid (DOPAC), two compounds which are detectable in vivo. Measurements of the DA signal in the presence of DOPAC or AA showed that interactions occurred between the oxidized forms of the various molecules. DOPAC decreased the DA sensitivity of the electrode, whereas a potentiation of the DA signal was observed with AA at high concentrations, showing the presence of an electro-catalytic effect. At lower AA concentrations a decreased DA sensitivity of the electrode was observed as in the case of DOPAC. The brain distribution of the in vivo voltammetric signal was studied in anesthetized hamsters, showing a regional specificity which was positively correlated to the dopaminergic innervation. In animals with chronically implanted electrodes, various pharmacological compounds known to interfere with DA metabolism or the activity of dopaminergic neurons were injected. alpha-Methyl-p-tyrosine and reserpine were shown to induce a decrease in signal amplitude. Similar data were obtained with gamma-hydroxybutyrate and gamma-butyrolactone, which have been previously shown to decrease the dopaminergic neuronal firing rate. An increase in the striatal response was on the contrary obtained in anesthetized rats following electrical stimulation of the medial forebrain bundle containing dopaminergic fibers. Drugs acting on dopaminergic receptors such as neuroleptics and apomorphine, were shown to increase and diminish the striatal signal, respectively. Finally, AA peripheral administration was found to reduce the striatal signal amplitude. These data reinforce the idea that DA mainly contributes to our in vivo brain voltammetric response, although extracellular DOPAC or AA levels may influence this response. Variations in the striatal voltammetric signal recorded in vivo in freely moving animals over very long periods of time after electrode implantation may thus reflect variations in the activity of the nigrostriatal dopaminergic neurons.

Animals↗
PubMed1986

Gamma-aminobutyric acid and the high pressure neurological syndrome.

Sodium valproate, nipecotic acid, diaminobutyric acid (DABA) and beta-alanine are drugs which enhance transmission mediated by gamma-aminobutyric acid (GABA) by a variety of mechanisms. They were used to study the role of GABA in the high pressure neurological syndrome (HPNS) in the rat. Sodium valproate, nipecotic acid and DABA reduced the increase in slow waves seen in the electroencephalogram (EEG) of control rats at pressures above 10-20 ATA; however, only sodium valproate had a beneficial effect on the behavioural signs of the high pressure neurological syndrome (tremor, myoclonus and convulsions). Sodium valproate is also thought to decrease neurotransmission produced by excitatory amino acids; thus, these results suggest that GABA is not one of the major neurotransmitters involved in all aspects of the high pressure neurological syndrome and that changes in excitatory neurotransmission may affect the behavioural signs.

Alanine↗
PubMed1985

An improved method for stainless steel wire mesh cranioplasty.

A method for stainless steel wire mesh cranioplasty is described. The method has proved simple and quick. Cosmetic results have been very good and no complications have been observed so far. This method seems particularly suitable in very large skull defects. It seems to reduce the incidence of the major complications of the wire mesh cranioplasties, viz. lifting of the margins, depression of the prosthetic vault and electrolytic interference with the circulating fluids.

Alloys↗
PubMed1984

Electrochemical detection of dopamine release in the striatum of freely moving hamsters.

It was proposed to characterize the electrochemical signal recorded with a multifibre carbon electrode chronically implanted in the striatum of freely moving hamsters when the electrode potential was increased from-175 mV to +325 mV. Both in vitro calibration in standard solutions of oxidative molecules and in vivo pharmacological studies were used for this purpose. Results show that after an appropriate electrochemical treatment of the electrode in vitro the oxidation of dopamine (DA) produces a characteristic signal, whereas standard solutions of DOPAC and ascorbic acid produce no response. The electrochemical response recorded in vivo from the striatum of freely moving hamsters when the potential of the electrode is raised from-175 mV to +325 mV seems to correspond to the in vitro response to DA. This in vivo response diminished considerably following the destruction of the nigro-striatal dopaminergic neurones by means of an intranigral injection of 6-hydroxydopamine, while the striatal levels of ascorbic acid are not affected by the lesion. The administration of both amphetamine (3 mg/kg, i.p.) and the inhibitor of monoamine oxidases, pargyline (90 mg/kg i.p.), enhances the amplitude of the electrochemical signal. These results suggest that the electrochemical response recorded with our device in the striatum of the freely moving hamster corresponds to the oxidation of DA and not that of its metabolite DOPAC. Ascorbic acid is also very unlikely to contribute to the signal since the dopaminergic lesion does not alter the striatal level of this acid and since pargyline increases the amplitude of the signal.

Animals↗
PubMed1984

HPNS of baboons during helium-nitrogen-oxygen slow exponential compressions.

From the results obtained with the experimental series CORASIN (fast compression with He-N2-O2), a method of compression has been developed for the baboon (Papio papio) to dive deeper than 600 m. This method utilizes an exponential compression profile with stages of 40 min every 100 m and with the introduction of N2 before each stage from 200 m onward to maintain a concentration of 5.5%. Between 0 and 800 m, this procedure did not produce myoclonus or epileptic seizures; tremor appeared beyond 400 m (578 +/- 109 m) but remained slight. If N2 was not introduced, the tremor appeared earlier (266 +/- 52 m) and became severe; between 600 and 800 m, muscular hypertonus, myoclonus, and muscular cramps occurred. The modifications of the electroencephalogram were slight; the increase in slow activity did not exceed 300% with or without N2. Beyond 800 m, the compression procedure with N2 injections revealed new phenomena. There was a general depression of EEG activity starting at 800 m; from 1,000 m and deeper, there were periods of motor disturbances (hypertonus, spasms, and shaking), palpebral clonus, and eye movements associated with peak EEG activities localized in the posterior region of the skull that sometimes evolved toward an epileptic seizure localized in this region. These symptoms differed from the classical description of high-pressure nervous syndrome, which comprises an increase in tremor followed by convulsions. These differences may perhaps be linked to our compression procedure using N2 injection, to the effect of the pressure itself, or to a combination of the two.

Animals↗