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Biomedical subjects

A Lazzaro

Publications and source records attributed to A Lazzaro.

35 records · Page 2Linked to original sources

Monosialoganglioside GM1 reduces NMDA neurotoxicity in neonatal rat brain.

Monosialoganglioside GM1 prevents excitatory amino acid (EAA)-related neuronal death in cultured central nervous system (CNS) neurons and reduces the severity of acute brain damage in different experimental models of cerebral ischemia. Using a model of brain damage induced by intracerebroventricular administration of N-methyl-D-aspartate (NMDA) in neonate rats, we evaluated whether GM1 is capable of exerting antiexcitotoxic effects following its systemic administration in vivo. Newborn rats subjected to brain damage by NMDA and contemporaneously treated subcutaneously with GM1 showed significantly reduced (i) loss in hemispheric weight, (ii) loss in tissue choline acetyltransferase activity, and (iii) morphological damage in various brain areas. These results indicate that systemic GM1 treatment is efficacious in reducing EAA-related neuronal damage in vivo and suggest that such a phenomenon may underlie its capability to ameliorate neurological outcome following cerebral ischemia.

Animals↗

Effects of monosialoganglioside GM1 in experimental models of ischemic brain damage.

Systemic administration of monosialoganglioside GM1 is efficacious in reducing excitatory amino acid (EAA)-related neurotoxicity in vivo following intracerebroventricular injection of N-methyl-D-aspartate (NMDA) in 7-day-old rats. Five days later, NMDA-treated animals showed extensive brain damage which was accompanied by significant decreases in brain weight, choline acetyltransferase activity and 3H-ouabain binding. All these neurotoxic effects were significantly reduced with ganglioside treatment. Since excessive activation of EAAS is implicated in hypoxic-ischemic brain damage, these results favor the hypothesis that a similar effect is involved in the ability of ganglioside to ameliorate outcome following cerebral ischemia.

Animals↗

Protective effects of a monosialoganglioside derivative following transitory forebrain ischemia in rats.

We evaluated the effects of treatment with the inner ester derivative of the monosialoganglioside GM1 on cortical electroencephalographic activity and hippocampal CA1 morphology after transitory, near-complete cerebral ischemia in rats. Ischemia was induced by the four-vessel occlusion method, and we studied only the 58 rats that showed flattening of the cortical electroencephalogram for the entire 30 minutes of occlusion. The ganglioside (n = 30) or saline (n = 28) was administered intravenously immediately after release of the carotid clips and then intramuscularly for 21 days of observation. Cortical electroencephalographic activity was monitored throughout the experiment. After 21 days of recirculation we assessed hippocampal CA1 damage by light microscopy. The results indicate that treatment with the ganglioside reduces postischemic secondary damage to the cortical circuitry (as indicated by significantly higher cortical electroencephalographic activity late after reperfusion) and limits neuronal loss in the CA1 region. Our results lend support to the possible therapeutic use of ganglioside in human pathologic conditions associated with cerebrovascular insufficiencies.

Animals↗

Monosialoganglioside effects following cerebral ischemia: relationship with anti-neuronotoxic and pro-neuronotrophic effects.

Increasing evidence is available indicating that systemically administered GM1 is able to provide for functional recovery in different experimental models of CNS injury, including cerebral ischemia. Current evidence indicates that the GM1 effects are associated, in the acute phase, with attenuation of secondary neuronal damage due to its capability to antagonize excitatory amino acid-related neurotoxicity in vivo as in vitro. Furthermore, the ganglioside is able to facilitate occurrence of long-term reparative processes, an effect most likely reflecting the potentiation of the action of neuronotrophic factors. This bifaceted action of GM1 makes the ganglioside ideally suited for clinical treatment of patients afflicted by cerebrovascular insufficiencies.

Animals↗

Hypoxic-ischemic damage and the neuroprotective effects of GM1 ganglioside.

In vitro studies have shown that monosialoganglioside GM1 reduces excitatory amino acid-related neurotoxicity by limiting the downstream consequences of abusive excitatory amino acid receptor stimulation. Systemic administration of GM1 appears to be efficacious in reducing acute neuronal damage and in facilitating medium- and long-term functional recovery after brain injury. We propose that GM1 protective effects in the acute injury phase results from attenuation of excitotoxicity, whereas the functional recovery seen at longer term could reflect GM1 potentiation of neuronotrophic factors. The potential therapeutic efficacy of GM1 administration in humans is suggested by clinical studies demonstrating improved neurologic outcome in stroke patients.

Amino Acids↗

[Prevention of recurrent respiratory infections in adults].

The authors compared the results obtained by using antibiotic therapy, vaccine, thymomodulin (a calf thymus acid lysate) and association of vaccine-thymomodulin in order to prevent acute infectious episodes in a group of 85 patients suffering with recurrent respiratory infections. The use of thymomodulin, alone and in association with vaccine, at the dose of 120 mg/die for 20 days/month during the period of observation (4 months), determined a higher reduction, (p less than 0.001) if compared with the other treatments, of the number and the duration of infectious episodes and moreover of the antibiotics' intake. Also the respiratory symptoms, and in particular the fits of coughing, showed an improvement. The pulmonary function indices and the laboratory parameters were unchanged in all groups studied.

Adult↗

Palliative and therapeutic activity of IL-2 immunotherapy in unresectable malignant pleural mesothelioma with pleural effusion: Results of a phase II study on 31 consecutive patients.

Malignant pleural mesothelioma is often unresectable at diagnosis, is refractory to cytotoxic agents and is frequently complicated by pleural effusion. The expected survival range for patients with or without involvement of visceral pleura is respectively 1-9 and 9-12 months; mesothelioma-related pleural effusion severely impairs the patients' quality of life and easily relapses after conservative treatments. Intrapleural administration of IL-2 is reported to be effective both in tumor-associated malignant pleurisy and on primary mesothelioma, whereas few data exist about IL-2 systemic administration. In order to assess the palliative and therapeutic activity of IL-2 in unresectable pleural malignant mesothelioma with pleural effusion, we performed a phase II study on 31 consecutive patients (M/F 16/15; median age 61 years, range 40-84; PS ECOG 0 n=7; ECOG 1 n=15; ECOG 2 n=9; stage IA n=13; IB n=9; II n=7; IV=2) who received first-line therapy with intrapleural repeated instillation of 9000000 I.U. IL-2 twice/weekly for 4 weeks, after needle thoracenthesis. In nonprogressing patients, 3000000 I.U. IL-2 were subcutaneously administered thrice weekly for up to 6 months. Toxicity (WHO criteria) with intrapleural IL-2 consisted of grade 3 fever in 6/31 (19%) patients and of cardiac toxicity (failure) grade 3 in one patient (3%); toxicity during subcutaneous treatment was mild to moderate, mainly a flu-like syndrome. In 28/31 (90%) of patients there was no further or minimal (asymptomatic) pleural fluid collection (according to Paladine criteria); pleurisy relapsed only in 1/28 patients after 19 months. Tumor objective response (WHO criteria), evaluated by CT, occurred in seven patients (one CR and six PR; ORR 22%); ten patients achieved SD and 14 patients progressed. Median overall survival was 15 months (range 5-39) in all patients. IL-2 intrapleural administration followed by low-dose IL-2 subcutaneously in pleurisy-complicated malignant mesothelioma is feasible and active both in palliation of pleural effusion and on primary tumor, with manageable toxicity. The overall survival observed in nonprogressing patients warrants further randomized studies with IL-2 aimed to the patient outcome.

Adult↗

Detection of gunshot residues on cadaveric skin using sodium rhodizonate and a counterstain.

We report a staining method for cadaveric tissue using sodium rhodizonate as a skin marker for gunshot residues and a counterstain for the surrounding connective tissue. We studied six well preserved subjects who had died of close range gunshot injury. Skin fragments were removed from the bullet entrance hole including both the disrupted area and adjacent macroscopically intact tissue. Because microscopic examination of postmortem material is difficult after histomorphologic alterations already have occurred as a consequence of postmortem tissue changes, it is necessary to use a staining method that, while detecting gunshot residues, can also make skin cell constituents recognizable from both qualitative and quantitative perspectives. Triphenylmethane dyes (acid fuchsin, aniline blue WS, light green SF yellowish, brilliant green and ethyl green) have proven appropriate for the purpose.

Cadaver↗

[Superselective monolateral subarachnoid anesthesia in saphenectomy by long stripping].

The authors describe a recent anaesthetic technique: the subarachnoid monolateral superselective anaesthesia. Currently they use it in the surgical operation of "long stripping" saphenectomy. They argue on the utility of codifying this technique for its numberless advantages and discuss on the opportunity to perform day-hospital saphenectomy.

Anesthesia, Spinal↗

[Antiphospholipid antibody syndrome as a possible cause of paresis in a child].

The Authors report on the case of a 4-year-old boy, admitted to the pediatric department for left hemiplegia. CT scan of the brain was negative on the day of admission but, on the following day, showed 3 small hypodense focal lesions in the posterior branch of the internal capsule, in the knee of the internal capsule and in the posterior parietal region of the cortex. The acute phase almost completely resolved in 10 days. Twenty days after presentation, cerebral angiography showed a thrombosis of an anterior, right perforating vessel, together with the hypoplasia of the horizontal portion of the cerebral anterior artery. The determination of anti-cardiolipin antibodies, even though performed far from the acute phase of the disease, showed a low IgG positivity. Two months after the onset the neurological symptoms completely resolved. In the presence of hypoplasia, narrowing and other lesions of cerebral vessel, it is possible to hypotesize that the occurrence of thrombotic fenomen, ascribable to anti-phaspholipid antibodies, is responsible for the neurological symptoms. The association of thrombosis and anti-phospholipid antibodies suggest that the assessment of anti-phospholipid antibodies should be routinely performed in the presence of thrombotic phenomena.

Antibodies, Antiphospholipid↗