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Biomedical subjects

G Tredici

Publications and source records attributed to G Tredici.

At least 19 recordsLinked to original sources
PubMed2006

Mesenchymal stem cells cultured on a collagen scaffold: In vitro osteogenic differentiation.

OBJECTIVE: Management of periodontal defects has always been a challenge in clinical periodontics. Recently mesenchymal stem cells (MSC) have been proposed for tissue regeneration in periodontal disease and repair of large bone defects. Bone regeneration has to be supported by a scaffold which has to be biocompatible, biodegradable, and able to support cell growth and differentiation. The aim of this study was to evaluate osteogenic differentiation of MSC seeded on a collagen scaffold. DESIGN: MSC were obtained from adult rat bone marrow, expanded and cultured in plastic dishes or seeded in a collagen scaffold (Gingistat). MSC were induced towards osteogenic differentiation using osteogenic supplements. Cell differentiation and calcium deposits were evaluated by immunoblotting, immunohistochemistry, histochemical techniques, enzymatic activity assay, and SEM-EDX analysis. Biomaterial in vitro degradation was evaluated by measuring mass reduction after incubation in culture medium. RESULTS: Rat MSC osteogenic differentiation was demonstrated by osteopontin and osteocalcin expression and an increase in alkaline phosphatase activity. MSC were distributed homogeneously in the collagen scaffold. Nodular aggregates and alizarin red stained calcium deposits were observed in MSC induced towards osteogenic differentiation cultured in dishes or seeded in the collagen scaffold. SEM-EDX analysis demonstrated that calcium co-localized with phosphorous. The biomaterial in vitro degraded in 4-5 weeks. CONCLUSIONS: MSC from bone marrow differentiate towards osteogenic lineage, representing a suitable cell source for bone formation in periodontal regeneration. Gingistat collagen scaffold supports MSC distribution and differentiation, but its short degradation time may be a limitation for a future application in bone tissue regeneration.

Alkaline Phosphatase↗
PubMed2005

APOE influences vasospasm and cognition of noncomatose patients with subarachnoid hemorrhage.

OBJECTIVE: To determine the influence of the APOE genotype on functional and cognitive outcome and on the incidence and prognosis of clinical vasospasm (delayed ischemic neurologic deficit [DIND]) in noncomatose patients with aneurysmal subarachnoid hemorrhage (SAH). METHODS: The authors reviewed the data of patients admitted for SAH to the Neurosurgical Departments of the San Gerardo Hospital of Monza (January 1996 to December 2001) and the Ospedali Riuniti of Bergamo (January 2002 to September 2003). The authors considered only noncomatose patients and evaluated outcome by means of the Rankin Disability Index and the Mini-Mental State Examination at least 6 months after the SAH. STATISTICAL ANALYSIS: Uni- and multivariate logistic regression. RESULTS: The authors included 101 patients. They found the epsilon4 allele in 26 patients (25.7%). The presence of the epsilon4 allele negatively affected the overall outcome (functional morbidity or cognitive morbidity, or both) (p = 0.0087) and, particularly, cognitive morbidity (p = 0.0028). Those with an epsilon4 allele had delayed ischemic neurologic deficit DINDs more frequently (p = 0.024) and, in the presence of DIND, they were more likely to show permanent neurologic deficits (p = 0.0051). CONCLUSIONS: ApoE4 negatively affects cognitive morbidity and delayed ischemic neurologic deficit recovery. The presence of an epsilon4 allele increases the risk of delayed ischemic neurologic deficit.

Adult↗
PubMed2004

Resveratrol interference with the cell cycle protects human neuroblastoma SH-SY5Y cell from paclitaxel-induced apoptosis.

In previous studies we demonstrated that resveratrol acts in an antiapoptotic manner on the paclitaxel-treated human neuroblastoma (HN) SH-SY5Y cell line inhibiting the apoptotic pathways induced by the antineoplastic drug. In the present study we evaluated the antiapoptotic effect of resveratrol, studying its activity on cell cycle progression. We determined the mitotic index of cultures exposed to resveratrol and paclitaxel alone or in combination, the cell cycle distribution by flow cytometric analysis (FACS), and the modulation of some relevant cell cycle regulatory proteins. Resveratrol is able to induce S-phase cell arrest and this interference with the cell cycle is associated with an increase of cyclin E and cyclin A, a downregulation of cyclin D1, and no alteration in cyclin B1 and cdk 1 activation. The resveratrol-induced S-phase block prevents SH-SY5Y from entering into mitosis, the phase of the cell cycle in which paclitaxel exerts its activity, explaining the antiapoptotic effect of resveratrol.

Antineoplastic Agents, Phytogenic↗
PubMed2004

Pixantrone (BBR2778) reduces the severity of experimental allergic encephalomyelitis.

Pixantrone is less cardiotoxic and is similarly effective to mitoxantrone (MTX) as an antineoplastic drug. In our study, pixantrone reduced the severity of acute and decreased the relapse rate of chronic relapsing experimental allergic encephalomyelitis (EAE) in rats. A marked and long-lasting decrease in CD3+, CD4+, CD8+ and CD45RA+ blood cells and reduced anti-MBP titers were observed with both pixantrone and MTX. In vitro mitogen- and antigen-induced T-cell proliferation tests of human and rodents cells evidenced that pixantrone was effective at concentrations which can be effectively obtained after i.v. administration in humans. Cardiotoxicity was present only in MTX-treated rats. The effectiveness and the favorable safety profile makes pixantrone a most promising immunosuppressant agent for clinical use in multiple sclerosis (MS).

Acute Disease↗
PubMed2003

Effect of trans-resveratrol on signal transduction pathways involved in paclitaxel-induced apoptosis in human neuroblastoma SH-SY5Y cells.

trans-Resveratrol (3,4',5-trihydroxystilbene) is able to significantly reduce paclitaxel-induced apoptosis in the human neuroblastoma (HN) SH-SY5Y cell line, acting on several cellular signaling pathways that are involved in paclitaxel-induced apoptosis. trans-Resveratrol reverses phosphorylation of Bcl-2 induced by paclitaxel and concomitantly blocks Raf-1 phosphorylation, also observed after paclitaxel exposure, thus suggesting that Bcl-2 inactivation may be dependent on the activation of the Raf/Ras cascade. trans-Resveratrol also reverses the sustained phosphorylation of JNK/SAPK, which specifically occurs after paclitaxel exposure.Overall, our observations demonstrate that (a) the toxic action of paclitaxel on neuronal-like cells is not only related to the effect of the drug on tubulin, but also to its capacity to activate several intracellular pathways leading to inactivation of Bcl-2, thus causing cells to die by apoptosis, (b) trans-resveratrol significantly reduces paclitaxel-induced apoptosis by modulating the cellular signaling pathways which commit the cell to apoptosis.

Antineoplastic Agents, Phytogenic↗
PubMed2002

Cisplatin-induced peripheral neurotoxicity in rats reduces the circulating levels of nerve growth factor.

The pathogenesis of the neurotoxicity of most antineoplastic drugs is unknown. Recent reports suggest that changes in the circulating levels of nerve growth factor (NGF) might be related to the dorsal root ganglia sensory neuron damage induced by cisplatin (CDDP), the first member of a family of widely used and very effective platinum-derived anticancer agents. Using a well-characterized model of CDDP neurotoxicity, we demonstrated that the NGF circulating level decreased during chronic CDDP administration in close accordance with the clinical course and returned to normal levels after recovery from the neurotoxic damage. Moreover, these changes were restricted to NGF and did not involve other trophic factors of the same neurotrophin family. Our findings are in agreement with previous in vitro and in vivo results and further suggest that NGF plays a specific role in the course of CDDP-induced primary sensory neuron damage.

Animals↗
PubMed2001

Anti-apoptotic effect of trans-resveratrol on paclitaxel-induced apoptosis in the human neuroblastoma SH-SY5Y cell line.

Paclitaxel, an anticancer drug, induces apoptosis in human neuroblastoma cell line SH-SY5Y. The addition of trans-resveratrol, a natural antioxidant present in grapes and red wine, to SH-SY5Y cultures exposed to paclitaxel significantly reduces cellular death. The neuroprotective action of trans-resveratrol is due neither to its antioxidant capacity nor to interference with the polymerization of tubulin induced by paclitaxel. However, trans-resveratrol is able to inhibit the activation of caspase 7 and degradation of poly-(ADP-ribose)-polymerase which occur in SH-SY5Y exposed to paclitaxel. Resveratrol, therefore, exerts its anti-apoptotic effect by modulating the signal pathways that commit these neuronal-like cells to apoptosis.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Effects of different schedules of oxaliplatin treatment on the peripheral nervous system of the rat.

The aim of this study was to determine the influence of oxaliplatin scheduling on the onset of peripheral neurotoxicity and ototoxicity in a rat model. Animals were treated with four different schedules of oxaliplatin using two cumulative doses (36 and 48 mg/kg intraperitoneally (i.p.)). The neuropathological examination evidenced dorsal root ganglia (DRG) nucleolar, nuclear and somatic size reduction with nucleolar segregation in the treated rats. Sensory nerve conduction velocity (SNCV) was reduced after oxaliplatin treatment, while the auditory pathway was unaffected. After treatment, platinum was detected in the kidney, DRG and sciatic nerve. After a 5-week follow-up period, recovery of the pathological changes in the DRG and sciatic nerves occurred, although platinum was still detectable in these tissues. The following conclusions may be drawn: the main targets of oxaliplatin neurotoxicity were the DRG; the shorter the interval between the injections, the higher the severity of peripheral neuropathy and this was also related to the cumulative oxaliplatin dose; the peripheral neurotoxicity tended to be reversible; ototoxicity was absent even with high cumulative doses of oxaliplatin.

Animals↗
PubMed2001

Immunomodulating effects of extracorporeal photochemotherapy in rat experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis (EAE) is a well-established model of human multiple sclerosis that is commonly used to evaluate the possible effectiveness of new treatments in this disease. Extracorporeal photochemotherapy (ECP) is an immunomodulating procedure currently used in several non-neurological diseases that, like multiple sclerosis, are likely to be due to T-cell-mediated autoimmunity. In this study we examined the effect of ECP using the EAE paradigm in the Lewis rat. In our model, ECP induced a significant modulation in peripheral blood T-cell distribution, changes which are typical of EAE. Remarkably, this effect was closely correlated with the clinical and pathological results, which showed reduced severity of the disease in the ECP-treated EAE animals vs. the EAE alone rats. We conclude that ECP induces modifications in the immunological events that occur during the course of EAE in rats, thus giving support to the hypothesis that it could be used in the treatment of multiple sclerosis.

Adjuvants, Immunologic↗
PubMed2000

Effect on the peripheral nervous system of systemically administered dimethylsulfoxide in the rat: a neurophysiological and pathological study.

The issue of dimethylsulfoxide (DMSO) neurotoxicity is an important one, given its wide use in experimental toxicology as a solvent for hydrophobic substances. We examined the effect of the intraperitoneal administration of different DMSO solutions (1.8-7. 2%) on the peripheral nervous system of Wistar rats treated for 10 consecutive days and followed-up for an additional 45 days. DMSO administration induced a dose-dependent reduction in nerve conduction velocity, with complete recovery occurring in the follow-up. No structural changes were found in the sciatic nerve at 1.8% and 3.6% DMSO concentrations, suggesting that the mechanism of action of DMSO involves a functional impairment (i.e. conduction block) similar to that already described for this substance in isolated systems. However, when DMSO was administered at the 7.2% concentration, evident structural changes were observed in the sciatic nerve, with myelin disruption and uncompacted myelin lamelle. The neurophysiological and pathological changes observed in our study are severe enough to merit careful consideration in the course of experimental studies involving DMSO as a solvent for drugs which are under evaluation for their potential neurotoxicity.

Animals↗
PubMed2000

Lipid-free versus lipid-bound P2 protein-induced experimental allergic neuritis: clinicopathological, neurophysiological, and immunological study.

The P2 protein of the peripheral nervous system myelin is a neuritogenic protein capable of inducing experimental allergic neuritis (EAN) in the Lewis rat. It has been suggested that the addition of some lipids to the protein isolated in the lipid-free form might enhance its immunogenicity. In this study, we compared lipid-free P2 (the EAN factor) and the corresponding lipid-bound form of the protein regarding their ability to induce EAN. Lipid-bound P2, copurified with all the myelin lipids, shows a conformation different from that of LF-P2. The timing of disease and the clinical scores of lipid-bound P2-induced EAN animals (n = 23) did not differ statistically from those injected with lipid-free P2 (n = 23), with only a tendency to higher clinical severity in the former group. Tail nerve conduction velocities did not differ in the two groups and in both were significantly lower in comparison to Freund adjuvant controls (n = 8). Inflammation and demyelination predominated in the spinal roots and were less evident in the sciatic nerve for both groups of animals. The ELISA determination of antibodies to lipid-free and lipid-bound P2 revealed the development of antibodies recognizing the lipid-free form of the protein in both groups of animals. Our results stand in contrast to results of previous studies performed after addition of exogenous lipids to the P2 purified in the lipid-free form and indicate that lipid-bound P2 is not significantly more immunogenic than lipid-depleted P2.

Adjuvants, Immunologic↗
PubMed2000

Further evidence for the involvement of epidermal growth factor in the signaling pathway of vitamin B12 (cobalamin) in the rat central nervous system.

In order to get further evidence for a mandatory involvement of epidermal growth factor (EGF) in the neutrophic action of vitamin B12 (cobalamin (Cbl)) in the central nervous system (CNS) of the rat, we observed the effects of repeated intracerebroventricular (ICV) microinjections of EGF in rats made Cbl-deficient through total gastrectomy. Morphometric analysis demonstrated a significant reduction in both intramyelinic and interstitial edema in the white matter of the spinal cord (SC) of totally gastrectomized (TGX) rats after treatment. Intramyelinic and interstitial edema are characteristic of Cbl-deficient central neuropathy in the rat. Similar lesions were also present in SC white matter of rats treated with repeated ICV microinjections of specific anti-EGF antibodies without any modification in their Cbl status. These results, together with those of a previous study showing the cessation of EGF synthesis in the CNS of TGX rats, demonstrate that: a) EGF is necessarily involved in the signaling pathway of Cbl in the rat CNS; and b) the lack of a neurotrophic growth factor EGF, and not the mere withdrawal of Cbl, causes or at least contributes to neurodegenerative Cbl-deficient central neuropathy.

Animals↗
PubMed2000

An improved in vivo rat model for the study of mechanical ventilatory support effects on organs distal to the lung.

OBJECTIVE: To study the influence of different mechanical ventilatory support strategies on organs distal to the lung, we developed an in vivo rat model, in which the effects of different tidal volume values can be studied while maintaining other indexes. DESIGN: Prospective, randomized animal laboratory investigation. SETTING: University laboratory of Ospedale Maggiore di Milano-Instituto di Ricovero e Cura a Carattere Scientifico. SUBJECTS: Anesthetized, paralyzed, and mechanically ventilated male Sprague-Dawley rats. INTERVENTIONS: Two groups of seven rats each were randomized to receive tidal volumes of either 25% or 75% of inspiratory capacity (IC), calculated from a preliminary estimation of total lung capacity. Ventilation strategies for the two groups were as follows: a) 25% IC, 9.9+/-0.8 mL/kg; frequency, 59+/-4 beats/min; positive end-expiratory pressure, 3.6+/-0.8 cm H2O; and peak inspiratory airway pressure (Paw), 13.2+/-2 cm H20; and b) 75% IC, 29.8+/-2.9; frequency, 23+/-13; positive end-expiratory pressure, 0; peak inspiratory Paw, 29.0+/-3. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure (invasively monitored) remained well above adequate perfusion pressure values throughout, and no significant difference was seen between the two groups. PaO2, pHa, and PaCO2 values were compared after 60 mins of ventilation and again, no significant difference was seen between the two groups (PaO2, 269+/-25 and 260+/-55 torr; pHa, 7.432+/-0.09 and 7.415+/-0.03; PaCO2, 35.4+/-8 and 32.5+/-2 torr, for the 25% IC and 75% IC groups, respectively). Mean Paws were not different (6.4+/-0.8 cm H2O in the 25% IC groups, and 6.1+/-1.2 in the 75% IC groups, respectively). At the end of the experiment, animals were killed and the liver and kidney isolated, fixed in 4% formalin, cut, and stained for optic microscopy. Kidneys from rats ventilated with 75% IC showed increased Bowman's space with collapse of the glomerular capillaries. This occurred in a greater percentage of rats ventilated with 75% IC (0.67+/-0.2 vs. 0.29+/-0.2, 75% IC vs. 25% IC, respectively; p < .05). Perivascular edema was also present in rats ventilated with 75% IC (p < .05). Morphometric determinations of the empty zones (index of edema) demonstrated a trend toward differences between 75% IC livers and 25% IC (0.14+/-0.05 vs. 0.11+/-0.02, respectively). CONCLUSION: We conclude that it is possible to study the effects of mechanical ventilatory support on organs distal to the lung by means of an in vivo rat model.

Animals↗
PubMed2000

Distribution of paclitaxel within the nervous system of the rat after repeated intravenous administration.

The distribution of paclitaxel (Taxol) within the central and peripheral nervous system after repeated administration of this antineoplastic agent is still largely unknown. In this study we determined for the first time paclitaxel tissue concentration in the brain, spinal cord, dorsal root ganglia (DRG) and sciatic nerve using an experimental paradigm in the rat which reproduces the features of paclitaxel peripheral neurotoxicity in humans. Pathological confirmation of the onset of paclitaxel-induced peripheral neurotoxicity was performed. In order to achieve reliable results even with low concentrations of paclitaxel, a newly reported analytical method (high-performance liquid chromatography with tandem mass spectrometry) was used. We demonstrated that paclitaxel has easy access to the DRG, where it accumulates, while the lowest concentrations of the drug were measured in the brain. The intermediate concentrations of paclitaxel observed in the sciatic nerve and spinal cord may be due to paclitaxel transport along the centrifugal and centripetal branches of the DRG neuron axons.

Animals↗
PubMed1999

Resveratrol-induced activation of the mitogen-activated protein kinases, ERK1 and ERK2, in human neuroblastoma SH-SY5Y cells.

Phosphorylation of the mitogen-activated protein (MAP) kinases, extracellular signal-regulated kinase 1 (ERK1) and extracellular signal-regulated kinase 2 (ERK2), induced by resveratrol, a natural antioxidant present in grapes and wine, has been studied in vitro on undifferentiated and differentiated (induction by retinoic acid) SH-SY5Y human neuroblastoma cells. In undifferentiated cells resveratrol 1 microM induced phosphorylation of ERK1 and ERK2, which was already evident at 2 min, peaked at 10 min and persisted at 30 min. A wide range (from 1 pM to 10 microM) of resveratrol concentrations were able to induce phosphorylation of ERK1 and ERK2, while higher concentrations (50-100 microM) inhibited MAP kinases phosphorylation. In retinoic acid (RA) differentiated cells resveratrol (1 microM) induced an evident increase in ERK1 and ERK2 phosphorylation. This study demonstrates that resveratrol, even at very low concentrations, may have a biological effect on neuron-like cells.

Antioxidants↗
PubMed1999

Effect of recombinant human nerve growth factor on cisplatin neurotoxicity in rats.

In this study we evaluated the effect of recombinant human nerve growth factor (rhNGF) on cisplatin (CDDP)-induced sensory neuronopathy in an experimental paradigm in the rat. Young adult female Wistar rats were treated with CDDP (2 mg/kg ip twice weekly for nine times) alone or in combination with rhNGF (1 mg/kg sc on alternate days). The effect of CDDP +/- NGF treatment was evaluated with behavioral (tail-flick test) and neurophysiological (nerve conduction velocity in the tail) methods immediately after treatment and after a follow-up period of 6 weeks. Pathological and morphometrical examinations of the dorsal root ganglia (DRG) and sciatic and saphenous nerves were also performed. rhNGF treatment induced a significant reduction in the CDDP-induced decrease in nerve conduction velocity (P < 0.05), and this was associated with a significant protection against the decrease in somatic (P < 0.05), nuclear (P < 0.05), and nucleolar size (P < 0.01) caused by CDDP treatment. However, for each of the parameters examined the neuroprotection obtained with rhNGF treatment was not complete. At the follow-up examination no differences between the three groups were observed in tail-flick test and nerve conduction velocity. We conclude that rhNGF, administered according to the schedule used in this experiment, exerts a biologically significant neuroprotective effect against CDDP peripheral neurotoxicity.

Animals↗
PubMed1999

Descending projections arising from the parafascicular nucleus in rats: trajectory of fibers, projection pattern and mapping of terminations.

The organization of the descending projections from the intralaminar parafascicular nucleus was studied using biocytin as an anterograde tracer in rats. After biocytin injection into the lateral parafascicular nucleus, three bundles of fibers descending throughout the brainstem were seen. Terminal fields were found in several structures, for example the lateral geniculate nucleus, nucleus reticularis thalami, subthalamus, zona incerta, substantia nigra, red nucleus, periaqueductal gray, superior colliculus, reticular formation, raphe nuclei, pontine nuclei, trigeminal complex, and ventral horn of the spinal cord. Different types of labeled terminals (small terminal boutons, en passant varicosities, large claw-like terminals) were observed, particularly in the substantia nigra and reticular formation where the density of terminals was highest. The organization of these extensive descending connections to both motor and sensory structures does not allow functions to be conclusively attributed to the parafascicular nucleus neurons. Further investigations are required to resolve this question.

Age Factors↗