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Biomedical subjects

A Cadoni

Publications and source records attributed to A Cadoni.

At least 19 recordsLinked to original sources
PubMed2001

Schwann cell-derived factors support serotoninergic neuron survival and promote neurite outgrowth.

During embryogenesis and the postnatal period, neurons and glia interact in the development and differentiation of specific populations of nerve cells. Both in the peripheral (PNS) and in the central nervous system (CNS), glial cells have been shown in various experimental conditions to constitute a favorable substrate for neural adhesion, neural polarity, shape and axonal extension, while numerous soluble molecules secreted by neurons influence the survival and differentiation of the glial cells themselves. The aim of the present work was to investigate the influence of postnatal Schwann cells (SC) on embryonic serotoninergic (5-HT) neurons of the raphe, in order to study the possible influence of the peripheral glia on the CNS neurons. Cultures of SC from sciatic nerve of postnatal rats and neurons from rat embryonic rhombencephalon were successfully established and cells were immunocytochemically characterized. The number of 5-HT neurons, and the number and length of their branches were quantified in the cultures of 5-HT neurons, in cultures added with Nerve Growth Factor (NGF) and Insulin-like Growth Factor I (IGF-I), in co-cultures with SC and in cultures added with conditioned medium obtained from SC cultures. The results indicated that SC have the capacity to promote the survival and growth of 5-HT neurons in culture, and that this activity is mediated by soluble factors. Although the precise nature and mechanism of action of the growth factor or factors produced by SC in the presence of 5-HT neurons was not identified, our results add more data on the possible activity of the peripheral glia in promoting and enhancing the survival and outgrowth of the CNS neurons.

Animals↗
PubMed2000

Reduction of cisplatin nephrotoxicity by procainamide: does the formation of a cisplatin-procainamide complex play a role?

Procainamide protects mice bearing P388 leukemic cells against the toxicity of cisplatin without diminishing antitumor activity. The mechanism of action of procainamide protection was investigated both in vitro and in vivo. HPLC studies showed that procainamide forms a complex with cisplatin in vitro that has a UV spectrum similar to that of DPR, a triamine platinum complex that contains procaine as ligand. We report here the effect of the reaction product of cisplatin and procainamide on both cisplatin-induced DNA interstrand cross-links (ISCLs) and on the total DNA platination of isolated DNA. Total DNA platination in vitro of isolated DNA was increased by 113% (P <.01) and 17% (P <.05) after incubation times of 1.75 and 6 h, respectively, compared with products from the reaction of cisplatin with water. Furthermore, the reaction product of cisplatin and procainamide was bound to DNA to a significantly greater extent than was cisplatin itself. ISCLs were decreased by 41% when this drug combination was incubated with DNA for 1.75 h, but no changes were observed after incubation for 6 h. We also examined the influence of the time interval between administration of cisplatin and procainamide on normal kidney injury, the renal distribution and urinary excretion of platinum, and the formation of cisplatin-DNA adducts in renal tissue of Sprague-Dawley rats after i.p. administration of 7.5 mg/kg cisplatin either with or without procainamide. The plasma concentrations of urea and creatinine and kidney histology demonstrated that procainamide provided effective protection in vivo in the rat when administered either simultaneously or at 0.5 and 1 h before or after cisplatin. The protection was accompanied by both higher renal levels of platinum and cisplatin-DNA adducts and by an increase in the formation of ISCLs. Moreover, a dose-dependent reduction of urinary excretion and concentration of platinum was also observed. We propose that procainamide, after accumulation in the kidney, may coordinate with cisplatin to form a less toxic DPR-like complex that renders rats less susceptible to cisplatin-induced toxicity.

Animals↗
PubMed1999

Forebrain white matter in spontaneously hypertensive rats: a quantitative image analysis study.

The volume and the morphology of brain white matter as well as the number and the size of glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes were investigated in 6-month-old spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto (WKY) rats. The volume of frontal and occipital cortex and of hippocampus was decreased in SHR in comparison with normotensive rats, whereas the volume of neostriatum was unchanged. A remarkable decrease of the volume of internal capsule and striosomes, a moderate reduction of that of corpus callosum and no changes of the volume of external capsule and of white matter of hippocampus were also observed in SHR. In SHR the number of astrocytes was higher in the frontal and occipital cortex and in the white matter of the CA1 and CA3 subfields of the hippocampus, but not in the corpus callosum or in the grey matter of the CA1 and CA3 subfields. Staining for myelin did not reveal alterations in single fibre sheath morphology. These findings indicate the occurrence of changes of forebrain white matter in SHR, consisting in the reduction of it without qualitative modifications of myelinated fibres. The development of gliosis apparently not related with changes of volume of white matter was also found.

Animals↗
PubMed1996

Effect of the antiarrhythmic drug procainamide on the toxicity and antitumor activity of cis-diamminedichloroplatinum(II).

The class I antiarrhythmic drug procainamide (Pd) was tested on BDF1 mice for its chemoprotective activity against cis-diamminedichloroplatinum(II) (DDP) toxicity. Pd at the dose of 50 mg/kg protected mice against otherwise lethal doses of DDP (survivors at Day 14 after 25 mg/kg DDP or 25 mg/kg DDP-Pd treatment: 0% vs 100%) and greatly reduced the weight loss induced by DDP. Moreover, the increased plasma urea nitrogen levels caused by a single ip administration of DDP in water (8 or 16 mg/kg) as well as the tubular degenerative changes detected by light microscopy were prevented by Pd. Pd had no effect on the sensitivity of P388 leukemic cells to DDP in vitro, but the administration of DDP (16 mg/kg) and Pd (50 mg/kg) to BDF1 mice bearing P388 leukemic cells produced a significant increase in survivals compared to mice receiving ip DDP alone diluted in 0.9% NaCl solution. The increased efficacy of this combination therapy in P388 leukemic mice compared to a single DDP treatment at the same dose was observed both when the drugs were administered ip simultaneously (p = 0.042) and when DDP and Pd were given ip and iv, respectively (p = 0.018). Since procaine, which differs from Pd merely in the replacement of the amide by the ester linkage, has also been reported to significantly enhance DDP efficacy (M. Esposito et al., 1990, J. Natl. Cancer Inst. 82, 677-684.), a comparison of their effects in tumored mice exposed to DDP has been made. Although both drug combinations were superior to that of DDP alone, in terms of both survival time and numbers of cures, Pd treatment seems to offer better protection against DDP-induced lethality than did procaine.

Animals↗
PubMed1995

Localization of calcium channels of the L-type in human epicardial arteries: a light microscope autoradiographic study.

The anatomical localization of Ca2+ channels of the L-type was analyzed in sections of the human right and anterior interventricular coronary arteries by using in vitro light microscope autoradiography associated with radioligand binding techniques. [3H]Nicardipine was utilised as a ligand. Binding of the radioligand to sections of the two coronary arteries was time-, temperature- and concentration-dependent. Analysis of binding isotherms revealed a dissociation constant value of about 0.5 nM in the two arteries and maximum binding capacities of 139 +/- 6.4 fmol/mg tissue for the right coronary artery and of 173 +/- 9.5 for the anterior interventricular branch. The pharmacological profile of [3H]nicardipine binding to sections of human coronary arteries was consistent with the labelling of Ca2+ channels of the L-type. Dihydropyridine derivatives were the most powerful competitors of [3H]nicardipine binding, whereas phenylalkylamines, benzothiazepine or non-selective channel modulators were weak competitors or ineffective. Light microscope autoradiography revealed the highest density of [3H]nicardipine binding sites in the tunica media of the coronary arteries. In this layer Ca2+ channels of the L-type are located within smooth muscle cells. A lower accumulation of the radioligand occurred in the tunica adventitia, whereas no specific binding was found in the tunica intima. Study of the localization of Ca2+ channels in sections of human coronary arteries may contribute to a better understanding of the mechanism of the marked coronary dilatory activity elicited by Ca2+ antagonists demonstrable in both in vitro preparations and in vivo.

Adolescent↗
PubMed1993

Expression of common acute lymphoblastic leukemia antigen (CD 10) by myelinated fibers of the peripheral nervous system.

The common acute lymphoblastic leukemia antigen (CALLA), CD10, is a 100-kDa surface glycoprotein endowed with neutral endopeptidase activity, shared by a number of hemopoietic and non-hemopoietic cells. In this report, immunohistochemical and Western blot techniques, using different anti-CD10 monoclonal antibodies, were utilized to demonstrate that CD10 is also expressed by myelin sheaths of the human peripheral nervous system (PNS), but not of the central nervous system. CD10-positive immunoreactivity appeared to be localized in the outer and inner borders of myelinated fibers, in nodes of Ranvier and in the Schmidt-Lantermann clefts, thus showing a distribution pattern very similar to that of myelin-associated glycoprotein (MAG). The above findings suggest that CD10 antigen, through its enzymatic activity, may have a functional role in the assembly and maintenance of PNS myelin. In addition, it is not known whether CD10, similarly to MAG, may be a target antigen in some PNS immune-mediated disorders.

Antibodies, Monoclonal↗
PubMed1993

Para-aminobenzoic acid suppression of cis-diamminedichloroplatinum(II) nephrotoxicity.

Concurrent administration of para-aminobenzoic acid (PABA) reduced the toxicity of cis-diamminedichloroplatinum(II) (DDP) in a dose-related manner in rats. When administered i.p. simultaneously with 7.5 mg/kg DDP, PABA (100 mg/kg) significantly reduced plasma urea nitrogen (PUN) and plasma creatinine levels as well as DDP-induced weight loss. Increasing doses of PABA (25, 50 and 100 mg/kg) correlated with progressively better parameters of renal activity and body wt and with lower levels of platinum in plasma and tissues in rats killed 5 days after drug administration. The formation of cisplatin-DNA adducts, the total platinum levels in kidney and testes and the DDP-induced tumor response were investigated in the presence and absence of PABA exposure in mice bearing P388 leukemic cells. Renal and testicular DNA-adducts in mice treated i.p. with 16 mg/kg DDP in normal saline were higher than those observed in mice receiving the same protocol and added PABA. Analysis of tissue platinum content demonstrated significantly lower platinum levels both in kidneys (P < 0.05) and testes (P < 0.01) of mice receiving DDP and PABA in normal saline compared to those receiving only DDP in normal saline. PABA did not affect the in vivo and in vitro antitumor activity of DDP against P388 leukemia, and there was no significant PABA-induced modification in the concentration of platinum both in the tumor cells and in DNA samples isolated from P388 leukemic cells of DDP-treated mice. We conclude that PABA may be a promising compound for reducing DDP-toxic side effects, including nephrotoxicity, without compromising its antitumor activity.

4-Aminobenzoic Acid↗
PubMed1992

GFAP expression of human Schwann cells in tissue culture.

We have studied the expression of the intermediate filament (IF) proteins, vimentin and glial fibrillary acidic protein (GFAP), in cultured human Schwann cells (SC) from patients with different neuropathies and normal control cases. SC cultures from sural nerve biopsies of 8 subjects with axonal neuropathies, 8 with demyelinating neuropathies and 3 normal controls were included in this study and processed with double immunofluorescence technique, using anti-vimentin and anti-GFAP antibodies, during the 2nd, 4th and 6th week of culture. Five cultures incubated with anti-GFAP antibodies were also processed for immunoelectron microscopy. Specificity tests of the used antibodies were performed. We have found that: (1) cultured human SC constantly express vimentin; (2) SC from normal controls are GFAP-negative in the first period of culture; (3) SC from pathologic nerves can contain GFAP-immunoreactive IF and the percentage of GFAP-positive SC is higher in axonal than in demyelinating neuropathies; (4) during the permanence in culture human SC from both normal and pathologic cases acquire the ability to synthesize GFAP. The obtained data suggest that the removal from axonal contact and the resulting loss of myelinating function induce a cytoskeletal cellular response in human SC characterized by the cytoplasmic accumulation of GFAP-immunoreactive IF.

Antibody Specificity↗
PubMed1991

Schwann cell GFAP expression increases in axonal neuropathies.

We studied the Schwann cell (SC) GFAP immunoreactivity in normal human peripheral nerves and in neuropathies of different origin. Immunofluorescence and immunocytochemistry were carried out on serial frozen sections of 58 peripheral nerve biopsies using monoclonal antibodies (mabs) antivimentin and anti GFAP, and antiserum anti S-100 and anti GFAP. To test the specificity of the mabs and antiserum used, proper competition controls on tissue sections of 2 selected cases, tissue cultures studies of human fibroblasts and immunoblotting of homogenates of human fibroblasts, 3 normal and 5 pathologic nerves were carried out. In order to evaluate a possible correlation between SC GFAP positivity and neuropathologic findings a quantitative study was performed, evaluating the SC GFAP reactivity in all the 58 cases, and relating the SC GFAP positivity to the index of nerve pathology (IP) in 9 selected cases, and to the percentage of teased fibers showing axonal degeneration or demyelination and remyelination in 25 representative cases. We demonstrate that in normal human sural nerves and in demyelinating neuropathies only a few scattered SC are recognized by the mabs or antiserum anti GFAP. On the contrary in axonal neuropathies the majority of SC gain the property to express intermediate filaments which show common antigenic properties with GFAP.

Antibodies, Monoclonal↗
PubMed1990

Improved therapeutic index of cisplatin by procaine hydrochloride.

The local anesthetic procaine hydrochloride (P.HCl) had little effect on the sensitivity of P388 leukemic cells to cisplatin (DDP) in vitro, but the simultaneous administration of DDP and P.HCl (40 mg/kg) to BDF1 mice produced 50% lethal dose (LD50) and 90% lethal dose (LD90) values approximately two times higher than those observed with DDP alone. DDP-P.HCl diluted in water and administered intraperitoneally (IP) on day 1 and on days 1 and 5 to BDF1 mice bearing P388 leukemic cells produced 33% and 50% cure rates, respectively, at the maximum tolerated dose (16 mg/kg for the single administration and 10 mg/kg given on days 1 and 5). In contrast, under the same conditions, the cure rates obtained with DDP alone (10 mg/kg for the single administration and 8 mg/kg given on days 1 and 5) were 17% and 9%, respectively. Protection from DDP nephrotoxicity seems to be the explanation for the higher doses of DDP that mice can tolerate when DDP is given simultaneously with P.HCl. In fact, the increased blood urea nitrogen (BUN) levels observed 4-7 days following a single IP administration of DDP (8 or 16 mg/kg), as well as the tubular degenerative changes detected by light microscopy, were not observed when the same doses of DDP were given simultaneously with P.HCl. Since DDP nephrotoxicity is known to be reduced when the drug is diluted in 0.9% NaCl solution, we compared the combinations DDP-P.HCl in water, and DDP and DDP-P.HCl in 0.9% NaCl solution. The antitumor activity of DDP diluted in water and administered with P.HCl was similar to that observed in mice treated with DDP alone diluted in 0.9% NaCl solution. However, further improvement of the therapeutic index was achieved after the administration of DDP-P.HCl diluted in 0.9% NaCl solution; this regimen produced a cure rate of 67% (12 of 18 animals). The clinical relevance of these findings is strengthened by the observation that similar results were obtained when P.HCl was given by the intravenous route.

4-Aminobenzoic Acid↗
PubMed1990

Evidence that human oral epithelium reconstituted in vitro and transplanted onto patients with defects in the oral mucosa retains properties of the original donor site.

Normal human skin--derived keratinocytes cultured in vitro reconstitute a stratified epidermis suitable for grafting onto burn patients and patients with skin defects such as giant nevi or chronic leg ulcers. In vitro experiments and long-term studies of patients receiving cultured epidermis autografts on muscular fascia suggest that skin keratinocytes possess an intrinsic site specific differentiation program that is fully expressed only when the reconstituted epidermis is transplanted in vivo to different body sites. In this study we cultivated for the first time palate-derived epithelial cells that were able to reconstitute a palatal epithelium. We also demonstrate that this epithelium can be successfully transplanted onto patients presenting lack of adherent keratinizing gingival mucosa and is able, in a relatively short time, to fully express the differentiation program typical of the original donor site. The possibility of obtaining large quantities of cultured epithelium, able to retain properties of the original donor site, starting from 1-3-mm2 biopsies, could prove extremely useful in the reconstructive surgery of the mouth and of other mucosal body areas.

Epithelium↗
PubMed1989

Class II antigen expression on human cultured Schwann cells from patients with Charcot-Marie-Tooth disease.

T lymphocytes control the extent of the immune reaction by recognizing the antigen in connection with class II histocompatibility surface molecules, coded by genes located on the HLA-D locus. The expression of HLA-DR antigens is confined to a few antigen presenting cells, like lymphocytes and macrophages, which can therefore induce the initial phase of the immune reaction. We report that also Schwann cells (SC) from patients with Charcot-Marie-Tooth disease (CMT), an hereditary disorder of the peripheral nervous system, are able to express HLA-DR antigens. Human SC cultures were carried out from sural nerve biopsies of CMT and normal control cases. Cultures were tested on day 7, 14, 21 and 28, with double immunofluorescence technique using rabbit antiserum anti-S-100 and mouse anti-HLA-DR monoclonal antibody. SC from CMT were HLA-DR positive since the first few days, continuing to express class II antigens for all the duration of the culture. The presence of class II antigens on cultured SC from CMT disease suggests that immune-mediated mechanisms may be relevant in the pathogenesis of this degenerative disorder of the peripheral nervous system.

Cells, Cultured↗
PubMed1989

[The culturing of human Schwann cells: a new contribution to the study of polyneuropathy].

We have established 44 Schwann cell cultures from human peripheral nerves that underwent biopsy for diagnostic purposes using a new "sandwich" connective tissue and cut into 1 mm cubic explants which were placed between two glass coverslips coated with D-poly-L-lysine, in HAM-F10 medium, 15% FCS, 600 mg/dl glucose and antibiotics. In the first 3 weeks this new sandwich technique yields a fairly great and homogeneous amount of Schwann cell growth, with only a few fibroblasts and virtually no macrophages and provides a suitable substrate on which immuno cytochemical studies could be performed.

Antigens, Surface↗
PubMed1989

[Hereditary sensory motor neuropathy: degenerative disease or a disease with an immune-mediated pathogenesis?].

The clinical data proving that some hereditary motor-sensory neuropathies (HMSN type 1) are steroid sensitive may indicate inflammatory or immunomediated mechanisms as cofactors contributing to the clinical course of these disorders. The finding of HLA-DR positivity of Schwann cells in HMSN type I along with the presence in some cases of inflammatory infiltrates in nerve sections provides further evidence for this hypothesis.

Autoimmune Diseases↗
PubMed1988

HLA-DR Schwann cell reactivity in peripheral neuropathies of different origins.

HLA-DR antigens have been found on Schwann cells in peripheral neuropathies of different origins but not in normal control cases. Class II antigen reactivity was more intense in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and hereditary motor and sensory neuropathy type 1 (HMSN), but was also observed in toxic or metabolic neuropathies. The expression of HLA-DR antigen on Schwann cells does not appear to be related to the inflammatory or autoimmune origin of the disease.

Antibodies, Monoclonal↗