Biomedical subjects

G Biagini

Publications and source records attributed to G Biagini.

At least 19 recordsLinked to original sources

PubMed2006

Immunohistochemical study of apoptosis markers and involvement of chemokine CXCR4 in skin Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive cancer of the skin that mainly affects elderly patients. Because of its rarity, there is no established treatment or proven markers to guide therapy or prognosis. Immunohistochemical expression of apoptosis proteins is considered a useful marker of both malignancy and tumour progression. Apoptosis plays a fundamental role in skin homeostasis, and apoptotic cells have been detected in normal and diseased skin. Chemokines possess a wide range of biological activities and CXCR4 is expressed in some cancer cells, where it plays an efficient role in metastasis formation. OBJECTIVE: To identify immunohistochemical parameters that can help clinicians select the most suitable therapy for skin MCC. DESIGN: Antibodies against ki67, bcl-2, p53, survivin, p16 and CXCR4 were tested to assess the usefulness of these antigens as indices of proliferation potential and predictors of prognosis. METHODS: Immunohistochemical detection of apoptosis inhibitors and CXCR4 was performed on tissue from 12 patients with primary MCC. After excision of the primary lesion, five survived and had no metastases, and seven experienced local recurrence or lymph node metastases. RESULTS: Expression of ki67 and survivin was increased in patients with local recurrence or metastasis (retrospectively classified as 'poor prognosis') compared with those with a 'good prognosis', and bcl-2 expression was significantly greater (P=0.003). P53 and p16 immunostaining was moderate in both groups. A positive correlation was observed between survivin and mutant p53 in the poor prognosis group (r=0.593, P=0.033; regression coefficient). High values of p53 were measured in patients with high levels of survivin and vice versa. CXCR4 was not detected at all. CONCLUSIONS: Our results show strong MCC cell apoptosis inhibition and a high cell proliferation capacity. The positive correlation between survivin and p53 may be a predictor of MCC spread via the lymphatic network. Absent CXCR4 expression may reflect a less aggressive form, with less efficient development of distant and non-organ-selective metastasis formation.

Apoptosis↗

PubMed2006

Synaptic hyperexcitability of deep layer neocortical cells in a genetic model of absence seizures.

We used sharp-electrode, intracellular recordings in an in vitro brain slice preparation to study the excitability of neocortical neurons located in the deep layers (>900 microm from the pia) of epileptic (180-210-days old) Wistar Albino Glaxo/Rijswijk (WAG/Rij) and age-matched, non-epileptic control (NEC) rats. Wistar Albino Glaxo/Rijswijk rats represent a genetic model of absence seizures associated with generalized spike and wave (SW) discharges in vivo. When filled with neurobiotin, these neurons had a typical pyramidal shape with extensive apical and basal dendritic trees; moreover, WAG/Rij and NEC cells had similar fundamental electrophysiological and repetitive firing properties. Sequences of excitatory postsynaptic potentials (EPSPs) and hyperpolarizing inhibitory postsynaptic potentials (IPSPs) were induced in both the strains by electrical stimuli delivered to the underlying white matter or within the neocortex; however, in 24 of 55 regularly firing WAG/Rij cells but only in 2 of 25 NEC neurons, we identified a late EPSP that (1) led to action potential discharge and (2) was abolished by the N-methyl-D-aspartate (NMDA) receptor antagonist 3,3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonate (20 microM; n = 8/8 WAG/Rij cells). Finally, we found that the fast and slow components of the stimulus-induced IPSPs recorded during the application of glutamatergic receptor antagonists had similar reversal potentials in the two strains, while the peak conductance of the fast IPSP was significantly reduced in WAG/Rij cells. These findings document an increase in synaptic excitability that is mediated by NMDA receptors, in epileptic WAG/Rij rat neurons located in neocortical deep layers. We propose that this mechanism may be instrumental for initiating and maintaining generalized SW discharges in vivo.

Animals↗

PubMed2006

Resin-based dentin restorative materials under accelerated ageing: bio-functional behavior.

OBJECT: The aim of the present study was the evaluation of the effect of different polishing and finishing procedures on Filtek Z250 FZ ESPE restorative material. Particularly, the consequence of artificial aging (UV-irradiation) on this resin-based dental material was investigated determining also its outcome on cell behavior. METHODS: 96 specimens of restorative material were prepared using a light emitting diode curing unit and randomly divided into four finishing and polishing groups: (I) No treatment (FZ); (II) Identoflex rubbers (ID); (III) Enhance System (EN) and (IV) Sof-Lex Pop-on XT discs (SF). The surface morphology of native and artificially aged materials was assessed with Atomic Force Microscopy (AFM) and Scanning Electron Microscopy (SEM). FTIR and biological (biocompatibility and bacterial adhesion) analyses were also performed. RESULTS: Among all, the ID procedure represented an acceptable compromise for efficiency of polymerization and biocompatibility both before and after artificial ageing. SF and EN techniques showed better interactions with the biological environment. CONCLUSION: UV artificial ageing of the tested specimens has shown an acceleration of the surface degrading processes, favoring a possible decrease in the mechanical properties and the release of toxic free radicals. Finishing and polishing procedure seemed to affect the photodegrading pathways, even though no differences among the techniques were observed. As the cytotoxicity of materials undergoing accelerated aging is relevant, further improvement of dental restorative materials are required to limit the long-term biological damage.

Animals↗

PubMed2006

In vitro evaluation of bio-functional performances of Ghimas titanium implants.

Titanium is the most widely used material for dental implants. The natural formation, in presence of oxygen, of different oxide films (passivation films) is correlated to titanium implant biocompatibility, resistance to corrosion and is responsible for implant bacteriostatic action. Surface roughness is another surface property of Ti-implants that, affecting implant-to-bone contact, improves integration. In the present study data concerning composition, surface roughness and biocompatibility of Ghimas implants and mini-implants undergoing sandblasting with Calcium Magnesium Carbonate (CaMg(CO3)2) are reported. AFM, SEM/EDX, XRD analyses and morpho-functional tests (MTT and ALP) were performed. Cell actin cytoskeletal modification (fluorescence phalloidin staining) was also observed with confocal laser microscopy (CLSM). Data related to surface geometry and chemical properties, associated with evidence of high purity of all the tested materials (XRD and EDX), highlighted the elevated biocompatibility of tested implants and mini-implants. CLSM investigation confirmed osteoblast features of an active cell behavior able to fit cell to chemico-mechanical stimuli present at the bone/implant interface and suggests an effective implant/alveolar bone integration in vivo.

Biocompatible Materials↗

PubMed2005

HA/alginate hybrid composites prepared through bio-inspired nucleation.

Poorly crystalline apatite has been directly nucleated on self-assembling alginate chains by neutralization synthesis to obtain a biomimetic artificial bone-like composite. It has been observed that in preparing HA/alginate composites, Ca2+ ions present on the apatitic surface cross-link the alginate chains to produce a material with different morphology and thermal stability, both functions of the HA/alginate weight ratio. In vitro tests were performed on different samples in terms of both the HA/alginate ratio and synthesis temperature. All the samples were cultured for seven days with MG63 osteoblast-like cells and then underwent morphological and biochemical analyses (MTT and ALP tests). Scaffolds showed a different solubility into the culture media, which was related to the temperature of synthesis and to the HA/alginate ratio. All our data confirm the ability of the tested materials to favour cell growth and to maintain their osteoblastic functionality, at least during the examined period.

Alginates↗

PubMed2005

High-resolution 3D scaffold model for engineered tissue fabrication using a rapid prototyping technique.

Rapid prototyping, automatic image processing (computer-aided design (CAD)) and computer-aided manufacturing techniques are opening new and interesting prospects for medical devices and tissue engineering, especially for hard tissues such as bone. The development of a bone high-resolution scaffold prototype using these techniques is described. The results testify to the fidelity existing between microtomographic reconstruction and CAD. Furthermore, stereolithographic manufacturing of this scaffold, which possesses a high degree of similarity to the starting model as monitored by morphological evaluations (mean diameter 569 +/- 147 microm), represents a promising result for regenerative medicine applications.

Bone Substitutes↗

PubMed2005

Prognostic role of Fuhrman grade and vascular endothelial growth factor in pT1a clear cell carcinoma in partial nephrectomy specimens.

PURPOSE: Conventional renal cell carcinoma (RCC) is characterized by rich neovascularization and shows a fine vascular network around tumor cells. Nephron sparing surgery has been established as a method of choice or necessity for localized tumors. We investigated the importance of microvessel density (MVD), vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (Flk-1) immunohistochemical expression in a large series of small conventional clear cell renal carcinomas treated with partial nephrectomy and assessed the prognostic value of their expression in terms of patients survival at long-term followup. MATERIALS AND METHODS: A total of 48 patients with a mean age +/- SD of 58.2 +/- 9.5 years who had conventional single RCC were considered. Median tumor diameter was 2.92 +/- 0.82 cm (range 1.3 to 5). Disease was grades 1 to 4 in 15, 29, 2 and 2 patients, respectively. Median followup was 92.9 months (range 17 to 186). RESULTS: Four patients (3.9%) had died of metastatic renal cancer at a median followup of 23.5 months, of whom 1 had a grade 2, 1 had a grade 3 and 2 had grade 4 RCC. Patients with MVD expression higher than the median (44.4 vessels per mm) did not show a significant difference in survival compared to patients with MVD expression lower than the median. Patients with VEGF expression higher than 25% in the histological specimen showed worse survival than patients with VEGF expression lower than 25%. Different Flk-1 expression did not determine a significant difference in survival. On univariate analysis of patient survival in relation to the different considered factors Fuhrman grading was the most important factor for survival. CONCLUSIONS: Our study shows that recurrence and death are possible even in patients with small renal tumors. MVD, VEGF and Flk-1 expression do not depend on tumor size in pT1a RCC. Therefore, to date Fuhrman grading appears to be the only factor predictive of survival even in small RCC. Thus, Fuhrman grading is predictive of mortality. While VEGF is not predictive of survival as a single parameter, based on its percent of expression (lower or higher than 25%) it can determine 2 groups that are different from the prognostic point of view.

Adenocarcinoma, Clear Cell↗

PubMed2005

Cell dynamics in the correct control of bone metabolism using natural treatments.

The present study was undertaken in order to assess the efficacy of a commercial product containing calcium and silicon (Osteosil-Calcium) on cell metabolism. MG-63 osteblast-like cells were cultured in the presence of three different drug concentrations (10, 5 and 2.5 microg/mL). Either serum-free culture and standard culture with serum were investigated. Morpho-functional tests (MTT and ALP), scanning electron microscopy (SEM), microanalysis (EDAX) and time-lapse video microscopy were performed. Cell actin cytoskeletal modification with fluorescence phalloidin staining was also tested. Our data show the in vitro functional efficacy of Osteosil-Calcium on MG63 cell viability and ALP production. This study demonstrates its positive effect on the metabolism of the single cell and suggests wider uses of this drug in health protection and or in Regenerative Medicine therapies which are currently applied to the elderly.

Analysis of Variance↗

PubMed2004

Expression of vascular endothelial growth factor, apoptosis inhibitors (survivin and p16) and CCL27 in alopecia areata before and after diphencyprone treatment: an immunohistochemical study.

BACKGROUND: Alopecia areata (AA) is a relatively common inflammatory form of nonscarring hair loss of unknown pathogenesis, but possibly of autoimmune origin. Topical immunotherapy, using a potent contact allergen such as diphencyprone (DPC), is currently considered the most effective mode of treatment. However, the way in which DPC operates on hair follicles in AA still remains to be elucidated. Vascular endothelial growth factor (VEGF), essential for angiogenesis and vascular permeability, may be responsible for maintaining proper vasculature around hair follicles, and several studies provide evidence that apoptosis is a central element in the regulation of hair follicle and vascular regression. The cutaneous lymphocyte-associated antigen (CLA) and the skin-associated chemokine CCL27 highlight an important role for epithelial cells in controlling homeostatic lymphocyte trafficking. OBJECTIVES: To determine the expression pattern of VEGF, factor (F)VIII, survivin, p16, CD4, CD8, CLA and CCL27 in alopecic skin before and after treatment with DPC. Methods Immunohistochemical staining methods were applied to skin biopsy specimens obtained from alopecic areas of 14 patients before and after DPC treatment and from five healthy subjects. Sections were incubated with monoclonal antibodies against VEGF, FVIII, survivin, p16, CCL27, CLA, CD4 and CD8, and their immunohistochemical expression was evaluated by light microscopy. RESULTS: The intensity of VEGF staining in alopecic human hair follicles was significantly lower than in healthy scalp tissue. FVIII immunostaining showed a significantly reduced development of the microvasculature in AA in comparison with healthy scalp tissue. After DPC therapy, cells of alopecic hair follicles showed a significant increase of VEGF immunopositivity, and the number of capillary vessels expressing FVIII was markedly increased in comparison with untreated scalp tissue. The increase in microvessels was associated with strong survivin expression in endothelial cells after treatment. All alopecic specimens showed expression of p16 in the hair follicle outer root sheath (ORS), with a significant increase after therapy. After treatment we observed a significantly decreased number of CD4+ cells and an increase of CD8+ cells (CD4/CD8 ratio 0.85) in alopecic skin compared with untreated scalp tissue (CD4/CD8 ratio 3.45). Most of the T lymphocytes found in inflammatory skin lesions expressed CLA antigen and after therapy we observed a significantly higher CLA positivity in hair follicles (50% or more) in comparison with untreated alopecic scalp tissue. Alopecic patients showed a CCL27 immunopositivity significantly lower than in normal scalp tissue. After DPC therapy the labelling intensity for CCL27 showed a significant increase both in the ORS and in the inner root sheath; similarly, in the basal interfollicular keratinocytes we observed a moderate increase in CCL27 expression. CONCLUSIONS: Topical immunotherapy exerts an important role in angiogenesis, upregulating VEGF in human hair follicle keratinocytes and upregulating survivin to preserve endothelial cell viability. Moreover, it considerably alters the peribulbar CD4/CD8 ratio, restoring a condition close to normal scalp skin. Our study could contribute to explaining some aspects of AA pathogenesis that are still unknown and aid understanding of how DPC could act in this complex disease.

Adult↗

PubMed2004

In vitro H2O2 stress and patterns of mitochondrial damage in the NCTC 2544 continuous cell line--a morphologic and morphometric study.

The morpho-functional and energy condition of NCTC 2544 cells exposed for 1 hr to a high concentration of H2O2 (500 microM) was studied at 4 and 24 hr to investigate the short- and medium-term biomolecular mechanisms affecting energetic mitochondrial capability. Morphometric data obtained from ultrastructural investigations clearly showed significant modifications of the different mitochondrial parameters--numerical density (Nv), volume density (Vv) and Vv/Nv ratio, in interkinetic, apoptotic and mitotic cells after H2O2 exposure (from 4 to 24 hr). These results were confirmed by the detection at 24 hr of mitochondrial cytochrome c release in the cytosol, indicating impairment in mitochondrial membrane permeability. Data supporting these observations were obtained from the MTT test which showed reduced cell viability in H2O2 treated cultures at 4 hr and an even greater decrement at 24 hr. In conclusion our data imply that significant cause-effect relationships exist between the toxicity of reactive oxygen species (i.e. 500 microM H2O2) and morpho-structural mitochondrial damage in interkinetic, apoptotic and mitotic cells, respectively. They support previous results present both in the literature and also in one of our earlier papers which show that early nuclear DNA damage could initiate mitochondrial or intrinsic apoptotic pathway after H2O2 exposure.

Apoptosis↗

PubMed2004

Mitochondrial changes induced by natural and synthetic asbestos fibers: studies on isolated mitochondria.

Asbestos fibers, such as chrysotile and crocidolite, are known to have cytotoxic effects on different cell types. in vivo exposure to asbestos fibers can induce both fibrotic and malignant lung diseases , however, the mechanisms linking exposure to the subsequent development of the diseases are unknown. Numerous investigations suggest the involvement of reactive oxygen species (ROS). ROS are known to damage biological macromolecules including proteins, cell membrane lipids and nucleic acids; alterations of these essential cellular components can alter cell function and can drive the cell to neoplastic transformation or to cell death. Because the mitochondrial respiratory chain is an important source of ROS and RNS (reactive nitogen species) in the cells, we have investigated the effects of aqueous extracts of asbestos (natural and synthetic) fibers on some mitochondrial activities. Our data show that crocidolite fibers release substances in solution that may interfere directly with the mitochondrial cytochrome oxidase complex. Moreover, the calcium ions released from these fibers induce opening of the permeability transition pore of the inner membrane leading to a possible cytotoxic effect due to the release of apoptotic factors normally localized in the mitochondrial intermembrane space. In addition, crocidolite extracts enhance the mitochondrial production of ROS. No significant biochemical effects are exerted by chrysotile, either natural or synthetic, on isolated mitochondria. Nevertheless, all asbestos fibers tested induce morphological alterations visualized by transmission electron microscopy and morphometric analysis.

Animals↗

PubMed2003

Histomorphometric, biochemical and ultrastructural changes in the aorta of salt-loaded stroke-prone spontaneously hypertensive rats fed a Japanese-style diet.

BACKGROUND AND AIM: It is demonstrated that dietary habits play a role in cardiovascular diseases. In stroke-prone spontaneously hypertensive rats (SHRsp), concomitant salt loading and a Japanese-style diet greatly accelerate hypertension and the appearance of cerebrovascular lesions by directly damaging arterial vessels. A number of studies have characterised medium and small vessel lesions in SHRsp, but little attention has been paid to the changes in the wall structure of large arteries induced by exposure to a salt-enriched diet. The aim of this study was to investigate the effects of a Japanese-style diet and salt loading on the thoracic aorta. METHODS AND RESULTS: Two-month-old SHRsp were kept on a Japanese-style diet with 1% sodium chloride solution replacing tap water. Two months later, they were sacrificed and compared with age-matched or two-month-old control SHRsp kept on a standard diet and tap water in terms of the histomorphometry, ultrastructure and biochemical composition of the thoracic aorta. The vessel was consistently thicker in the four-month-old SHRsp (+20%, p < 0.05 vs two-month-old rats) regardless of diet. The salt-loaded SHRsp showed a significant reduction in elastic fibre density (-20%, p < 0.05 vs two-month-old rats) and an increase in the other matrix components (%), whereas the four-month-old controls showed preserved elastic fibres and a significant increase in the other matrix components (+65%, p < 0.05 vs two-month-old rats). There was a considerable increase in the amounts of 4-OH-proline (+147%), 5-OH-lysine (+174%) and desmosines (+360%) in the four-month-old controls vs their two-month-old counterparts (p < 0.01), but not in the salt-loaded animals. Ultrastructural analysis revealed clear damage and accelerated aging in the thoracic aorta of the salt-loaded SHRsp. CONCLUSIONS: Salt loading and a Japanese-style diet destabilize thoracic aorta architecture in SHRsp after two months of treatment.

Aging↗

PubMed2003

Exploring the damage limitation possibilities of mineral fibres for future integrated solutions: an in vitro study.

Owing to their possible carcinogenic effect, asbestos and other silica derivatives have been identified as priority substances for risk reduction and prevention of pollution. Neutralisation procedures have thus become a topical research subject in many European and American countries. In the present study, silica derivatives (asbestos-containing and asbestos substitutes like slag wool, rock wool, cement asbestos) were fully impregnated with an epoxy resin according to the procedure used for the in situ impregnation with viscous polymeric media, which penetrate and cement the fibres in place and reduce the risk of their dispersion in air. Untreated and treated samples were used to investigate their in vitro interaction with a human continuous epithelial cell line (NCTC 2544 keratinocytes) and test the resin's efficiency in passivating the surface activity of the fibrous particulate. SEM and morpho-quantitative data evidenced that impregnation with the epoxy resin modifies the mineral fibres' bioactivity (reduction of cell adhesion and decreased spread/round cell ratio) and demonstrated the value of in vitro cell testing after passivation as a risk-assessment procedure. These tests could be used for the rapid determination of the level of passivation of new synthetic mineral fibrous materials subjected to resin impregnation.

Air Pollutants, Occupational↗

PubMed2003

Tailoring biomaterial compatibility: in vivo tissue response versus in vitro cell behavior.

Biocompatibility relies essentially on surface phenomena, represented by cell-cell, cell-material and material (polymer)-protein interactions. An in vivo and in vitro experimental investigation was carried out on the biomaterials of two different classes with a good potential for in situ utilisation. Non-resorbable (Polypyrrole, Polyaniline, Polyimide) and resorbable (PLLA-PDXO-PLLA) materials for tissue engineering were studied for their overall tissue tolerance and cellular interactions. These non-resorbable polymers conceived for biosensor applications and implantable drug-delivery systems are intrinsically conductive. The PLLA-PDXO-PLLA triblock copolymer showed interesting tensile properties for bone and cartilage tissue engineering due to the presence of 1,5-dioxepan-2-one. In vitro and in vivo parallel studies showed an interesting correspondence: a) the cells in contact with the resorbable material that appeared to be capable of migratory-regenerative aspects in vitro exhibited good compatibility in vivo; whereas b) the non-resorbable materials, which are designed to remain in situ in vivo, were seen to have the potential to represent an adverse factor (inflammation, fibrotic reactions) that correlated with some aspects of cell behaviour in vitro.

Absorbable Implants↗

PubMed2002

Fabricated hyalS micropatterns and surface guidance of NCTC 2544 continuous cell line: an in vitro study.

Surface topography is important in establishing tissue organisation adjacent to implants, smooth surfaces generally being associated with fibrous encapsulation. By virtue of its large hydrated molecular volume and its capacity to form molecular matrix, hyaluronic acid can expand the interfibrillar collagen spaces to allow the movement of cells, although it can also hamper their locomotion. Low molecular-weight hyaluronan can also stimulate cell proliferation, especially at low concentrations. The aim of the present work was to evaluate in vitro the growth and migratory behaviour of NCTC 2544 keratinocytes cultured on different materials microstructured with hyaluronic acid or sulfated hyaluronic acid to assess the possibility of using these devices in the repair process of soft tissues. Ultrastructural morphological analyses, morphometric evaluations and detection of cytoskeletal elements were performed. Our observations provide evidence that micrometer-size parallel grooves of hyaluronic acid can influence cell growth behaviour since cells seeded onto the microstructured substrate arranged themselves according to a shape and an orientation that clearly reflected the chemotropism exerted on them by the two forms of acid. These data also highlight the importance of accurate microtexture fabrication. We intend to follow up these in vitro studies with in vivo experimental applications using PET and gelatin substrates structured with HyalS to evaluate wound healing responses, and to extend our investigations of the cytoskeletal modifications induced by different microstructures.

Adjuvants, Immunologic↗

PubMed2001

Electrophysiology of regular firing cells in the rat perirhinal cortex.

The electrophysiological properties of neurons in the rat perirhinal cortex were analyzed with intracellular recordings in an in vitro slice preparation. Cells included in this study (n = 59) had resting membrane potential (RMP) = -73.9 +/- 8.5 mV (mean +/- SD), action potential amplitude = 95.5 +/- 10.4 mV, input resistance = 36.1 +/- v 15.7 M omega, and time constant = 13.9 +/- 3.4 ms. When filled with neurobiotin (n = 27) they displayed a pyramidal shape with an apical dendrite and extensive basal dendritic tree. Injection of intracellular current pulses revealed: 1) a tetrodotoxin (TTX, 1 microM)-sensitive, inward rectification in the depolarizing direction (n = 6), and 2) a time- and voltage-dependent hyperpolarizing sag that was blocked by extracellular Cs+ (3 mM, n = 5) application. Prolonged (up to 3 s) depolarizing pulses made perirhinal cells discharge regular firing of fast action potentials that diminished over time in frequency and reached a steady level (i.e., adapted). Repetitive firing was followed by an afterhyperpolarization that was decreased, along with firing adaptation, by the Ca(2+)-channel blocker Co2+ (2 mM, n = 6). Action potential broadening became evident during repetitive firing. This behavior, which was more pronounced when larger pulses of depolarizing current were injected (and thus when repetitive firing attained higher rates), was markedly decreased by Co2+ application. Subthreshold membrane oscillations at 5-12 Hz became apparent when cells were depolarized by 10-20 mV from RMP, and action potential clusters appeared with further depolarization. Application of glutamatergic and GABAA receptor antagonists (n = 4), CO2+ (n = 6), or Cs+ (n = 5) did not prevent the occurrence of these oscillations that were abolished by TTX (n = 6). Our results show that pyramidal-like neurons in the perirhinal cortex are regular firing cells with electrophysiological features resembling those of other cortical pyramidal elements. The ability to generate subthreshold membrane oscillations may play a role in synaptic plasticity and thus in the mnemonic processes typical of this limbic structure.

Action Potentials↗

PubMed2001

Regional and subunit-specific downregulation of acid-sensing ion channels in the pilocarpine model of epilepsy.

Acid-sensing ion channels (ASICs) constitute a recently discovered family of excitatory cation channels, structurally related to the superfamily of degenerin/epithelial sodium channels. ASIC1b and ASIC3 are highly expressed in primary sensory neurons and are thought to play a role in pain transmission related to acidosis. ASIC1a, ASIC2a, and ASIC2b are also distributed in the central nervous system where their function remains unclear. We investigated here the regulation of their expression during status epilepticus (SE), a condition in which neuronal overexcitation leads to acidosis. In animals treated with pilocarpine (380 mg/kg) to induce SE, we observed a marked decrease of ASIC2b mRNA levels in all hippocampal areas and of ASIC1a mRNA levels in the CA1-2 fields. These changes were also observed after protective treatment from neuronal cell death with diazepam (10 mg/kg) and pentobarbital (30 mg/kg). These findings suggest a key role of channels containing ASIC1a and ASIC2b subunits in both normal and pathological activity of hippocampus.

Acid Sensing Ion Channels↗

PubMed2001

Cutaneous carcinomas and preinvasive neoplastic lesions. Role of MMP-2 and MMP-9 metalloproteinases in neoplastic invasion and their relationship with proliferative activity and p53 expression.

BACKGROUND: Metalloproteinases (MMPs) are thought to be involved in the process of destruction of basement membranes and stromal invasion by neoplastic epithelial cells. AIMS: In order to investigate the role of MMPs in cutaneous oncogenesis we studied the expression of MMP-2 and MMP-9 in 34 cases of epidermal preinvasive neoplastic lesions and invasive carcinomas. We also studied their relationship with the expression of tissue inhibitors of MMPs and with proliferative activity and p53 expression in neoplastic epithelial cells. RESULTS: MMP-9 was found to be focally expressed by neoplastic epithelial cells at the infiltrative edges in microinvasive carcinomas and in dyskeratotic foci in Bowen's disease and widely invasive carcinomas. Gradation of Mib-1 positivity and p53 expression was found with increasing abnormality in the spectrum of malignancy. CONCLUSIONS: Our results seem to suggest the involvement of MMPs in microinvasive carcinomas, which show also low proliferative activity and p53 expression, whether other factors seem to be more important in widely invasive carcinomas.

Aged↗