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Biomedical subjects

M Tonetti

Publications and source records attributed to M Tonetti.

At least 55 records · Page 3Linked to original sources
PubMed1994

Digital image processing. II. In vitro quantitative evaluation of soft and hard peri-implant tissue changes.

The aim of this study was to evaluate the ability of computer-assisted densitometric image analysis (CADIA) to detect small changes in mineralized and nonmineralized tissues adjacent to dental implants and to correlate these changes with CADIA values. A section of a pig mandible including all soft tissues and in which a hollow cylinder ITI Bonefit implant with an artificial mesial and a buccal infrabony defect was placed was used to obtain pairs of standardized radiographs. Series of radiographs were obtained with exposure times of 0.13, 0.20, 0.44, and 0.53 s. Specimens of mineralized or nonmineralized tissues were placed arbitrarily in the defects before each radiographic exposure. The radiographs were captured through a video camera, digitized and stored in a personal computer. Every radiographic image was then subtracted from a baseline one without any change. The result of the subtraction was evaluated with CADIA. A linear correlation (r2 = 0.99) was found between the bone chips (1-5 mg of dry weight) placed in the mesial defect and the CADIA values. Bone chips in the buccal defect (behind the implant), however, were not detected unless their weight reached 14 mg or more. For conventionally exposed radiographs, it was not possible to recognize soft tissue specimens (1-6 mg), either in the buccal or the mesial defect. However, when "underexposed" radiographs (exposure time: 0.13 s) were obtained, a linear correlation (r2 = 0.80) was calculated for soft tissue specimens in the mesial defect and CADIA values. In normally exposed radiographs, the CADIA system could detect even the smallest change in bone density (bone chip of 1 mg of dry bone weight) and correlated almost linearly with these changes. Provided that the radiographic images are obtained with standardized geometry and normal exposure time, the tissue density changes detected by this system within bone defects represent only mineralized tissue changes. By underexposing radiographs, CADIA may even reveal soft tissue changes around dental implants.

Absorptiometry, Photon↗
PubMed1994

Periodontal regeneration of human infrabony defects (V). Effect of oral hygiene on long-term stability.

The aim of this investigation was to assess the role of supportive periodontal care in the maintenance of clinical attachment gained, after surgical treatment according to the principles of GTR, in deep infrabony defects. Following GTR treatment, 40 deep infrabony defects in 23 patients gained 4.1 mm of probing attachment level (PAL) after 1 year of stringent plaque control. In the subsequent 3 years, 15 patients (22 sites, group A) were recalled every 3 months. In this group, the gained attachment level remained stable. Conversely, 8 patients (18 sites, group B), who received only sporadic care, lost at 4 years, 2.8 +/- 2.7 mm of the PAL gained at 1 year. Group A patients had significantly lower full mouth plaque and bleeding scores than group B at 4 years. Furthermore, detection of bleeding on probing, plaque, P. gingivalis and P. intermedia was significantly more frequent in regenerated sites of group B patients. Risk assessment analysis indicated that GTR sites in patients receiving only sporadic care had a 50-fold increase in risk of PAL loss between 1 and 4 years with respect to patients undergoing regular recall. It was concluded that stability of gained clinical attachment was dependent upon stringent oral hygiene.

Adolescent↗
PubMed1994

Clinical efficacy and toxicity of doxorubicin encapsulated in glutaraldehyde-treated erythrocytes administered to dogs with lymphosarcoma.

Doxorubicin was encapsulated in canine erythrocytes, treated with 0.32% glutaraldehyde, and administered at a dosage equivalent to 30 mg of free doxorubicin/m2 of body surface area to dogs with diagnosis of lymphosarcoma. Compared with administration of free doxorubicin, this method of drug delivery substantially reduced peak plasma concentration and prolonged higher plasma concentration of doxorubicin. As such, this method was comparable to continuous IV infusion. Previous studies have indicated this method's potential for reduction in toxic side effects, particularly cardiotoxicosis, while allowing higher total doses of doxorubicin to be administered. In this study, doxorubicin encapsulated in glutaraldehyde-treated erythrocytes induced a triphasic exponential decay of doxorubicin from plasma, the highest relative contribution to the total area of the curve being the terminal phase. The treatment was effective in inducing complete and partial remissions of lymphosarcoma, with minimal acute toxicosis and no evidence of cardiotoxicosis. However, substantial, unanticipated, chronic, nonregenerative myelosuppression developed, and was mot strikingly expressed as profound thrombocytopenia. Efforts to ameliorate or circumvent this toxic effect will be required prior to further consideration of this doxorubicin delivery system for treatment of systemic neoplasia.

Animals↗
PubMed1993

Enhanced formation of reactive species from cis-diammine-(1,1-cyclobutanedicarboxylato)-platinum(II) (carboplatin) in the presence of oxygen free radicals.

Experiments were designed to investigate the influence of oxygen free radicals on the rate of conversion of the anticancer drug cis-diammine-(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA) to reactive species able to bind to DNA. A system containing the Fe-EDTA chelate and ascorbate was used to generate free radicals. The rate of drug conversion to by-products, during incubation in chloride-free phosphate buffer at 37 degrees, was determined by HPLC analysis and found to be approximately 10 times faster in the presence of the free radical generating system, compared to CBDCA alone. The hydroxyl radical scavenger, mannitol, was able to reduce the rate of CBDCA conversion significantly, while an enhancing effect was observed in the presence of superoxide dismutase. The platinum containing species, which are formed in the presence of free radicals, were demonstrated to react with isolated salmon sperm DNA. The rate of platinum binding to DNA during incubation of CBDCA in the presence of the Fe-EDTA/ascorbate system was markedly enhanced. No effect on platinum binding to DNA during incubation with cis-diamminedichloroplatinum(II) (CDDP) in the same experimental conditions was observed, thus excluding an increased susceptibility of DNA itself to binding of platinum, due to DNA damage induced by free radicals. These findings support the hypothesis that the increased conversion of CBDCA, previously observed in our laboratory, which occurs in the presence of hemoglobin could be mediated by a Fenton-like reaction resulting in oxygen free radical production, thus providing potential clues to improvements in the clinical use of this drug.

Animals↗
PubMed1992

Enhanced intracellular activation of carboplatin in hemoglobin-synthesizing versus undifferentiated erythroleukemic cells.

The formation of DNA interstrand cross-links following exposure of target cells to the antineoplastic drugs Cisplatin and Carboplatin was measured in murine erythroleukemic cells either native or induced to differentiate and to synthesize hemoglobin by treatment with hexamethylene bisacetamide. The uptake of both drugs was identical in the uninduced and the induced cells, thus excluding differences in permeability due to differentiation. Both cell types formed comparable levels of DNA interstrand cross-links when submitted to treatment with Cisplatin. Conversely, significant differences were observed after exposure to Carboplatin. Specifically, the induced, hemoglobin containing cells showed significantly enhanced intracellular activation of the drug and subsequent binding to DNA, compared to the uninduced cells. These data suggest that, in agreement with previous results obtained with erythrocytes, the hemoglobin present in the committed cells enhances the aquation process that mediates the activation of Carboplatin.

Acetamides↗
PubMed1992

Interaction of carboplatin with carrier human erythrocytes.

The antineoplastic drug Carboplatin (CBDCA) was encapsulated in human erythrocytes by means of transient hypotonic hemolysis, followed by isotonic resealing. Up to 5 mg/ml of packed cells could be entrapped, with about 70% cell recovery. In vitro incubation of the CBDCA-loaded erythrocytes in autologous plasma caused a very slow release of the drug from the cells (12% approximately in 3 h). The encapsulation conditions, performed at a low hematocrit, in order to obtain high amounts of the drug inside the carriers, impaired the metabolic properties of the loaded erythrocytes significantly. In particular, an almost complete disappearance of GSH was observed. Analysis of the intraerythrocytic metabolism of CBDCA showed that, in spite of its relatively high stability in aqueous solutions, in hemolysates and in the loaded erythrocytes a significant percentage of CBDCA is rapidly converted to other species that still retain an antiproliferative activity in vitro. This fast conversion could be extensively inhibited by previous conversion of oxyhemoglobin to methemoglobin or carbomonoxyhemoglobin, suggesting an important role of heme iron in this process. Encapsulation of CBDCA in selectively targeted human erythrocytes may represent a therapeutic strategy for increasing the drug concentration in specific organs, notably liver.

Carboplatin↗
PubMed1991

Intracellular pH regulates the production of different oxygen metabolites in neutrophils: effects of organic acids produced by anaerobic bacteria.

The effects of short chain carboxylic acids (SCCA), namely succinic, butyric, and iso-butyric, on neutrophil metabolic activation were assessed. SCCA induced a significant decrease in O2.- recovery and chemiluminescent response in neutrophils activated with the diacylglycerol analog tetradecanoyl-phorbol-acetate (TPA). SCCA did not alter O2 consumption, H2O2 production, or the calorimetrically determined energy expenditure occurring during the metabolic burst. SCCA also induced a significant acidification of intracellular pH (pHi). These results are consistent with an increased divalent versus univalent O2 reduction performed by the NADPH oxidase at a more acidic intracellular pH.

Bacteria, Anaerobic↗
PubMed1991

Divergent effect of the anaerobic bacteria by-product butyric acid on the immune response: suppression of T-lymphocyte proliferation and stimulation of interleukin-1 beta production.

The effects of short-chain fatty acids (SCFA) produced by anaerobic bacteria, namely propionic, butyric and iso-butyric on T-cell proliferation was investigated. A dose-dependent inhibition of both phytohemagglutinin-induced blastogenesis and mixed lymphocyte culture was observed in the millimolar range of SCFA concentrations. The tested SCFA displayed different levels of suppression. The degree of activity was in the following order: butyrate greater than propionate greater than isobutyrate. T-cell inhibition was partially reversed, at least for propionic and isobutyric acids, by increasing the concentration of macrophages in the assay system. Furthermore, butyric acid displayed an interesting biphasic stimulation of monocyte interleukin-1 beta production, a cytokine with a powerful bone-resorbing activity. Since millimolar concentrations of SCFA are present in gingival fluid from periodontal pockets, the observed results support the role of these by-products of anaerobic metabolism in the pathogenesis of periodontal diseases.

Alveolar Bone Loss↗
PubMed1991

Pharmacokinetic properties of doxorubicin encapsulated in glutaraldehyde-treated canine erythrocytes.

Canine erythrocytes were loaded with the antineoplastic drug doxorubicin and then treated with 0.16% glutaraldehyde. This procedure has been previously shown to slow down the efflux of doxorubicin from erythrocytes and to result in the selective targeting of the carrier erythrocytes to liver. Three dogs were treated each with 2 different schedules of IV bolus administration of doxorubicin (0.4 mg/kg of body weight): free drug and doxorubicin encapsulated in glutaraldehyde-treated erythrocytes. The 2 treatments yielded consistent differences in the plasma pharmacokinetic properties of doxorubicin and of its only metabolite, doxorubicinol. A triphasic exponential decay of doxorubicin plasma concentrations was observed on injection of the free drug. Conversely, in the case of erythrocyte-encapsulated doxorubicin, 4 phases of plasma concentrations of doxorubicinol were found. The plasma concentrations of doxorubicinol, after a steady increase during the first hour, followed patterns of decay comparable to those of the parent drug. On the basis of the kinetic variables calculated with the 2 administration schedules, area under curve concentrations of plasma doxorubicin were 136 micrograms.h/L (free infusion) and 734 micrograms.h/L (erythrocyte-encapsulated drug). Significant alterations of hematologic and hematochemical factors were not observed in the 3 dogs during and after the 2 treatments. On the basis of our findings, doxorubicin-loaded and glutaraldehyde-treated erythrocytes may potentially be used in the treatment of systemic and hepatic tumors in dogs.

Animals↗
PubMed1991

[The therapy of odontogenic abscesses. Pharmacological experimentation with lincomycin or amoxicillin].

A clinical and microbiological study was carried out to assess the therapeutic efficacy of two different antibiotics, lincomycin and amoxicillin, in the treatment of patients suffering from odontogenic abscesses. Microbiological analyses revealed that the majority of infections were supported by mixed aerobic and anaerobic bacterial flora. The assessment of clinical parameters clearly showed that patients receiving pharmacological treatment with lincomycin achieved a more rapid and efficacious recovery from disease in comparison to patients treated with amoxicillin.

Abscess↗
PubMed1990

Receptor-stimulated actin polymerization requires cytoplasmic acidification in human PMNs.

Cytoplasmic alkalinization has received considerable attention as a regulatory event In cell growth, transformation and signal transduction (Busa, W.B. (1986) Annu. Rev. Physiol. 48, 389-402 and Moolenar, W.H. (1986) Annu. Rev. Physiol. 48, 363-376). In contrast the current paper presents evidence for the role of an early cytoplasmic acidification, during signal transduction in the polymorphonuclear leukocyte (PMN). Following PMN stimulation with a chemotactic peptide, there is a significant decrease in cytoplasmic pH concomitant with a dramatic increase in cytoskeletal actin. The data indicate that this drop in pHi is necessary, but not sufficient, for signal transduction leading to cytoskeletal reorganization in these cells.

Actins↗
PubMed1990

Multiple small molecular weight guanine nucleotide-binding proteins in human erythrocyte membranes.

Native membranes from human erythrocytes contain the following G proteins which are ADP-ribosylated by a number of bacterial toxins: Gi alpha and Go alpha (pertussis toxin), Gs alpha (cholera toxin), and three proteins of 27, 26 and 22 kDa (exoenzyme C3 from Clostridium botulinum). Three additional C3 substrates (18.5, 16.5 and 14.5 kDa) appeared in conditions of unrestrained proteolysis during hemolysis. SDS-PAGE separation of erythrocyte membrane proteins followed by electroblotting and incubation of nitrocellulose sheets with radiolabeled GTP revealed consistently four GTP-binding proteins with Mr values of 27, 26, 22 and 21 kDa. Although a 22 kDa protein was immunochemically identified as ras p21, the C3 substrate of 22 kDa is a different protein probably identifiable with a rho gene product. Accordingly, at least five distinct small molecular weight guanine nucleotide-binding proteins, whose functions are so far undetermined, are present in native human erythrocyte membranes.

ADP Ribose Transferases↗