PubMed Health⌕ Search

Biomedical subjects

M Praet

Publications and source records attributed to M Praet.

At least 55 records · Page 3Linked to original sources
PubMed1993

In-vivo and in-vitro mitochondrial membrane damages induced in mice by adriamycin and derivatives.

A major limitation to a prolonged use of adriamycin (ADM) during a clinical treatment is its dose-dependent cardiotoxicity. This toxicity has been related to a general disturbance of the inner mitochondrial membrane structure and its essential biological functions, associated to the production of free radicals by the anthracyclines. 4'-Epiadriamycin (4'-epiADM), 4'-deoxyadriamycin (4'-deoxyADM), 4'-deoxy-4'-iodoadriamycin (4'-deoxy-4'-iodoADM) and 4'-demethoxydaunorubicin (4-demethoxyDNR) are ADM and daunorubicin (DNR) derivatives differing from their parent compounds by minor structural modifications. They are nevertheless documented as less cardiotoxic. Our purpose was to establish whether mitochondrial membrane damages induced in vivo in mice heart by those compounds are correlated with the free radical formation. Heart mitochondria of treated mice were isolated 48 h after a single drug injection in order to measure the acute mitochondrial toxicity. Enzymatic activities of complex I-III and complex IV of the mitochondrial respiratory chain, mitochondrial membrane fluidity and lipid peroxidation were measured. None of the ADM and DNR derivatives displayed a significant acute mitochondrial toxicity. A mitochondrial toxicity was however detected for 4-deoxyADM and 4-demethoxyDNR when drugs were given chronically, but it was strongly reduced as compared with ADM and DNR. Electron transfer between NADH and cytochrome c, formation of superoxide radicals and lipid peroxidation were measured in vitro for the various drugs. Comparison of the in-vivo and in-vitro results provides evidence that free radical production explains only partly the in-vivo toxicities.

Animals↗
PubMed1993

Comparison of adriamycin and derivatives uptake into large unilamellar lipid vesicles in response to a membrane potential.

The uptake of adriamycin (ADM) and several derivatives into large unilamellar vesicles (LUV) displaying a transmembrane potential and having a lipid composition close to that of the inner mitochondrial membrane has been measured. Drug association to neutral liposomes, made of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) (70:30, w/w) was shown to be potential-dependent: in the absence of potential, accumulation of drug was almost undetectable, whereas between 11 and 50 nmol of drug/mumol phospholipid, depending on the anthracycline used, was associated to LUV exhibiting a membrane potential after 1 h incubation. Association of drugs to LUV with a lipid composition closer to that of the inner mitochondrial (cardiolipin, CL, 20%; PC 50%; PE, 30%, w/w) and displaying a membrane potential is higher than with neutral vesicles (between 40 and 76 nmol of anthracycline/mumol phospholipid after 1 h incubation). Since it is known that ADM and derivatives have a high affinity for CL, a fraction of the associated drug may bind to CL on the outer side of the vesicles. This was confirmed by the fact that, in the absence of potential, between 40 and 56 nmol of anthracycline/mumol phospholipid was still associated to LUV containing CL. In order to discriminate between drug adsorbed at the surface of the LUV and drug accumulated inside the LUV, an anthracycline fluorescence quencher (I-) was used. It was shown on neutral LUV displaying a membrane potential, that between 55 and 81% of the associated drug is actually entrapped inside the vesicles, inaccessible to the quencher. These percentages decreased to between 41 and 68%, respectively, in the presence of LUV containing CL and exhibiting a membrane potential, whereas for LUV of the same composition but displaying no membrane potential almost all the associated drug is adsorbed on the outer face of the LUV, accessible to the quencher, and likely bound to CL. This study brings evidence that antitumour anthracyclines despite important structural homologies do not accumulate to the same extent into vesicles mimicking the lipid composition and the membrane potential of mitoplasts. This ability to reach the matrix compartment of mitochondria could partly explain the differences of cardiotoxicities associated to anthracyclines with closely related molecular structure.

Antibiotics, Antineoplastic↗
PubMed1993

Primary corneal epithelial dysplasia (corneal intraepithelial neoplasia).

A 49 year-old man consulted in March 1980 for pain, eyestrain and decreased vision at the right eye. He presented a slightly elevated and transparent lesion, strictly limited to the corneal epithelium and treated with eyedrops until November 1980. The patient was seen again 12 years later in October 1992 with still the same complaints and a practically unchanged corneal lesion. The diagnosis of primary corneal epithelial dysplasia (Corneal Intraepithelial Neoplasia-Corin) was made and the abnormal epithelium completely removed under local anesthesia. After the operation the cornea became normal again and the patient free of complaints. The authors discuss the clinical symptoms, pathology, pathogeny and treatment of primary corneal epithelial dysplasia (Corneal Intraepithelial Neoplasia-Corin).

Carcinoma in Situ↗
PubMed1993

Down-staging prostate cancer. Is it possible by androgen depletion and Mitomycin C therapy?

The study was carried out in order to investigate the possibility of tumor reduction in prostate cancer patients. As a reduction of the primary tumor was observed with hormonal treatment and complete response of soft tissue tumor markers with Mitomycin C, this combined treatment was given in seven patients to evaluate if it was able to down-stage those cases which were thought to be incurable (T3N1-2M0/T4N0-2M0). Although the clinical evaluation suggested a significant down-staging, the explorative lymphadenectomy was unable to confirm this. The proposed treatment is able to reduce the tumor bulk significantly of the primary cancer as well as of its metastases; progression during the treatment was not seen.

Aged↗
PubMed1993

[Liver and liver segment transplantation in adults and children. Experiences with the first 50 cases].

The experience with 50 liver transplants performed in 42 patients within a 16 months period is reviewed. There were 15 transplantations in 12 children and 35 in 30 adults. The series was analysed regarding the source of transplant, i.e. living related (LR) n = 2 or cadaver (CAD) n = 48, graft size i.e. full size (FS) n = 34, reduced size (RED) n = 12 and split grafts (SG) n = 4. Regarding the preservation time or operating time there was no statistically significant difference between the groups. The overall function rate was 88%, 94% for FS and 73.4% for the remaining partial grafts (RED and SG). The difference was not significant (p = 0.062). Biliary leakage occurred in one (2%) reduced graft. Hepatic artery complications (kinking, intima dissection) were encountered in two (4%) patients receiving a FS. It is concluded that the use of partial liver grafts is a safe procedure to alleviate organ shortage while preservation time and operating time are not prolonged as compared to the transplantation of full size grafts.

Adolescent↗
PubMed1992

Concentrations of 5-ASA and Ac-5-ASA in human ileocolonic biopsy homogenates after oral 5-ASA preparations.

Intramucosal 5-aminosalicylic acid (5-ASA) and acetylated 5-ASA (Ac-5-ASA) concentrations were determined in ileocolonic biopsy specimens from 61 patients with irritable bowel syndrome treated for one week with near equimolar doses of different slow release preparations of 5-ASA (Claversal, Asacol, or Pentasa) or azo-bound drugs (Salazopyrin, Dipentum). The transit time in these patients was accelerated by a laxative, metoclopramide, and colonic lavage. The presence of 5-ASA in the mucosa was confirmed by autofluorescence. The highest concentrations of 5-ASA were obtained after Asacol (mean (SEM), 298.5 (37.3) ng/mg wet wt), followed by Claversal 500 mg (108.8 (11.7) ng/mg wet wt) and Pentasa (25.7 (2.2) ng/mg wet wt). Very low concentrations only were observed after Claversal 250 mg (0.3 (0.03) ng/mg wet wt), Salazopyrine (1.2 (0.1) ng/mg wet wt), and Dipentum (11.0 (3.2) ng/mg wet wt). The results for Ac-5-ASA were similar but the concentrations were generally lower. Serum concentration-time curves over eight hours were obtained from 34 healthy volunteers after a single oral dose of 400 to 500 mg of the different drugs. For the slow release forms, an apparently inverse relationship was found between the area under the curve of the serum concentrations and the intramucosal concentrations, supporting the importance of the local availability of the drug. This inverse relationship was absent for the azo-bound drugs. Colonic washout induced mechanical removal of intraluminal 5-ASA with a secondary disturbance in absorption resulting in a rapid decline in the serum concentrations. However, only for Dipentum did this result in significantly lower 5-ASA mucosal concentrations. This is the first reported attempt to evaluate the mucosal availability of 5-ASA after different oral preparations. It shows that where transit time is accelerated higher mucosal concentrations occur after slow release preparations (except for Claversal 250 mg) than after azo-bound drugs. Additional studies are necessary to correlate these concentrations with clinical effects.

Administration, Oral↗
PubMed1992

Primary pulmonary Hodgkin's disease.

26 months after the onset of alcohol-induced pain, a diagnosis of primary pulmonary Hodgkin's (PPHD) disease could be made in a 34-year-old woman. Standard radiology of the thorax remains normal up to 18 months after the onset of symptoms. A short review of the literature concerning PPHD is given.

Adult↗
PubMed1991

Vimentin expression of renal cell carcinoma in relation to DNA content and histological grading: a combined light microscopic, immunocytochemical and cytophotometrical analysis.

An immunocytochemical and cytophotometrical analysis of 30 renal cell carcinomas was carried out in order to investigate the expression of cytokeratin and vimentin in relation to the ploidy and mitotic index. Thirty renal cell carcinomas were studied using monoclonal antibodies CAM 5.2 and anti-vimentin in a biotin-streptavidin staining procedure. The renal cell carcinomas were classified according to the criteria of Fuhrman with a nuclear grading from I to IV. All carcinomas expressed cytokeratin, whereas co-expression with vimentin was present only in 53%. Expression for both intermediate filaments was present in aneuploid tumours with a marked nuclear pleomorphism and was more frequently related to a tubulo-papillary and pseudosarcomatous growth pattern. It is suggested that vimentin expression in renal cell carcinomas may be useful as a prognostic index in addition to nuclear grade. DNA content, mitotic rate and tumour stage.

Biomarkers, Tumor↗
PubMed1991

Interstitial pneumonitis and pulmonary vasculitis in a patient taking an L-tryptophan preparation.

A case is presented of interstitial pneumonitis and pulmonary vasculitis ascribed to the ingestion of an L-tryptophan preparation. An unintended rechallenge supported the causal relationship. There was neither myalgia nor peripheral eosinophilia. Bronchoalveolar lavage fluid contained 12% eosinophils but few were present in the surgical lung biopsy specimen. Lung infiltrates receded after withdrawal of the drug and treatment with steroids. Dyspnoea and pulmonary hypertension persisted. Cyclophosphamide had no effect. Sclerodermiform skin lesions appeared as a late sequel. Chromatographic analysis of the L-tryptophan revealed no suspect impurities.

Aged↗
PubMed1990

Structure of the adriamycin-cardiolipin complex. Role in mitochondrial toxicity.

Adriamycin and its derivatives are among the most efficient antimitotics used in clinical therapy. A specific cardiotoxicity places a limit on the total dose of adriamycin that may be administered. The mechanism of cardiac toxicity is complex. Data accumulated from in vitro and in vivo studies indicate a possible common cause for the inhibition of numerous enzymes and tissue degradation by a free radical mechanism: the binding of adriamycin to the inner mitochondrial membrane cardiolipin. The structure of the adriamycin-cardiolipin complex has been investigated by using physico-chemical techniques and via conformational analysis. The results open a rational way to design new structures that are less cardiotoxic.

Animals↗
PubMed1989

Increasing therapeutic effect and reducing toxicity of doxorubicin by N-acyl dehydroalanines.

Doxorubicin toxicity is generally accepted to be free radical-mediated. N-Substituted dehydroalanines (indexed as AD compounds) are capto-dative olefins which react and scavenge free radicals, especially the superoxide anion (O2-) and hydroxyl radical (HO). AD-20, an orthomethoxyphenylacetyl dehydroalanine derivative, decreases the mortality of mice when administered before an acute single dose or multiple non-toxic doses of doxorubicin. Doxorubicin administered to mice induces elevated serum transaminase levels, and the pretreatment of mice with AD-20 decreases significantly these serum enzymatic activities. Preliminary histological examinations suggest that these serum transaminase elevations reflect most likely liver injury. In addition to its cardiotoxicity, doxorubicin induces a severe bone marrow depletion. Although this initial decrease in the peripheral leukocytes induced by doxorubicin is not prevented by the administration of AD-20, it produces a fast recuperation in the white blood cells levels after 1 week, supporting a protective effect at this level. Moreover, the antitumor effect of doxorubicin in L1210 tumor-bearing mice was enhanced when AD-20 was injected before doxorubicin. We postulate that these effects may be related to the free radical scavenging ability of AD-20.

Alanine↗
PubMed1988

A new class of free radical scavengers reducing adriamycin mitochondrial toxicity.

Beef heart mitochondria were incubated with ADM and NADH. An adriamycin semiquinone radical was detected using ESR spectroscopy. The semiquinone radical production rate is decreased upon addition of a scavenger (AD 20) in the reaction medium. NMRI mice were treated with AD 20 (70 mg/kg, i.p.) 15 min prior ADM injection (20 mg/kg, i.p.) or with ADM alone. Heart mitochondria were isolated 48 hr later. The enzymatic activities of complex I-III and complex IV of the mitochondrial respiratory chain were strongly depressed in animals receiving ADM alone, whereas these activities were almost completely restored in animals receiving AD 20 and ADM. Fluorescence depolarization measurements indicated that only mice treated with ADM alone presented a decreased fluidity of their cardiac mitochondrial membrane.

Alanine↗
PubMed1988

Detection of lytic antimycobacterial antibodies by immune lysis of liposomes sensitized to tuberculin.

Two procedures were used in order to incorporate purified protein derivative tuberculin (PPD) from M. tuberculosis, strain H37Rv, into calcein-containing liposomes: formation of multilamellar vesicles (MLV) in a PPD solution or exposure of preformed MLV to this solution. Immune lysis of these PPD-sensitized MLV was studied in the presence of a hyperimmune anti-M. tuberculosis sheep serum using a specific pathogen-free rabbit serum as a source of complement. A 50% release of encapsulated calcein was observed spectrofluorometrically after 30 min and remained unchanged up to 2 h. The release of calcein in the absence of complement or of anti-H37Rv serum or by liposomes which did not contain PPD never exceeded 1-2%. Liposomes formed in PPD solution were more sensitive to anti-H37Rv serum than preformed liposomes exposed to PPD. Trials with human sera from ten tuberculous patients revealed the presence of specific lytic immunoglobulins. In the presence of sera from skin test negative, non-tuberculous subjects, calcein release was significantly lower. This opens the way to a new method for the study of the humoral immunity in tuberculosis.

Animals↗
PubMed1988

Hypoplastic left heart syndrome and 45X karyotype.

A review of 63 patients with 45X karyotype (Turner's syndrome) admitted to a hospital from 1972 to 1985 showed that 20 (32%) had one or more major cardiac malformations (mostly coarctation and aortic stenosis). Four (20%) died in the neonatal. One infant had mitral stenosis and severe aortic stenosis and died at the age of 35 days. The three (15%) other patients who died had a typical hypoplastic left heart syndrome, with an atretic aortic valve in two and pinpoint aortic valve in one. Turner's syndrome was clinically suspected in three of the cases. One of these had mosaicism (46XX,45X) the others had a 45X pattern. During the same period (1972-85) 39 patients (14 girls and 25 boys) were admitted with diagnosis of hypoplastic left heart syndrome. Three (21.4%) girls had a 45X karyotype. The high incidence of hypoplastic left heart syndrome in Turner's syndrome and of Turner's syndrome in girls with hypoplastic left heart syndrome suggests that hypoplastic left heart syndrome can be another expression of the 45X karyotype.

Female↗