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Biomedical subjects

M Losi

Publications and source records attributed to M Losi.

9 recordsLinked to original sources

Ultrastructural identification of a membrane-like structure on the surface of normal articular cartilage.

Cytochemical and immunocytochemical approaches have been applied to the study of the surface of articular cartilage in humans, bovine and rats. Specimens were fixed in situ or soon after bioptic sampling with chemicals able to preserve and visualize proteins (glutaraldehyde, tannic acid), lipids (osmium tetroxide, malachite green, uranyl acetate) and proteoglycans (toluidine blue O, cuprolinic blue, cetyl pyridinium chloride). Mixtures of reagents were also used. Oriented serial thin sections were observed as such or after treatment with chemicals (chloroform-methanol, Triton X 100) or enzymes (chondroitinases, hyaluronidases, trypsin). Hyaluronan was detected by the use of glial-hyaluronate-binding-protein and antibodies against it. High concentration of osmium tetroxide or fixatives containing markers for lipid or for proteoglycans revealed that the surface of the articular cartilage, in all animal species examined, was covered by mono-multilayered discontinuous three-laminar sheets, which could be partly removed by chloroform-methanol and Triton X 100, were sensitive to hyaluronidase, chondroitinase and trypsin, and were immunopositive for hyaluronan. Each three-laminar sheet was 12-14 nm thick, was always separated from the cartilage itself and could be easily displaced. It is proposed that the surface of normal articular cartilage is covered by a discontinuous mono/multilayered pseudo-membrane, that can be better preserved by fixatives injected into the joint cavity and seems to consist of phospholipids, glycosaminoglycans and proteins. This membrane-like structure might have a protecting role in preventing direct contacts between the articular cartilage and toxic agents present in the synovial fluid and/or exert a lubricating effect within the articular joint.

Animals

Annular abscesses and GRF glue.

Infective endocarditis of the aortic prosthesis is a serious complication of valve surgery. The correction of this condition is difficult and complex procedures are often required. Two patients with aortic bioprosthetic endocarditis complicated with annular abscesses were operated on. The aortic valve was replaced with a bioprosthesis and the annular abscesses were debrided and closed with the aid of gelatin-resorcin-formalin (GRF) glue, which completely sealed the abscess cavities. One year later the patients were asymptomatic and had no clinical or echocardiographic signs of aortic incompetence.

Abscess

Synthesis and physicochemical characterization of a new material (PUPA) based on polyurethane and poly(amido-amine) components capable of strongly adsorbing quantities of heparin.

The synthesis of new materials (PUPAs) based on a commercial polyurethane and a heparin-complexing polymer, poly(amido-amine), was studied. PUPAs are capable of adsorbing heparin because the basic nitrogens of poly(amido-amine), once protonated, interact with the negative charges carried by the heparin molecule. Six different samples of PUPA were synthesized having a varied ratio of the components. The quantity of basic nitrogen on the surface and the bound heparin for each sample was determined. Two different kinds of heparin are present on a PUPA surface: one is strongly bound but can be detached by 0.1 M NaOH solution, the other is physically adsorbed and is slowly released by a stream of saline solution. A relationship between the quantity of strongly bound heparin and basic nitrogen was found. SEM and FTIR-ATR analysis were performed on all the PUPA samples. The mechanical characteristics change according to chemical composition.

Adsorption

Long-term experience with indapamide.

Indapamide, 2.5 mg administered once daily for periods up to 36 months, was found to be safe and effective for the long-term control of mild to moderate hypertension. The effects of hydrochlorothiazide, 50 mg, and indapamide, 2.5 mg, were studied in two randomized, double-blind, multicenter trials. Data from the two multicenter trials (20 study sites) were pooled for purposes of comparison. Significant reductions in systolic and diastolic blood pressure, with patients in both supine and standing positions, occurred in both groups within the first 8 weeks of treatment. This effect was maintained throughout the active treatment period. Success, as determined by the therapeutic success rate (percentage of patients with decreases of standing phase V diastolic blood pressure of at least 10 mm Hg or to below 90 mm Hg), occurred in 53% of the patients given hydrochlorothiazide and in 56% of the indapamide-treated patients. During the study period, the nature, frequency, and severity of adverse reactions were similar for both groups. There was no clinically significant difference between the treatment groups for the laboratory assessments. Patients who completed the multicenter trials were eligible for participation in an ongoing long-term extension study of the safety of indapamide. Data are available for periods up to 36 months and demonstrate neither augmentation of clinical or laboratory adverse effects nor any potentially harmful indicators that could be attributed to prolonged treatment.

Adult

Multi-centre clinical investigation of indapamide in the United States: a review.

Indapamide, a new indoline antihypertensive agent, has been the subject of a worldwide programme to develop this drug for general clinical use. The results are described of the multi-centre U.S. clinical programme demonstrating the effectiveness and tolerance of indapamide for the treatment of hypertension. All work was conducted under U.S. Federal Food and Drug Administration guidelines, and resulted recently in a New Drug Application. A total of 1891 subjects or patients participated in 27 separate studies conducted by 91 investigators. In controlled clinical trials comparing 2.5 mg indapamide once daily with 50 mg hydrochlorothiazide once daily for 40 weeks in patients with mild to moderate essential hypertension, indapamide produced a reduction of supine blood pressure of -9.5/-14.3 mmHg as compared with -7.6/-11.4 mmHg for hydrochlorothiazide. In combination with methyldopa, propranolol, clonidine, guanethidine and hydralazine, indapamide consistently produced a greater decrease in arterial pressure than did those agents given alone. Indapamide added to these step-care agents did not result in a meaningful increase in adverse reactions. Indapamide has been the subject of a long-term safety study in which over 100 hypertensive patients have been followed up for 2 years or longer. During this period of time, indapamide was well tolerated and remained effective. No biochemical, electrocardiographic or ophthalmological changes were associated with its use. Other studies with indapamide are discussed describing the systemic and renal haemodynamic effects, pharmacokinetic properties and special safety studies conducted with this agent. The use of indapamide in patients with hepatic or renal impairment is reviewed in detail.

Antihypertensive Agents

Circulating endothelial-like cells in arterial peripheral blood of hypercholesterolemic rabbits.

In blood smears obtained from the central ear artery of rabbits after 7 days of cholesterol-rich diet, a high number of well staining cells, morphologically very similar to endothelial cells may be found. After 15 days, macrophage-like cells are found in the smears together with degenerated (endothelial or macrophagic) cells. The presence of circulating endothelial cells is in agreement with the findings of de-endothelialized areas of aortic intima observed at scanning and transmission electron microscopy in short term hypercholesterolemic rabbits.

Animals