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Biomedical subjects

R A Muzzarelli

Publications and source records attributed to R A Muzzarelli.

At least 19 recordsLinked to original sources
PubMed1999

Native, industrial and fossil chitins.

Countless living organisms continuously synthesize and degrade chitin enzymatically, for nutritional, morphogenetic and defensive or aggressive purposes. Chemically modified chitins are important in the light of their biochemical significance in medicine and crop protection; their environmentally friendly behaviour permits industrial exploitation of the huge chitinous biomasses generated by fishing activities and biotechnology. Chitin is promptly metabolized in sediments, and fossil chitin is not frequently encountered.

Animals↗
PubMed1999

Analytical biochemistry and clinical significance of N-acetyl-beta-D-glucosaminidase and related enzymes.

Human N-acetyl-beta-D-glucosaminidase, N-acetyl-alpha-D-glucosaminidase, endo-beta-N-acetylglucosaminidase, hexosaminidase, beta-N-acetylgalactosaminidase and glucocerebrosidase have not been so widely studied as the beta-N-acetylhexosaminidases in bacteria, fungi and arthropods. Their biochemical role has been elucidated, however, and their urinary and plasma determination is being adopted for the early detection of diseases before clinical manifestation, in particular for hypertension, renal injuries and disorders, depression and lysosomal storage diseases. The spectrophotometric determinations of N-acetyl-beta-D-glucosaminidase, most often done with 3-cresolsulphone phthaleinyl N-acetyl-beta-D-glucosaminide, have been recently simplified and adapted to automatic instruments.

Acetylglucosaminidase↗
PubMed1999

Biochemistry, histology and clinical uses of chitins and chitosans in wound healing.

Biodegradability, biocompatibility and capacity to promote the synthesis of hyaluronan are main characteristics of chitin-derived wound healing materials, whose biological significance in the human body depends largely on the actions that certain hydrolases exert on them. The resulting chitooligomers stimulate various cells, while the released monomers are phosphorylated and incorporated into hyaluronan, keratan sulphate and chondroitin sulphate, components of the intracellular matrix and connective tissue. The healing process favoured by these materials is examined in terms of macrophage activation, cytokine production by macrophages and fibroblasts, antiinflammatory action, angiogenesis stimulation, granulation and scar formation. Current biomedical applications are illustrated by the treatment of leg ulcers, the use of skin substitutes, and the regeneration of bone, nerve and meniscus tissues.

Biocompatible Materials↗
PubMed1999

Clinical and biochemical evaluation of chitosan for hypercholesterolemia and overweight control.

After providing basic information on enzymes involved in cholesterol homeostasis, and on management of hypertriglyceremia and hypercholesterolemia, with the aid of cholestyramine and fibric acid, this chapter examines the effects of the ingestion of chitosan. Dietary chitosan is effective on serum cholesterol and in atherosclerosis in normal and diabetic mice, and lends itself to the treatment of hypercholesterolemia in humans. It also exhibits antiulcer, antiarthritic, antihypertension and antiuricemic properties. The published human trials, analysed statistically, further indicate that chitosan is effective to control overweight when associated to a diet. This chapter discusses several issues raised against the use of chitosan, namely, depletion of zinc and liposoluble vitamins, as well as advantages such as enhanced absorption of nutrients and competitive inhibition of lipases. It also directs attention to the unexplored areas of fungal and algal chitosans, and the use of chitins instead of chitosans.

Animals↗
PubMed1999

Microparticulate drug delivery systems.

Chitosan was proposed as a drug carrier for mucosal administration in ocular, buccal, nasal, gastroenteric and vaginal-uterine therapies based on its bioadhesive properties and biodegradability in vivo under the action of hydrolases. Examples are the delivery of acyclovir via ocular administration, and the delivery of 5-aminosalicylic acid to the colon. Microparticles may need to be cross-linked to retard their degradation in acidic media; yet cross-linking with glutaraldehyde introduces cytotoxic characteristics and depresses bioadhesion. Alternative cross-linking approaches are discussed along with the suitability of chitosan for the oral delivery of vaccines.

Acyclovir↗
PubMed1999

N,N-dicarboxymethyl chitosan as delivery agent for bone morphogenetic protein in the repair of articular cartilage.

Bone morphogenetic protein (BMP), associated with N,N-dicarboxymethyl chitosan, is used to induce or facilitate the repair of articular cartilage lesions. This association is intended for the synergistic potentiation of the respective biological effects. Data show that BMP-7 enhances the in vivo proliferation of cells with chondrocytes phenotype in the articular environment, leading to partial healing of the articular surface of the lesions. N,N-dicarboxymethyl chitosan is found to be useful as a molecular carrier or drug delivery agent.

Animals↗
PubMed1998

Effect of low-molecular-weight chitosans on the adhesive properties of oral streptococci.

It was previously shown that a low-molecular-weight chitosan and its derivatives N-carboxymethyl chitosan and imidazolyl chitosan inhibit Streptococcus mutans adsorption to hydroxyapatite. The ability of the same molecules to interfere with adhesive properties of other oral streptococci (Streptococcus sanguis, Streptococcus gordonii, Streptococcus constellatus, Streptococcus anginosus, Streptococcus intermedius, Streptococcus oralis, Streptococcus salivarius, Streptococcus vestibularis) was tested. When saliva-coated or -uncoated hydroxyapatite beads were treated with N-carboxymethyl chitosan, a reduction varying from 60% to 98% depending on strains was observed. Low-molecular-weight chitosans and imidazolyl chitosan did not have any effect. Growth in N-carboxymethyl chitosan-supplemented medium (final concentrations ranging from 20 to 500 micrograms.ml-1) caused a dose related reduction in the adsorption of all strains to hydroxyapatite and in their affinity towards xylene. No effect was observed with low-molecular-weight chitosans and imidazolyl chitosan. In contrast to what observed with S. mutans, the three polysaccharides did not affect detachment from hydroxyapatite beads and adherence to cheek epithelial cells of the other streptococci. These results suggest that low-molecular-weight chitosans and/or imidazolyl chitosan, selectively affecting S. mutans adsorption to hydroxyapatite, may be very interesting as potential anti-dental caries agents.

Adult↗
PubMed1997

Human enzymatic activities related to the therapeutic administration of chitin derivatives.

Three cases are presented where modified chitins have been extensively administered to volunteers, as dressings for wounded soft and bone tissues, as anticholesterolemic dietary foods, and in the controlled delivery of anti-inflammatory drugs. The interactions of the modified chitins with human enzymes is critically examined. In the context of drug carrier resorption and wound healing, chitooligomers and monomers, generated by lysozyme, N-acetylglucosaminidase and human chitinase, activate macrophages and stimulate fibroblasts, respectively; the effects are production of smooth, vascularized and physiologically normal tissues. In the dietary food area, lipase, amylase, 3-hydroxy-3-methylglutaryl CoA reductase, glucokinase and the enzymes of prostaglandin synthesis are involved in the oral administration of chitosan: lipid adsorption is depressed mainly because of the physical form of the chitosan-lipid aggregates, which are unsuitable as substrates. When chitosan is used as a drug carrier, chitosan-drug complexes are present. The uniqueness of chitosan among polysaccharides is underlined in terms of susceptibility to enzymatic depolymerization, cationicity, supply of cell-activating oligomers, and supply of N-acetylglucosamine for rebuilding of other biopolymers. Advances in molecular recognition and biocompatibility are also presented.

Animals↗
PubMed1997

Inhibition of Streptococcus mutans adsorption to hydroxyapatite by low-molecular-weight chitosans.

The role of Streptococcus mutans in the initiation of dental caries has been recognized and attributed, at least in part, to its ability to colonize the tooth surface. Therefore, factors which prevent S. mutans attachment to hydroxyapatite (HA) are of considerable interest for the prophylaxis of this infectious disease. Chitosan, a chitin derivative by N-deacetylation, is an interesting candidate in this respect, since it stimulates the ordered regeneration of oral soft tissues, prevents the deleterious action of organic acid, and exhibits bactericidal action against several pathogens. In the present work, the efficacy of a low-molecular-weight chitosan (LMWC) and its derivatives N-carboxymethyl chitosan (NCMC) and imidazolyl chitosan (IMIC) in preventing S. mutans attachment to HA beads was assessed. The effects of chitosan on both sucrose-dependent and -independent adherence were evaluated. In both cases, when saliva-coated or uncoated HA beads were treated with any of the chitosans, a reduction in S. mutans adsorption ranging from 47 to 66% was observed. When HA beads were coated with saliva after the treatment with chitosan, neither carbohydrate caused a statistically significant reduction in S. mutans adsorption, suggesting that saliva deposition restores HA binding properties. Bacteria grown in the presence of chitosan subminimal inhibitory concentrations (sub-MICs) ranging from 12 to 500 micrograms mL-1 adsorbed poorly to HA and exhibited a lower affinity toward xylene than untreated controls. In the presence of chitosan sub-MICs up to 60 micrograms mL-1, an increase in the percentage of detached bacteria from two- to nine-fold was observed. The desorptive effect of chitosan was weaker when S. mutans had adhered to saliva-coated HA in the presence of sucrose. These results demonstrate that the presence of minor amounts of modified chitosans prevents S. mutans adsorption to HA and suggest that colonization of the tooth surface might be impaired by the use of toothpastes, mouthrinses, or chewing gums containing any of the tested polysaccharides.

Adsorption↗
PubMed1994

Solubility and structure of N-carboxymethylchitosan.

N-Carboxymethylchitosan from crab and shrimp chitosans was obtained in water-soluble form by proper selection of the reactant ratio, i.e. using equimolar quantities of glyoxylic acid and amino groups. HPLC determinations of glyoxylic and glycolic acids, in conjunction with NMR analysis, permitted identification of the structure of the product, which is partly N-mono-carboxymethylated (0.3), N,N-dicarboxymethylated (0.3) and N-acetylated depending on the level of deacetylation of the starting chitosan (0.08-0.15). The preparation can be made successfully even in the presence of large concentrations of glycolic acid. The use of enzymes exerting hydrolysing activity on the high-molecular-weight fractions helps to avoid gel formation during storage and precipitate formation on addition of anti-microbial agents.

Chitin↗
PubMed1994

Stimulatory effect on bone formation exerted by a modified chitosan.

A novel modified chitosan carrying covalently linked imidazole groups (average molecular weight 700,000, degree of substitution 0.28, degree of acetylation 0.08) was used to stimulate bone formation in an animal model. Lesions (7 mm diameter) were surgically made in the femoral condyle of sheep and treated with the modified chitosan. Within 40 d after surgery, the neoformed tissue occluded the surgical hole and assumed a trabecular structure in the peripheral area of the lesion, while looking like a mineralization nodule in the central part in association with a fibrous component. In the control, no sign of osteoinduction or reparative process was observed and bone marrow was rich in adipocytes.

Adipocytes↗
PubMed1994

Chitin-based poly(urea-urethane)s.

Chitins of various origins in DMA-LiCl solution have been reacted with excess 1,6-diisocyanatohexane (three or twelve equivalents per repeating unit) for 4-20 h. The resulting solutions were exposed to water vapor for 2 days and flexible and opaque materials were produced, which upon drying yielded powders whose main characteristics were insolubility in aqueous and organic solvents, remarkable crystallinity, typical infrared spectrum, high N/C ratio (0.287), and a high degree of substitution (0.29). Under the SEM structural features reminiscent of chitin were absent but no thermoplastic behavior was found by differential scanning calorimetry. Chitosan was similarly treated under heterogeneous conditions in anhydrous pyridine, and yielded reaction products with a lower degree of substitution (0.17). With partially hydrolysed chitosan, highly crystalline products were obtained.

Chitin↗
PubMed1993

Osteoconduction exerted by methylpyrrolidinone chitosan used in dental surgery.

Surgical wounds from wisdom tooth avulsions were medicated with freeze-dried methylpyrrolidinone chitosan, a gel-forming resorbable biopolymer obtained from crab chitosan by chemical modification. Methylpyrrolidinone chitosan promoted osteoconduction and the space left after avulsion was filled with newly formed bone tissue, which conferred desirable mechanical and physiological characteristics to the healed would site. Morphological evidence obtained from biopsies confirmed the radiographic data. Methylpyrrolidinone chitosan was progressively depolymerized by lysozyme and was no longer detected 6 months after surgery. None of the 10 patients reported adverse effects over one year of observation.

Bone Regeneration↗
PubMed1993

Osteoconductive properties of methylpyrrolidinone chitosan in an animal model.

Bone defects were surgically produced in the tibiae of rabbits and medicated with freeze-dried methylpyrrolidinone chitosan. Histological observations 60 d after surgery showed a considerable presence of neoformed bone tissue, as opposed to controls, originating from the pre-existing bone as well as from the periosteum. The cationic nature and the chelating ability of the methylpyrrolidinone chitosan apparently favoured mineralization. Endosteal-periosteal and bone marrow osteoblast-like precursors, stimulated by growth factors entrapped in the coagulum-polysaccharide mixture, gave rise to intramembranous bone formation. The ultrastructural examination evidenced that bone osteoid was followed by mineralization of the tissue.

Animals↗
PubMed1984

Sulfated N-(carboxymethyl)chitosans: novel blood anticoagulants.

N-(Carboxymethyl)chitosan was subjected to sulfation in a mixture of concentrated sulfuric acid (oleum) and N,N-dimethylformamide, under anhydrous conditions. The resulting product contained 11% of sulfur and degree of substitution: N-acetyl, 42%; N-carboxymethyl, 58%; and sulfate, 100%. Sonication of the sulfated N-(carboxymethyl)chitosan gave two main fractions whose molecular weights were 39,000 and 80,000. In human blood, complexes of sulfated N-(carboxymethyl)chitosan and antithrombin inhibited both thrombin and factor Xa, and produced neither hemolysis nor alterations in erythrocytes and lymphocytes. Sulfated N-(carboxymethyl)chitosan is therefore proposed as a blood anticoagulant.

Anticoagulants↗
PubMed1980

Chelating, film-forming, and coagulating ability of the chitosan-glucan complex from Aspergillus niger industrial wastes.

Waste mycelia of Aspergillus niger from a citric acid production plant are simply treated with boiling 30-40% NaOH aqueous solutions for 4-6 hr to obtain the insoluble chitosan-glucan complex whose infrared, ESR, and x-ray diffraction spectra are reported. A number of transition- and post-transition-metal ions are chelated and collected by chitosan-glucan with higher yields than by animal chitosan. Immediate flocculation occurs upon mixing chitosan-glucan dispersions with alginate and polymolybdate solutions. Membranes are also obtained from chitosan-glucan dispersions in acetic acid or in chloral and dimethyl formamide mixtures.

Aspergillus niger↗