Effect of surfactant monomers on chloramphenicol association to an albumin-lecithin complex: a model for modified drug absorption.

The binding of chloramphenicol to an albumin-lecithin complex in the presence or absence of premicellar concentrations of both ionic and non-ionic surfactants has been examined. Long chain, strong ionic detergents, such as sodium dodecyl sulphate or cetyltrimethylammonium bromide, severely perturb protein structure and eventually allow full separation of the complex into lecithin and albumin-detergent complexes. The dissociation process is reversible upon the removal of the detergent by exhaustive dialysis. After the splitting of the complex, the amount of antibiotic associated with the lipid-protein mixture increases. Structural alteration of the albumin-lecithin complex and the increase in the binding of chloramphenicol have an effect on the transfer rate of this antibiotic across an artificial barrier consisting of an aqueous dispersion of the same complex, as observed in a model system. It is suggested that a reversible alteration in membrane structure, and consequently in membrane permeability, might be easily effected, at the molecular level, through a reversible dissociation of structural lipoproteins into their components, operated by premicellar concentrations of ionic surfactants. This represents a tentative picture of the possible events taking place within the membrane and modifying the absorption rate of a drug, when it is associated with surfactants in a pharmaceutical preparation.

Effect of a second solubilizate on the partition coefficient of drugs in micellar solution and their permeation rate across an artificial membrane.

The distribution of a solubilizate between micelles and the aqueous phase does not obey a simple partition law when a second solubilizate species is present. Alterations of the apparent partition coefficient cannot be explained in terms of a simple displacement mechanism, following the interaction of both solubilizates with the same site of the micelle. A non linear increase in solubilizate association to micelles following an increase in surfactant concentration is observed in the presence of a second solubilizate. A depression in the cloud point temperature follows the addition of a second species and is such that cannot be interpreted as a simple additive effect. Alteration of the apparent partition coefficient in a miscellar solution has an effect on the permeation rate of the solubilizate across an artificial membrane. Biopharmaceutical implications are discussed.

[Autosomal chromosomes and anomalies of the oromaxillofacial area]. / I cromosomi autosomici e le anomalie del distretto oro-maxillo-facciale.

The study deals with genetic diseases due to anomalies in the number and structure of autosomal chromosomes associated with oro-facial malformations. Pertinent literature from 1980 and clinical cases for each defect were analyzed. By comparing clinical signs and symptoms with chromosome abnormalities it was possible to build an analytical diagram showing the prevalence of malformation exhibited by each anatomical oro-facial region (cranial, labial, palatal, nasal, ocular, dental, lingual region). A very high prevalence of malformation was assessed for lip-and-palate regions (78%). These region often shows "micro-signs" of cleft lip and/or palate (deep palatal vault, maxillary hypoplasia, congenitally missing upper central incisors) which may indicate the presence of a mildly expressed chromosome abnormality. The whole sample of autosomal chromosome abnormalities induce anomalies in structures lying along body and face mid-line. The phenotypic expression of such anomalies may be defective (cleft lip and/or palate), or excessive as well (excessive thickness of the lingual frenum, broadening of the nasal bridge).

[Mucopolysaccharidosis. A case report of Morquio's type-A disease (MPS IV-A)]. / Mucopolisaccaridosi. Descrizione di un caso di Morquio di tipo A (MPS IV-A).

The mucopolysaccharidosis represent a broad spectrum of disorders due to the deficiency of one of a group of enzymes which degrade three classes of mucopolysaccharides: heparan sulfate, dermatan-sulfate and keratan sulfate. The general phenotype includes coarse facies, corneal clouding, hepatosplenomegaly, joint stiffness, hernias, dysostosis multiplex, mucopolysaccharides excretion in the urine and metachromatic staining in peripheral leukocytes and bone marrow. Various components of the MPS phenotype are also found in the mucolipidoses, glycoprotein storage diseases. Detailed clinical and radiologic evaluation and identification of the type of MPS excreted in the urine help to narrow the diagnosis possibilities. Definitive diagnosis requires assay of specific enzymes in various tissues such as cultured skin fibroblasts. For the moment there are 14 types of known mucopolysaccharidoses, including several subtypes. They are classified into Hurler's syndrome (MPS I-H); Scheie's syndrome (MPS I-S); Hurler-Scheie's syndrome (MPS I-H/S); Hunter's syndrome A, B (MPS II-A, B); Sanfilippo's syndrome A,B,C,D (MPS II-A,B,C,D); Morquio's syndrome A,B,C (MSP IV-A,B,C); Maroteaux-Lamy's syndrome (MPS VI) and Sly's syndrome MPS VII). The mucopolysaccharidosis incidence is around 0.04-0.3% of the newborn and they are 1.5% of all congenital disorders. All mucopolysaccharidosis are autosomal recessive disorders, except for Hunter's syndrome that is X-linked and recessive. Patient suffering of MPS, usually, don't show clinical sign from their birth in fact they develop later their characteristics. The average surviving of this patients is around 20-30 years old, and the exitus is due to cardiac failure or to infections to the gastrointestinal tract or to instability of atlantoaxial joint.(ABSTRACT TRUNCATED AT 250 WORDS)