ABSTRACT
Different water-soluble MPEO-PLA diblock copolymers with various alpha-methoxy-omega-hydroxyl polyethylene (MPEO) and poly(lactic acid) (PLA) block lengths have been synthesized. Their surface-active properties were evidenced by surface tension (water/air) measurements. In each case the surface tension leveled down above a critical polymer concentration, which was attributed to the formation of a dense polymer layer at the liquid-air interface. The applicability of copolymers as emulsion stabilizers in the preparation of PLA nanospheres by an o/w emulsion/evaporation technique was then investigated. Four copolymers presenting sufficient water solubility and good surfactive properties were used to prepare PLA nanospheres with MPEO chains firmly anchored at the particle surface. The effect of polymer concentration in emulsion on particle size and surface coverage was examined. Whatever the copolymer characteristics, it was found that the optimal concentration to obtain a large amount of MPEO at the particle surface was similar (around 2 g/l). The effect of the copolymer composition on MPEO layer characteristics and on colloidal stability was also evaluated. The conformation of MPEO blocks at the PLA particle surface is discussed in relation to the layer thickness and the surface area occupied per molecule.
ABSTRACT
Second generation antihistamines (anti H1) are effective for seasonal and perennial rhinoconjunctivitis curative or preventive treatment in children. They are better tolerated than first generation drugs. They probably do not act specifically against asthma itself, but are nevertheless useful for relief of nasal obstruction, which is an asthmogenic factor frequently linked with bronchial asthma. The therapeutic relevance of oral ketotifen and inhaled chromones (sodium cromoglycate, nedocromil sodium) is unequally considered among pediatricians. However, their efficacy has been clearly demonstrated as a ground treatment in mild-to-moderate asthmatic children. Chromones are also useful in preventing exercise-induced asthma. Because of their low cost and the lack of potential side effects, and according to the guidelines established in 1997 by the National Heart, Lung and Blood Institute, they should be prescribed at first sight in these indications.
Subject(s)
Anti-Allergic Agents/therapeutic use , Anti-Asthmatic Agents/therapeutic use , Histamine H1 Antagonists/therapeutic use , Respiratory Hypersensitivity/drug therapy , Adolescent , Adult , Aged , Asthma/drug therapy , Child , Child, Preschool , Clinical Trials as Topic , Double-Blind Method , Humans , Infant , Infant, Newborn , Ketotifen/therapeutic use , Middle Aged , Nedocromil/therapeutic use , Rhinitis, Allergic, Perennial/drug therapyABSTRACT
Protein C is a plasmatic inhibitor which regulates the blood coagulation mechanism by modulating the anticoagulant response. The improvement of its bioavailability would be beneficial for the treatment of the disorders caused by its homozygous deficiency or by an other plasmatic inhibitor deficiency. In this context, the protein C encapsulation into biodegradable nanoparticles could be used to approach the problem. However, the method used to prepare the nanoparticles requires the use of ultrasonication and of an organic solvent such as methylene chloride which interferes with protein activity. Sodium dodecyl sulfate polyacrylamide gel electrophoresis showed that neither ultrasonication nor methylene chloride, singly or in combination, led to protein C aggregation or cleavage. Thus, a binding study using an ELISA assay with four characterized monoclonal antibodies was carried out to identify the epitopes damaged by these experimental constraints. The correlation between the immunological assay and a functional one i.e. by the means of the assay of its anticoagulant activity (activated partial thromboplastin time) made it possible to show that protein C amino acids 166-169 of the activation peptide were probably altered after ultrasonication and methylene chloride treatment. Indeed, it is likely that these residues were no longer surface-exposed but had moved inside the protein core.
Subject(s)
Anticoagulants/chemistry , Epitopes/chemistry , Protein C/chemistry , Anticoagulants/administration & dosage , Anticoagulants/pharmacokinetics , Biological Availability , Circular Dichroism , Drug Compounding , Electrophoresis, Polyacrylamide Gel , Enzyme-Linked Immunosorbent Assay , Methylene Chloride/chemistry , Protein C/administration & dosage , Protein C/pharmacokinetics , Protein Conformation , UltrasonicsABSTRACT
Two girls with mosaicism for an extra chromosome 9 are reported. Clinical findings included growth and mental retardation, facial dysmorphism, delayed ossification, single flexion crease, gastro-oesophageal reflux in one girl, and ventricular and atrial septal defects in the other patient. These findings are compared to the other previously reported cases of trisomy 9 mosaicism.
Subject(s)
Abnormalities, Multiple/genetics , Chromosomes, Human, Pair 9 , Intellectual Disability/genetics , Mosaicism , Trisomy , Facial Bones/abnormalities , Female , Growth Disorders/congenital , Growth Disorders/genetics , Humans , InfantABSTRACT
We report two sibs with Angelman syndrome or an apparently new syndrome. In addition to severe mental retardation and seizures, clinical examination showed an ataxic and stiff legged gait, truncal hypotonia with hypertonia of the limbs, dysmorphic facial features (brachycephaly, large mouth, pointed chin and a prominent jaws) and scoliosis. Brain CT scan and MRI revealed ventricular enlargement and squared frontal horns. Pregnancy and delivery were uneventful. Karyotypes were normal. No deletion of chromosome 15q11-13 region was shown by molecular genetic techniques. The parents who are normal are second cousins. The condition is therefore probably inherited as an autosomal recessive one.
