Protection of photosensitized rats against long ultraviolet radiation by topical application of compounds with structures similar to that of dihydroxyacetone

Dihydroxyacetone (DHA), a browning agent, protects photosensitive rats and humans against long ultraviolet radiation (UVA, 320-400 nm) and visible (blue) light. The photoprotective efficacy of DHA and structurally similar compounds was assessed as prevention of edema in the paws of psoralen-sensitized rats, after exposure to blacklight fluorescent lamps. Methylglyoxal produced a yellow-brown color and provided nearly the same protection as DHA, whereas monohydroxyacetone did not color the skin and afforded little or no protection. Glyceraldehyde provided a moderate amount of protection, which was enhanced by prior exposure of the agent to alkaline pH. A solution of 5-hydroxymethylfurfuraldehyde was yellow and provided minimal protection by staining the skin rather than browning it. We conclude that the ability to produce a brown color in skin is a useful criterion for screening compounds for photoprotective efficacy against UVA radiation.     

The effect of pressurized carbon dioxide as a temporary plasticizer and foaming agent on the hot stage extrusion process and extrudate properties of solid dispersions of itraconazole with PVP-VA 64.

The aim of the current research project was to explore the possibilities of combining pressurized carbon dioxide with hot stage extrusion during manufacturing of solid dispersions of itraconazole and polyvinylpyrrolidone-co-vinyl acetate 64 (PVP-VA 64) and to evaluate the ability of the pressurized gas to act as a temporary plasticizer as well as to produce a foamed extrudate. Pressurized carbon dioxide was injected into a Leistritz Micro 18 intermeshing co-rotating twin-screw melt extruder using an ISCO 260D syringe pump. The physicochemical characteristics of the extrudates with and without injection of carbon dioxide were evaluated with reference to the morphology of the solid dispersion and dissolution behaviour and particle properties. Carbon dioxide acted as plasticizer for itraconazole/PVP-VA 64, reducing the processing temperature during the hot stage extrusion process. Amorphous dispersions were obtained and the solid dispersion was not influenced by the carbon dioxide. Release of itraconazole from the solid dispersion could be controlled as a function of processing temperature and pressure. The macroscopic morphology changed to a foam-like structure due to expansion of the carbon dioxide at the extrusion die. This resulted in increased specific surface area, porosity, hygroscopicity and improved milling efficiency.     

HLA-DPB1 gene polymorphism and multiple sclerosis: a large case-control study in the southwest of France

The polymorphism at the HLA-DPB1 locus has been characterized in a large number of patients with multiple sclerosis (n = 112) and in healthy controls (n = 115). Both patients and controls lived in the southwest of France (in the Pyrénées Atlantiques) and had similar ethnic background. The typing procedure involved the selective amplification of the second exon of the DPB1 locus by polymerase chain reaction, followed by hybridization of the amplified DNA with 14 sequence-specific oligonucleotide probes. Individual alleles were identified by the pattern of hybridization of the different probes. The distribution of the DPB1 alleles was not significantly different in multiple sclerosis patients and controls (p = 0.11). This does not corroborate the reported association of multiple sclerosis with the primed lymphocyte typing (PLT)-defined DPw4 specificity and is not in favour of a role played by polymorphic residues of the DP molecule in susceptibility to multiple sclerosis.     

Xylose disposition in humans as a function of age

D-xylose disposition was examined in 24 healthy men between 32 and 85 years of age. Xylose was administered as a 5 gm iv infusion and as a 25 gm po solution. Serum xylose concentrations and urinary excretion of intact xylose were determined. There were statistically significant inverse relationships with age for each of the following parameters after intravenous infusion: elimination rate constant (r2 = 0.71); systemic clearance (r2 = 0.66); renal clearance (r2 = 0.66); and nonrenal clearance (r2 = 0.35). Similar inverse relationships were found after oral dosing for the elimination rate constant (r2 = 0.69) and renal clearance (r2 = 0.54). There was no significant age relationship for the apparent volume of distribution or the steady-state volume of distribution. The percentage of the oral and intravenous dose recovered in urine up to 5 hours after dosing was significantly and inversely correlated with age. The implications of the latter finding are discussed with regard to the interpretation of the xylose tolerance test used to assess gastrointestinal absorptive capacity.     

Familial achalasia associated with adrenocortical insufficiency, alacrima, and neurological abnormalities

We report on two brothers with achalasia, adrenocortical insufficiency, alacrima, short stature, microcephaly, ataxia, optic atrophy, and developmental delay. The parents and three sibs are unaffected. Achalasia, adrenocortical insufficiency, and alacrima comprise a recently characterized familial multisystem disorder of unknown cause. Achalasia has also been described in association with microcephaly and mental retardation in one family and ataxia, optic atrophy, and mental retardation in another. The above reports and these sibs may represent variants of a single pleiotropic recessive gene. We suggest that abnormalities of the central nervous system are a manifestation of the achalasia, adrenocortical insufficiency, alacrima syndrome.