N(epsilon)(carboxymethyl)lysin and the AGE receptor RAGE colocalize in age-related macular degeneration.

PURPOSE: To investigate whether glycoxidation products and the receptor for advanced glycation end products (RAGE) are present and colocalize in subfoveal membranes of patients with age-related macular degeneration (ARMD). METHODS: Surgically removed subfoveal fibrovascular membranes from 12 patients, 11 related to ARMD and 1 to an idiopathic membrane, were analyzed for the presence of the glycoxidation product N(epsilon)-(carboxymethyl)lysin (CML), one of the receptors for advanced glycation end products, RAGE, and the activation of NFkB, using immunohistochemistry. RESULTS: CML-like immunoreactivity was found in all ARMD specimens examined adjacent or colocalized with RAGE, but not in the idiopathic membrane. RAGE immunoreactive material was found in CD68-positive cells and in the fibrous matrix. CD68-positive cells and surrounding areas stained for p50, the activated form of NFkB. CONCLUSIONS: These results indicate that glycoxidation products are present in subretinal membranes of patients with ARMD. The concomitant expression of RAGE in these membranes and the finding of activated NFkB is suggestive of an implication of glycoxidation product formation in the pathogenesis of the disease.     

Complexity of the immunoglobulin light chain V kappa 1 gene family in the New Zealand black mouse

The immunoglobulin light chain V kappa 1 gene family is polymorphic in murine inbred strains and this family has been subdivided into five sub-groups (V kappa 1A-E). The V kappa 1A sub-group contributes to approximately 2% of the total serum immunoglobulin light chains in several mouse strains. However, it has been reported that this sub-group is absent in New Zealand Black (NZB) mouse serum. Amino acid sequencing of myeloma proteins from this inbred mouse has shown that they belong to the V kappa 1B sub-group. We report here the structure of nine functional germline genes from NZB mice that have high homologies to the V kappa 1A, V kappa 1B, V kappa 1C, and V kappa 1D sub-groups. In addition, a novel germline gene representing the prototype of a new sub-group (designated V kappa 1F) has been identified. We have isolated different V kappa 1 germline genes from a single restriction fragment length polymorphism (RFLP) fragment, as well as identical V genes from two different RFLP migrating bands. Therefore, the complexity of the genes encoding the immunoglobulin variable region cannot be determined solely by RFLP analysis. Nucleotide sequence analysis of 16 V kappa 1 genes which code for NZB autoantibodies indicate that they belong to five different V kappa 1 sub-groups with five hybridomas (31%) expressing the V kappa 1A sub-group. Comparison of the sequences of V kappa 1 genes expressed in hybridomas with corresponding germline genes show no somatic mutations.     

SIDS: parental awareness and infant care practices in contrasting socioeconomic areas in Cardiff

Parental awareness of risk factors for sudden infant death syndrome (SIDS) and infant care practices were compared in an area of relative deprivation and one of relative affluence in Cardiff. Awareness was high in both areas. More infants slept on the side in the deprived area (p < 0.02). One in three babies was exposed to cigarette smoking, significantly more in the deprived area (p < 0.001). Health professionals should discourage side sleeping and smoking, especially in areas of deprivation.     

Inhaled corticosteroid use in HIV‐positive individuals taking protease inhibitors: a review of pharmacokinetics,case reports and clinical management

As a consequence of inhibition of the hepatic cytochrome P450 3A4 isozyme, treatment with HIV protease inhibitors can result in significant drug?drug interactions. One noteworthy interaction is between protease inhibitors and inhaled or intranasal corticosteroids. This interaction can result in adrenal insufficiency and iatrogenic Cushing's syndrome (with symptoms such as rapid weight gain, obesity, facial hirsutism and swelling), as well as hypertension, osteoporosis and decreased CD4 cell count. In this paper, we review and unite pharmacokinetic data, case reports and current research regarding this drug?drug interaction in order to suggest options for the clinical management of HIV‐positive patients requiring treatment with protease inhibitors and inhaled or intranasal corticosteroids.     

Unusual bifid crista galli in a patient with cleft lip and palate

One of the most common craniofacial malformations observed in newborn babies is cleft lip and palate (CLP). This syndrome presents with some anatomic variations. The aim of this study was to understand an anatomic variation of the crista galli that had not been reported previously in patients with CLP. A 17-year-old boy with CLP was referred to an orthodontic clinic for cone-beam computed tomography (CBCT) imaging before treatment. Axial and coronal sections and three-dimensional images showed that the crista galli had bifid heads that were attached to each other. Incomplete ossification had resulted in a bifid crista galli and the appearance of a suture in the anterior coronal section of the CBCT images. This anatomic variation could allow penetration of the anterior fossa during endoscopic surgery, which could be dangerous for the patient.