Wnt pathway genes in osteoporosis and osteoarthritis: differential expression and genetic association study.

UNLABELLED: In comparison with hip fractures, increased expression of genes in the Wnt pathway and increased Wnt activity were found in bone samples and osteoblast cultures from patients with osteoarthritis, suggesting the involvement of this pathway in subchondral bone changes. No consistent differences were found in the genetic association study. INTRODUCTION: This study aims to explore the allelic variations and expression of Wnt pathway genes in patients with osteoporosis and osteoarthritis. METHODS: The expression of 86 genes was studied in bone samples and osteoblast primary cultures from patients with hip fractures and hip or knee osteoarthritis. The Wnt-related activity was assessed by measuring AXIN2 and in transfection experiments. Fifty-five SNPs of the LRP5, LRP6, FRZB, and SOST genes were analyzed in 1,128 patients. RESULTS: Several genes were differentially expressed in bone tissue, with the lowest values usually found in hip fracture and the highest in knee osteoarthritis. Overall, seven genes were consistently upregulated both in tissue samples and in cell cultures from patients with knee osteoarthritis (BCL9, FZD5, DVL2, EP300, FRZB, LRP5, and TCF7L1). The increased expression of AXIN2 and experiments of transient transfection of osteoblasts with the TOP-Flash construct confirmed the activation of Wnt signaling. Three SNPs of the LRP5 gene and one in the LRP6 gene showed marginally significant differences in allelic frequencies across the patient groups, but they did not resist multiple-test adjustment. CONCLUSIONS: Genes in the Wnt pathway are upregulated in the osteoarthritic bone, suggesting their involvement not only in cartilage distortion but also in subchondral bone changes.

Aspirin or acetaminophen? A comparison from data collected by the Spanish Drug Monitoring System.

To characterize and compare the toxicity profiles of aspirin and acetaminophen when used by large populations, all records of adverse drug reactions to these drugs reported to the Spanish Drug Monitoring System from 1982 to 1991 were analyzed. According to these data, aspirin-induced reactions were more serious than those reactions to acetaminophen; the severity of all the reactions in both cases was associated with time of exposure and with the accumulated dose administered. For GI reactions to aspirin no association was found between severity and time of exposure or dose, although an association with age was found. There were no differences between the proportions of deaths, malformations, and renal damage recorded for either of the two groups. Proportions of hematological and hepatic disturbances were greater with acetaminophen. Adverse drug reaction data for aspirin and acetaminophen from spontaneous reporting seem to be consistent with data coming from observational studies.

[Cannabis and alcohol use as prognosis factors in the short-term progress of schizophrenia]. / Consumo de cannabis y alcohol como factores pronósticos en la evolución a corto plazo de la esquizofrenia.

Data from 62 schizophrenic patients (DSM III), aged 18 to 30, who were treated in the public medical system, and showed a relapse in 1987, after an one-year-follow up, were analyzed. It was observed that cannabis and alcohol use increased the probability of a relapse of schizophrenia in the follow-up period, whilst moderate alcohol use (less than 70 cc of pure alcohol/day) had no influence in the probability of relapse.

Cannabis consumption as a prognostic factor in schizophrenia.

Data were analysed from 62 schizophrenic patients between 18 and 30 years of age, treated at the community mental health centres in Navarra, who had relapsed and then completed a one-year follow-up study. Factors influencing the course of illness during follow-up were: continuing cannabis consumption; previous cannabis intake; non-compliance with treatment; and stress.