SUMMARYAutotaxin (ATX) is a 125-kD ectonucleotide pyrophosphate/phosphodiesterase, which was initially isolated and cloned from human melanoma cells as a potent stimulator of tumour cell motility. ATX shows 44% identity to the plasma cell membrane marker PC-1. Recently, we described the decreased expression of ATX mRNA in cultured fibroblast-like synoviocytes (SFC) of patients with RA by interferon-gamma. In this study using a competitive reverse transcriptase-polymerase chain reaction, we show an increased ATX mRNA expression in SFC from patients with RA in comparison with synoviocytes from non-RA patients. The median ATX mRNA amount in SFC of RA patients (440 pg/ m g total RNA) was five-fold higher than the expression in synoviocytes from non-RA patients (80 pg/ m g total RNA) or foreskin fibroblasts (MRHF cells, 90 pg/m g total RNA). In contrast to the elevated ATX mRNA expression in SFC of patients with RA, we did not measure increased mRNA amounts of PC-1 in these cells. Both the ATX mRNA amount and the 5 H -nucleotide phosphodiesterase (PDE) activity of SFC lysate were reduced after treatment of SFC with the cytokines IL-1b or IL-4. IL-1b and IL-4 induced a down-regulation of PC-1 mRNA and protein expression in SFC. In SFC treated with transforming growth factor-beta the expression of PC-1 mRNA and protein was increased, whereas no significant effect on ATX mRNA expression was detectable. Pharmacological drugs used in therapy for RA, such as dexamethasone, cyclosporin, methotrexate and indomethacin, did not show a statistically significant effect on either ATX mRNA or PC-1 mRNA expression. Only pentoxifylline suppressed ATX mRNA as well as PC-1 mRNA expression. In conclusion, we show a tight regulation of ATX and PC-1 gene expression by cytokines detectable in the inflamed tissue of RA. Further investigations will deal with the regulation of ATX protein expression as well as with the function of ATX in RA.

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We studied the effect of nutritional rehabilitation with a 6, 18 or 50% casein diet in undernourished rats on histidase (Hal) expression. Undernutrition was induced by feeding rats a 0.5% casein diet for 5 wk. Over this period, growth, serum total proteins and insulin-like growth factor-I (IGF-I) levels were significantly lower than those of rats that freely consumed an 18% casein diet. During this period, undernutrition also significantly reduced Hal activity and Hal-mRNA concentration. Nutritional rehabilitation for 21 d with a 6% casein diet did not change any of these variables. Nutritional rehabilitation with an 18 or 50% casein diet for 1 d initiated the restoration of Hal activity and mRNA concentration. After 10 d of consuming 18 or 50% casein diets, Hal activity was 5- and 14-fold, and mRNA concentration was 8.5- and 23-fold higher, respectively, than in the protein-undernourished group (PU). During this period, body weight, total serum proteins and IGF-I levels were also significantly (P < 0.05) higher than those of the PU group. At the end of 21 d of rehabilitation with an 18 or 50% casein diet, Hal activity was 14- and 31-fold higher and Hal mRNA concentration was 10- and 24-fold higher, respectively, than in the PU group. In conclusion, our data showed that rehabilitation of undernourished rats with a 6% casein diet was not sufficient to re-establish growth indicators, Hal activity or gene expression, and that nutritional rehabilitation with an 18 or 50% casein diet effectively re-established body weight , biochemical variables and the capacity of histidase gene expression to eliminate the excess of protein.

Objectives: To estimate the prevalence of cardiometabolic diseases and their association with polypharmacy in elderly people at the University of the Third Age (Portuguese acronym: UnATI). Methods: A cross-sectional, descriptive, analytical study with 121 elderly patients. The prevalence ratio, Pearson’s Chi-square test and Fisher’s exact test were used as measures of association. Results: At the mean age of 68.3, most elderly had at least one cardiometabolic disease (82.6%), of which hypertension was the most prevalent (71.1%), and consumed prescription drugs of continuous use (92.6%). Almost half of the elderly (48.2%) used combinations of drugs, which suggests a high cardiovascular risk. Polypharmacy due to prescription was observed in almost one-third (28.6%) of the sample, associated with the use of antihypertensives (p=0.004), antidiabetics (p=0.000) or lipid-lowering agents (p<0.000). Conclusions: Clinical guidelines recommend changes in lifestyle, but increased pharmacotherapy prevails in practice, which increases the risk of adverse events, especially in old age.

Objective: to identify the prevalence of self-medication, the therapeutic classes used without medical prescription, the symptoms treated with such medication and associated factors among participants of an Open University of the Third Age (OU3A). Method: a cross-sectional, descriptive and analytical study was carried out, the sample of which was composed of 138 OU3A attendees. To estimate the association between the variables, prevalence ratios (PR), confidence intervals (95% CI), the chi-squared test and Fisher's exact test were used. Results: the majority were aged 60-69 years (61.6%), were female (75.4%), had a health plan (63%) and claimed to self-medicate (59.4%, 95% CI, 0-64.8). The most frequently mentioned therapeutic classes were analgesics (31.9%), muscle relaxants (13.8%), anti-inflammatories (13.0%) and first-generation antihistamines (7.2%). The most commonly reported self-medication symptoms were muscle and joint pain (21.0%), headaches (10.1%) and colds and flu (8.7%). There was a significant association (p = 0.049) among those who self-medicated more frequently and anti-inflammatory use (PR = 1.46, 95% CI = 1.10-1.99). The complaint of muscular and articular pain exhibited a significant association with the diagnosis of arthrosis (p = 0.003, RP = 3.75, 95% CI = 2.07-6.76) and hypothyroidism (p = 0.002, RP = 2.77 ; 95% CI = 1.50-5.10). Conclusion: the most frequently mentioned reasons for self-medicating were previous experience using the drug and the certainty that it is safe. Most of the above medications are potentially inappropriate for the elderly. However, the elderly consider them safe and are unaware of the risks to which they expose them. They may also be unaware that pain treated by self-medication may be related to pre-existing diseases, which require the appropriate professional and treatment.