CCL4L polymorphisms and CCL4/CCL4L serum levels are associated with psoriasis severity

Psoriasis is a common inflammatory skin disease with key immunological and genetic components. Recruitment of leukocytes into the skin is a central step in its pathogenesis, mediated by cytokines. Among the cytokines expressed in psoriatic lesions, C-C chemokine ligand 4 (CCL4) and C-C chemokine ligand 4-like (CCL4L) chemokines appear to be pivotal elements for the skin recruitment of proinflammatory cells. The aim of this study is to evaluate the relationship between CCL4L polymorphisms (including single-nucleotide polymorphisms (SNPs) and copy number variation (CNV)) and the course and prognosis of psoriasis. We analyzed the CNV and the rs4796195 SNP in 211 psoriatic patients and 234 controls; sera from both populations were also quantified for CCL4/CCL4L protein. Our results showed that a high CNV (≥3 copies) is associated with psoriasis severity, whereas moderate disease correlated with a lower CNV (≤2 copies); specifically, the CCL4L1 allele frequency is higher in severe psoriasis, whereas CCL4L2 is more frequent in patients with a milder disease. In addition, we found a positive correlation between the CNV and sera protein levels. Our results suggest that CCL4L genotyping could not only allow a better understanding of the psoriatic pathogenesis but could also be used as a prognostic tool, even helping to modulate the efficacy of treatments.     

Detection of methylation in promoter sequences by melting curve analysis-based semiquantitative real time PCR

Background

Conjugated linoleic acid (CLA), a naturally occurring fatty acid found in ruminant products such as milk and beef, has been shown to possess anti-cancer activities in in vivo animal models and in vitro cell culture systems. In human breast cancer, the overall duration of estrogen exposure is the most important risk factor for developing estrogen-responsive breast cancer. Accordingly, it has been suggested that estrogen exposure reduces apoptosis through the up-regulation of the anti-apoptosis protein, Bcl-2. Bcl-2, an anti-apoptotic protein, regulates apoptosis and plays a crucial role in the development and growth regulation of normal and cancerous cells. Our research interest is to examine the effects of CLA on the induction of apoptosis in human breast tissues.

Methods

The localization of Bcl-2 in both normal and cancerous human breast tissues was determined by immunohistochemical staining and the Bcl-2 protein expression was tested by western blot analysis. Co-culture of epithelial cells and stromal cells was carried out in the presence or absence of CLA to evaluate apoptosis in the context of a cell-cell interaction.

Results

The results showed that both normal and cancerous breast tissues were positive for Bcl-2 staining, which was higher overall in mammary ducts but very low in the surrounding stromal compartment. Interestingly, by quantifying the western blot data, basal Bcl-2 protein levels were higher in normal breast epithelial cells than in cancerous epithelial cells. Furthermore, treatment with 17β-estradiol (E₂) stimulated growth and up-regulated Bcl-2 expression in estrogen responsive breast epithelial cells; however, these carcinogenic effects were diminished by either CLA or 4-Hydroxytamoxifen (Tam) and were suppressed further by the combination of CLA and Tam. In both one cell type cultured and co-culture systems, CLA induced cell apoptosis in ERα transfected MDA-MB-231 cells but not in the wild type MDA-MB-231 cells.

Conclusion

These data, therefore, demonstrate that ERα plays important roles in CLA induced apoptosis in human breast tissues.     

La investigación en atención primaria como área de conocimiento. Informe SESPAS 2012

Primary care offers huge potential for research. This setting is an area of knowledge that must expand to improve the quality of its services and patients’ health. Population-based clinical studies with a focus on health promotion and primary, secondary and tertiary disease prevention offer unique research opportunities. Developing research in the biopsychosocial model of clinical practice and new models of integrated healthcare and community care is therefore a priority. The framework and activities carried out by the Research Network in Preventive Activities and Health Promotion have been instrumental in the development of research in primary care in Spain. Despite the efforts invested by various institutions, foundations, teaching and research departments in primary care research, the projected outputs in terms of volume, quality and impact have not been achieved. The involvement of primary care professionals in research platforms is insufficient, with scarce contribution toward investment in specific primary care research projects. To change the current status of research in primary care, a number of measures are required, namely, the consolidation of research organisms specific to primary care with adequate allocation of funding and staff, and the allocation of specific time for research to primary care professionals to enable them to produce significant projects and consolidate established research lines in their areas of expertise, with applications mainly in quality improvement and innovation of primary care services.     

Recursos y modelos de atención al pie diabético en Cataluña (España): estudio descriptivo sobre espacios de mejora

ObjectivesTo identify areas of improvement in diabetic foot care as regards the availability of materials and specialties in primary and secondary care. To determine the model of care for surgical centres and hospitals caring for diabetic foot problems and their relation to amputations.DesignCross-sectional studySetting and participantsRandom sample of 36 basic health areas (BHA) and all hospital surgery centres in Catalonia (Spain).MeasurementsInformation was collected by structured interview of managers of each centre on: availability of specialists, material off-loading and examination. The models were established according to the classification of Van Acker, and amputations from hospital discharge records.ResultsAn endocrinologist was available in 36.1 % [confidence interval (CI) 95 %:19.0-53.2] of the BHA and 11.1 % [95 % CI: 3.1-26.1] had a podiatrist,100 % [95 % CI: 90.3-100.0] had Doppler, 91.7 % [95 % CI:77.5-98.2] a monofilament, 5.6 % [95 % CI: 0.7-18.7] a quantitative tuning fork, 11.1 % [95 % CI:3,1-26, 1] material off-loading, and 8.3 % [95 % CI: 1.8 - 22.5] a specialist reference centre. A total of 85 surgical centres and hospitals dealt with these problems: 11(13.0 %) excellent model, 29 (34.1 %) intermediate and 45 (52.9 %) basic/insufficient. Centres with a basic model/insufficient performed 12.5 % of the amputation, intermediate models, 56.4 %, and 31.1 % in excellent models.ConclusionsThe proportion of ABS with materials, specialists and/or specialist reference centres was low. The basic/insufficient model was the most common among surgical/hospital centres. Most amputations were performed in centres with excellent and intermediate model; nevertheless, a considerable percentage was performed in centres with basic/insufficient models.     

Nutrition and metabolic syndrome

Sufficient evidence exists in relation to the association in clinical practice between disorders in the metabolism of glucose, lipoproteins, insulin action, arterial hypertension and centrally-distributed obesity. This association is named Metabolic Syndrome. Despite the existence thereof had been questioned by the ADA and EASD, it is a useful tool affording the possibility of identifying individuals at high risk of developing cardiovascular disease. Metabolic syndrome and/or its individual components are associated with a high incidence rate of cardiovascular disease. Obesity and a sedentary lifestyle are underlying risk factors along this syndrome's pathway to disease, changes in living habits therefore being a first-line intervention in the prevention and treatment of insulin resistance, hyperglycemia, aterogenic dyslipemia and arterial hypertension. Weight loss and exercise are the keys to the overall plan, one of the most important non-pharmacological cardiovascular risk reduction strategies however still being diet. Epidemiological studies have found a high intake of simple sugars, of foods having a glycemic index and of diets with a high glycemic load to be associated to insulin resistance, type II diabetes mellitus, hypertriglyceridemia and low HDL-cholesterol figures. Los saturated fat intake in favor of polyunsaturated and monounsaturated fatty acids has been implied in a reduction of the incidence of type II diabetes mellitus and dyslipemia, although the debate is ongoing. Unrefined grain fiber in the diet has been beneficial in reducing the risk of diabetes. Among the diet patterns, the Mediterranean diet has been related to a lower incidence of diabetes and a reduction in the risk of death. Studies for intervention in the prevention of type II diabetes have suggested low-fat diets (reducing saturated and trans-fats), with a high degree of fiber and low glycemic index. Clinical trials have shown diets with small amounts of carbohydrates, low glycemic index and the Mediterranean and DASH diets to be beneficial in reducing aterogenic dyslipemia. There is currently no good evidence for choosing diets with restricted carbohydrates. On the other hand, different guides recommend low-calorie diets with a low content in saturated fats, trans-fats, cholesterol and sugars in favor the eating fruits, green vegetables, unrefined grains and fish.