Effectiveness of a motivational intervention based on spirometry results to achieve smoking cessation in primary healthcare patients: randomised, parallel, controlled multicentre study

Dejar de fumar; Espirometría; Ateción primariaDeixar de fumar; Espirometria; Atenció primàriaSmoking cessation; Spirometry; Primary healthcareObjective: This 12-month study in a primary healthcare network aimed to assess the effectiveness of usual smoking cessation advice compared with personalised information about the spirometry results. Design: Randomised, parallel, controlled, multicentre clinical trial. Setting: This study involved 12 primary healthcare centres (Tarragona, Spain). Participants: Active smokers aged 35–70 years, without known respiratory disease. Each participant received brief smoking cessation advice along with a spirometry assessment. Participants with normal results were randomised to the intervention group (IG), including detailed spirometry information at baseline and 6-month follow-up or control group (CG), which was simply informed that their spirometry values were within normal parameters. Main outcome: Prolonged abstinence (12 months) validated by expired-CO testing. Results: Spirometry was normal in 571 patients in 571 patients (45.9% male), 286 allocated to IG and 285 to CG. Baseline characteristics were comparable between the groups. Mean age was 49.8 (SD ±7.78) years and mean cumulative smoking exposure was 29.2 (±18.7) pack-years. Prolonged abstinence was 5.6% (16/286) in the IG, compared with 2.1% (6/285) in the CG (p=0.03); the cumulative abstinence curve was favourable in the IG (HR 1.98; 95% CI 1.29 to 3.04). Conclusions: In active smokers without known respiratory disease, brief advice plus detailed spirometry information doubled prolonged abstinence rates, compared with brief advice alone, in 12-month follow-up, suggesting a more effective intervention to achieve smoking cessation in primary healthcare

Heme iron intake and risk of new-onset diabetes in a Mediterranean population at high risk of cardiovascular disease: an observational cohort analysis

BACKGROUND: Several epidemiological studies have observed an increased risk of type 2 diabetes mellitus (T2DM) among subjects with a higher consumption of red and processed meat. Heme iron intake has been directly associated with a higher risk of T2DM in healthy adult Chinese and U.S populations. The objective of the present study was to evaluate the association between heme iron intake and the incidence of T2DM in a Mediterranean population at high cardiovascular risk. METHODS: We assessed a subset of participants in the PREDIMED trial as an observational cohort, followed up for a maximum of eight years. We initially included 1073 non-diabetic subjects (57.1% women) aged 67.3 ± 6.0 years, at high cardiovascular risk. Diet was assessed at the study baseline using a validated, semi-quantitative food frequency questionnaire. RESULTS: During the follow-up period 131 diabetics were newly diagnosed. The risk of developing T2DM was assessed using baseline heme iron intake and proportional hazard models, first unadjusted, then adjusted for energy, and finally adjusted for dietary, anthropometric, socio-demographic and lifestyle variables. Significant direct associations with the incidence of T2DM were found for heme iron (Hazard Ratio [HR] 1.30, 95% confidence interval [CI], 1.02 to 1.66). Secondarily, we have also observed that coffee (HR:0.93, 95% CI, 0.89 to 0.98) and alcoholic beverages (HR: 1.02, 95% CI, 1.01 to 1.04) were also found to reduce and increase the risk of T2DM, respectively. CONCLUSION: High dietary intake of heme iron was associated with an increased risk of developing T2DM in a Mediterranean population at high cardiovascular risk. TRIAL REGISTRATION: Identifier: ISRCTN35739639

Integrin α6Bβ4 inhibits colon cancer cell proliferation and c-Myc activity

<p>Abstract</p> <p>Background</p> <p>Integrins are known to be important contributors to cancer progression. We have previously shown that the integrin β4 subunit is up-regulated in primary colon cancer. Its partner, the integrin α6 subunit, exists as two different mRNA splice variants, α6A and α6B, that differ in their cytoplasmic domains but evidence for distinct biological functions of these α6 splice variants is still lacking.</p> <p>Methods</p> <p>In this work, we first analyzed the expression of integrin α6A and α6B at the protein and transcript levels in normal human colonic cells as well as colorectal adenocarcinoma cells from both primary tumors and established cell lines. Then, using forced expression experiments, we investigated the effect of α6A and α6B on the regulation of cell proliferation in a colon cancer cell line.</p> <p>Results</p> <p>Using variant-specific antibodies, we observed that α6A and α6B are differentially expressed both within the normal adult colonic epithelium and between normal and diseased colonic tissues. Proliferative cells located in the lower half of the glands were found to predominantly express α6A, while the differentiated and quiescent colonocytes in the upper half of the glands and surface epithelium expressed α6B. A relative decrease of α6B expression was also identified in primary colon tumors and adenocarcinoma cell lines suggesting that the α6A/α6B ratios may be linked to the proliferative status of colonic cells. Additional studies in colon cancer cells showed that experimentally restoring the α6A/α6B balance in favor of α6B caused a decrease in cellular S-phase entry and repressed the activity of c-Myc.</p> <p>Conclusion</p> <p>The findings that the α6Bβ4 integrin is expressed in quiescent normal colonic cells and is significantly down-regulated in colon cancer cells relative to its α6Aβ4 counterpart are consistent with the anti-proliferative influence and inhibitory effect on c-Myc activity identified for this α6Bβ4 integrin. Taken together, these findings point out the importance of integrin variant expression in colon cancer cell biology.</p

Integrin α8β1 regulates adhesion, migration and proliferation of human intestinal crypt cells via a predominant RhoA/ROCK-dependent mechanism

Background. Integrins are transmembrane αβ heterodimer receptors that function as structural and functional bridges between the cytoskeleton and ECM (extracellular matrix) molecules. The RGD (arginine-glycine-aspartate tripeptide motif)-dependent integrin α8β1 has been shown to be involved in various cell functions in neuronal and mesenchymal-derived cell types. Its role in epithelial cells remains unknown

Cross-sectional assessment of nut consumption and obesity, metabolic syndrome and other cardiometabolic risk factors: the PREDIMED study

INTRODUCTION: Prospective studies have consistently suggested that nut consumption is inversely related to fatal and non-fatal coronary heart disease. Limited data are available on the epidemiological associations between nut intake and cardiometabolic risk factors. OBJECTIVE: To evaluate associations between frequency of nut consumption and prevalence of cardiometabolic risk factors [obesity, metabolic syndrome (MetS), type-2 diabetes, hypertension, and dyslipidemia] in a Mediterranean population at high cardiovascular risk. MATERIALS AND METHODS: Cross-sectional study of 7,210 men and women (mean age, 67 y) recruited into the PREDIMED study. MetS was defined by the harmonized ATPIII and IDF criteria. Diabetes and hypertension were assessed by clinical diagnosis and dyslipidemia (high triglycerides, low HDL-cholesterol, and hypercholesterolemia) by lipid analyses. Nut consumption was assessed using a validated food frequency questionnaire and categorized as 3 servings/wk. Control of confounding was done with multivariate logistic regression. RESULTS: Compared to participants consuming 3 servings/wk had lower adjusted odds ratios (OR) for obesity (0.61, 95% confidence interval 0.54 to 0.68; P-trend <0.001), MetS (0.74, 0.65 to 0.85; P-trend<0.001), and diabetes (0.87, 0.78 to 0.99; P-trend = 0.043). Higher nut consumption was also associated with lower risk of the abdominal obesity MetS criterion (OR 0.68, 0.60 to 0.79; P-trend<0.001). No significant associations were observed for the MetS components high blood pressure, dyslipidemia, or elevated fasting glucose. CONCLUSIONS: Nut consumption was inversely associated with the prevalence of general obesity, central obesity, MetS, and diabetes in subjects at high cardiovascular risk

Étude de dérivés N-acylés du chitosane comme porteurs de médicaments

Résumé: Ce travail étudie la possibilité d'utiliser des dérivés N-acylés du chitosane comme porteurs de médicaments pour des préparations absorbées par voie orale. Pour ce faire le chitosane a été modifié par N-acylation en utilisant les anhydrides symétriques de résidus d'acides gras. Deux types de dérivé ont été synthétisés: l'un préparé en utilisant des résidus d'acides gras aliphatiques et l'autre en utilisant des résidus d'acides gras aromatiques. Les différentes modifications donnent au chitosane de nouvelles propriétés hydrophobes. Ces dérivés de chitosane ont ensuite été comprimés en pastilles avec l'un des quatres médicaments étudiés afin de déterminer leur capacité à ralentir le relâchement du médicament in vitro. Les études préliminaires ont été effectuées avec l'acide 0-acétylsalicylique (ASA, Aspirine), un composé peu soluble dans l'eau. Les résultats indiquent que le relâchement de ce médicament est inversement relié au degré d'hydrophobicité du substituant alkyle ou aryle. Les données démontrent qu'en présence d'acides biliaires, la vitesse initiale de relâchement (apparente) d'ASA augmente mais que, par contre, l'ordre de la réaction de relâchement reste égal à un. Les dérivés ayant les propriétés les plus intéressantes ont été employés dans une deuxième série d'expériences avec trois autres médicaments: l'indométhacine, le fluoro-5 uracile et la cyclosporine A. Dans chaque cas, aucune relation entre le relâchement et le degré d'hydrophobicité du polymère modifié n'existe. Par contre, la contribution d'un effet hydrophobe dans la rétention d'indométhacine et de cycloporine A a pu être mise en évidence par l'addition d'acides biliaires qui ont augmenté la vitesse initiale de relâchement pour ces deux composés. Les résultats de ce travail permettent d'envisager l'exploitation de ce concept nouveau qu'est l'utilisation des chitosanes modifiés par des substitutions de type N-acyl et N-aryl comme porteurs de médicaments à action prolongée.||Abstract: This work studies the possibility of using chitosan N-acyl derivatives as drug carriers in slow release oral formulations. For this purpose the preparation of chitosans modified by N-acylation with varions symmetrical anhydrides of fatty acyl residues was undertaken. Two classes of derivatives were prepared; the first with aliphatic fatty residues and the second with aromatic fatty residues aLL contributing various degrees of hydrophobicity to the original polymer. The chitosan derivatives were directly compressed into tablets with one of four different drugs in order to investigate their slow releasing properties in vitro. Preliminary experiments were undertaken using 0-acetylsalicylic acid (ASA, Aspirin) a low water soluble drug as a model. Results indicate that the release of this drug is inversely related to the degree of hydrophobicity of the alkyl or aryl substituent. The data also show that bile salts, used to study the possible contribution of a hydrophobic effect, enhanced the (apparent) initial rate of release of ASA but did not change the (first) order of the release. A second set of experiments considered the use of the more interesting chitosan derivatives as drug vehicles for three other drugs; indomethacin, 5-fluorouracil and cyclosporin A. No relationship between the release of the drug and the hydrophobic nature of the polymer could be established for any of the three drugs. However, the contribution of a hydrophobic effect in the retention of indomethacin and cyclosporin A was confirmed by the addition of bile salts which increased the (apparent) rate of release of these two compounds. The data presented in this work purposes the suitability of exploiting the novel concept of using N-acyl and N-aryl substituted chitosans as the slow releasers of drugs

Involvement of laminin binding integrins in human intestinal epithelial cell functions

In this study we sought to determine the expression of three laminin binding integrins, previously poorly or uncharacterized, in intestinal epithelial cells: [alpha]9[bêta]1, [alpha]7[bêta]1 and [alpha]6[bêta]4. The expression and distribution of each of these integrins was characterized in the developing and mature, human small and large intestine. Complementary studies were carried out using two intestinal epithelial cell models, HIEC, which are crypt-like cells, and Caco-2/15 cells, which are villus-like. These experiments allowed us to associate each individual integrin to a particular cellular function. [alpha]9[bêta]1 was shown to be absent in mature intestinal epithelium. It was however, associated with highly proliferative cells, such as those found in the developing crypts in fetal intestine, as well as in HIEC and Caco-215 cells where, in the latter, [alpha]9[bêta]1 expression was down-regulated as the cells stopped proliferating and undertook their differentiation. This integrin was also found to be reexpressed in an onco-fetal like pattern of expression in a subset of colon cancers. [alpha]7B[bêta]1 was present in the intestine and was found to be restricted to the crypt-villus junction, which suggested a correlation with the onset of differentiation. This pattern of expression was reproduced in Caco-2/15 cells where [alpha]7B protein levels peaked between confluence and five days post-confluence coinciding almost perfectly with laminin-1 deposition, which was shown to be critical for triggering terminal differentiation in these cells. We determined that [alpha]6 associates predominantly with [bêta]4 in HIEC and Caco-2/15 cells and have identified a novel [bêta]4 variant expressed by HIEC, confirming the pattern of expression of [bêta]4 in crypt cells observed in vivo. Moreover, we have determined that the [alpha]6[bêta]4 receptor in HIEC is inactive in terms of adhesion to laminin-5, contrary to Caco-2/15 cells which use [alpha]6[bêta]4 to bind this ligand. Taken together, these results show that intestinal epithelial cells express a number of laminin binding integrins and that each is associated with a distinct cell function

Involvement of laminin binding integrins in human intestinal epithelial cell functions

In this study we sought to determine the expression of three laminin binding integrins, previously poorly or uncharacterized, in intestinal epithelial cells: [alpha]9[bêta]1, [alpha]7[bêta]1 and [alpha]6[bêta]4. The expression and distribution of each of these integrins was characterized in the developing and mature, human small and large intestine. Complementary studies were carried out using two intestinal epithelial cell models, HIEC, which are crypt-like cells, and Caco-2/15 cells, which are villus-like. These experiments allowed us to associate each individual integrin to a particular cellular function. [alpha]9[bêta]1 was shown to be absent in mature intestinal epithelium. It was however, associated with highly proliferative cells, such as those found in the developing crypts in fetal intestine, as well as in HIEC and Caco-215 cells where, in the latter, [alpha]9[bêta]1 expression was down-regulated as the cells stopped proliferating and undertook their differentiation. This integrin was also found to be reexpressed in an onco-fetal like pattern of expression in a subset of colon cancers. [alpha]7B[bêta]1 was present in the intestine and was found to be restricted to the crypt-villus junction, which suggested a correlation with the onset of differentiation. This pattern of expression was reproduced in Caco-2/15 cells where [alpha]7B protein levels peaked between confluence and five days post-confluence coinciding almost perfectly with laminin-1 deposition, which was shown to be critical for triggering terminal differentiation in these cells. We determined that [alpha]6 associates predominantly with [bêta]4 in HIEC and Caco-2/15 cells and have identified a novel [bêta]4 variant expressed by HIEC, confirming the pattern of expression of [bêta]4 in crypt cells observed in vivo. Moreover, we have determined that the [alpha]6[bêta]4 receptor in HIEC is inactive in terms of adhesion to laminin-5, contrary to Caco-2/15 cells which use [alpha]6[bêta]4 to bind this ligand. Taken together, these results show that intestinal epithelial cells express a number of laminin binding integrins and that each is associated with a distinct cell function

Étude de dérivés N-acylés du chitosane comme porteurs de médicaments

Résumé: Ce travail étudie la possibilité d'utiliser des dérivés N-acylés du chitosane comme porteurs de médicaments pour des préparations absorbées par voie orale. Pour ce faire le chitosane a été modifié par N-acylation en utilisant les anhydrides symétriques de résidus d'acides gras. Deux types de dérivé ont été synthétisés: l'un préparé en utilisant des résidus d'acides gras aliphatiques et l'autre en utilisant des résidus d'acides gras aromatiques. Les différentes modifications donnent au chitosane de nouvelles propriétés hydrophobes. Ces dérivés de chitosane ont ensuite été comprimés en pastilles avec l'un des quatres médicaments étudiés afin de déterminer leur capacité à ralentir le relâchement du médicament in vitro. Les études préliminaires ont été effectuées avec l'acide 0-acétylsalicylique (ASA, Aspirine), un composé peu soluble dans l'eau. Les résultats indiquent que le relâchement de ce médicament est inversement relié au degré d'hydrophobicité du substituant alkyle ou aryle. Les données démontrent qu'en présence d'acides biliaires, la vitesse initiale de relâchement (apparente) d'ASA augmente mais que, par contre, l'ordre de la réaction de relâchement reste égal à un. Les dérivés ayant les propriétés les plus intéressantes ont été employés dans une deuxième série d'expériences avec trois autres médicaments: l'indométhacine, le fluoro-5 uracile et la cyclosporine A. Dans chaque cas, aucune relation entre le relâchement et le degré d'hydrophobicité du polymère modifié n'existe. Par contre, la contribution d'un effet hydrophobe dans la rétention d'indométhacine et de cycloporine A a pu être mise en évidence par l'addition d'acides biliaires qui ont augmenté la vitesse initiale de relâchement pour ces deux composés. Les résultats de ce travail permettent d'envisager l'exploitation de ce concept nouveau qu'est l'utilisation des chitosanes modifiés par des substitutions de type N-acyl et N-aryl comme porteurs de médicaments à action prolongée.||Abstract: This work studies the possibility of using chitosan N-acyl derivatives as drug carriers in slow release oral formulations. For this purpose the preparation of chitosans modified by N-acylation with varions symmetrical anhydrides of fatty acyl residues was undertaken. Two classes of derivatives were prepared; the first with aliphatic fatty residues and the second with aromatic fatty residues aLL contributing various degrees of hydrophobicity to the original polymer. The chitosan derivatives were directly compressed into tablets with one of four different drugs in order to investigate their slow releasing properties in vitro. Preliminary experiments were undertaken using 0-acetylsalicylic acid (ASA, Aspirin) a low water soluble drug as a model. Results indicate that the release of this drug is inversely related to the degree of hydrophobicity of the alkyl or aryl substituent. The data also show that bile salts, used to study the possible contribution of a hydrophobic effect, enhanced the (apparent) initial rate of release of ASA but did not change the (first) order of the release. A second set of experiments considered the use of the more interesting chitosan derivatives as drug vehicles for three other drugs; indomethacin, 5-fluorouracil and cyclosporin A. No relationship between the release of the drug and the hydrophobic nature of the polymer could be established for any of the three drugs. However, the contribution of a hydrophobic effect in the retention of indomethacin and cyclosporin A was confirmed by the addition of bile salts which increased the (apparent) rate of release of these two compounds. The data presented in this work purposes the suitability of exploiting the novel concept of using N-acyl and N-aryl substituted chitosans as the slow releasers of drugs