Dietary phylloquinone intake as a potential marker for a heart-healthy dietary pattern in the Framingham Offspring cohort

Abstract Associations were evaluated among self-reported dietary intakes of phylloquinone (vitamin K-1), lifestyle characteristics, and intermediary markers of cardiovascular disease risk in a population-based cohort of men and women. Dietary phylloquinone intakes were assessed by food frequency questionnaire in 1,338 men and 1,603 women (mean age, 54 years) participating in the Framingham Heart Study. Cross-sectional associations with lifestyle characteristics and lipid profiles, including total cholesterol, low-density lipoprotein and high-density lipoprotein cholesterol, and triglyceride concentrations, were estimated across increasing quintile categories of phylloquinone intakes. Participants in the highest quintile category of phylloquinone intake consumed more fruit, vegetables, fish, dietary fiber, and dietary supplements ( P <.001), and consumed less meat and less saturated fat ( P <.001). Higher phylloquinone intakes were also associated with lower triglyceride concentrations ( P <.001). In conclusion, a high phylloquinone intake may be a marker for an overall heart-healthy dietary pattern.     

Low birthweight and Type 2 diabetes: a study on 11 162 Swedish twins

BACKGROUND: To investigate the association between low birthweight and diabetes in a population-based Swedish twin sample. Method A cohort of 11 162 same-sexed Swedish twins born between 1906 and 1958 was used in order to investigate the risk of developing Type 2 diabetes between and within twin pairs by utilizing random effects linear models. RESULTS: Between pairs there was a significant increase in risk of developing Type 2 diabetes for a 1-kg increase in their mean birthweight (odds ratio [OR] = 2.13; P < 0.01), adjusted for age, sex, body mass index (BMI), and smoking status. The corresponding risk within pair was 2.03 (P = 0.07) for monozygotic twins and 1.15 (P = 0.71) for dizygotic twins. The test of the heterogeneity of the within and between effects showed no significant difference between the estimates. CONCLUSIONS: The study suggests that reduced fetal growth increase the risk of Type 2 diabetes due to an in utero programming effect possibly caused by intrauterine malnutrition. However, it does not exclude the possibility of a common genetic mechanism.     

Pulmonary embolism and stroke in relation to pregnancy: how can high-risk women be identified?

OBJECTIVE: Risks of circulatory diseases are increased substantially during late pregnancy and around the time of delivery. This study was undertaken to determine whether preeclampsia, multiple pregnancy, or cesarean delivery account for the majority of pregnancy-related risks of pulmonary embolism and stroke (caused by hemorrhage, infarction, and intracranial venous thrombosis). STUDY DESIGN: We analyzed a population-based cohort of 1,003,489 deliveries in Sweden. Relative risks of pulmonary embolism and stroke were modeled by use of Poisson regression. RESULTS: Preeclampsia was associated with 3- to 12-fold increases in risks of pulmonary embolism and stroke during late pregnancy, at delivery, and in the puerperium, and similar increases in risks were also observed for multiple pregnancies and cesarean delivery. These strong associations could not explain the overall pregnancy-related risks of pulmonary embolism and stroke. CONCLUSION: Preeclampsia, multiple birth, and cesarean delivery are important risk factors for pulmonary embolism and stroke, but they do not account for the majority of the excess risks associated with pregnancy.     

Corticosteroids in Crohn's disease

Crohn's disease is a lifelong illness characterized by chronic recurrent flares. The precise etiology of Crohn's disease is unknown. However, it appears to involve an enhanced systemic immune response and intensified local intestinal mucosal inflammatory activity, mediated through various inflammatory cells and an array of proinflammatory cytokines. Corticosteroids have been the mainstay of treatment of Crohn's disease. The controlled trials of the National Cooperative Crohn's Disease Study and the European Cooperative Crohn's Disease Study established that corticosteroids were effective for the induction of remission in Crohn's disease for the duration of the studies (6-17 wk). However, corticosteroids have not been shown to have an impact on the maintenance of long term remission in patients with Crohn's disease. In addition, they are associated with a high potential for dependence and serious toxic side effects. Alternative classes of medical therapy for Crohn's disease, including modified corticosteroids and a group of new biological therapies, have proven to be efficacious in the management of active and/or quiescent Crohn's disease.     

Preferential killing of PTEN-null myelomas by PI3K inhibitors through Akt pathway

We recently reported that internal deletion of PTEN tumor suppressor gene in OPM2 and Delta47 myeloma lines led to high Akt activation. Re-expression of PTEN induced strong apoptosis and growth inhibition. To understand the biologic importance of the phosphatidylinositol 3 kinase (PI3K)/Akt activation affected by PTEN deletion, we analysed apoptosis and growth inhibition by applying PI3K inhibitors to myeloma lines and by expressing Akt constructs. The PI3K inhibitors preferentially suppressed PTEN-null myeloma growth to those expressing PTEN, indicating that PI3K activation is more critical for growth and survival of those lines with PTEN mutations than others expressing a functional PTEN gene. Since PTEN-null myeloma lines exhibited much stronger Akt activation than PTEN-expressing cells in response to insulin-like growth factor I stimulation, we determined whether Akt could be responsible for PI3K-mediated cell survival and growth of PTEN-null myeloma lines. Expression of an active Akt, but not its kinase dead mutant, reversed wortmannin- and dexamethasone-induced apoptosis and growth inhibition in PTEN-null myeloma lines, suggesting that Akt lies downstream of PI3K for PTEN-null myeloma survival and dexamethasone resistance. In summary, we have provided evidence that PTEN-null myeloma cells are stringently dependent on the PI3K/Akt activation for cell survival. These results may provide a basis to treat myeloma patients with PI3K and Akt inhibitors.     

The role of biological therapy in inflammatory bowel disease

Substantial evidence suggests a central role for TNF-alpha in the pathogenesis of IBD. This molecular observation has been supported by clinical trials with anti-TNF therapies. The most extensively investigated among the various anti-TNF agents is infliximab. Clinical trials to date have demonstrated its efficacy in inducing remission in patients with moderately active, refractory Crohn's disease (CD) and in managing patients with CD complicated by fistulas. One advantage of infliximab is its rapid onset of action. However, as expected with most medications used to treat patients with IBD, the effect of infliximab is of limited duration, with the response lasting 2-3 months in most patients. The efficacy of repeated infusions of infliximab in maintaining remission in patients with inflammatory CD has been demonstrated in one trial to date. The results from the ACCENT I trial should soon be available. Many other important questions regarding the use of infliximab remain unanswered. These include the optimal schedules of infusions, the effect of concomitant therapy with aminosalicylates, immunomodulators and antibiotics, and the timing and indication of using infliximab in the general management algorithm of a patient with CD. Certainly, the efficacy of infliximab in the treatment of ulcerative colitis (UC) remains to be further explored in a controlled fashion, though preliminary uncontrolled data suggests efficacy. As experience with infliximab use accumulates, more data will become available regarding its safety with either short-term or long-term use. A large body of evidence exists regarding the short-term safety of infliximab. The concern of increased risk of hypersensitivity-like reactions with longer interval between treatments will also need to be addressed. The currently available data supports that infliximab is safe and well tolerated. Other anti-TNF therapies will also need to be investigated with the same rigor before widespread use can be advocated. In addition to these agents, advances in molecular engineering techniques have further expanded the array of biologic therapies available to treat IBD. These newer therapies hold promise in targeting specific pathways of the pathogenesis of IBD that may be different from all prior therapies. Certainly, the anti-TNF therapies and others aforementioned have taken the field of IBD into a new and exciting generation, the biological era. (c) 2001 Prous Science. All rights reserved.