Refined and whole grain cereals and the risk of oral, oesophageal and laryngeal cancer

OBJECTIVE: To investigate the possible differential role of refined and whole grain cereals on the risk of upper digestive and respiratory tract neoplasms. DESIGN: Hospital-based case-control study. SETTING: University Hospital of Lausanne, Switzerland. SUBJECTS: A total of 156 incident cases of cancers of the oral cavity and pharynx, 101 of the oesophagus, 40 of the larynx, and 349 control subjects admitted for a wide spectrum of acute non-neoplastic conditions. INTERVENTION: Trained interviewers collected information using a structured and validated questionnaire. Odds ratios (OR) of various cancers for a tertile increment of intake of refined and whole grains were estimated using unconditional multiple logistic regression. RESULTS: Refined grains were directly related to the risk of cancer of the oral cavity and pharynx (OR=1.9 for the highest tertile), oesophagus (OR=3.7) and larynx (OR=4.0). In contrast, whole grain cereals were protective, with OR of 0.6 for oral cavity and pharynx, 0.3 for oesophagus, and 0.7 for larynx. For the three sites combined, the OR for the highest tertile was 5.7 for refined grains and 0.5 for wholegrains. The trends in risk for refined grains were significant for all sites and their combination, and for wholegrain for oesophageal cancer and all sites. CONCLUSIONS: Even if inference on causality and the biological interpretation remain open to discussion, the present data indicate and further quantify that refined cereals are an unfavourable, but whole grain ones a favourable indicator of the risk of upper aerodigestive and respiratory tract neoplasms.     

Bioactive lipids are altered in the kidney of chronic undernourished rats: is there any correlation with the progression of prevalent nephropathies?

Background

Undernutrition during childhood leads to chronic diseases in adult life including hypertension, diabetes and chronic kidney disease. Here we explore the hypothesis that physiological alterations in the bioactive lipids pattern within kidney tissue might be involved in the progression of chronic kidney disease.

Methods

Membrane fractions from kidney homogenates of undernourished rats (RBD) were submitted to lipid extraction and analysis by thin layer chromatography and cholesterol determination.

Results

Kidneys from RBD rats had 25% lower cholesterol content, which disturb membrane microdomains, affecting Ca²⁺ homeostasis and the enzymes responsible for important lipid mediators such as phosphatidylinositol-4 kinase, sphingosine kinase, diacylglicerol kinase and phospholipase A₂. We observed a decrease in phosphatidylinositol(4)-phosphate (8.8?±?0.9 vs. 3.6?±?0.7 pmol.mg^?1.mim^?1), and an increase in phosphatidic acid (2.2?±?0.8 vs. 3.8?±?1.3 pmol.mg^?1.mim^?1), being these lipid mediators involved in the regulation of key renal functions. Ceramide levels are augmented in kidney tissue from RBD rats (18.7?±?1.4 vs. 21.7?±?1.5 fmol.mg^?1.min^?1) indicating an ongoing renal lesion.

Conclusion

Results point to an imbalance in the bioactive lipid generation with further consequences to key events related to kidney function, thus contributing to the establishment of chronic kidney disease.

     

Determinants of Post-acute Care Costs in Acutely Hospitalized Older Adults: The Hospital-ADL Study

ObjectivesAfter hospitalization, many older adults need post-acute care, including rehabilitation or home care. However, post-acute care expenses can be as high as the costs for the initial hospitalization. Detailed information on monthly post-acute health care expenditures and the characteristics of patients that make up for a large share of these expenditures is scarce. We aimed to calculate costs in acutely hospitalized older patients and identify patient characteristics that are associated with high post-acute care costs.DesignProspective multicenter cohort study (between October 2015 and June 2017).Setting and participants401 acutely hospitalized older persons from internal medicine, cardiology, and geriatric wards.MeasurementsOur primary outcome was mean post-acute care costs within 90 days postdischarge. Post-acute care costs included costs for unplanned readmissions, home care, nursing home care, general practice, and rehabilitation care. Three costs categories were defined: low [0-50th percentile (p0-50)], moderate (p50-75), and high (p75-100). Multinomial logistic regression analyses were conducted to assess the associations between costs and frailty, functional impairment, health-related quality of life, cognitive impairment, and depressive symptoms.ResultsCosts were distributed unevenly in the population, with the top 10.0% (n = 40) accounting for 52.1% of total post-acute care costs. Mean post-acute care costs were €4035 [standard deviation (SD) 4346] or $4560 (SD 4911). Frailty [odds ratio (OR) 3.44, 95% confidence interval (CI) 1.78-6.63], functional impairment (OR 1.80, 95% CI 1.03-3.16), and poor health-related quality of life (OR 1.89, 95% CI 1.09-3.28) at admission were associated with classification in the high-cost group, compared with the low-cost group.Conclusions/ImplicationsPost-acute care costs are substantial in a small portion of hospitalized older adults. Frailty, functional impairment, and poor health-related quality of life are associated with higher post-acute care costs and may be used as an indicator of such costs in practice.     

In vivo blockade of the Fas-Fas ligand pathway inhibits cyclophosphamide-induced diabetes in NOD mice.

There is compelling evidence to show that insulin dependent diabetes ensues from selective apoptosis of pancreatic beta-cells mediated by autoreactive T-lymphocytes. The respective implication in this phenomenon of the various apoptotic pathways driven by Fas, perforin, or tumor necrosis factor is still ill- defined. Here we took advantage of the cyclophosphamide-induced model of accelerated diabetes in NOD mice to explore the physiopathological role of the Fas-Fas Ligand pathway. A single injection of cyclophosphamide (200 mg/kg) to 7-8 week-old prediabetic NOD mice triggered diabetes within 10-15 days in 85-100% of the animals. Cyclophosphamide also induced a significant decrease in spleen T cells, that was most evident by days 6-10 after treatment, and selectively affected the CD3(+)CD62L(+)compartment that includes immunoregulatory T cells. To block the in vivo Fas-Fas ligand (Fas L) interaction we administered a biologically active recombinant fusion protein coupling mouse Fas to the Fc portion of human IgG1 (FAS-Fc). Mice treated with FAS-Fc (10 doses iv of 15 microg) starting on the day of cyclophosphamide injection up to day 22, were fully protected from disease. Unexpectedly this protective effect was not due to blockade of Fas-FasL-mediated beta-cell apoptosis but rather to the inhibition of the cyclophosphamide effect on T cells. Indeed FAS-Fc treatment prevented the drug-induced T cell depletion in general and that of immunoregulatory T cells in particular. Additionally, FAS-Fc administration limited to the phase of beta-cell destruction did not afford any protection.     

Dopaminergic neurons expressing Fos during waking and paradoxical sleep in the rat

Formerly believed to contribute to behavioural waking (W) alone, dopaminergic (DA) neurons are now also known to participate in the regulation of paradoxical sleep (PS or REM) in mammals. Indeed, stimulation of postsynaptic DA1 receptors with agonists induces a reduction in the daily amount of PS. DA neurons in the ventral tegmental area were recently shown to fire in bursts during PS, but nothing is known about the activity of the other DA cell groups in relation to waking or PS. To fulfil this gap, we used a protocol in which rats were maintained in continuous W for 3 h in a novel environment, or specifically deprived of PS for 3 days with some of them allowed to recover from this deprivation. A double immunohistochemical labeling with Fos and tyrosine hydroxylase was then performed. DA neurons in the substantia nigra (A9) and ventral tegmental area (A10), and its dorsocaudal extension in the periaqueductal gray (A10dc), almost never showed a Fos-immunoreactive nucleus, regardless of the experimental condition. The caudal hypothalamic (A11) group showed a moderate activation after PS deprivation and novel environment. During PS-recovery, the zona incerta (A13) group contained a significant number and percentage of double-labeled neurons. These results suggest that some DA neurons (A11) could participate in waking and/or the inhibition of PS during PS deprivation whereas others (A13) would be involved in the control of PS.     

Renin-angiotensin system in the kidney: What is new?

The renin-angiotensin system (RAS) has been known for more than a century as a cascade that regulates body fluid balance and blood pressure. Angiotensin II(Ang II) has many functions in different tissues; however it is on the kidney that this peptide exerts its main functions. New enzymes, alternative routes for Ang IIformation or even active Ang II-derived peptides have now been described acting on Ang II AT₁ or AT₂ receptors, or in receptors which have recently been cloned, such as Mas and AT₄. Another interesting observation was that old members of the RAS, such as angiotensin converting enzyme (ACE), renin and prorenin, well known by its enzymatic activity, can also activate intracellular signaling pathways, acting as an outside-in signal transduction molecule or on the renin/(Pro)renin receptor. Moreover, the endocrine RAS, now is also known to have paracrine, autocrine and intracrine action on different tissues, expressing necessary components for local Ang II formation. This in situ formation, especially in the kidney, increases Ang II levels to regulate blood pressure and renal functions. These discoveries, such as the ACE2/Ang-(1-7)/Mas axis and its antangonistic effect rather than classical deleterious Ang II effects, improves the development of new drugs for treating hypertension and cardiovascular diseases.     

Anti-tumor necrosis factor modulates anti-CD3-triggered T cell cytokine gene expression in vivo.

De novo expression of TNF, IFN gamma, IL-3, IL-4, and IL-6 genes was initiated rapidly by treatment of mice with anti-CD3. A specific feature of this reaction was that TNF was derived exclusively from T cells. TNF was produced both as a mature soluble trimeric protein and as a 26-kD anti-TNF-reactive protein compatible with membrane-anchored TNF. Pretreatment with anti-TNF did not affect anti-CD3-triggered TNF mRNA expression in T cells. In contrast, in vivo and in vitro anti-TNF treatment upregulated anti-CD3-induced IFN gamma mRNA expression and inhibited IL-4 mRNA expression. These latter effects were not dependent on TNF neutralization: pretreatment with soluble recombinant 55-kD TNF receptor (TBPI) as an alternative TNF-neutralizing agent did not modify the anti-CD3-induced cytokine profile. These results suggest that a direct interaction between anti-TNF and T cell membrane-anchored TNF could account for the observed modulation of cytokine gene expression. The increased expression of INF gamma mRNA observed in anti-TNF-treated animals correlated with a decrease in IL-3 and IL-6 mRNA expression. Conversely, IFN gamma blockade by a neutralizing anti-IFN gamma mAb led to a substantial increase in both IL-3 and IL-6 gene expression induced by anti-CD3. Taken together, these results strongly argue for the existence, in the anti-CD3-induced cytokine cascade, of IFN gamma-dependent regulation of IL-3 production, which in turn modulates IL-6 production.