The assignment of the Ca2+-ATPase activity of chromaffin granules to the proton translocating ATPase

AbstractCaATP is shown to function as a substrate for the proton translocating ATPase of chromaffin granule ghosts at concentrations which are comparable to that of MgATP. Using the initial rate of the proton pump activity as the measure (ΔpH/Δt), an apparent Km-value of 139 ± 8 μM was estimated for CaATP and 59 ± 3 μM for MgATP. The maximal rate was markedly higher with MgATP than with CaATP, partly due to an inhibition of the hydrolytic activity at the higher concentrations of CaATP. The proton pump activity with CaATP was inhibited by N-ethylmaleimide and N,N'-dicyclohexylcarbodiimide at concentrations similar to that found for MgATP. No inhibition was observed with sodium vanadate in the concentration range 0–15 μM. Calmodulin and trifluoperazine had no effect on the overall ATPase activity with CaATP. These findings establish this acitivity as an intrinsic property of the chromaffin granules, i.e., linked to the H+-ATPase. No evidence was obtained for the presence of a Ca2+-translocating ATPase ((Ca2+ + Mg2+)-ATPase) in the chromaffin granules.Ca2+-ATPaseH+-ATPaseProton pumpChromaffin granuleAdrenal medull

Prolonged Survival in Patients with Lung Cancer with Diabetes Mellitus

IntroductionPatients with lung cancer have a high frequency of comorbidity. Data on the impact of diabetes mellitus, the most frequent endocrine disorder, on the prognosis of lung cancer are conflicting. The aim was to investigate the impact of diabetes mellitus on survival in lung cancer.MethodWe analyzed data from a cohort, the Nord-Trøndelag Health Study (HUNT study) linked to the Norwegian Cancer Registry and controlled the results using two lung cancer studies, the Pemetrexed Gemcitabine study and the Norwegian Lung Cancer Biobank. Survival in lung cancer with and without diabetes mellitus was compared using the Kaplan-Meier method and Cox regression model for each study and the studies combined.ResultsOne thousand six hundred seventy-seven cases of lung cancer were included, 1031 from HUNT study, 436 from the Pemetrexed Gemcitabine study, and 210 from the Norwegian Lung Cancer Biobank registry, and among these 77 patients had diabetes mellitus. In the combined analysis, patients with lung cancer with diabetes mellitus had increased survival compared with those without (p = 0.005). The 1-, 2-, and 3-year survival in patients with lung cancer with and without diabetes mellitus were 43% versus 28%, 19% versus 11%, and 3% versus 1%, respectively. Adjusting for age, gender, histology, and stage of disease in the Cox regression model, the hazard ratio for survival in patients with lung cancer with diabetes mellitus was 0.55 (95% CI, 0.41–0.75) as compared with without.ConclusionPatients with lung cancer with diabetes mellitus have an increased survival compared with those without diabetes mellitus

Intake of dairy products and associations with major atherosclerotic cardiovascular diseases:a systematic review and meta-analysis of cohort studies

Abstract Specific types of dairy products may be differentially associated with atherosclerotic cardiovascular disease (CVD). We conducted a systematic review and meta-analysis of cohort studies to summarize findings on the associations between total dairy product intake and intake of dairy product subgroups and the risk of major atherosclerotic CVDs in the general adult population. Our protocol was registered in PROSPERO (CRD42019125455). PubMed and Embase were systematically searched through 15 August 2019. For high versus low intake and dose–response meta-analysis, random-effects modelling was used to calculate summary risk ratios (RR). There were 13 cohort studies included for coronary heart disease (CHD), 7 for ischemic stroke and none for peripheral artery disease. High-fat milk was positively associated with CHD (RR 1.08 (95% confidence interval 1.00–1.16) per 200 g higher intake/day) and cheese was inversely associated with CHD (RR 0.96 (95% confidence interval 0.93–0.98) per 20 g higher intake/day). Heterogeneity, however, was observed in high versus low meta-analyses. Milk was inversely associated with ischemic stroke in high versus low meta-analysis only. In conclusion, this systematic review indicates a positive association of high-fat milk and an inverse association of cheese with CHD risk. The findings should be interpreted in the context of the observed heterogeneity

Cognitive Trajectories in Older Patients with Cancer Undergoing Radiotherapy—A Prospective Observational Study

Cognitive function can be affected by cancer and/or its treatment, and older patients are at a particular risk. In a prospective observational study including patients 65 years referred for radiotherapy (RT), we aimed to investigate the association between patient- and cancer-related factors and cognitive function, as evaluated by the Montreal Cognitive Assessment (MoCA), and sought to identify groups with distinct MoCA trajectories. The MoCA was performed at baseline (T0), RT completion (T1), and 8 (T2) and 16 (T3) weeks later, with scores ranging between 0 and 30 and higher scores indicating better function. Linear regression and growth mixture models were estimated to assess associations and to identify groups with distinct MoCA trajectories, respectively. Among 298 patients with a mean age of 73.6 years (SD 6.3), the baseline mean MoCA score was 24.0 (SD 3.7). Compared to Norwegian norm data, 37.9% had cognitive impairment. Compromised cognition was independently associated with older age, lower education, and physical impairments. Four groups with distinct trajectories were identified: the very poor (6.4%), poor (8.1%), fair (37.9%), and good (47.7%) groups. The MoCA trajectories were mainly stable. We conclude that cognitive impairment was frequent but, for most patients, was not affected by RT. For older patients with cancer, and in particular for those with physical impairments, we recommend an assessment of cognitive function.This work was funded by Innlandet Hospital Trust, Norway. This research received no external funding.publishedVersio