Effect of Pyrimidine Nucleosides on Body Temperatures of Man and Rabbit in Relation to Pharmacokinetic Data

The effect of high-dose uridine on body temperatures of rabbits and man has been studied in relation to plasma concentrations of uridine and its catabolite uracil. Uridine induced fever in both rabbits and man. High-dose cytidine had no influence on body temperature in rabbits. Plasma concentrations of uridine were between 1 and 1.5 mM at 30 min after an iv bolus injection of 400 mg uridine/kg in rabbits and reached peak levels of 2 mM after a 1-hr infusion of 12 g uridine/m² in man. The plasma concentration of cytidine in rabbits was about 0.5 mM and that of uridine was 0.30 mM at 30 min after an iv bolus injection of 400 mg cytidine/kg. The mean residence time for uridine in patients and rabbits varied between 80 and 195 min. The area under the plasma concentration–time curve (AUC) for uridine in rabbits was 2.0 mmol · hr/liter, and that for cytidine was 0.6 mmol · hr/liter. A large AUC for uridine indicates a prolonged exposure of tissues to uridine, which might lead to extensive formation of degradation products. The administration of some of these catabolites, dihydrouracil (at 20–40 mg/kg), carbamyl--alanine (at 60 mg/kg), and -alanine (at 300–400 mg/kg), resulted in a significant increase in body temperature. It is concluded that the change in body temperature associated with uridine administration was not due to bacterial pyrogens but that one of the degradation products might be involved in thermoregulation.     

Integrin expression in correlation to clinicopathological features and prognosis of prostate cancer: A systematic review and meta-analysis

Background: The prompt identification of patients with poor prognosis is essential in order to improve the treatment outcomes in prostate cancer (CaP); as a novel approach, several molecular markers, including integrins, have been discussed as prognostic biomarkers. Our aim was to comprehensively examine aberrant expression of integrins in correlation with clinicopathological features and prognosis in CaP by synthesizing all available evidence, in a systematic review and meta-analysis. Methods: A systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. Scientific literature databases (Pubmed, Embase, and Scopus) were systematically searched until May 10, 2020. Random-effects (DerSimonian-Laird) models were used to estimate pooled odds ratios (ORs) for cross-sectional correlations with clinicopathological characteristics and relative risks for longitudinal associations with prognosis. Results: Fourteen studies were included with a total number of 3,194 CaP cases examined (13 cross-sectional and four longitudinal cohort study arms). Correlation of low expression of α₆ (pooled OR = 0.10, 95% confidence interval [CI]: 0.04–0.28, P < 0.001) and β₁ (pooled OR = 0.45; 95% CI: 0.21–1.00, P = 0.049) integrin with high Gleason score was noted. A borderline trend between reduced expression of α₆ integrin and an advanced clinical stage of CaP (pooled OR = 0.48; 95% CI: 0.22-1.03, P = 0.06) was observed. No associations with biochemical recurrence and survival were documented. Conclusions: Evidence on the association of low expression of integrins α₆ and β₁ and more advanced CaP exist, whereas significant results on survival were not documented; further studies are warranted.     

The use of third-party packed red blood cells during ex situ normothermic machine perfusion of organs for transplantation: Underappreciated complexities?

Ex situ normothermic machine perfusion (NMP) is being used increasingly in the assessment of higher risk deceased donor organs and to facilitate prolonged organ storage. Third-party packed red blood cells (pRBCs) are often used as an oxygen carrier in the perfusate of ex situ NMP. Despite the increasing interest in NMP, comparatively little attention has been paid to the appropriate selection of pRBCs. This includes the choice of ABO blood group and Rhesus D status, the need for special requirements for selected recipients, and the necessity for traceability of blood components. Flushing organs with cold preservation solution after NMP removes the overwhelming majority of third-party allogeneic pRBCs, but residual pRBCs within the organ may have biologically relevant effects following implantation as they enter the recipient's circulation. This review considers these issues, and suggests that national transplant and blood transfusion agencies work together to develop a co-ordinated approach within each country. This is especially important given the possibility of organ re-allocation between centers after ex situ NMP, and the ongoing development of organ perfusion hubs.     

Whole Grain Consumption and Breast Cancer: A Case-Control Study in Women

Objective: Whole grain consumption has long been associated with human health. However, its relationship with breast cancer remains not well understood and appreciated. The aim of this work was to evaluate the association between whole grain consumption and breast cancer in women. Methods: A case-control study was designed. Two hundred and fifty consecutive, newly diagnosed breast cancer female patients (56 ± 12 years) and 250 one-to-one age-matched controls were enrolled. A standardized, validated questionnaire assessing various sociodemographic, clinical, lifestyle, and dietary characteristics was applied through face-to-face interviews. Moreover, data on regular consumption of whole grains (i.e., never/rarely, 1–6 times/week, >7 times/week) were recorded. Overall dietary habits were assessed through the level of adherence to the Mediterranean diet using the MedDietScore (theoretical range 0–55). Results: Whole grain consumption of more than 7 times/week was associated with a 0.49-fold (odds ratio = 0.49; 95% confidence interval, 0.29, 0.82) lower likelihood of having breast cancer, after adjustments were made. Conclusions: This study suggested that whole grain consumption more than 7 times/week was consistently associated with reduced risk of breast cancer.