Functional and Morphological Changes in Endocrine Pancreas following Cola Drink Consumption in Rats

We report the effects of long-term cola beverage drinking on glucose homeostasis, endocrine pancreas function and morphology in rats.Wistar rats drank: water (group W), regular cola beverage (group C, sucrose sweetened) or "light" cola beverage (group L, artificially sweetened). After 6 months, 50% of the animals in each group were euthanized and the remaining animals consumed water for the next 6 months when euthanasia was performed. Biochemical assays, insulinemia determination, estimation of insulin resistance (HOMA-IR), morphometry and immunohistochemistry evaluations were performed in pancreas.Hyperglycemia (16%, p<0.05), CoQ10 (coenzyme-Q10) decrease (-52%,p<0.01), strong hypertriglyceridemia (2.8-fold, p<0.01), hyperinsulinemia (2.4 fold, p<0.005) and HOMA-IR increase (2.7 fold, p<0.01) were observed in C. Group C showed a decrease in number of α cells (-42%, p<0.01) and β cells (-58%, p<0.001) and a moderate increase in α cells' size after wash-out (+14%, p<0.001). Group L showed reduction in β cells' size (-9%, p<0.001) and only after wash-out (L12) a 19% increase in size (p<0.0001) with 35% decrease in number of α cells (p<0.01). Groups C and L showed increase in α/β-cell ratio which was irreversible only in C (α/β = +38% in C6,+30% in C12, p<0.001vs.W6). Regular cola induced a striking increase in the cytoplasmic expression of Trx1 (Thioredoxin-1) (2.25-fold in C6 vs. W6; 2.7-fold in C12 vs. W12, p<0.0001) and Prx2 (Peroxiredoxin-2) (3-fold in C6 vs. W6; 2-fold in C12 vs. W12, p<0.0001). Light cola induced increase in Trx1 (3-fold) and Prx2 (2-fold) after wash-out (p<0.0001, L12 vs. W12).Glucotoxicity may contribute to the loss of β cell function with depletion of insulin content. Oxidative stress, suggested by increased expression of thioredoxins and low circulating levels of CoQ10, may follow sustained hyperglycemia. A likely similar panorama may result from the effects of artificially sweetened cola though via other downstream routes

The risk of Plasmodium vivax parasitaemia after P. falciparum malaria: An individual patient data meta-analysis from the WorldWide Antimalarial Resistance Network

Background There is a high risk of Plasmodium vivax parasitaemia following treatment of falciparum malaria. Our study aimed to quantify this risk and the associated determinants using an individual patient data meta-analysis in order to identify populations in which a policy of universal radical cure, combining artemisinin-based combination therapy (ACT) with a hypnozoitocidal antimalarial drug, would be beneficial. Methods and findings A systematic review of Medline, Embase, Web of Science, and the Cochrane Database of Systematic Reviews identified efficacy studies of uncomplicated falciparum malaria treated with ACT that were undertaken in regions coendemic for P. vivax between 1 January 1960 and 5 January 2018. Data from eligible studies were pooled using standardised methodology. The risk of P. vivax parasitaemia at days 42 and 63 and associated risk factors were investigated by multivariable Cox regression analyses. Study quality was assessed using a tool developed by the Joanna Briggs Institute. The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42018097400). In total, 42 studies enrolling 15,341 patients were included in the analysis, including 30 randomised controlled trials and 12 cohort studies. Overall, 14,146 (92.2%) patients had P. falciparum monoinfection and 1,195 (7.8%) mixed infection with P. falciparum and P. vivax. The median age was 17.0 years (interquartile range [IQR] = 9.0–29.0 years; range = 0–80 years), with 1,584 (10.3%) patients younger than 5 years. 2,711 (17.7%) patients were treated with artemether-lumefantrine (AL, 13 studies), 651 (4.2%) with artesunate-amodiaquine (AA, 6 studies), 7,340 (47.8%) with artesunate-mefloquine (AM, 25 studies), and 4,639 (30.2%) with dihydroartemisinin-piperaquine (DP, 16 studies). 14,537 patients (94.8%) were enrolled from the Asia-Pacific region, 684 (4.5%) from the Americas, and 120 (0.8%) from Africa. At day 42, the cumulative risk of vivax parasitaemia following treatment of P. falciparum was 31.1% (95% CI 28.9–33.4) after AL, 14.1% (95% CI 10.8–18.3) after AA, 7.4% (95% CI 6.7–8.1) after AM, and 4.5% (95% CI 3.9–5.3) after DP. By day 63, the risks had risen to 39.9% (95% CI 36.6–43.3), 42.4% (95% CI 34.7–51.2), 22.8% (95% CI 21.2–24.4), and 12.8% (95% CI 11.4–14.5), respectively. In multivariable analyses, the highest rate of P. vivax parasitaemia over 42 days of follow-up was in patients residing in areas of short relapse periodicity (adjusted hazard ratio [AHR] = 6.2, 95% CI 2.0–19.5; p = 0.002); patients treated with AL (AHR = 6.2, 95% CI 4.6–8.5; p < 0.001), AA (AHR = 2.3, 95% CI 1.4–3.7; p = 0.001), or AM (AHR = 1.4, 95% CI 1.0–1.9; p = 0.028) compared with DP; and patients who did not clear their initial parasitaemia within 2 days (AHR = 1.8, 95% CI 1.4–2.3; p < 0.001). The analysis was limited by heterogeneity between study populations and lack of data from very low transmission settings. Study quality was high. Conclusions In this meta-analysis, we found a high risk of P. vivax parasitaemia after treatment of P. falciparum malaria that varied significantly between studies. These P. vivax infections are likely attributable to relapses that could be prevented with radical cure including a hypnozoitocidal agent; however, the benefits of such a novel strategy will vary considerably betwee