Observed long-term land cover vs climate impacts on the West African hydrological cycle: lessons for the future ? [P-3330-65]

West Africa has experienced a long lasting, severe drought as from 1970, which seems to be attenuating since 2000. It has induced major changes in living conditions and resources over the region. In the same period, marked changes of land use and land cover have been observed: land clearing for agriculture, driven by high demographic growth rates, and ecosystem evolutions driven by the rainfall deficit. Depending on the region, the combined effects of these climate and environmental changes have induced contrasted impacts on the hydrological cycle. In the Sahel, runoff and river discharges have increased despite the rainfall reduction (“less rain, more water”, the so-called "Sahelian paradox "). Soil crusting and erosion have increased the runoff capacity of the watersheds so that it outperformed the rainfall deficit. Conversely, in the more humid Guinean and Sudanian regions to the South, the opposite (and expected) “less rain, less water” behavior is observed, but the signature of land cover changes can hardly be detected in the hydrological records. These observations over the past 50 years suggest that the hydrological response to climate change can not be analyzed irrespective of other concurrent changes, and primarily ecosystem dynamics and land cover changes. There is no consensus on future rainfall trend over West Africa in IPCC projections, although a higher occurrence of extreme events (rainstorms, dry spells) is expected. An increase in the need for arable land and water resources is expected as well, driven by economic development and demographic growth. Based on past long-term observations on the AMMA-CATCH observatory, we explore in this work various future combinations of climate vs environmental drivers, and we infer the expected resulting trends on water resources, along the west African eco-climatic gradient. (Texte intégral

Characterization of 9-Nitrocamptothecin Liposomes: Anticancer Properties and Mechanisms on Hepatocellular Carcinoma In Vitro and In Vivo

BACKGROUND: Hepatocellular carcinoma (HCC) is the third most common cause of cancer related mortality worldwide. 9-Nitrocamptothecin (9NC) is a potent topoisomerase-I inhibitor with strong anticancer effect. To increase the solubility and stability, we synthesized a novel 9NC loaded liposomes (9NC-LP) via incorporating 9NC into liposomes. In the present study, we determined the effects of 9NC and 9NC-LP on in vitro and in vivo, and the underlying mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: We first analyzed the characteristics of 9NC-LP. Then we compared the effects of 9NC and 9NC-LP on the proliferation and apoptosis of HepG2, Bel-7402, Hep3B and L02 cells in vitro. We also investigated their anticancer properties in nude mice bearing HCC xenograft in vivo. 9NC-LP has a uniform size (around 190 nm) and zeta potential (∼-11 mV), and exhibited a steady sustained-release pattern profile in vitro. Both 9NC and 9NC-LP could cause cell cycle arrest and apoptosis in a dose-dependent and p53-dependent manner. However, this effect was not ubiquitous in all cell lines. Exposure to 9NC-LP led to increased expression of p53, p21, p27, Bax, caspase-3, caspase-8, caspase-9 and apoptosis-inducing factor, mitochondrion-associated 1 and decreased expression of Bcl-2, cyclin E, cyclin A, Cdk2 and cyclin D1. Furthermore, 9NC-LP exhibited a more potent antiproliferative effect and less side effects in vivo. Western blot analysis of the xenograft tumors in nude mice showed similar changes in protein expression in vivo. CONCLUSIONS/SIGNIFICANCE: In conclusion, 9NC and 9NC-LP can inhibit HCC growth via cell cycle arrest and induction of apoptosis. 9NC-LP has a more potent anti-tumor effect and fewer side effects in vivo, which means it is a promising reagent for cancer therapy via intravenous administration

New potential antitumoral fluorescent tetracyclic thieno[3,2-b]pyridine derivatives: interaction with DNA and nanosized liposomes

Fluorescence properties of two new potential antitumoral tetracyclic thieno[3,2-b]pyridine derivatives were studied in solution and in liposomes of DPPC (dipalmitoyl phosphatidylcholine), egg lecithin (phosphatidylcholine from egg yolk; Egg-PC) and DODAB (dioctadecyldimethylammonium bromide). Compound 1, pyrido[2',3':3,2]thieno[4,5-d]pyrido[1,2-a]pyrimidin-6-one, exhibits reasonably high fluorescence quantum yields in all solvents studied (0.20 ≤ ΦF ≤ 0.30), while for compound 2, 3-[(p-methoxyphenyl)ethynyl]pyrido[2',3':3,2]thieno[4,5-d]pyrido[1,2-a]pyrimidin-6-one, the values are much lower (0.01 ≤ ΦF ≤ 0.05). The interaction of these compounds with salmon sperm DNA was studied using spectroscopic methods, allowing the determination of intrinsic binding constants, Ki = (8.7 ± 0.9) × 103 M-1 for compound 1 and Ki = (5.9 ± 0.6) × 103 M-1 for 2, and binding site sizes of n = 11 ± 3 and n = 7 ± 2 base pairs, respectively. Compound 2 is the most intercalative compound in salmon sperm DNA (35%), while for compound 1 only 11% of the molecules are intercalated. Studies of incorporation of both compounds in liposomes of DPPC, Egg-PC and DODAB revealed that compound 2 is mainly located in the hydrophobic region of the lipid bilayer, while compound 1 prefers a hydrated and fluid environment

P2 receptors in atherosclerosis and postangioplasty restenosis

Atherosclerosis is an immunoinflammatory process that involves complex interactions between the vessel wall and blood components and is thought to be initiated by endothelial dysfunction [Ross (Nature 362:801–09, 1993); Fuster et al. (N Engl J Med 326:242–50, 1992); Davies and Woolf (Br Heart J 69:S3–S11, 1993)]. Extracellular nucleotides that are released from a variety of arterial and blood cells [Di Virgilio and Solini (Br J Pharmacol 135:831–42, 2002)] can bind to P2 receptors and modulate proliferation and migration of smooth muscle cells (SMC), which are known to be involved in intimal hyperplasia that accompanies atherosclerosis and postangioplasty restenosis [Lafont et al. (Circ Res 76:996–002, 1995)]. In addition, P2 receptors mediate many other functions including platelet aggregation, leukocyte adherence, and arterial vasomotricity. A direct pathological role of P2 receptors is reinforced by recent evidence showing that upregulation and activation of P2Y2 receptors in rabbit arteries mediates intimal hyperplasia [Seye et al. (Circulation 106:2720–726, 2002)]. In addition, upregulation of functional P2Y receptors also has been demonstrated in the basilar artery of the rat double-hemorrhage model [Carpenter et al. (Stroke 32:516–22, 2001)] and in coronary artery of diabetic dyslipidemic pigs [Hill et al. (J Vasc Res 38:432–43, 2001)]. It has been proposed that upregulation of P2Y receptors may be a potential diagnostic indicator for the early stages of atherosclerosis [Elmaleh et al. (Proc Natl Acad Sci U S A 95:691–95, 1998)]. Therefore, particular effort must be made to understand the consequences of nucleotide release from cells in the cardiovascular system and the subsequent effects of P2 nucleotide receptor activation in blood vessels, which may reveal novel therapeutic strategies for atherosclerosis and restenosis after angioplasty

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Engineering nanoparticles for targeting rheumatoid arthritis: Past, present, and future trends

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial joint inflammation and cartilage and bone tissue destruction. Although there exist some treatment strategies for RA, they are not completely safe and effective. Therefore, it is important to develop and test new drugs for RA that specifically target inflamed/swollen joints and simultaneously attenuate other possible damages to healthy tissues. Nanotechnology can be a good alternative to consider when envisioning precise medication for treating RA. Through the use of nanoparticles, it is possible to increase bioavailability and bioactivity of therapeutics and enable selective targeting to damaged joints. Herein, recent studies using nanoparticles for the treatment of RA, namely with liposomes, polymeric nanoparticles, dendrimers, and metallic nanoparticles, have been reviewed. These therapeutic strategies have shown great promise in improving the treatment over that by traditional drugs. The results of these studies confirm that feasibility of the use of nanoparticles is mainly due to their biocompatibility, low toxicity, controlled release, and selective drug delivery to inflamed tissues in animal RA models. Therefore, it is possible to claim that nanotechnology will, in the near future, play a crucial role in advanced treatments and patient-specific therapies for human diseases such as RA.Financial support under the ARTICULATE project (No. QREN-13/SI/2011-23189). This study was also funded by the Portuguese Foundation for Science and Technology (FCT) project OsteoCart (No. PTDC/CTM-BPC/115977/2009), as well as the European Union’s FP7 Programme under grant agreement no REGPOT-CT2012-316331-POLARIS. The FCT distinction attributed to J. M. O. under the Investigator FCT program (No. IF/00423/2012) is also greatly acknowledged. C. G. also wished to acknowledge FCT for supporting her research (No. SFRH/BPD/94277/2013)info:eu-repo/semantics/publishedVersio