A randomized trial of amodiaquine and artesunate alone and in combination for the treatment of uncomplicated falciparum malaria in children from Burkina Faso

Combining artesunate (AR) with existing antimalarial drugs may improve cure rates, delay emergence of resistance and reduce parasite clearance time. In order to investigate the latter, we conducted a randomized clinical trial testing the AR plus amodiaquine (AQ) combination for the treatment of uncomplicated Plasmodium falciparum malaria in Burkina Faso. Children aged 1-15 years were randomly assigned to either AQ (10 mg/kg) or AR (4 mg/kg first day then half dose) or AQ + AR (AQAR) as a single daily dose under supervision for three consecutive days for all groups. Follow-up lasted 28 days. Primary endpoints were parasite and fever clearance time. Eighty-seven children were evaluated: 27 received AQ, 27 AR and 33 AQAR. Using an intention to treat analysis, fever clearance time was similar in the three groups. However, it was significantly faster in the AR (1.21 days; P = 0.02) and AQAR groups (1.19 days; P < 0.01) than in the AQ group (1.46 days) when excluding other concomitant causes of fever. Parasite clearance time was faster in AR (1.13 days; P = 0.008) and AQAR groups (1.13 days; P < 0.01) than in the AQ group (1.6 days). All children cleared their parasites by day 14, including the child with Late Parasitological Failure (LPF) at day 7 after rescue treatment. Only one child (4%) from the AR group and one (4%) from the AQ group presented with asymptomatic parasitaemia at day 7 and day 21, respectively (LPF). Gametocyte carriage was not detectable in any group during follow-up nor was any adverse reaction observed. While resistance to first-line treatment (chloroquine) is already established in the country, AQ and AR used alone or in combination therapy proved highly efficacious in our study. Burkina Faso stands in a very good situation for an internationally recommended switch to AR-containing combination as first-line treatment for uncomplicated malaria. Including AQ in this regimen seems the best option.     

Genotoxic and oxidative responses in coelomocytes of Eisenia fetida and Hediste diversicolor exposed to lipid‐coated CdSe/ZnS quantum dots and CdCl2

The emerging of Quantum Dots utilization in industrial or medicinal fields involved a potentially increase of these nanoparticles in environment. In this work, the genotoxic (comet assay) and oxidative effects (SOD activity, TBARS) of functionalized‐QDs and cadmium chloride were investigated on Hediste diversicolor and Eisenia fetida coelomocytes. Results demonstrated that functionalized‐QDs (QDNs) and cadmium chloride induced DNA damages through different mechanisms that depended on the nano‐ or ionic nature of Cd. The minimal genotoxic concentrations for H. diversicolor (<0.001ng/g for QDNs and CdCl₂) were lower than for E. fetida (between 0.01 and 0.1 ng/g for QDNs, and between 0.001 and 0.01 ng/g for CdCl₂). These results showed that H. diversicolor was more sensitive than E. fetida. The two contaminants had a low impact on the oxidative stress markers. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 918–926, 2015.     

Expression of iron absorption genes in mouse large intestine

OBJECTIVE: The large intestine has been reported to have a capacity for iron absorption and expresses genes for iron absorption normally found in the duodenum. The importance and function of these genes in the large intestine are not understood. We therefore investigated the cellular localization and regulation of expression of these genes in mouse caecum and colon. MATERIAL AND METHODS: Gene expression was measured by real-time PCR using RNA extracted from iron-deficient and hypoxic mouse large intestine, compared to controls. Protein localization and regulation were measured by immunohistochemistry using frozen sections of the large intestine from the same mice. RESULTS: Dcytb (duodenal ferric reductase) was expressed at very low levels in the large intestine, compared to the duodenum, while Ireg1 and DMT1 were expressed at significant levels in the large intestine and were increased in iron-deficient caecum, proximal and distal colon, with the most significant increases seen in the distal colon. Hypoxia increased Ireg1 expression in the proximal colon. Immunohistochemistry detected significant levels of only IREG1, which was localized to the basolateral membrane of colonic epithelial cells. CONCLUSIONS: Iron absorption genes were expressed at lower levels in mouse caecum and colon than in the duodenum. They are regulated by body iron requirements. Colonic epithelial cells express basolateral IREG1in the same fashion as in the duodenum and this protein could regulate colonic epithelial cell iron levels.     

Vitamin C,cancer and aging

Oxidative damage to DNA, proteins and lipids appears to be a major contributing factor in aging and the degenerative processes that accompany it, including cancer, heart disease, cataracts, and cognitive dysfunction. Numerous epidemiologic studies have found that persons with lower intake of antioxidant nutrients or the fruits and vegetables that provide them have a higher risk of almost every type of cancer. In many studies, those with low intake had twice the risk of those with high intake. A large-scale follow-up study found that persons with a low vitamin C intake had a statistically significantly higher risk of heart disease mortality and total mortality over the subsequent 10 years. In addition, several studies have found that persons with low intake of antioxidant nutrients such as vitamin C and carotene had significantly increased risk of developing age-related eye diseases such as cataracts. Although many older people consume more antioxidants than younger people, very substantial proportions of older persons have very low intakes and blood levels. Among white men 65–74 in the U.S., 15% have blood ascorbate levels below 0.4 mg/dl, the lower boundary of “normal.” Among black men of that age, 25% have levels below 0.4 mg/dl. Persons with high intakes of dietary vitamin C or citrus fruit have repeatedly been found to have a lower risk of developing cancer. In addition, recent research indicates an important role in heart disease and other disabilities of aging. This paper will summarize the epidemiologic literature briefly, and provide data on intake of this vitamin in the United States. Vitamin C has numerous biologic functions, including collagen, hormone and neurotransmitter synthesis. Its role as an antioxidant and free radical scavenger may be of primary importance in many of its roles in disease prevention. Oxidative and free radical damage to DNA and cell membranes is an important factor in cancer initiation, and it is clear that ascorbic acid can help prevent such damage.     

Branching out: a molecular fingerprint of endothelial differentiation into tube-like structures generated by Affymetrix oligonucleotide arrays

The process of endothelial differentiation into a network of tube-like structures with patent lumens requires an integrated program of gene expression. To identify genes upregulated in endothelial cells during the process of tube formation, RNA was prepared from several different time points (0, 4, 8, 24, 40, and 48 hours) and from three different experimental models of human endothelial tube formation: in collagen gels and fibrin gels driven by the combination of PMA (80), bFGF (40 ng/ml) and bFGF (40 ng/ml) or in collagen gels driven by the combination of HGF (40 ng/ml) and VEGF (40 ng/ml). Gene expression was evaluated using Affymetrix Gene Chip oligonucleotide arrays. Over 1000 common genes were upregulated greater than twofold over baseline at one or more time points in the three different models. In the present study, we discuss the identified genes that could be assigned to major functional classes: apoptosis, cytoskeleton, proteases, matrix, and matrix turnover, pumps and transporters, membrane lipid turnover, and junctional molecules or adhesion proteins.     

Clinical, endoscopic, and functional studies in 408 patients with Barrett's esophagus, compared to 174 cases of intestinal metaplasia of the cardia

OBJECTIVE: The pathophysiology of gastroesophageal reflux disease (GERD) has been studied extensively in patients with long-segment Barrett's esophagus (LSBE), but few reports have explored GERD pathophysiology in patients who have short-segment Barrett's esophagus (SSBE) or intestinal metaplasia at the cardia (IMC). We aimed to compare clinical, endoscopic, histological, and functional features in patients with LSBE, SSBE, and IMC. METHODS: We identified 582 patients who had intestinal metaplasia at the squamocolumnar junction in the distal esophagus and divided them into three groups based on the extent of columnar-lined esophagus observed endoscopically: 1) patients with IMC who had no columnar-lined esophagus (i.e., the squamocolumnar and gastroesophageal junctions coincided), 2) patients with LSBE who had >3 cm of columnar-lined esophagus, and 3) patients with SSBE who had <3 cm of columnar-lined esophagus. All patients had esophageal manometric evaluation, and 24-h esophageal pH monitoring was performed to determine the extent of acid and bile (bilirubin) reflux. RESULTS: There were 174 patients with IMC, 155 with LSBE, and 25 with SSBE. Compared to patients with LSBE and SSBE, patients with IMC had significantly lower frequencies of GERD symptoms, hiatal hernia, and erosive esophagitis; significantly higher lower esophageal sphincter pressures; and significantly shorter durations of acid and bile reflux. Between patients with SSBE and LSBE, significant differences were found in the frequency of hiatal hernia and duration of acid reflux (both greater in the patients with LSBE). Also, dysplasia was significantly more frequent in patients with LSBE than in those with SSBE or IMC. CONCLUSION: GERD symptoms, signs, and physiological abnormalities are found more often in patients with Barrett's esophagus than in those with IMC, and the duration of acid reflux in patients with LSBE is greater than that in patients with SSBE. These findings suggest that the extent of intestinal metaplasia in the esophagus is related directly to the severity of underlying GERD.