Assessment of glucose-6-phosphate dehydrogenase activity using CareStart G6PD rapid diagnostic test and associated genetic variants in Plasmodium vivax malaria endemic setting in Mauritania

International audienceBackgroundPrimaquine is recommended by the World Health Organization (WHO) for radical treatment of Plasmodium vivax malaria. This drug is known to provoke acute hemolytic anemia in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Due to lack of data on G6PD deficiency, the use of primaquine has been limited in Africa. In the present study, G6PD deficiency was investigated in blood donors of various ethnic groups living in Nouakchott, a P. vivax endemic area in Mauritania.Methodology/Principal findingsVenous blood samples from 443 healthy blood donors recruited at the National Transfusion Center in Nouakchott were screened for G6PD activity using the CareStart G6PD deficiency rapid diagnostic test. G6PD allelic variants were investigated using DiaPlexC G6PD genotyping kit that detects African (A-) and Mediterranean (B-) variants. Overall, 50 of 443 (11.3%) individuals (49 [11.8%] men and 1 [3.7%] woman) were phenotypically deficient. Amongst men, Black Africans had the highest prevalence of G6PD deficiency (15 of 100 [15%]) and White Moors the lowest (10 of 168, [5.9%]). The most commonly observed G6PD allelic variants among 44 tested G6PD-deficient men were the African variant A- (202A/376G) in 14 (31.8%), the Mediterranean variant B- (563T) in 13 (29.5%), and the Betica-Selma A- (376G/968C) allelic variant in 6 (13.6%). The Santamaria A- variant (376G/542T) and A variant (376G) were observed in only one and two individuals, respectively. None of the expected variants was observed in 8 (18.2%) of the tested phenotypically G6PD-deficient men.ConclusionThis is the first published data on G6PD deficiency in Mauritanians. The prevalence of phenotypic G6PD deficiency was relatively high (11.3%). It was mostly associated with either African or Mediterranean variants, in agreement with diverse Arab and Black African origins of the Mauritanian population

Glucocorticoids Inhibit Basal and Hormone-Induced Serotonin Synthesis in Pancreatic Beta Cells

International audienceDiabetes is a major complication of chronic Glucocorticoids (GCs) treatment. GCs induce insulin resistance and also inhibit insulin secretion from pancreatic beta cells. Yet, a full understanding of this negative regulation remains to be deciphered. In the present study, we investigated whether GCs could inhibit serotonin synthesis in beta cell since this neurotransmitter has been shown to be involved in the regulation of insulin secretion. To this aim, serotonin synthesis was evaluated in vitro after treatment with GCs of either islets from CD1 mice or MIN6 cells, a beta-cell line. We also explored the effect of GCs on the stimulation of serotonin synthesis by several hormones such as prolactin and GLP 1. We finally studied this regulation in islet in two in vivo models: mice treated with GCs and with liraglutide, a GLP1 analog, and mice deleted for the glucocorticoid receptor in the pancreas. We showed in isolated islets and MIN6 cells that GCs decreased expression and activity of the two key enzymes of serotonin synthesis, Tryptophan Hydroxylase 1 (Tph1) and 2 (Tph2), leading to reduced serotonin contents. GCs also blocked the induction of serotonin synthesis by prolactin or by a previously unknown serotonin activator, the GLP-1 analog exendin-4. In vivo, activation of the Glucagon-like-Peptide-1 receptor with liraglutide during 4 weeks increased islet serotonin contents and GCs treatment prevented this increase. Finally, islets from mice deleted for the GR in the pancreas displayed an increased expression of Tph1 and Tph2 and a strong increased serotonin content per islet. In conclusion, our results demonstrate an original inhibition of serotonin synthesis by GCs, both in basal condition and after stimulation by prolactin or activators of the GLP-1 receptor. This regulation may contribute to the deleterious effects of GCs on beta cells

Correction: Glucocorticoids Inhibit Basal and Hormone-Induced Serotonin Synthesis in Pancreatic Beta Cells.

[This corrects the article DOI: 10.1371/journal.pone.0149343.]

The deletion of the GR in the pancreas increases serotonin synthesis is islets.

<p>(A) Tph1, (B) Tph2 mRNA levels and (C) serotonin contents in islets from control mice (GR^Lox/Lox, white bars), mice that carry the PdxCre transgene (GR^+/+—PdxCre, gray bars) and mice that are deleted for the GR in the pancreas (GR^Lox/Lox–PdxCre, black bars). Values are means ± SD. * p<0.05, ** p<0.01 when comparing GR^- to control mice using a non parametric Mann-Whitney test (n = 3–4 per group).</p

GCs inhibit exendin-4 activation of Tph1 and Tph 2 in beta cells.

<p>(A) Tph1 and (B) Tph2 mRNA levels in MIN6 cells cultured in control conditions (white bars) or treated with 10⁻⁷M Dexamethasone (black bars), with 100 ng/ml exendin-4 (Ex) (dark grey bars) or with both for 24h (light grey bars). (C) Representative immunoblot for Tph1 and Actin on protein extracts from MIN6 cells under the same conditions (upper panel) and quantification of the signals (lower panel). (D) Tph activity in MIN6 cells in the same conditions. (E) Serotonin contents measured in the same conditions. Results are expressed as means ± SD for n = 6 independent experiments. * p<0.05 ** p<0.01 and *** p<0.001 when comparing the different groups using a ANOVA test.</p

GCs inhibit prolactin activation of Tph1 and Tph 2 in beta cells.

<p>(A) Tph1 and (B) Tph 2 expression in MIN6 cells cultured in control conditions (white bars) or treated with Dexamethasone 10⁻⁷ M (black bars), with prolactin (100 ng/ml) (dark grey bars) or with both for 24h (light grey bars). (C) Representative immunoblot for Tph1 and Actin on protein extracts from MIN6 cells under the same conditions (upper panel) and quantification of the signals (lower panel). (D) Tph activity in MIN6 cells in the same conditions. (E) Serotonin contents measured in MIN6 cells in the same conditions. Results are expressed as means ± SD for n = 6 independent experiments. * p<0.05 and ** p<0.01 when comparing the different groups using an ANOVA test.</p

GCs inhibit Tph1 and Tph 2 expression and serotonin synthesis in beta cells.

<p>(A) Tph1 and (B) Tph 2 mRNA levels in isolated wild type mouse islets cultured in control conditions (white bars) or treated with 10⁻⁷M Dexamethasone for 24h (black bars). (C) Serotonin contents in mouse islets cultured in control conditions (white bars) or treated with 10⁻⁷M Dex for 24h (black bars). (D) Tph1 and (E) Tph 2 mRNA levels in MIN6 cells cultured in control conditions (white bars) or treated with 10⁻⁷M Dex for 24h (black bars). (F) Serotonin contents in MIN6 cells cultured in control conditions (white bars) or treated with 10⁻⁷M Dex for 24h (black bars). Results are expressed as means ± SD for n = 4 independent experiments. * p<0.05 and ** p<0.01 when comparing Dex-treated <i>vs</i> control islets or MIN6 cells, using a Mann-Whitney non parametric test.</p

Mosquitoes (Diptera: Culicidae) in Mauritania: a review of their biodiversity, distribution and medical importance

International audienceAlthough mosquitoes (Diptera: Culicidae) are important disease vectors, information on their biodiversity in Mauritania is scarce and very dispersed in the literature. Data from the scientific literature gathered in the country from 1948 to 2016 were collected and analyzed. Overall 51 culicid species comprising 17 Anopheles spp., 14 Aedes spp., 18 Culex spp. and two Mansonia spp. have been described in Mauritania among which Anopheles arabiensis, Aedes vexans, Culex poicilipes and Culex antennatus are of epidemiological significance. Anopheles arabiensis is widely distributed throughout the country and its geographic distribution has increased northwards in recent years, shifting its northern limit form 17 degrees 32'N in the 1960s to 18 degrees 47'N today. Its presence in the central region of Tagant highlights the great ecological plasticity of the species. Conversely, the distribution of Anopheles gambiae (s.s.) and Anopheles melas has shrunk compared to that of the 1960s. Anopheles rhodesiensis and An. d'thali are mainly confined in the mountainous areas (alt. 200-700 m), whereas Anopheles pharoensis is widely distributed in the Senegal River basin. Culex poicilipes and Cx. antenattus were naturally found infected with Rift valley fever virus in central and northern Mauritania following the Rift valley outbreaks of 1998 and 2012. Recently, Ae. aegypti emerged in Nouakchott and is probably responsible for dengue fever episodes of 2015. This paper provides a concise and up-to-date overview of the existing literature on mosquito species known to occur in Mauritania and highlights areas where future studies should fill a gap in knowledge about vector biodiversity. It aims to help ongoing and future research on mosquitoes particularly in the field of medical entomology to inform evidence-based decision-making for vector control and management strategies