Acute third ventricular administration of leptin decreases protein and fat in self-selecting rats

The peripheral administration of leptin reduces food intake (FI) body weight gain (BWG) and modifies food choice. The aim of this study was to examine the effect of acute cerebral injections of leptin on food selection in rats. Male rats were first adapted to the food choice paradigm (protein, carbohydrate, fat) for 3 weeks. They were then implanted with a cannula in the third ventricle. Leptin (leptin group=L) or saline (control group=C) injections were performed at either the beginning or the end of the night at 4-day intervals. FI was recorded continuously, 3 days before, during and then after injections. Rats were sacrificed 86 h after the second injection. After both injections, BWG and FI were reduced. The reduction in FI concerned only nocturnal intake, whatever the timing of the injection. When the injection was given at the beginning of the night, the reductions after a 1-h latency period were -45% and -27.5% during the first and second days, respectively. Following the second injection, the same effects were observed immediately (-16% and -41%, respectively). Only the fat and protein intakes were significantly reduced. This lower FI was due to a reduction in meal size and duration. The reduction resulted in a lower BWG and total white adipose tissue mass. At the time of sacrifice, 6 h after food deprivation, leptinemia and insulinemia were reduced in leptin-treated rats. Glycemia values were identical. It was thus demonstrated that central leptin was a satiation factor rather than a satiety factor.     

Decoctions of Bridelia micrantha and Croton macrostachyus may have anticonvulsant and sedative effects

Bridelia micrantha and Croton macrostachyus are medicinal plants used empirically in traditional medicine to treat epilepsy. In vivo mice model (maximal electroshock, strychnine, pentylenetetrazol, picrotoxin, isonicotinic hydrazide acid)-induced convulsions were used to evaluate the anticonvulsant activities of those plants. Diazepam-induced sleep was used for the evaluation of the sedative properties. B. micrantha protected 100, 80, 80, and 80% of mice against PIC, STR, PTZ and MES-induced seizures, respectively. C. macrostachyus at the doses 34 and 67 mg/kg protected 80, 80, 80 and 60% of mice from PIC, STR, PTZ and MES-induced seizures, respectively. B. micrantha and C. macrostachyus also delayed the onset to seizures in INH test. B. micrantha was more potent than C. macrostachyus in protecting mice against convulsions. The co-administration of the sub effective dose of the decoction of B. micrantha or C. macrostachyus with the sub effective dose of diazepam or clonazepam resulted in a synergistic effect. The decoctions of B. micrantha and C. macrostachyus also exerted sedative activity by increasing the total duration of sleep induced by diazepam and by reducing the latency time to sleep. The effect of the decoctions of B. micrantha and C. macrostachyus suggests the presence of anticonvulsant activities that might show efficacy against secondarily generalized tonic-clonic seizures and primary generalized seizures in humans.     

Acquisition of antibodies to variant antigens on the surface of Plasmodium falciparum-infected erythrocytes during pregnancy

Pregnancy-associated malaria is characterized by Plasmodium falciparum adherence to chondroitin sulfate A (CSA) in placenta, through a particular variant surface antigen (VSA). VSA(CSA)-specific IgG are involved in protection against placental malaria. In order to assess the relationship between VSA(CSA)-specific antibody responses and parity as well as protection against placental malaria, the occurrence of P. falciparum infection was assessed in 306 pregnant women from a low malaria transmission area of Senegal. Anti-VSA(CSA) antibodies against three placental parasite isolates were measured by flow cytometry, at enrollment and delivery. Placental infection prevalence rates were highest in primigravidae, but no clear decreasing trend was observed from the second pregnancy onwards. Anti-VSA(CSA) antibody prevalence rates increased with parity. Both anti-VSA(CSA) antibody prevalence rates and levels increased during pregnancy only in women infected with P. falciparum. Although a single or a very limited number of P. falciparum infections were able to induce an anti-VSA(CSA) antibody response, the level or the quality of this response did not appear to confer protection against placental malaria infection.     

The role of the subgenual anterior cingulate cortex in dorsomedial prefrontal–amygdala neural circuitry during positive‐social emotion regulation

Positive‐social emotions mediate one's cognitive performance, mood, well‐being, and social bonds, and represent a critical variable within therapeutic settings. It has been shown that the upregulation of positive emotions in social situations is associated with increased top‐down signals that stem from the prefrontal cortices (PFC) which modulate bottom‐up emotional responses in the amygdala. However, it remains unclear if positive‐social emotion upregulation of the amygdala occurs directly through the dorsomedial PFC (dmPFC) or indirectly linking the bilateral amygdala with the dmPFC via the subgenual anterior cingulate cortex (sgACC), an area which typically serves as a gatekeeper between cognitive and emotion networks. We performed functional MRI (fMRI) experiments with and without effortful positive‐social emotion upregulation to demonstrate the functional architecture of a network involving the amygdala, the dmPFC, and the sgACC. We found that effortful positive‐social emotion upregulation was associated with an increase in top‐down connectivity from the dmPFC on the amygdala via both direct and indirect connections with the sgACC. Conversely, we found that emotion processes without effortful regulation increased network modulation by the sgACC and amygdala. We also found that more anxious individuals with a greater tendency to suppress emotions and intrusive thoughts, were likely to display decreased amygdala, dmPFC, and sgACC activity and stronger connectivity strength from the sgACC onto the left amygdala during effortful emotion upregulation. Analyzed brain network suggests a more general role of the sgACC in cognitive control and sheds light on neurobiological informed treatment interventions.     

Stiffness imaging of the kidney and adjacent abdominal tissues measured simultaneously using magnetic resonance elastography

To date, non-invasive methods to detect kidney malignancies and mild tumors remain a challenge. The purpose of this study was to establish the proper imaging protocol to determine kidney stiffness and its spatial distribution within the various kidney compartments such as the renal sinus, medulla, and cortex. Here, we have used magnetic resonance elastography (MRE) along with coronal oblique acquisition to simultaneously measure kidney stiffness in comparison with other tissues including the liver, spleen, and psoas.     

Anticonvulsant, anxiolytic, and sedative properties of the roots of Nauclea latifolia Smith in mice

Root bark of Nauclea latifolia Smith (Rubiaceae) was evaluated for its anticonvulsant, anxiolytic, and sedative activity in mice. Animal models (maximal electroshock-, pentylenetetrazol-, and strychnine-induced convulsions; N-methyl-d-aspartate-induced turning behavior; elevated plus maze; stress-induced hyperthermia; open field; and diazepam-induced sleep) were used. The decoction from the bark of the roots of N. latifolia strongly increased the total sleep time induced by diazepam. It also protected mice against maximal electroshock-, pentylenetetrazol-, and strychnine-induced seizures. In addition, turning behavior induced by N-methyl-d-aspartate was inhibited. N. latifolia antagonized, in a dose-dependent manner, stress-induced hyperthermia and reduced body temperature. In the elevated plus maze, N. latifolia increased the number of entries into, percentage of entries into, and percentage of time in open arms, and reduced rearing, head dipping, and percentage of time in closed arms. In the open field test, N. latifolia increased crossing and reduced rearing and defecation. It could be concluded that the decoction of N. latifolia, used in traditional medicine in Cameroon in the treatment of fever, malaria, insomnia, anxiety and epilepsy seemed to possess, sedative, anticonvulsant, anxiolytic and antipyretic properties in mice.     

High prevalence of Plasmodium falciparum pfcrt K76T mutation in pregnant women taking chloroquine prophylaxis in Senegal

OBJECTIVES: The risk of malaria infection is increased during pregnancy, and many countries recommend chloroquine prophylaxis in pregnant women, despite Plasmodium falciparum chloroquine resistance. Chloroquine resistance is associated with the pfcrt gene K76T mutation. The aim of this study was to compare the prevalence rate of pfcrt T76 mutation in P. falciparum isolates from infected pregnant and non-pregnant individuals from Senegal. METHODS: The study was conducted in the rural maternity hospital of Thiadiaye, Senegal, where malaria is seasonal. Sixty-nine P. falciparum isolates from infected women were collected at delivery. These women were part of a cohort study; they were followed from their first antenatal visit and advised to take chloroquine prophylaxis. For each woman, the earliest P. falciparum-infected blood sample was also used. A control group of 49 non-pregnant individuals with asymptomatic P. falciparum infection was enrolled. RESULTS: During pregnancy, prevalence of T76 mutant parasites was higher than in the 49 non-pregnant controls (P<0.001). Among pregnant women, this rate was highest at delivery (P=0.06), and tended to be higher in women who had taken chloroquine prophylaxis, as assessed in urine samples (P=0.08). CONCLUSIONS: Chloroquine prophylaxis is responsible for increased drug consumption and increased drug pressure that may lead to the selection of drug-resistant parasites. This is the first report showing that P. falciparum-infected pregnant women harbour pfcrt T76 mutant parasites more often than non-pregnant individuals, and that the prevalence of this mutation is higher at term than earlier during pregnancy.     

Sulfadoxine/pyrimethamine intermittent preventive treatment for malaria during pregnancy

For monitoring efficacy of sulfadoxine/pyrimethamine intermittent preventive treatment for malaria during pregnancy, data obtained from studies of children seemed inadequate. High prevalence of triple and quadruple mutants in the dihydropteroate synthase and dihydrofolate reductase genes of Plasmodium falciparum parasites contrasts with the efficacy of sulfadoxine/pyrimethamine in reducing low birthweights and placental infection rates. In light of this discrepancy, emphasis on using molecular markers for monitoring efficacy of intermittent preventive treatment during pregnancy appears questionable. The World Health Organization recently proposed conducting in vivo studies in pregnant women to evaluate molecular markers for detecting resistance precociously. Other possible alternative strategies are considered.     

High urokinase expression contributes to the angiogenic properties of endothelial cells derived from circulating progenitors

Endothelial progenitor cells (EPC) display a unique ability to repair vascular injury and promote neovascularization although the underlying molecular mechanisms remain poorly understood. Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) play a critical role in cell migration and angiogenesis by facilitating proteolysis of extracellular matrix. The aim of the present study was to characterize the uPA/uPAR-dependent proteolytic potential of EPC outgrown from human umbilical cord blood and to analyze its contribution to their angiogenic properties in vitro. Cells derived from EPC (EPDC), presenting typical features of late outgrowth endothelial cells, were compared to mature endothelial cells, represented by human umbilical vein endothelial cells (HUVEC). Using quantitative flow cytometry, enzyme-linked immunosorbent assays and zymography, we demonstrated that EPDC displayed higher levels of uPA and uPAR. In conditioned culture media, uPA-dependent proteolytic activity was also found to be significantly increased in EPDC. This activity was paralleled by a higher secretion of pro-metalloproteinase-2 (pro-MMP-2). Inhibition of EPDC-associated uPA by monoclonal antibodies that block either uPA activity or receptor binding, significantly reduced proliferation, migration and capillary like tube formation. Moreover, tumor necrosis factor-alpha and vascular endothelial growth factor, known to be locally secreted in ischemic areas, further increased the proteolytic potential of EPDC by up-regulating uPA and uPAR expression respectively. The EPDC response to these factors was found to be more pronounced than that of HUVEC. In conclusion, these findings indicated that EPDC are characterized by high intrinsic uPA/uPAR-dependent proteolytic potential that could contribute to their invasive and angiogenic behaviour.