Prévalence du VIH chez la Femme Enceinte et Transmission Mère-Enfant du VIH à la Maternité de l’Hôpital Général de Douala, Cameroun

Nous rapportons ici une évaluation sommaire de nos activités de prévention transmission mère-enfant du VIH sur 6 ans (2002 à 2007). Il s’agissait d’une étude descriptive et rétrospective effectuée à l’Hôpital Général de Douala. Les enfants inclus étaient âgés d’au moins 18 mois. La technique d’ELISA GENSCREEN 3ème génération pour le VIH a été utilisée. Sur 5261 accouchements effectués pendant cette période, 138 étaient de mères VIH positifs (prévalence : 2,62%). Quatre de nos patientes étaient testées négatives au premier trimestre de gestation. Des 138 bébés, 87 seulement ont pu être testés (63%), dont 4 contaminés (prévalence de transmission : 4,6%). Des 4 enfants contaminés, un seul a reçu la prévention adéquate en grossesse, soit un taux de transmission sous prévention de 1,19%. Une meilleure organisation des stratégies de réduction de la transmission mèreenfant du VIH/SIDA, même dans un environnement à ressources limitées, peut conduire à des résultats similaires à ceux des pays du Nord. A la lumière de cette étude, nous recommandons fortement un deuxième test du VIH au 3ème rimestre de la grossesse afin de réduire davantage le risque de sa transmission périnatale.Mots Clés prévalence du VIH ; femme enceinte ; transmission mère-enfant du VI

Strong neuroprotection with a novel platinum nanoparticle against ischemic stroke- andtissue plasminogen activator-related brain damages in mice

Reactive oxygen species (ROS) are major exacerbation factor in acute ischemic stroke, and thrombolytic agent tissue plasminogen activator (tPA) may worsen motor function and cerebral infarcts. The platinum nanoparticle (nPt) is a novel ROS scavenger, and thus we examined the clinical and neuroprotective effects of nPt in ischemic mouse brains. Mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 60 min and divided into the following four groups by intravenous administration upon reperfusion, vehicle, tPA, tPA + nPt, and nPt. At 48 h after tMCAO, motor function, infarct volume, immunohistochemical analyses of neurovascular unit (NVU), in vivo imaging of matrix metalloproteinase (MMP), and zymography for MMP-9 activity were examined. Superoxide anion generation at 2 h after tMCAO was also examined with hydroethidine (HEt). As a result, administration of tPA deteriorated the motor function and infarct volume as compared to vehicle. In vivo optical imaging of MMP showed strong fluorescent signals in affected regions of tMCAO groups. Immunohistochemical analyses revealed that tMCAO resulted in a minimal decrease of NAGO and occludin, but a great decrease of collagen IV and a remarkable increase of MMP-9. HEt stain showed increased ROS generation by tMCAO. All these results became pronounced with tPA administration, and were greatly reduced by nPt. The present study demonstrates that nPt treatment ameliorates neurological function and brain damage in acute cerebral infarction with neuroprotective effect on NVU and inactivation of MMP-9. The strong reduction of ROS production by nPt could account for these remarkable neurological and neuroprotective effects against ischemic stroke

Neutrophil a-defensins promote thrombosis in vivo by altering fibrin formation, structure, and stability

© 2019 by The American Society of Hematology. Inflammation and thrombosis are integrated, mutually reinforcing processes, but the interregulatory mechanisms are incompletely defined. Here, we examined the contribution of a-defensins (a-defs), antimicrobial proteins released from activated human neutrophils, on clot formation in vitro and in vivo. Activation of the intrinsic pathway of coagulation stimulates release of a-defs from neutrophils. a-Defs accelerate fibrin polymerization, increase fiber density and branching, incorporate into nascent fibrin clots, and impede fibrinolysis in vitro. Transgenic mice (Def 11 ) expressing human a-Def-1 developed larger, occlusive, neutrophil-rich clots after partial inferior vena cava (IVC) ligation than those that formed in wild-type (WT) mice. IVC thrombi extracted from Def 11 mice were composed of a fibrin meshwork that was denser and contained a higher proportion of tightly packed compressed polyhedral erythrocytes than those that developed in WT mice. Def 11 mice were resistant to thromboprophylaxis with heparin. Inhibiting activation of the intrinsic pathway of coagulation, bone marrow transplantation from WT mice or provision of colchicine to Def 11 mice to inhibit neutrophil degranulation decreased plasma levels of a-defs, caused a phenotypic reversion characterized by smaller thrombi comparable to those formed in WT mice, and restored responsiveness to heparin. These data identify a-defs as a potentially important and tractable link between innate immunity and thrombosis

Neutrophil a-defensins promote thrombosis in vivo by altering fibrin formation, structure, and stability

© 2019 by The American Society of Hematology. Inflammation and thrombosis are integrated, mutually reinforcing processes, but the interregulatory mechanisms are incompletely defined. Here, we examined the contribution of a-defensins (a-defs), antimicrobial proteins released from activated human neutrophils, on clot formation in vitro and in vivo. Activation of the intrinsic pathway of coagulation stimulates release of a-defs from neutrophils. a-Defs accelerate fibrin polymerization, increase fiber density and branching, incorporate into nascent fibrin clots, and impede fibrinolysis in vitro. Transgenic mice (Def 11 ) expressing human a-Def-1 developed larger, occlusive, neutrophil-rich clots after partial inferior vena cava (IVC) ligation than those that formed in wild-type (WT) mice. IVC thrombi extracted from Def 11 mice were composed of a fibrin meshwork that was denser and contained a higher proportion of tightly packed compressed polyhedral erythrocytes than those that developed in WT mice. Def 11 mice were resistant to thromboprophylaxis with heparin. Inhibiting activation of the intrinsic pathway of coagulation, bone marrow transplantation from WT mice or provision of colchicine to Def 11 mice to inhibit neutrophil degranulation decreased plasma levels of a-defs, caused a phenotypic reversion characterized by smaller thrombi comparable to those formed in WT mice, and restored responsiveness to heparin. These data identify a-defs as a potentially important and tractable link between innate immunity and thrombosis

Glucagon Protects Against Impaired NMDA-Mediated Cerebrovasodilation and Cerebral Autoregulation during Hypotension after Brain Injury by Activating cAMP Protein Kinase A and Inhibiting Upregulation of tPA

Outcome of traumatic brain injury (TBI) is impaired by hyperglycemia, hypotension, and glutamate, and improved by insulin. Insulin reduces glutamate concentration, making it uncertain whether its beneficial effect accrues from euglycemia. Glucagon decreases CNS glutamate, lessens neuronal cell injury, and improves neurological scores in mice after TBI. In vitro, glucagon limits NMDA-mediated excitotoxicity by increasing cAMP and protein kinase A (PKA). NMDA receptor activation couples cerebral blood flow (CBF) to metabolism. Dilation induced by NMDA is impaired after fluid percussion brain injury (FPI) due to upregulation of endogenous tPA, which further disturbs cerebral autoregulation during hypotension after fluid percussion injury (FPI). We hypothesized that glucagon prevents impaired NMDA receptor-mediated dilation after FPI by upregulating cAMP, which decreases release of tPA. NMDA-induced pial artery dilation (PAD) was reversed to vasoconstriction after FPI. Glucagon 30 min before or 30 min after FPI blocked NMDA-mediated vasoconstriction and restored the response to vasodilation. PAD during hypotension was blunted after FPI, but protected by glucagon. Glucagon prevented FPI-induced reductions in CSF cAMP, yielding a net increase in cAMP, and blocked FPI-induced elevation of CSF tPA. Co-administration of the PKA antagonist Rp 8Br cAMPs prevented glucagon-mediated preservation of NMDA-mediated dilation after FPI. The pKA agonist Sp 8Br cAMPs prevented impairment of NMDA-induced dilation. These data indicate that glucagon protects against impaired cerebrovasodilation by upregulating cAMP, which decreases release of tPA, suggesting that it may provide neuroprotection when given after TBI, or prior to certain neurosurgical or cardiac interventions in which the incidence of perioperative ischemia is high

Brain to blood glutamate scavenging as a novel therapeutic modality: a review

It is well known that abnormally elevated glutamate levels in the brain are associated with secondary brain injury following acute and chronic brain insults. As such, a tight regulation of brain glutamate concentrations is of utmost importance in preventing the neurodegenerative effects of excess glutamate. There has been much effort in recent years to better understand the mechanisms by which glutamate is reduced in the brain to non-toxic concentrations, and in how to safely accelerate these mechanisms. Blood glutamate scavengers such as oxaloacetate, pyruvate, glutamate–oxaloacetate transaminase, and glutamate-pyruvate transaminase have been shown to reduce blood glutamate concentrations, thereby increasing the driving force of the brain to blood glutamate efflux and subsequently reducing brain glutamate levels. In the past decade, blood glutamate scavengers have gained increasing international interest, and its uses have been applied to a wide range of experimental contexts in animal models of traumatic brain injury, ischemic stroke, subarachnoid hemorrhage, epilepsy, migraine, and malignant gliomas. Although glutamate scavengers have not yet been used in humans, there is increasing evidence that their use may provide effective and exciting new therapeutic modalities. Here, we review the laboratory evidence for the use of blood glutamate scavengers. Other experimental neuro-protective treatments thought to scavenge blood glutamate, including estrogen and progesterone, beta-adrenergic activation, hypothermia, insulin and glucagon, and hemodialysis and peritoneal dialysis are also discussed. The evidence reviewed here will hopefully pave the way for future clinical trials

Serologic response to SARS-CoV-2 in an African population

Official case counts suggest Africa has not seen the expected burden of COVID-19 as predicted by international health agencies, and the proportion of asymptomatic patients, disease severity, and mortality burden differ significantly in Africa from what has been observed elsewhere. Testing for SARS-CoV-2 was extremely limited early in the pandemic and likely led to under-reporting of cases leaving important gaps in our understanding of transmission and disease characteristics in the African context. SARS-CoV-2 antibody prevalence and serologic response data could help quantify the burden of COVID-19 disease in Africa to address this knowledge gap and guide future outbreak response, adapted to the local context. However, such data are widely lacking in Africa. We conducted a cross-sectional seroprevalence survey among 1,192 individuals seeking COVID-19 screening and testing in central Cameroon using the Innovita antibody-based rapid diagnostic. Overall immunoglobulin prevalence was 32%, IgM prevalence was 20%, and IgG prevalence was 24%. IgM positivity gradually increased, peaking around symptom day 20. IgG positivity was similar, gradually increasing over the first 10 days of symptoms, then increasing rapidly to 30 days and beyond. These findings highlight the importance of diagnostic testing and asymptomatic SARS-CoV-2 transmission in Cameroon, which likely resulted in artificially low case counts. Rapid antibody tests are a useful diagnostic modality for seroprevalence surveys and infection diagnosis starting 5-7 days after symptom onset. These results represent the first step towards better understanding the SARS-CoV-2 immunological response in African populations