Functional impacts of transgenic overexpression of UDP-galactose : ceramide galactosyltransferase and polysialyltransferase on the development of oligodendrocytes and myelin maintenance

1 PLP-CGT TRANSGENIC MICE Galactosylceramide (GalC) and its sulfated derivative (sulfatide) are major lipid components of the myelin membrane constituting about 30% of its lipid content. They fulfill essential functions in oligodendrocyte differentiation, formation and maintenance of myelin. Transgenic mice overexpressing UDPgalactose: ceramide galactosyltransferase (CGT) in oligodendrocytes under the control of the proteolipid protein (PLP) promoter were generated. Elevated CGT activity led to a significant increase in non-hydroxy fatty acid galactosylceramide. In contrast, however, a substantial decrease in the normally predominant alpha-hydroxy fatty acid form of GalC was observed. As a consequence, total GalC levels were only marginally elevated in the transgenic mice. These mice exhibit deficits in motor behavior and develop a progressive hind limbs paralysis. In vitro study of oligodendrocyte development indicates an increase in oligodendrocyte number. This result was confirmed in vivo, where a significant increase of PLP positive cells was observed in the corpus callosum of PLP-CGT mice. Surprisingly, more cells expressing the MBP protein in vitro did not have the morphology of a myelin-forming oligodendrocyte, indicating a possible inhibition of the synthesis of the myelin membrane in vitro. Ultrastructural analysis revealed severe impairment in the formation of compact myelin and a progressive demyelination in the central nervous system, accompanied by axonal degeneration, vacuolation and massive astrogliosis. The composition of myelin proteins was unchanged with the exception of a significant progressive up regulation of the raft-associated MAL protein. MAL up regulation was not due to an increase in mRNA expression, suggesting reduced degradation of MAL. Taken together these results strongly suggest that the HFA- to NFA-GalC ratio is an important factor in the formation and maintenance of compact myelin. 2 PLP-PST TRANSGENIC MICE Oligodendrocyte differentiation and myelin formation are two subsequent cellular mechanisms timely separated. During development, oligodendrocyte progenitor cells migrate from their place of origin to their destination, expressing a high level of the polysialic acid (PSA). PSA is a long linear homopolymer of sialic acid. In the vertebrate embryo, PSA appears exclusively attached covalently to a cell surface protein called neural cell adhesion molecule (NCAM). In this context, PSA has been shown to be an important modulator of cell interactions during development, for example, in axonal pathfinding and branching, response of axons to loss of synaptic activity and in the migration of muscle cells. The function of PSA has been proposed to influence not only interactions mediated by NCAM itself, but cell-cell interactions in general. PSA is also known to be involved in the migration, proliferation and differentiation of oligodendrocyte precursors (OPCs). In order to investigate potential physiological consequences of increased level of polysialic acid (PSA) in oligodendrocytes, we generated transgenic mice that overexpress polysialyltransferase (PST/ST8Sia IV) under the control of the proteolipid protein (PLP) promoter. In the central nervous system of PLP-PST mice (PLP-PST), PST was overexpressed by oligodendrocytes. furthermore, increase of PSA concentration in the CNS induces no behavioral deficit of PLP-PST mice. Most importantly, elevation of PSA concentration induces increase of differentiated oligodendrocytes of the spinal cord and brainstem, but a reduction of oligodendrocyte numbers in the corpus callosum. The number of oligodendrocyte progenitor cells was unchanged in all the brain regions investigated. Moreover, biochemical analysis indicates reduction of MBP level during myelination but normal expression of other oligodendrocyte/myelin specific proteins. Structural analysis of the myelin sheath indicates a normal myelination in the CNS and PNS of PLP-PST transgenic mice. Importantly, PLP-PST mice demyelinate at adult age. Demyelination was accompanied by redundant myelinated axons and axonal degeneration leading to vacuolation

Antibiotic resistance pattern of extended-spectrum-beta lactamases-producing Escherichia coli isolated from pregnant women and their new born

The incidence of healthy pregnant women carrying CTX-M-type extended-spectrum beta-lactamase (ESBL)-producing E. coli and their transmission to neonates is increasing worldwide. ESBL-E coli and especially the carriage of CTX-M-type causes early or late onset of neonatal sepsis, resulting in increased morbidity and mortality rates. Although maternal carriage and maternal-neonatal transmissions of ESBL-E have been reported in several countries, the prevalence of CTX-M-type ESBL-producing E. coli in pregnant women and its transmission to newborns at birth in Cameroon has not been reported yet. We describe here the carriage of CTX-M-type ESBL-producing E. coli pregnant women in neonatal ward of the Yaoundé gyneco-obstetric and pediatric hospital and their transmission to newborns. Among the 102 pregnant women and their newborns present in the ward, 88 (86.3%) and 75 (73.5%) E. coli strains were detected in rectal colonization, respectively. Antibiotic susceptibility testing of E. coli isolated from the mothers indicated a higher resistance rate to antibiotics of the β-lactams and sulfamide families, while the resistances to other antibiotic families (aminosides, quinolones and fluoroquinolones) were low. Comparatively, only cefotaxime (100%) showed a higher resistance rate to E. coli isolated from newborns. This may suggest a different source of contamination between mothers and newborns. Moreover, the rate of carriage of CTX-M-type ESBL-producing E. coli in pregnant mother and their newborns were 30.7 % and 14.7 %, respectively. This suggests that newborns had other colonization sources than the mothers. Indeed, multiple regression analysis indicated that newborns were exposed to CTX-M-type ESBL-producing E. coli from mothers and that from the hospital environment (eg. caregivers). Overall, the current investigation may provide insight on establishing an efficient therapeutic strategy against materno-neonatal and nosocomial transmission of CTX-M-type ESBL-producing E. coli

Aspects histo-épidémiologiques des cancers génitaux de la femme dans la région du Littoral, Cameroun

Décrire les caractéristiques épidémiologiques et histopathologiques des tumeurs malignes génitales de la femme dans la région du littoral du Cameroun. Il s'agissait d'une étude rétrospective descriptive et analytique portant sur les cancers des organes génitaux de la femme, histologiquement prouvés pendant une période de 10 ans (2004-2013), répertoriés dans les registres des trois laboratoires d'anatomopathologie de la région (Hôpital Laquintinie de Douala, Hôpital Général de Douala, laboratoire Anapathos) et des services d'oncologie de ces hôpitaux. Les variables étudiées étaient : la fréquence, l'âge, le sexe , la localisation de la tumeur et le type histopathologique. Au total, 802 cas de cancers génitaux de la femme ont été recensés, soit une fréquence annuelle de 80,2 cas en moyenne. Le col utérin avec 580 cas (72,32%) a été la localisation la plus fréquente ; suivi de l'endomètre (corps utérin) avec 93 cas (11,60%), puis des ovaires 91 cas (11,35%). L'âge moyen despatientes était de 50, 30±12,67 ans, avec les extrêmes allant de 14 à 85 ans. Selon le type histologique, les tumeurs épithéliales ont été les plus fréquemment rencontrées, soit 758 patientes (94,51%), les lymphomes venaient en seconde position avec 29 cas (3, 62%), les autres variétés histologiques (sarcomes, tumeurs germinales, tumeurs du mésenchyme et du cordon) représentant moins chacune de 1%. Les tumeurs malignesdes organes génitaux féminins sont fréquentes dans la région du littoral du Cameroun, elles sont dominées essentiellement par le cancer du col utérin. Les tumeurs épithéliales sont le type histologique le plus fréquent

Bloodstream infections initiated by ESBL-producing Escherichia coli in neonates and infants at two hospitals in Yaoundé, Cameroon

Early diagnosis and probabilistic antibiotic therapy based on known bacterial ecology and antibiotic sensibility can reduce mortality and morbidity in pathologies caused by a bacterial infection. This study aimed at determining the prevalence and risk factors of extended-spectrum β-lactamases (ESBLs)-producing Escherichia coli isolated from blood cultures of neonates and infants population. We conducted a cross-sectional study during which pathogenic bloodstream isolates were identified. Antibiotic susceptibility test was performed on Escherichia coli isolates and phenotypic confirmation of ESBL production by Escherichia coli was performed by a double-disc synergy test. Over the course of this study, 298 blood cultures were performed and 129 (43.3%) positive cultures were obtained. Of the 129 bacterial isolates, 90 (69.7%) were Escherichia coli and 39 (30.2%) were other bacteria strains that included Klebsiella oxytoca, Streptococcus pneumonia, and Coagulase-negative staphylococci. Antibiotic susceptibility test indicated that Escherichia coli isolates were resistant to cephalosporin, penicillin, sulfonamide, and aminoglycoside antibiotic families. Further analysis indicated that 31 (34.4%) Escherichia coli strains were ESBL producers and risk factors for bloodstream infection by ESBL-producing Escherichia coli were prior to exposure to antibiotics and immune system depression. These findings clearly extend our understanding of the type of resistant initiated by ESBL-producing Escherichia coli in bloodstream infection of neonates, and infants and also provides useful information that can guide the establishment of an efficient therapeutic strategy for the community- and hospital-acquired bloodstream infection

C1q-targeted inhibition of the classical complement pathway prevents injury in a novel mouse model of acute motor axonal neuropathy

Introduction Guillain-Barré syndrome (GBS) is an autoimmune disease that results in acute paralysis through inflammatory attack on peripheral nerves, and currently has limited, non-specific treatment options. The pathogenesis of the acute motor axonal neuropathy (AMAN) variant is mediated by complement-fixing anti-ganglioside antibodies that directly bind and injure the axon at sites of vulnerability such as nodes of Ranvier and nerve terminals. Consequently, the complement cascade is an attractive target to reduce disease severity. Recently, C5 complement component inhibitors that block the formation of the membrane attack complex and subsequent downstream injury have been shown to be efficacious in an in vivo anti-GQ1b antibody-mediated mouse model of the GBS variant Miller Fisher syndrome (MFS). However, since gangliosides are widely expressed in neurons and glial cells, injury in this model was not targeted exclusively to the axon and there are currently no pure mouse models for AMAN. Additionally, C5 inhibition does not prevent the production of early complement fragments such as C3a and C3b that can be deleterious via their known role in immune cell and macrophage recruitment to sites of neuronal damage. Results and Conclusions In this study, we first developed a new in vivo transgenic mouse model of AMAN using mice that express complex gangliosides exclusively in neurons, thereby enabling specific targeting of axons with anti-ganglioside antibodies. Secondly, we have evaluated the efficacy of a novel anti-C1q antibody (M1) that blocks initiation of the classical complement cascade, in both the newly developed anti-GM1 antibody-mediated AMAN model and our established MFS model in vivo. Anti-C1q monoclonal antibody treatment attenuated complement cascade activation and deposition, reduced immune cell recruitment and axonal injury, in both mouse models of GBS, along with improvement in respiratory function. These results demonstrate that neutralising C1q function attenuates injury with a consequent neuroprotective effect in acute GBS models and promises to be a useful new target for human therapy

Entomophtoromycose rhino faciale: A propos d'un cas

Les auteurs rapportent un cas rare d'entomophtoromycose rhinofaciale avec les difficultés diagnostiques et thérapeutiques liées à cette mycose exotique. L'intérêt de la biopsie devant la présentation clinique d'une tumeur centro-faciale est rappelé pour éviter tout retard diagnostic. Clinics in Mother and Child Health Vol. 3(1) 2006: 495-49

Carriage of extended-spectrum beta-lactamase-producing Enterobacteriaceae by healthy school children from two remote villages in western Cameroon

Carriage of extended-spectrum beta-lactamases (ESBL)-producing Enterobacteriaceae by healthy children can increase the risk of developing a lethal pathological infection. The objective of this study was to determine the rate of ESBL-producing Enterobacteriaceae carriage among children in remote villages in western Cameroon. We collected fresh stool samples from 110 healthy primary school children between 2 to 5 years old in two remote villages. The bacteria isolates were characterized using the Api 20E gallery, disc diffusion, and double-disc synergy test. Logistic regression analysis was used to determine the risk factors associated with the carriage of ESBL-producing Enterobacteriaceae. Data analysis indicated that a total of 24 children in 110 (22%) investigated were positive to ESBL-producing Enterobacteriaceae. Moreover, 24 (67%) out of 36 bacteria isolates were ESBL producers and 15 (61%) out of 24 being Escherichia coli. Other ESBL-producing bacteria were Klebsiella pneumoniae (3%) and Kluyvera spp (3%). We also isolated a small proportion of bacteria showing resistance to high-level cephalosporins, which overall represented 33% of the total bacteria isolates. Furthermore, risk factors associated with the carriage of ESBL-producing Enterobacteriaceae were the use of pesticides in agriculture and farming practice. The current result suggests that frequent contact to antibiotics is not the only reason for the development of resistance and confirm that resistance can be induced by chemicals from pesticide origin

Réseaux sociaux et défi démocratique : l’exemple du cyberespace camerounais

L’accès des minorités (ethniques) et des entités marginalisées (femmes, jeunes) au pouvoir démocratique au Cameroun via les réseaux et médias socionumériques connaît un tournant majeur avec la prolifération des nouvelles technologies de l’information et de la communication. Au travers de deux plateformes camerounaises de discussion en ligne, à savoir Camer be et Cameroun.info-net, nous montrons qu’elles constituent désormais un vecteur d’émancipation qui permet à ces entités sociales longtemps muselées par les différents pouvoirs en place de reprendre l’initiative en matière de liberté d’expression et de culture démocratique. Dès lors, Internet assure non seulement une grande visibilité sociopolitique malgré la chape de plomb de la censure qui demeure menaçante pour ces usagers singuliers du web, mieux ils profitent de ces moments d’échanges interactifs pour éprouver leur compétence communicationnelle, même si celle-ci est parfois limitée, sinon embryonnaire. L’idée d’une démocratie participative impulsée par les groupes étudiés devient ainsi une réalité en marche, le cyberespace camerounais se dotant de plus en plus d’un pouvoir de libérer et fédérer, ce qui leur donne la possibilité de participer pleinement au grand débat national sur des questions touchant aussi bien le politique, l’économique, le social que le culturel.The access of (ethnic) minorities and marginalized entities (women, young people) to the democratic power in Cameroon through socio-numeric networks and media is experiencing a major turning point with the proliferation of new information and communication technologies. Through two Cameroonian platforms of online discussion, namely Camer be and Cameroun.info-net, I show that they constitute from now on a vector of empowerment that allows these social entities for a long time muzzled by the various powers in place to take back the initiative regarding freedom of expression and democratic culture. Therefore, Internet not only insures a great sociopolitical visibility despite the leaden weight of censorship that remains a threat to these singular web users, better they take advantage of these moments of interactive exchanges to test their communicational skills, even if it is sometimes limited, otherwise embryonic. The idea of a participative democracy driven by the studied groups so becomes a reality on the move, the Cameroonian cyberspace acquiring more and more power to liberate and unite, what gives them the opportunity to fully participate in the great national debate on issues affecting as well as the political, the economic, the social as the cultural

Effects of the Methanol Extract of Basella alba L (Basellaceae) on Steroid Production in Leydig Cells

In this study, Leydig cells were purified from 70 day-old Sprague Dawley male rats and incubated with 10 and 100 μg/mL of methanol extract of Basella alba (MEBa) for 4 hours followed by the evaluation of cell viability, steroid (testosterone and estradiol) production, and the level of aromatase mRNA. Results showed that MEBa did not affect Leydig cell viability. At the concentration of 10 μg/mL, MEBa significantly stimulated testosterone and estradiol production (p < 0.01 and p < 0.03, respectively), and enhanced aromatase mRNA level (p < 0.04). These observations suggest that MEBa directly stimulated testosterone, estradiol and aromatase mRNA levels in isolated Leydig cells

Effects of the aqueous extract of Pycnanthus angolensis (Myristicaceae) on male rat sexual behavior and nitric oxide release

Erectile dysfunction is a major public health problem leading to harmful consequences for couples. Hence the need to find adequate treatments using medicinal plants such as Pycnanthus angolensis, a Cameroonian plant used to treat erectile dysfunction. The effects of aqueous extract of Pycnanthus angolensis wood were evaluated on male rat sexual behavior and nitric oxide release. Adult male Wistar rats were divided into 4 groups of 5 each that included a group receiving orally: distilled water (10 ml/Kg BW), plant extract treatment (43 or 86 or 172 mg/kg BW). Sexual behaviors were monitored on days 1, 4, 7, and 14 by pairing male rats to receptive females and nitric oxide levels were assessed in penile homogenate. At the end of the 14 days of treatment, rats were killed and sexual organs weighed. No significant effect was observed on sexual organs weights. When administered at a dose of 43 mg/Kg, body weight; the plant extract significantly increased (p<0.05) the sexual performance as well as the libido of male rats. Nitric oxide release was significantly increased (p<0.05) in that group of extract-treated rats, while compared to the control group. The study demonstrates that Pycnanthus angolensis is a medicinal plant which can enhance the sexual behaviors of male rat. Hence, it can be used for the management of erectile dysfunction, mainly at a dose of 43 mg/Kg, body weight