Paludisme à la première consultation prénatale : prévalence et facteurs associés en milieu rural au Sud Kivu à l'Est de la République Démocratique du Congo

Contexte : Les femmes enceintes constituent un groupe vulnérable face au paludisme. Dans l'objectif de déterminer la prévalence et les facteurs associés au paludisme pendant la grossesse, une étude a été menée dans la zone de santé rurale de Miti-Murhesa, à l'Est de la République Démocratique du Congo (RDC), trois ans après une distribution de Moustiquaires Imprégnées d'Insecticide (MII).Méthodes : Les données de 478 femmes enceintes recueillies à leur première consultation prénatale entre novembre 2010 et juillet 2011 ont été analysées. Les femmes étaient recrutées au deuxième trimestre de la grossesse aux centres hospitaliers de Murhesa et de Lwiro. Un cas de paludisme était défini par une goutte épaisse positive pour le plasmodium. L'altitude de la résidence d'origine de chacune des femmes était mesurée par un GPS. Résultats : A l'admission 9,5% (n = 453) de femmes présentaient une infection palustre. En régression logistique, la fréquence du paludisme était plus élevée chez les primigestes, chez les femmes avec niveau socio-économique bas et chez celles vivant à moins de 1683 m d'altitude ; les rapports de cote ajustés (IC 95%) étaient respectivement de [2,55 (1,05-6,19) ; P = 0,039] ; [4,78 (1,36-16,76) ; P = 0,033] et [2,34 (1,10-5,02) ; P = 0,029].Conclusion : Ces résultats montrent que le paludisme est resté présent chez les femmes enceintes trois ans après une distribution de moustiquaires à Miti-Murhesa. La première grossesse, le niveau socioéconomique bas et la résidence en basse altitude étaient des facteurs significativement associés au paludisme. Ces résultats appellent à intensifier les activités de prévention contre le paludisme dans la communauté de manière à protéger plus efficacement les femmes en âge de procréer

Detection of K(ATP) channels subunits in human term placental explants and evaluation of their implication in human placental lactogen (hPL) and human chorionic gonadotropin (hCG) release.

INTRODUCTION: ATP-sensitive potassium channels (KATP channels) have been identified in a variety of tissues. Nevertheless, the presence and role of such metabolism-sensitive K+ channels still remain to be unraveled in the reproductive system. METHODS: The study evaluates the presence of KATP channel subunits in human term placental explants by immunohistochemistry, proximity ligation assay, Western blot and RT-PCR techniques. The potential involvement of KATP channels in human placental lactogen (hPL) and human chorionic gonadotrophin (hCG) release has been assessed radioimmunologically from human term placental explants incubated in the presence of different KATP channel modulators. RESULTS: Immunolocalization of the KATP channel subunits documented both the Kir6.2 and SUR2 subunits in the syncytiotrophoblast of human term placenta. Their colocalization was demonstrated by proximity ligation assay and their presence was further confirmed by immunoblotting and RT-PCR. Kir6.1 subunit was immunolocalized in blood vessels media. SUR1 was not expressed at the mRNA level. Incubation of human term placental explants in the presence of increasing concentrations of modulators of KATP channels such as glibenclamide, tolbutamide, pinacidil or diazoxide did not affect the measured hCG and hPL secretory rates. DISCUSSION: Our study reports, for the first time, the presence of the KATP channel subunits Kir6.2 and SUR2 in the human term syncytiotrophoblast. However, under the present experimental conditions, the activation or inhibition of these putative KATP channels by different pharmacological agents did not affect the hPL and hCG secretory rate of human term placental explants. CONCLUSION: The present findings suggest that the human term syncytiotrophoblast might be endowed with KATP channels. Further studies should clarify their implication in the syncytiotrophoblast ionic homeostasis and hormone regulation.

[Impact of aging on sexuality]. / Impact des vieillissements physiologique et pathologique sur la relation sexuelle.

Numerous authors on sexual behaviors have studied the link between the persistence of a sexually active life and progressive aging. The knowledge of sexual health in the elderly has shown that biological sexual aging is extremely diverse and heterogeneous in men as well as in women, and contradicts the stereotype of age that would inevitably alter the sexual biological response in each human. Sexual diseases (lubrication, dyspareunia, erectile dysfunction, inability to achieve orgasm) and diseases of aging that impact sexual function have a growing incidence but don't never touch 100% of individuals. There is a decline in sexual interest correlated with the life-span, but the negative effects of age on desire are related to health problems. Moreover, sexual desire is more correlated with personal attitudes toward sexuality than with biological factors and diseases. Several predictors account for the pursuit of an active sexuality (including the presence of a partner, good health, having good sexual self-esteem, enjoyable past experience, an attitude that values the importance of sex in couple relationship), but the most decisive factor to successfully face the specific markers of aging is the ability to adapt to a more sensory sexuality, less focused on performance and coitus.

[Sexuality of our seniors: happy end or new beginning?]. / Sexualité après 55 ans: fin du ou faim de sexe?

Comparing surveys from successive periods demonstrates that elderly people now enjoy a better and more varied sexual life than previous generations. The proportion of older people who remain sexually active has significantly increased, and the practices of masturbation or oral sex have spread considerably. The generation effect has an incidence upon sexual behaviour: older people's repertoire of sexual practices differs from that of younger people, in the sense that it focuses less on sexual intercourse and oral sex. Women and men, beyond the common trends towards sexuality characterised by a more open repertoire of sexual practices, differ in terms of sexual interest and subjective sexual wellbeing. The cessation of sexual activity by individuals who had previously been sexually active is often the result of a cascade of reactions, such as the occurrence of a sexual dysfunction in one or both partners, anticipation of failure, increased anxiety, lack of adaptation of sexuality and/or avoidance behaviour.

[Elderly people's sexuality]. / La sexualité de la personne âgée.

In a context of ageing human population, the question of the elderly people's sexuality, a recent phenomenon, remains without precise and obvious answer. Still, the sexuality of the older person must be viewed as the continuation of the adult's sexuality. However, it is partially or completely, depending on gender, dissociated from the concept of reproduction. Partly for this functional reason, the society estimates that the elderly person cannot feel sexual desire, are not physically attractive, therefore not desirable. Even if they felt sexual need, they would be physiologically unable. Sexuality is an integral part of the quality of life, well-being, and undoubtedly of the person's health whatever their age. It is thus important to deal with this matter from a physiological and biological point of view. Sexuality and deteriorations related to the process of ageing have to be taken into consideration. These deteriorations are not automatically linked to the increase in longevity. It is in the responsibility of health workers, professionally in charge of the elderly people, to help them better understand their desires which lies in a framework of normality. A greater knowledge of their sexuality will fight the current repression of the sexuality of the elder ones.

Evidence for a clathrin-mediated recycling of albumin in human term placenta.

During human pregnancy, the trophoblast layer is in direct contact with maternal albumin. In contrast to immunoglobulins, albumin does not cross the placental barrier. However, albumin affects the trophoblast placental lactogen and chorionic gonadotroph secretion. The present study investigated the interaction between albumin and syncytiotrophoblast using human term placental explants. Bovine serum albumin, labeled with either 125I or fluorescein isothio-cyanate, was taken up rapidly by placental explants. This process was temperature-sensitive. The internalized labeled BSA quickly outflowed from the tissue at the maternal side, largely without any major modification in molecular weight. Colchicine (1 mM), which disrupts the microtubule network, or cytochalasin B (40 microM), which disassembles filamentous actin, did not interfere with the placental transmembrane movements of labeled BSA. Megalin, clathrin, and caveolin 1 are three membrane proteins associated with albumin endocytosis in other tissues, but only megalin and clathrin were detected in the syncytiotrophoblast layer by immunohistochemistry. The uptake of labeled BSA into placental explants was not modified by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (1 mM) or 5-nitro-2-(3-phenylpropylamino)benzoic acid (100 microM), two pharmacological tools known to disturb megalin-mediated albumin endocytosis. By contrast, methyl-beta-cyclodextrin (10 mM) and chlorpromazine (1.4 mM), both of which disrupt the clathrin-mediated endocytotic system, significantly reduced the uptake of labeled BSA. These data suggest, to our knowledge for the first time, that maternal albumin is actively internalized into the human trophoblast according to an apical recycling pathway. This temperature-sensitive process does not depend on an intact cytoskeleton, but it is associated with a clathrin-mediated endocytotic system.

Colloidal effect of albumin on the placental lactogen and chorionic gonadotrophin releases from human term placental explants.

Albumin has been reported to stimulate the release of placental lactogen and chorionic gonadotrophin from human term placental explants within physiological concentrations. This study aimed at characterizing further its effect on the placental hormonal secretion. The placental lactogen and chorionic gonadotrophin secretory response of incubated explants to 5% albumin was reproduced by colloidal agents, i.e., dextran (4.5%) and polygelin (4%), indicating that a rise in colloidal osmotic pressure can elicit hormonal release from the syncytiotrophoblast. Their secretory effects were not modified by the absence of extracellular calcium or the presence of verapamil in the medium. The three agents also provoked a marked increase in (45)calcium outflow from preloaded and perifused explants that persisted in absence of extracellular calcium. These data indicate that the triggering effect of albumin on placental lactogen and chorionic gonadotrophin release can be partly reproduced by colloidal agents and is independent of extracellular calcium.

Stimulation of Kaposi's sarcoma cell growth by urine from women in early pregnancy, the current source for clinical-grade human chorionic gonadotropin preparations.

Clinical-grade preparations of human chorionic gonadotropin (hCG) have been shown to be toxic to Kaposi's sarcoma (KS) cells. However, the results of clinical studies using commercial hCG preparations KS remain highly contradictory. More particularly, some hCG preparations could have a paradoxical growth effect on KS. Such discrepant results may be explained by the fact that the anti-KS activity is not associated with hCG itself but with one or more factors that are co-purified with the hormone. We found here that crude urine from first trimester pregnant women, the current source for commercial hCG, had a growth stimulatory effect on KS cells. By contrast, urine from last trimester pregnant women, from non-pregnant young women, from menopausal women and from men exhibited neither a growth stimulatory nor a growth inhibitory effect on KS cells. The amplitude of this pregnancy urine-associated pro-KS activity/hCG unit was higher than that achieved with clinical-grade hCG preparations. Partial co-purification of pregnancy-associated factors during the extraction procedure of commercial hCG from urine may explain the pro-KS activity achieved with some hCG preparations. We, therefore, suggest a cautious use of hCG purified from pregnancy urine for the treatment of KS.

Treatment of Kaposi's sarcoma with human chorionic gonadotropin.

Clinical-grade preparations of human chorionic gonadotropin (hCG) have been shown to be toxic to Kaposi's sarcoma (KS) cells. However, the mechanism of the anti-KS activity achieved with these preparations remains unclear. The results of clinical studies using commercial hCG preparations in human KS are also highly contradictory. The apparent controversy between different studies may be due to the fact that pro- and anti-KS components are present in varying proportions in different hCG preparations. As certain hCG preparations could not only lack the ability to control KS but also contain some contaminant KS growth factor(s), we suggest a cautious use of crude hCG for the treatment of KS.

Physiological concentrations of albumin stimulate chorionic gonadotrophin and placental lactogen release from human term placental explants.

This study investigates whether albumin, a major plasma protein in direct contact with the trophoblast in vivo, can modulate human chorionic gonadotrophin (HCG) and human placental lactogen (HPL) releases from placental explants. Incubating explants with a near physiological, i.e. 5%, concentration of human or bovine albumin during 30 min increased HCG and HPL release by at least 150%. This albumin effect was not mediated by any difference in hormone adsorption onto glass surfaces. In contrast to the sustained stimulation of hormone releases elicited by the addition of 10 mmol/l extracellular calcium, the albumin-mediated secretory responses were transient. However, the albumin- and calcium-stimulatory effects were abolished at 4 degrees C, depressed by 0.36 mmol/l cycloheximide or 1 mmol/l colchicine and potentiated by 40 micromol/l cytochalasin B. Moreover, the stimulatory effect of albumin on the hormone releases was not modified in the absence of Ca(2+) or in the presence of 1 or 10 mmol/l Ca(2+) in the extracellular milieu. These data suggest that albumin is involved, at physiological concentration, in the secretion of HCG and HPL by human placenta. The cellular mechanism(s) underlying the albumin-mediated secretory responses may be partly different from those involved during the calcium-mediated stimulation.

Maturation of the auditory system in clinically normal puppies as reflected by the brain stem auditory-evoked potential wave V latency-intensity curve and rarefaction-condensation differential potentials.

OBJECTIVE: To evaluate auditory maturation in puppies. ANIMALS: Ten clinically normal Beagle puppies. PROCEDURE: Puppies were examined repeatedly from days 11 to 36 after birth (8 measurements). Click-evoked brain stem auditory-evoked potentials (BAEP) were obtained in response to rarefaction and condensation click stimuli from 90 dB normal hearing level to wave V threshold, using steps of 10 dB. Responses were added, providing an equivalent to alternate polarity clicks, and subtracted, providing the rarefaction-condensation differential potential (RCDP). Steps of 5 dB were used to determine thresholds of RCDP and wave V. Slope of the low-intensity segment of the wave V latency-intensity curve was calculated. The intensity range at which RCDP could not be recorded (ie, pre-RCDP range) was calculated by subtracting the threshold of wave V from threshold of RCDP RESULTS: Slope of the wave V latency-intensity curve low-intensity segment evolved with age, changing from (mean +/- SD) -90.8 +/- 41.6 to -27.8 +/- 4.1 micros/dB. Similar results were obtained from days 23 through 36. The pre-RCDP range diminished as puppies became older, decreasing from 40.0 +/- 7.5 to 20.5 +/- 6.4 dB. CONCLUSION AND CLINICAL RELEVANCE: Changes in slope of the latency-intensity curve with age suggest enlargement of the audible range of frequencies toward high frequencies up to the third week after birth. Decrease in the pre-RCDP range may indicate an increase of the audible range of frequencies toward low frequencies. Age-related reference values will assist clinicians in detecting hearing loss in puppies.

Association between external pelvimetry and vertex delivery complications in African women.

OBJECTIVE: To assess association between external pelvimetry and delivery complications in vertex presentation. METHODS: Prospective cohort study of 2,413 pregnant women antenatally measured for height and external pelvimetry in four hospitals of the former Republic of Zaire. OUTCOME MEASURES: Complications during delivery of single fetus weighing 2,000 g or more in vertex presentation. Cut-off values at risk for delivery complications were height and pelvic distances closest to the study population 10th percentile. RESULTS: In univariate analysis, maternal height showed significant relative risk for predicting primary cesarean section for failure to progress: 2.0 (95% CI=1.0-4.1; p=0.050) and vacuum or forceps delivery: 15.7 (95%, CI=6.6-37.5; p<0.001). Selected external pelvic distances showed significant relative risks for predicting the following complications: primary cesarean section for failure to progress, elective repeat cesarean section, vacuum or forceps delivery and spontaneous intrapartum stillbirth. Among pelvic predictors, transverse diagonal (TD) of Michaelis sacral rhomboid area was associated with all of these complications. Intertrochanteric (IT) diameter was associated with three of them. The relative risks ranged from 2.3 (95% CI=1.1-6.3; p=0.030) to 9.6 (95% CI=4.1-22.5; p<0.001) for these strongest predictors. CONCLUSIONS: External pelvic distances help to predict vertex delivery complications in African women. The predicted complications are compatible with the cephalopelvic disproportion concept (CPD). After validation of current results in a separate cohort, measurements of IT and/or TD are recommended to improve antenatal screening of women at risk for CPD in limited resources settings.

Maternal height and external pelvimetry to predict cephalopelvic disproportion in nulliparous African women: a cohort study.

OBJECTIVE: To assess external pelvimetry and maternal height, as predictors of cephalopelvic disproportion. DESIGN: Prospective cohort study. SETTING: Four hospitals in Zaire. POPULATION: Six hundred and five nulliparous women. METHODS: Maternal height and external pelvimetry were assessed during the third trimester antenatal visit. Cut off values for considering women at risk for cephalopelvic disproportion were height < 150 cm and external pelvic distances < 10th centile for the population. Logistic regression analysis, combining height and pelvic measurements, was performed to predict women at risk for cephalopelvic disproportion. MAIN OUTCOME MEASURE: Cephalopelvic disproportion was considered when there was caesarean section for failure to progress, vacuum or forceps delivery or intrapartum stillbirth. RESULTS: Cephalopelvic disproportion was present in 42 women. In univariate analysis, height, intertrochanteric diameter and the transverse diagonal of Michaelis sacral rhomboid area were found to be associated with cephalopelvic disproportion. Logistic regression analysis showed that maternal height < 150 cm and/or transverse diagonal < 9.5 cm were the variables most associated with cephalopelvic disproportion. The adjusted odds ratios were 2 x 2 (95% CI 0.9 to 5.4) and 6.5 (95% CI 3.2 to 13.2), respectively. The positive predictive value and likelihood ratio were 24% and 4.0 (95% CI 2.8 to 5.8), respectively. The addition of transverse diagonal to maternal height increased the sensitivity in predicting cephalopelvic disproportion from 21% to 52%. CONCLUSION: In addition to height, transverse diagonal measurement is able to predict one out of two cases of cephalopelvic disproportion in nulliparous women. After validation in a separate cohort, this simple predictive method may be used in peripheral centres for timely referral of pregnant women at risk for cephalopelvic disproportion.

Secretory characteristics and viability of human term placental tissue after overnight cold preservation.

Collection of human term placentae for research purposes is generally limited during working hours. Preserving placental tissue overnight might help to postpone experiments and, by extent, to increase material availability. In this study, fragments from normal placentae were incubated at 37 degrees C either immediately after delivery or after preservation at 4 degrees C in a HEPES-buffered solution or in a Roswell Park Memorial Institute (RPMI) 1640 culture medium. Protein, human chorionic gonadotrophin (HCG), human placental lactogen (HPL) and lactate dehydrogenase (LDH) contents within preserved explants were similar to those within freshly delivered ones. In contrast, HCG and HPL amounts released during incubation of preserved tissue were lower than with freshly delivered tissue. Differences were significant only during the first 3 h of incubation. Hormone releases were similarly Ca(2+)-stimulated, and Co(2+)- and low temperature-inhibited in preserved and freshly delivered tissues. After preservation, LDH leakage was also reduced. Furthermore, before and after 37 degrees C incubation during 6 h, preserved tissue was morphologically indistinguishable from freshly delivered tissue and showed neither higher incidence of DNA fragmentation, nor elevated caspase-3 activity, both of which are markers of apoptosis. This study validates an original, useful and rapid method to preserve placental tissue. Consequently, this preservation model may facilitate the study of physiological processes regulating placental hormone secretion in normal and pathological conditions.

HCG concentration and receptor gene expression in placental tissue from trisomy 18 and 21.

Trisomy 21 is associated with high maternal serum concentrations of intact human chorionic gonadotrophin alpha(HCG) and free beta-HCG whereas these concentrations are markedly decreased in trisomy 18. In this study, we investigated the effect of trisomy 21 and 18 on endogenous HCG concentrations and luteinizing hormone (LH)/HCG receptor expression in placental villous tissue in eight trisomy 21, six trisomy 18 and 42 chromosomally normal samples, collected at 12-16 weeks gestation. The tissue concentrations of intact HCG, free alpha-HCG and free beta-HCG subunits were measured using solid-phase two-site immunoradiometric assay. LH/HCG receptor expression was evaluated with immunohistochemistry and in-situ hybridization. Villous tissue in trisomy 21 contained higher beta-HCG concentrations than the controls (P < 0.05). In trisomy 18 cases, the beta-HCG concentration was lower than in the control group (P < 0.01). Both immunocytochemistry and in-situ hybridization demonstrated a more intense staining of the trophoblast in cases of trisomy 21 and 18, compared with controls with the strongest signal in cases of trisomy 18 (P < 0.01). We concluded that in trisomy 21 the high tissue HCG concentration and expression of LH/HCG receptor in the trophoblast may reflect the relative immaturity of the trophoblastic tissue whereas in trisomy 18, the very low concentration of endogenous HCG, associated with an over-expression of LH/HCG receptor in the trophoblast, is probably secondary to the poor differentiation of the cytotrophoblast.

Epitope analysis and molecular modeling reveal the topography of the C-terminal peptide of the beta-subunit of human chorionic gonadotropin.

Human chorionic gonadotropin (hCG) belongs to a family of heterodimeric glycoprotein hormones that share a common alpha-subunit and a hormone-specific beta-subunit. Among the gonadotropin beta-subunits, greater than 85% homology exists between lutropin (hLH)beta and hCGbeta in their first 114 amino acid residues. However, unlike hLHbeta, hCGbeta contains a 31-amino acid hydrophilic stretch at its carboxyl end (CTPbeta: C-terminal peptide). Although the crystal structure of deglycosylated hCG has been solved, the topography of CTPbeta remains unknown. In this study, we have attempted to define the topology of CTPbeta using mAb probes. We investigated three epitopes on hCGalpha, which are hidden in the hCGalphabeta dimer. However, these epitopes are not hidden in hLH, which has a similar subunit interface to that of hCG, but lacks CTPbeta. This suggested that these epitopes are not masked at the subunit interface of hLH or hCG. Hence, we hypothesized that, in the case of hCG, these epitopes are masked by the CTPbeta. Consistent with this view, several treatments of hCG that removed CTPbeta unmasked these epitopes and enhanced their reactivity with the corresponding mAbs. In order to localise the position of CTPbeta on the alpha-subunit, we used an epitope-mapping strategy [N. Venkatesh & G. S. Murthy (1997) J. Immunol. Methods 202, 173-182] based on differential susceptibility of epitopes to covalent modifications. This enabled us to predict the possible topography of CTPbeta. Further, we were also able to build a model of CTPbeta, completely independently of the epitope-mapping studies, using a homology-based modeling approach [S. Krishnaswamy, I. Lakshminarayanan & S. Bhattacharya (1995) Protein Sci. 4 (Suppl. 2), 86-97]. Results obtained from these two different approaches (epitope analysis and homology modeling) agree with each other and indicate that portions of CTPbeta are in contact with hCGalpha in the native hCG dimer.

Apoptosis in human term placenta is not increased during labor but can be massively induced in vitro.

Apoptosis in human placental villi is reported to increase until close to delivery. However, the involvement of the apoptotic process in the initiation of labor, and more particularly in relation to the decrease in placental perfusion during uterine contractions, remains unknown. The purpose of the study was to examine the reactivity of the apoptotic machinery in term placentae obtained before or after the onset of labor and after in vitro incubations. The incidence of apoptotic nuclei (< 1%) as evidenced by the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) method, and the histological distribution of immunoreactive Bcl-2, Bax, and Bcl-x proteins, were similar in placentae collected after delivery and before the onset of labor and in placental explants maintained overnight at 4 degrees C in a minimal salt-Hepes medium. By contrast, 28% of nuclei contained fragmented DNA when placental explants were incubated overnight at 37 degrees C. This marked increase was associated with a decrease in the intensity of the Bcl-2 immunostaining and an increase in the intensity of Bax and Bcl-x immunostaining. In conclusion, the present study clearly evidences the presence of an active apoptotic machinery in term placental cells that is not involved in normal parturition.