Aspects of the reproductive biology of the shortfin mako, Isurus oxyrinchus (Elasmobranchii Lamnidae), in the Southeastern region of Brazil

Quatro úteros provenientes de quatro fêmeas prenhas e dois indivíduos recém-nascidos de anequim, Isurus oxyrinchus, foram coletados na região Sudeste do Brasil durante os meses de setembro a novembro de 1993 e 1994. Todos os embriões estavam bem desenvolvidos, próximos ao estágio de nascimento, apresentando a dentição e órgãos internos bastante desenvolvidos. O comprimento total desses embriões variou entre 64,5 e 72,0 cm, e o maior número de embriões observado no interior de uma única fêmea foi 20. As observações aqui realizadas confirmam a oofagia como forma de nutrição dos embriões dessa espécie e sua periodicidade. A presença de dentes no estômago dos embriões sugere que a substituição dos dentes se inicia na fase uterina.

Sildenafil for pulmonary hypertension treatment after cardiac surgery

Objective: To report on the use of sildenafil for pulmonary hypertension treatment of a newborn patient after cardiac surgery. Description: A female, full term newborn infant with diagnosis of double outlet right ventricle, pulmonary hypoplasia and subaortic ventricular septal defect, was submitted to Blalock surgery in the first week of life. In postoperative the newborn had pulmonary hypertension and persistent hypoxia, without response to nitric oxide, but with improved oxygenation after continuous intravenous infusion of prostaglandin E1. After several failed attempts to discontinue prostaglandin E1, oral sildenafil was used. There was a decrease in pulmonary vascular resistance with consequent oxygenation improvement and 48 hours later it was possible to discontinue prostaglandin E1 infusion. Comments: Sildenafil can be an alternative therapy for pulmonary hypertension, especially when there is no response to conventional therapy. Copyright © 2005 by Sociedade Brasileira de Pediatria.

Determinação dos níveis sangüíneos de frutose em recém-nascidos de termo com pesos adequados para a idade gestacional com 48 horas de vida

Pós-graduação em Pediatria - FMB

Estresse oxidativo em recém-nascidos de mães hipertensas: relação com prognóstico neonatal no curto prazo

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Expression of 8-oxoguanine Glycosylase in Human Fetal Membranes

Problem The most common DNA lesion generated by oxidative stress (OS) is 7, 8-dihydro-8-oxoguanine (8-oxoG) whose excision repair is performed by 8-oxoguanine glycosylase (OGG1). We investigated OGG1 expression changes in fetal membranes from spontaneous preterm birth (PTB) and preterm premature rupture of the membranes (pPROM) and its changes in vitro in normal fetal membranes exposed to OS inducer water-soluble cigarette smoke extract (CSE). Method of study DNA damage was determined in amnion cells treated with CSE by comet and FLARE assays. OGG1 mRNA expression and localization in fetal membranes from clinical specimens and in normal term membranes exposed to CSE were examined by QRT-PCR and by immunohistochemistry. Results DNA strand and base damage was seen in amnion cells exposed to CSE. OGG1 expression was 2.5-fold higher in PTB samples compared with pPROM (P=0.045). No significant difference was seen between term and pPROM or PTB and term. CSE treatment showed a nonsignificant decrease in OGG1. OGG1 was localized to both amnion and chorion with less intense staining in pPROM and CSE-treated membranes. Conclusion Increased OS-induced DNA damage predominated by 8-oxoG is likely to persist in fetal cells due to reduced availability of base excision repair enzyme OGG1. This can likely lead to fetal cell senescence associated with some adverse pregnancy outcome.

Relazione gestante-feto, modalità del parto e sviluppo fisico del bambino

Extensive literature outlined that the quality of the mother-foetus relationship is considered the main feature with regard to the quality of postnatal mother-infant interaction and also to the child’s psychical development. Nowadays the relationship between the pregnant woman and her foetus is viewed as the central factor of the somatic dialogue between the functioning of the maternal and the foetal organisms. This dialogue is responsible for the physic development of the child, as well as of its psychosomatic structure. Therefore the research area has necessarily had to extend to the analysis of psychological processes concerning: the pregnancy, the couple that is bound by parenthood, the influence of intergenerational dynamics. In fact, the formation of maternal identity, as well as that of the relationship between the woman and the foetus, refers to the pregnant woman’s relationship with her parents, especially with her mother. The same pregnancy, considered as a psychosomatic event, is directly influenced by relational, affective and social factors, particularly by the quality of the interiorized parental relations and the quality of the current relationships (such as that with her partner and with her family of origin). Some studies have begun to investigate the relationship between the pregnant woman and the foetus in term of “prenatal attachment” and its relationship with socio-demographic, psychological e psychopathological aspects (such as pre and post partum depression), but the research area is still largely unexplored. The present longitudinal research aimed to investigate the quality of the pregnant womanfoetus relationship by the prenatal attachment index, the quality of the interiorized relationship with woman’s parents, the level of alexithymic features and maternity social support, in relation with the modulation of the physiology of delivery and of postpartum, as well as of the physical development of the child. A consecutive sample of 62 Italian primipara women without any kind of pathologies, participated in the longitudinal study. In the first phase of this study (third trimester of the pregnancy), it has investigated the psychological processes connected to the affective investment of the pregnant women towards the unborn baby (by Prenatal Attachment Inventory), the mothers’ interiorized relationship with their own parents (by Parental Bonding Instrument), the social and affective support from their partner and their family of origin are able to supply (by Maternity Social Support Scale), and the level of alexithymia (by 20-Toronto Alexithymia Scale). In the second phase of this study, some data concerning the childbirth course carried out from a “deliverygram” (such as labour, induction durations and modalities of delivery) and data relative to the newborns state of well-being (such as Apgar and pH indexes). Finally, in the third phase of the study women have been telephoned a month after the childbirth. The semistructured interview investigated the following areas: the memory concerning the delivery, the return to home, the first interactions between the mother and the newborn, the breastfeeding, the biological rhythms achieved from newborns. From the data analysis a sample with a good level of prenatal attachment and of support social and a good capability to mental functioning emerged. An interesting result is that the most of the women have a great percentage of “affectionless control style” with both parents, but data is not sufficient to interpret this result. Moreover, considering the data relative to the delivery, medical and welfare procedures, that have been necessary, are coherent with the Italian mean, while the percentage of the caesarean section (12.9%) is inferior to the national percentage (30%). The 29% of vaginal partum has got epidural analgesia, which explains the high number (37%) of obstetrician operations (such as Kristeller). The data relative to the newborn (22 male, 40 female) indicates a good state of well-being because Apgar and pH indexes are superior to 7 at first and fifth minutes. Concerning the prenatal phase, correlation analysis showed that: the prenatal attachment scores positively correlated with the expected social support and negatively correlated with the “externally oriented thinking” dimension of alexithymia; the maternity social support negatively correlated with total alexithymia score, particularly with the “externally oriented thinking” dimension, and negatively correlated with maternal control of parental bonding. Concerning the delivery data, there are many correlations (after all obvious) among themselves. The most important are that the labour duration negatively correlated with the newborn’s index state of well-being. Finally, concerning the data from the postpartum phase the women’ assessments relative to the partum negatively correlated with the duration of the delivery and positively correlated with the assessment relative to the return to home and the interaction with the newborn. Moreover the length of permanence in the hospital negatively correlated with women’s assessments relative to the return to home that, in turn, positively correlated with the quality of breastfeeding, the interaction between the mother and the newborn and the biological regulation of the child. Finally, the women’ assessments relative to breastfeeding positively correlated with the mother-child interactions and the biological rhythms of children. From the correlation analysis between the variables of the prenatal phase and the data relative to the delivery, emerged that the prenatal attachment scores positively correlated with the dilatation stage scores and with the newborn’s Apgar index at first minute, the paternal care dimension of parental bonding positively correlated with the lengths of the various periods of childbirth like so the paternal control dimension with placental stage. Moreover, emerged that the expected social support positively correlated with the lengths of the various periods of childbirth and that the global alexithymia scores, particularly “difficulty to describe emotions” dimension, negatively correlated with total childbirth scores. From the correlation analysis between the variables of the prenatal phase and variable of the postpartum phase emerged that the total alexithymia scores positively correlated with the time elapsed from the childbirth to the breastfeeding of the child, the difficulty to describe emotions dimension of the alexithymia negatively correlated with the quality of the breastfeeding, the “externally oriented thinking” dimension of the alexithymia negatively correlated with mother-child interactions, and finally the paternal control dimension of the parental bonding negatively correlated with the time elapsed from the child to the breastfeeding of the child. Finally, from the analysis of the correlation between the data of the partum and the women’s assessments of the postpartum phase, emerged the negative correlation between the woman’s assessment relative to the delivery and the quantitative of obstetrician operations and the lengths of the various periods of childbirth, the positive correlation between the women’s assessment about the length of delivery periods and the real lengths of the same ones, the positive relation between woman’s assessment relative to the delivery and the Apgar index of children. In conclusion, there is a remarkable relation between the quality of the relationship the woman establishes with the foetus that influences the course of the pregnancy and the delivery that, in turn, influences the postpartum outcome, particularly relative to the mother-children relationship. Such data should be confirmed by heterogeneous populations in order to identify vulnerable women and to project focused intervention.

Differential expression of the receptor tyrosine kinase EphB4 and its ligand Ephrin-B2 during human placental development

Normal placentation involves the development of an utero-placental circulation following the migration of the extravillous cytotrophoblasts into the decidua and invasion of the spiral arteries, which are thereby transformed into large vessels of low resistance. Given the documented role of the receptor tyrosine kinase EphB4 and its ligand ephrin-B2 in the establishment of the embryonal vascular network, we hypothesized that these molecules are also instrumental in the development of the human placenta. Monitoring the expression during placental development revealed that in first trimester and term placentae both molecules are equally expressed at the RNA level. In contrast, the protein levels were significantly reduced during gestation. Immunohistochemistry revealed a distinct localization of the EphB4 and ephrin-B2 proteins. EphB4 was predominantly expressed in the villous syncytial trophoblast layer and in a subset of intravillous capillaries. Prominent expression was also observed in the extravillous cytotrophoblast giant cells. In contrast, ephrin-B2 expression was detected in the villous cytotrophoblast and syncytial trophoblast cell layers, as well as initially in all intravillous capillaries. Strong expression was also observed in extravillous anchoring cytotrophoblast cells. Hypoxia is a major inducer of placental development. In vitro studies employing trophoblast-derived cell lines revealed that predominantly ephrin-B2 expression is induced by hypoxia, however, in an Hif-1alpha independent manner. These experiments suggest that EphB4 and ephrin-B2 are instrumental in the establishment of a functional placental structure and of the utero-placental circulation.

The paradox of adult respiratory distress syndrome in neonates

Six full-term newborn infants are described who suffered from severe adult respiratory distress syndrome (ARDS). The triggering event was intrauterine/perinatal asphyxia in five, and group B streptococcal (GBS) septicemia in three. All had severe respiratory distress/failure and were ventilated mechanically with high concentrations of inspired oxygen and positive end-expiratory pressure. Radiography of the chest showed dense bilateral consolidation with air bronchograms and reduced lung volume. Persistent pulmonary hypertension (PPH) was documented in all cases. The coincidence of ARDS and PPH rendered respiratory management extremely difficult. For this reason high-frequency ventilation was instituted in all patients in order to improve CO2 elimination and induce respiratory alkalosis. Acute complications of respiratory therapy were encountered in five patients (pneumothorax, pulmonary interstitial emphysema, pneumopericardium). Three infants died (irreversible septic shock, progressive severe hypoxemia, and sudden cardiac arrest) after 17, 80, and 175 h of life. Histologic examination of the lungs was possible in all fatal cases and revealed typical changes of acute to subacute stages of ARDS. Three infants survived, the mean time of mechanical respiratory support being 703 h. Two patients were still dependent on oxygen after 1 month of life, and all survivors had increased interstitial markings and increased lung volumes on their chest roentgenograms at this time.

Volumetric capnography in infants with bronchopulmonary dysplasia.

OBJECTIVES To assess the feasibility of using volumetric capnography in spontaneously breathing small infants and its ability to discriminate between infants with and without bronchopulmonary dysplasia (BPD). STUDY DESIGN Lung function variables for 231 infants (102 term, 52 healthy preterm, 77 BPD), matched for post-conceptional age of 44 weeks, were collected. BPD was defined as supplemental oxygen requirement at 36 weeks post-menstrual age. Tidal breath-by-breath volume capnograms were obtained by mainstream capnography. The capnographic slope of phase II (SII) and slope of phase III (SIII) were calculated and compared between study groups. The effect of BPD, tidal volume (VT), respiratory rate (RR), and prematurity on the magnitude of the slopes was assessed. RESULTS SII was steeper in infants with BPD (100 ± 28/L) compared with healthy preterm (88 ± 22/L; P = .007) and term infants (79 ± 18/L; P < .001), but this finding was attributed to differences in VT, RR, and gestational age. SIII was steeper in the BPD group (26.8 ± 14.1/L) compared with healthy preterm (16.2 ± 6.2/L; P < .001) and term controls (14.8 ± 5.4/L; P < .001). BPD was a significant predictor of SIII independently of VT, RR, and gestational age. The ability of SIII to discriminate between BPD and controls was significantly higher compared with lung clearance index (area under the curve 0.83 vs 0.56; P < .001). CONCLUSIONS Volumetric capnography may provide valuable information regarding functional lung alterations related to BPD and might be considered as an alternative to more involved lung function techniques for monitoring chronic lung disease during early infancy.

An investigation of the pica practices of pregnant women in Houston and Prairie View, Texas

Pregnant African American women are at higher risk of having a preterm delivery and/or a low birthweight infant. Many factors are associated with adverse pregnancy outcomes but a food habit that deserves further study in the causal process is pica, a craving for, and ingestion of, nonnutritive substances such as laundry starch, clay, dirt, or ice. This food habit is more common in the African American population but has not been adequately studied in relation to preterm and/or low birth weight infants.^ Mothers (n = 281) with infants less than one year of age who participated in the Special Supplementary Food Program for Women, Infants, and Children (WIC) at clinics in Houston and Prairie View, Texas were interviewed regarding pica practices during pregnancy, dietary practices, and some demographic indices. Hospital records were abstracted for health information on the mothers and infants, including birthweight and gestational age at birth of the infant.^ The subjects were 88.6% African American, 6.8% Hispanic, and 4.6% Caucasian. Overall prevalence of pica was 76.5%. Pica prevalence by substance(s) was as follows: ice 53.7%; ice and freezer frost 14.6%; other substances such as baking soda, baking powder, cornstarch, laundry starch, and clay or dirt 8.2%; and 23.5% reported no pica. The women who reported ice/freezer frost pica had a higher percentage of illegal drug use and alcohol use during pregnancy. The women who reported other pica substances had the lowest mean educational level, highest gravidity, and a higher percentage smoked during pregnancy.^ There were no significant differences in nutrient intakes measured by the mean 24-hour dietary recalls between women who reported ice pica (n = 103) and women who denied pica (n = 50). The women who reported ice/freezer frost pica or other pica substances had more food cravings and food dislikes during pregnancy than those who reported ice pica or no pica.^ There were no differences in mean birthweight or mean gestational age at birth of infants born to mothers from the three pica groups and the no pica group but regression analyses revealed a possible relationship between pica, low maternal hemoglobin at delivery, and preterm birth. ^

Improving children’s cognitive performance – Effect of a memory strategy training in children born very preterm

Aims: To examine the effect of memory strategy training on different aspects of memory in children born very preterm and to determine whether there is a generalization of the training effect to non-trained functions. The influence of individual factors such as age and performance level on the training success will be determined. Methods: In a randomized, controlled and blinded clinical trial, 46 children born very preterm (aged 7-12 years) were allocated to a memory strategy training (MEMO-Training, n=23) or a control group (n=23). Neuropsychological assessment was performed before, immediately after the training and at a 6-month follow-up. In the MEMO-Training, five different memory strategies were introduced and practiced in a one-to-one setting (4 hour-long training sessions over 4 weeks, 20 homework sessions). Results: A significant training-related improvement occurred in trained aspects of memory (verbal and visual learning and recall, verbal working memory) and in non-trained functions (inhibition, mental arithmetic). No performance increase was observed in the control group. At six months follow-up, there was a significant training-related improvement of visual working memory. Age and performance level before the training predicted the training success significantly. Conclusion: Teaching memory strategies is an effective way to improve different aspects of memory but also non-trained functions such as inhibition and mental arithmetic in children born very preterm. Age and performance level influence the success of memory strategy training. These results highlight the importance of teaching children memory strategies to reduce scholastic problems.

A costing exercise of provision of prevention of HIV transmission from mother to child services in Vietnam

Objectives. This dissertation focuses on estimating the cost of providing a minimum package of prevention of mother-to-child HIV transmission (PMTCT) in Vietnam from a societal perspective and discussing the issues of scaling-up the minimum package nationwide. ^ Methods. Through collection of cost-related data of PMTCT services at 22 PMTCT sites in 5 provinces (Hanoi, Quang Ninh, Thai Nguyen, Hochiminh City, and An Giang) in Vietnam, the research investigates the item cost of each service in minimum PMTCT packages and the actual cost per PMTCT site at different organizational levels including central, provincial, and district. Next, the actual cost per site at each organizational level is standardized by adjusting for HIV prevalence rate to arrive at standardized costs per site. This study then uses the standardized costs per site to project, by different scenarios, the total cost to scale-up the PMTCT program in Vietnam. ^ Results. The cost for HIV tests, infant formula, and salary of health workers are consistently found to be the biggest expenditures in the PMTCT minimum package program across all organizational levels. Annual cost for drugs for prophylaxis treatment, operating and capital, and training costs are not substantial (less than 5% of total costs at all levels). The actual annual estimated cost for a PMTCT site at the central level is nearly VND 1.9 billion or US$ 107,650 (exchange rate US$ 1 = VND 17,500) while the annual cost for a provincial site is VND 375 million or US$ 21,400. The annual cost for a district site is VND 139 million (∼US$ 8,000). ^ The estimated total annual cost to roll out the PMTCT minimum package to the 5 studied provinces is approximately US$ 1.1 million. If the PMTCT program is to be scaled-up to 14 provinces until 2008 and up to 40 provinces through the end of 2010 as planned by the Ministry of Health, it would cost the health system an approximate annual amount of US$ 2.1 million and US$ 5.04 million, respectively. The annual cost for scaling-up the PMTCT minimum package nationwide is around US$ 7.6 million. Meanwhile, the total annual cost to implement PMTCT minimum packages to achieve PMTCT national targets in 2010 (providing counseling service to 90% of all pregnant women; 60% of them will receive HIV tests and 100% of HIV (+) mother and their newborn will receive prophylaxis treatment) would be US$ 6.1 million. ^ Recommendations. This study recommends: (1) the Ministry of Health of Vietnam should adjust its short-term national targets to a more feasible and achievable level given the current level of available resources; (2) a detailed budget for scaling-up the PMTCT program should be developed together with the national PMTCT action plan; (3) the PMTCT scaling-up plan developed by the Ministry of Health should focus on coverage of high prevalence population and quality of services provided rather than number of physical provinces reached; (4) exclusive breastfeeding strategy should be promoted as part of the PMTCT program; and (5) for a smooth and effective rolling out of PMTCT services nationwide, development of a national training plan and execution of this plan must precede any other initiations of the PMTCT scaling-up plan. ^

Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and risk of molecularly defined subtypes of childhood acute leukemia

Low folate intake as well as alterations in folate metabolism as a result of polymorphisms in the enzyme methylenetetrahydrofolate reductase (MTHFR) have been associated with an increased incidence of neural tube defects, vascular disease, and some cancers. Polymorphic variants of MTHFR lead to enhanced thymidine pools and better quality DNA synthesis that could afford some protection from the development of leukemias, particularly those with translocations. We now report associations of MTHFR polymorphisms in three subgroups of pediatric leukemias: infant lymphoblastic or myeloblastic leukemias with MLL rearrangements and childhood lymphoblastic leukemias with either TEL-AML1 fusions or hyperdiploid karyotypes. Pediatric leukemia patients (n = 253 total) and healthy newborn controls (n = 200) were genotyped for MTHFR polymorphisms at nucleotides 677 (C→T) and 1,298 (A→C). A significant association for carriers of C677T was demonstrated for leukemias with MLL translocations (MLL+, n = 37) when compared with controls [adjusted odd ratios (OR) = 0.36 with a 95% confidence interval (CI) of 0.15–0.85; P = 0.017]. This protective effect was not evident for A1298C alleles (OR = 1.14). In contrast, associations for A1298C homozygotes (CC; OR = 0.26 with a 95% CI of 0.07–0.81) and C677T homozygotes (TT; OR = 0.49 with a 95% CI of 0.20–1.17) were observed for hyperdiploid leukemias (n = 138). No significant associations were evident for either polymorphism with TEL-AML1+ leukemias (n = 78). These differences in allelic associations may point to discrete attributes of the two alleles in their ability to alter folate and one-carbon metabolite pools and impact after DNA synthesis and methylation pathways, but should be viewed cautiously pending larger follow-up studies. The data provide evidence that molecularly defined subgroups of pediatric leukemias have different etiologies and also suggest a role of folate in the development of childhood leukemia.

Haploinsufficiency of Sox9 results in defective cartilage primordia and premature skeletal mineralization

In humans, SOX9 heterozygous mutations cause the severe skeletal dysmorphology syndrome campomelic dysplasia. Except for clinical descriptions, little is known about the pathogenesis of this disease. We have generated heterozygous Sox9 mutant mice that phenocopy most of the skeletal abnormalities of this syndrome. The Sox9+/− mice died perinatally with cleft palate, as well as hypoplasia and bending of many skeletal structures derived from cartilage precursors. In embryonic day (E)14.5 heterozygous embryos, bending of radius, ulna, and tibia cartilages was already prominent. In E12.5 heterozygotes, all skeletal elements visualized by using Alcian blue were smaller. In addition, the overall levels of Col2a1 RNA at E10.5 and E12.5 were lower than in wild-type embryos. We propose that the skeletal abnormalities observed at later embryonic stages were caused by delayed or defective precartilaginous condensations. Furthermore, in E18.5 embryos and in newborn heterozygotes, premature mineralization occurred in many bones, including vertebrae and some craniofacial bones. Because Sox9 is not expressed in the mineralized portion of the growth plate, this premature mineralization is very likely the consequence of allele insufficiency existing in cells of the growth plate that express Sox9. Because the hypertrophic zone of the heterozygous Sox9 mutants was larger than that of wild-type mice, we propose that Sox9 also has a role in regulating the transition to hypertrophic chondrocytes in the growth plate. Despite the severe hypoplasia of cartilages, the overall organization and cellular composition of the growth plate were otherwise normal. Our results suggest the hypothesis that two critical steps of the chondrocyte differentiation pathway are sensitive to Sox9 dosage. First, an early step presumably at the stage of mesenchymal condensation of cartilage primordia, and second, a later step preceding the transition of chondrocytes into hypertrophic chondrocytes.