Os histricomorfos sul-americanos: uma análise comparativa do desenvolvimento embriológico

O objetivo do estudo foi realizar uma análise embriológica dos roedores histricomorfos (paca, cutia, preá e capivara), a fim de comparar com a de outros roedores e com a morfogênese humana um padrão embriológico. Utilizaram-se 8 espécimes de roedores sendo, 2 embriões para cada espécie coletada, ambas em inicio de gestação. Estes foram retirados dos úteros gestantes através de ovariosalpingohisterectomia parcial, seguido de fixação em solução de paraformaldeído 4%. Para as mensurações de Crow-Rump, adotou-se como referência a crista nucal numa extremidade e da última vértebra sacral na extremidade oposta. De forma geral, os embriões analisados mostraram as seguintes características morfológicas: divisão dos arcos branquiais, o não fechamento do neuróporo cranial em alguns embriões estudados, a curvatura cranial acentuada e os somitos delimitados e individualizados. O broto dos membros apresentava-se em desenvolvimento em formato de remo, além da impressão cardíaca e fígado. Na região caudal, visualizou-se a curvatura crânio-caudal, a vesícula óptica com e sem pigmentação da retina, a abertura do tubo neural na região do quarto ventrículo encefálico, a fosseta nasal e a formação das vesículas encefálicas. Concluímos que desenvolvimento embriológico dos roedores histricomorfos pode ser comparado à morfogênese de ratos, cobaios, coelhos e humanos nos diferentes estágios de desenvolvimento, tomando apenas o cuidado com as particularidades de cada espécie, além da implementação de tecnologias reprodutivas, especialmente a de embriões, a qual requer o conhecimento do desenvolvimento pré-implantação referente às fases de desenvolvimento.

Validação de um radioimunoensaio para a quantificação de metabólitos fecais de testosterona em hamster Sírio (Mesocricetus auratus)

Modelo para o estudo de diversas doenças humanas, o hamster tem sido objeto de numerosos estudos comportamentais e envolvendo estresse e/ou comportamento agonístico que supõem, muitas vezes, o monitoramento das flutuações hormonais nos indivíduos envolvidos. O objetivo do presente trabalho foi confirmar a adequação de um conjunto comercial para dosagem de testosterona em sangue humano para a quantificação de metabólitos fecais de testosterona (MFT) em hamsters Sírios machos e fêmeas. Dez machos foram submetidos a um desafio com um agonista de GnRH para estimular a atividade testicular, elevando os níveis circulantes de testosterona. Cinco fêmeas receberam uma injeção de testosterona enquanto cinco outras receberam uma injeção de solução salina. Amostras de fezes coletadas antes e depois dos procedimentos, assim como amostras fecais de 20 fêmeas gestantes coletadas ao longo da gestação foram analisadas com um conjunto comercial para radioimunoensaio. Um pico de MFT 12h após a injeção seguido de uma queda abaixo do nível basal comprovou que, nos machos, as alterações nos níveis de MFT refletem as alterações da concentração de testosterona no sangue. Nestes observou-se um ciclo circadiano das concentrações de MFT com acrofase no início do período claro correspondendo ao ciclo descrito para as concentrações sanguíneas na literatura. Nas fêmeas a administração de testosterona exógena provocou uma elevação importante dos níveis de MFT, mas as concentrações medidas ao longo da gestação não refletiram o padrão dos níveis sanguíneos do hormônio endógeno. O conjunto para radioimunoensaio para testosterona em sangue humano mostrou-se adequado para o monitoramento da função testicular no hamster macho, mas um ensaio mais específico seria necessário para as fêmeas.

Vidas arriscadas: uma reflexão sobre a relação entre o número de gestações e mortalidade materna

Este estudo teve por objetivo identificar o risco e os fatores associados à mortalidade materna de multigestas (cinco ou mais gestações). Descreve a tendência da Taxa de Fecundidade Total (TFT) e da Razão de Mortalidade Materna (RMM) de 1998 a 2004 no Paraná. Apresenta uma análise dos 822 óbitos maternos deste período, o cálculo da Razão de Mortalidade Materna Específica, o Risco Relativo, a freqüência e o Odds Ratio para algumas variáveis segundo número de gestações. Analisa também as causas e a evitabilidade dos óbitos maternos. Os resultados apontaram TFT baixa (1,8 filhos por mulher) e a RMM elevada (69,7/100.000 nascidos vivos) no Paraná em 2004. Um quarto dos 822 óbitos maternos (206) era de multigestas (cinco ou mais gestações), o risco relativo de morte materna foi seis vezes superior do que para as mulheres com até duas gestações, e os perfis sociodemográfico e o reprodutivo foram mais desfavoráveis para aquele grupo de mulheres. A baixa escolaridade, a idade igual ou acima de 30 anos e o pré-natal com menos de quatro consultas apresentaram associação com o maior número de gestações. A proporção de mortes por causas obstétricas indiretas, hemorragias e aborto, foi maior entre as multigestas, e cerca de 90% dos óbitos deste grupo foi considerado evitável. Concluiu-se que o monitoramento das multigestas com idade avançada e em desvantagem social, bem como ações efetivas de planejamento familiar, e serviços obstétricos qualificados para gestação de alto risco são medidas que podem contribuir para a redução da mortalidade materna

Two successful pregnancies in a woman with chronic myeloid leukemia exposed to nilotinib during the first trimester of her second pregnancy: case study

The occurrence of chronic myeloid leukemia in pregnancy is rare and its management poses a clinical challenge for physicians treating these patients. We report a 30-year-old woman with chronic myeloid leukemia who became pregnant twice successfully. Philadelphia-positive CML in its chronic phase was diagnosed at 16 weeks of her first gestation. At that time, she received no treatment throughout her pregnancy. At 38 weeks of gestation, a normal infant was delivered by cesarean section. At six weeks postpartum, the patient underwent imatinib mesylate therapy but she could not tolerate the treatment. The treatment was then changed to nilotinib at 400 mg orally b.i.d. Two years later, she became pregnant again while she was on nilotinib 200 mg b.i.d. The unplanned pregnancy was identified during her 7.4 weeks of gestation. Because the patient elected to continue her pregnancy, nilotinib was stopped immediately, and no further treatment was given until delivery. Neither obstetrical complications nor structural malformations in neonates in both pregnancies were observed. Both babies' growth and development have been normal. Although this experience is limited to a single patient, the success of this patient demonstrates that the management of chronic myeloid leukemia in pregnant women may be individualized based on the relative risks and benefits of the patient and fetus.

Hemangiossarcoma primário intrauterino em um macaco aranha de cara vermelha (Ateles paniscus)

Hemangiosarcoma is a common neoplasm in dogs and less frequently seen in cats. In nonhuman primates, this tumor is rarely reported. A 17 year-old female spider monkey (Ateles paniscus) was submitted an ultrasound exam due to gestation suspicion, which was seen a circular mass intra-uterine measuring 1.3 cm. New exams shown increase of the mass to 4.4 x 3.0 cm associated with a viable fetus. Was realized cesarean with ovariohysterectomy and excision of the mass; however the animal died in less than 24 hours after the surgery. In the necropsy, severe hemoabdomen was evidenced, although the surgical stumps were properly ligated and the complete sutures. Macroscopically, the uterine mass was soft, dark heterogeneous and measuring 5.0 cm in diameter. Histologically was visualized proliferation of spindle cells that form vascular channels replete of erythrocytes and some with thrombus, marked pleomorphism, nucleolus evident, binucleated cells and mitotic figures were rare. The immunohistochemistry (IHC) was performed, using streptavidin-biotin peroxidase technique (Dako Cytomation, USA) with the use of antibodies CD31 (clone JC/70A), CD34 (clone QB-END/10). The IHC showed a specific antigen-antibody reaction for CD31. According to localization, morphology and IHC, the present study reports a primary uterine hemangiosarcoma in a spider monkey that caused hemostatic abnormalities and consequent death of the animal.

In utero protein restriction causes growth delay and alters sperm parameters in adult male rats

Background: Recent studies have supported the concept of ""fetal programming"" which suggests that during the intrauterine development the fetus may be programmed to develop diseases in adulthood. The possible effects of in utero protein restriction on sexual development of rat male offspring were evaluated in the present study. Methods: Pregnant Wistar rats were divided into two experimental groups: one group treated with standard chow (SC, n = 8, 17% protein) and the other group treated with hypoproteic chow (HC, n = 10, 6% protein) throughout gestation. After gestation the two experimental groups received standard chow. To evaluate the possible late reproductive effects of in utero protein restriction, the male offspring of both groups were assessed at different phases of sexual development: prepubertal (30 days old); peripubertal (60 days old); adult (90 days old). Student's t test and Mann-Whitney test were utilized. Differences were considered significant when p < 0.05. Results: We found that in utero protein restriction reduced the body weight of male pups on the first postnatal day and during the different sexual development phases (prepubertal, peripubertal and adult). During adulthood, Sertoli cell number, sperm motility and sperm counts in the testis and epididymal cauda were also reduced in HC. Furthermore, the numbers of sperm presenting morphological abnormalities and cytoplasmic drop retention were higher in HC. Conclusions: In conclusion, in utero protein restriction, under these experimental conditions, causes growth delay and alters male reproductive-system programming in rats, suggesting impairment of sperm quality in adulthood.

Gene silencing during development of in vitro-produced female bovine embryos

In early development, female embryos (XX) produce twice the transcripts of X-linked genes compared with male embryos (XY). During the course of development, inactivation of the X chromosome equilibrates gene dosage, making the development of female embryos viable. Moreover, the biotechnologies used for producing embryos in vitro seem to work better with male embryos, making it easier for them to reach the blastocyst stage and allow for complete gestation. We investigated the expression of three X-linked genes that are involved in development, XIST, G6PD, and HPRT, and of the transcript interferon-tau, in male and female bovine blastocysts produced by nuclear transfer (NT) and by in vitro fertilization (IVF). Oocytes that had been matured in vitro were enucleated and reconstructed with somatic cells from adult animals at 18 h post-maturation. After fusion (two pulses of 2.25 kv/cm) and chemical activation (5.0 mu M ionomycin for 5 min and 2.0 mM 6-DMAP for 3 h), the oocytesomatic cell units were cultivated in CR2 with a monolayer of granulosa cells at 38.8 degrees C, in a humidified 5% CO(2) atmosphere. IVF embryos were inseminated, after centrifugation in a Percoll gradient, with 2 x 10(6) sperm/mL TALP medium supplemented with BSA and PHE and cultivated under the same conditions as the cloned embryos. We used real-time PCR to analyze the gene expression of individual blastocysts compared to expression of the housekeeping gene, GAPDH. The gene XIST was expressed in female embryos and not in male embryos produced by IVF, though it was expressed at low levels in male embryos produced by NT. Unlike previous reports, we found lower levels of the transcript of G6PD in females than in males, suggesting double silencing or other mechanisms of control of this gene. Female embryos produced by IVF expressed the HPRT gene at a higher level than female embryos produced by NT, suggesting that gene silencing proceeds faster in NT-produced female embryos due to ""inactivation memory"" from the nucleus donor. In conclusion, male and female embryos express different levels of X-chromosome genes and failures of these genes that are essential for development could reduce the viability of females. Nuclear transfer can modify this relation, possibly due to epigenetic memory, leading to frequent failures in nuclear reprogramming.

Spatiotemporal patterns of macrophage migration inhibitory factor (Mif) expression in the mouse placenta

Background: Macrophage migration inhibitory factor (MIF) has special pro-inflammatory roles, affecting the functions of macrophages and lymphocytes and counter-regulating the effects of glucocorticoids on the immune response. The conspicuous expression of MIF during human implantation and early embryonic development also suggests this factor acts in reproductive functions. The overall goal of this study was to evaluate Mif expression by trophoblast and embryo placental cells during mouse pregnancy. Methods: Mif was immunolocalized at implantation sites on gestation days (gd) 7.5, 10.5, 13.5 and 17.5. Ectoplacental cones and fetal placentas dissected from the maternal tissues were used for Western blotting and qRT-PCR assays on the same gestation days. Results: During the post-implantation period (gd7.5), trophoblast giant cells showed strong Mif reactivity. In later placentation phases (gds 10.5-17.5), Mif appeared to be concentrated in the junctional zone and trophoblast giant cells. Mif protein expression increased significantly from gd7.5 to 10.5 (p = 0.005) and from gd7.5 to 13.5 (p = 0.03), remaining at high concentration as gestation proceeded. Higher mRNA expression was found on gd10.5 and was significantly different from gd13.5 (p = 0.048) and 17.5 (p = 0.009). Conclusions: The up-regulation of Mif on gd10.5 coincides with the stage in which the placenta assumes its three-layered organization (giant cells, spongiotrophoblast and labyrinth zones), fetal blood circulation begins and population of uNK cells reaches high proportions at the maternal counter part of the placenta, suggesting that Mif may play a role in either the placentation or in the adaptation of the differentiated placenta to the uterus or still in gestational immunomodulatory responses. Moreover, it reinforces the possibility of specific activities for Mif at the maternal fetal interface.

Cow/calf preweaning efficiency of Nellore and Bos taurus x Bos indicus crosses

The objectives of this study were to determine if percentage Bos taurus (0 or 50%) of the cow had an effect on ME requirements and milk production, and to compare cow/calf efficiency among 3 mating systems. Metabolizable energy requirements were estimated during a feeding trial that encompassed a gestation and lactation feeding trial for each of 2 groups of cows. Cows were 0 or 50% Bos taurus ( 100 or 50% Nellore) breed type: Nellore cows (NL; n = 10) mated to Nellore bulls, NL cows ( n = 9) mated to Angus bulls, Angus x Nellore (ANL; n = 10) and Simmental x Nellore (SNL; n = 10) cows mated to Canchim (5/ 8 Charolais 3/ 8 Zebu) bulls. Cows were individually fed a total mixed diet that contained 11.3% CP and 2.23 Mcal of ME/kg of DM. At 14-d intervals, cows and calves were weighed and the amount of DM was adjusted to keep shrunk BW and BCS of cows constant. Beginning at 38 d of age, corn silage was available to calves ad libitum. Milk production at 42, 98, 126, and 180 d postpartum was measured using the weigh-suckle-weigh technique. At 190 d of age, calves were slaughtered and body composition estimated using 9-10-11th-rib section to obtain energy deposition. Regression of BW change on daily ME intake (MEI) was used to estimate MEI at zero BW change. Increase in percentage Bos taurus had a significant effect on daily ME requirements (Mcal/d) during pregnancy (P < 0.01) and lactation (P < 0.01). Percentage Bos taurus had a positive linear effect on maintenance requirements of pregnant (P = 0.07) and lactating (P < 0.01) cows; during pregnancy, the ME requirements were 91 and 86% of those in lactation (131 +/- 3.5 vs. 145 +/- 3.4 Mcal.kg(-0.75).d(-1)) for the 0 and 50% B. taurus groups, respectively. The 50% B. taurus cows, ANL and SNL, suckling crossbred calves had greater total MEI (4,319 +/- 61 Mcal; P < 0.01) than 0% B. taurus cows suckling NL (3,484 +/- 86 Mcal) or ANL calves (3,600 +/- 91 Mcal). The 0% B. taurus cows suckling ANL calves were more efficient (45.3 +/- 1.6 g/Mcal; P = 0.03) than straightbred NL (35.1 +/- 1.5 g/Mcal) and ANL or SNL pairs (41.0 +/- 1.0 g/Mcal). Under the conditions of this study, crossbreeding improved cow/ calf efficiency and showed an advantage for cows that have lower energy requirements.

Winter-feeding systems for gestating sheep II. Effects on feedlot performance, glucose tolerance, and carcass composition of lamb progeny

Mature pregnant crossbred ewes (n = 90) were used in a randomized complete block design experiment and were assigned to 1 of 3 winter-feeding systems differing in primary feed source: haylage (HL), limit-fed corn (CN), or limit-fed dried distillers grains (DDGS). Effects of these winter-feeding strategies on postweaning progeny performance were determined. Lamb progeny (n = 96) were weaned at 61 +/- 4 d of age and fed a common high-concentrate diet. Lambs were assigned to feedlot pen (n = 18) based on dam mid-gestation pen. Growth rate, DMI, and ADG were determined for the first 40 d of the finishing period. At 96 +/- 4 d of age, 1 wether lamb was randomly selected from each pen (n = 18) for a glucose tolerance test. The experiment was terminated, and lambs were slaughtered individually when they were determined to have achieved 0.6-cm 12th-rib fat thickness. After a 24-h chill, carcass data were collected and a 2.54-cm chop was removed from each lamb from the LM posterior to the 12th rib for ether extract analysis. Additional carcass measurements of bone, muscle, and fat from the shoulder, rack, loin, and leg were collected on 35 carcasses. At weaning, lamb BW was not different among treatments, whereas final BW tended to be greater (P = 0.09) for lambs from ewes fed DDGS and CN during gestation than from those fed HL. Overall lamb growth rate from birth to slaughter was not different among treatments. Lambs from ewes fed DDGS vs. CN or HL tended to have a greater initial insulin response (P = 0.09). Dressing percent was less (P = 0.04) in lambs from ewes fed DDGS, but no difference (P = 0.16) was detected in HCW among treatments. As expected, 12th rib fat thickness was similar among treatments, whereas LM area was largest to smallest (P = 0.05) in lambs from ewes fed CN, HL, and DDGS, respectively. Proportion of internal fat tended to be greatest to smallest (P = 0.06) in lambs from ewes fed DDGS, CN, and HL, respectively. Calculated boneless trimmed retail cuts percentage was less (P = 0.04) in lambs from ewes fed DDGS than CN or HL. Loin muscle weight as a percentage of wholesale cut tended (P = 0.10) to be greater in lambs from ewes fed CN and HL than DDGS, whereas other muscle, bone, and fat weights and proportions were similar (P > 0.24) among treatments. Prepartum diet during mid to late gestation of ewes altered postnatal fat and muscle deposition and may be associated with alterations in insulin sensitivity of progeny.

Fluoride increases lead concentrations in whole blood and in calcified tissues from lead-exposed rats

Higher blood lead (BPb) levels have been reported in children living in communities that receive fluoride-treated water. Here, we examined whether fluoride co-administered with lead increases BPb and lead concentrations in calcified tissues in Wistar rats exposed to this metal from the beginning of gestation. We exposed female rats and their offspring to control water (Control Group), 100 mg/L of fluoride (F Group), 30 mg/L of lead (Pb Group), or 100 mg/L of fluoride and 30 mg/L of lead (F+ Pb Group) from 1 week prior to mating until offspring was 81 days old. Blood and calcified tissues (enamel, dentine, and bone) were harvested at day 81 for lead and fluoride analyses. Higher BPb concentrations were found in the F+ Pb Group compared with the Pb Group (76.7 +/- 11.0 mu g/dL vs. 22.6 +/- 8.5 mu g/dL, respectively: p <0.001). Two-to threefold higher lead concentrations were found in the calcified tissues in the F+ Pb Group compared with the Pb Group (all p <0.001). Fluoride concentrations were similar in the F and in the F+ Pb Groups. These findings show that fluoride consistently increases BPb and calcified tissues Pb concentrations in animals exposed to low levels of lead and suggest that a biological effect not yet recognized may underlie the epidemiological association between increased BPb lead levels in children living in water-fluoridated communities. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Effect of zinc supplementation in pregnant mice during experimental Trypanosoma cruzi infection

Zinc is an essential micronutrient and has significant effects on human growth, development, and immune function. Zinc supplementation or deficiency may affect the course of infection. Zinc enhances immune response against a wide range of viral, bacterial, and parasitic pathogens. In the present study, we investigated the effects of zinc sulphate (ZnSO(4)) supplementation (20 mg/kg/day) during pregnancy in mice, Swiss Webster strain infected by the Y strain of Trypanosoma cruzi. Oral supplementation of zinc sulphate in pregnant and non-pregnant infected animals did not affect the count of blood parasites as well as tissue parasitism in the heart, liver, and spleen. Zinc supplementation did not alter female body weight, the length of fetuses and neonates, placental size/weight and mortality rate. Among zinc supplied animals, no significant plasmatic zinc concentrations were observed. Concerning to tissue zinc concentrations, only the liver displayed enhanced values as compared to other organs. For placental parasitism, zinc supplied group displayed a significant decrease in amastigote burdens (P < 0.05). However due to the reduced number of parasite burdens in placenta of animals supplied with zinc, these data suggest that zinc was partially effective in up-regulating the host`s immune response against parasite, probably attenuating the infection in fetuses. (C) 2010 Elsevier Ltd. All rights reserved.

Metformin pharmacokinetics in nondiabetic pregnant women with polycystic ovary syndrome

The use of metformin throughout gestation by pregnant women with polycystic ovary syndrome (PCOS) significantly reduces the number of first trimester spontaneous abortions and the rate of occurrence of gestational diabetes. The objective of this study was to investigate the pharmacokinetics and the placental transfer of metformin in pregnant women with PCOS. Eight pregnant women with PCOS taking 850 mg metformin every 12 h during the third trimester of pregnancy were evaluated. Maternal blood samples were collected at steady state during the dose interval (0-12 h). Maternal and umbilical cord blood samples were also obtained at delivery. Metformin plasma concentrations were analyzed by high-performance liquid chromatography, and pharmacokinetic parameters were determined using a non-compartmental model. Data are reported as median and minimum and maximum values. Metformin pharmacokinetic parameters were: t(A1/2), 3.8 (2.8-5.4) h; t(max), 2.0 (0.5-3.0) h; C(max), 1.4 (0.5-2.1) mg/L; C(mean), 0.5 (0.2-0.9) mg/L; AUC(0-12), 6.4 (1.1-9.2) mg h/L; Cl/f, 105 (60-274) L/h; Vd/f, 551 (385-1173) L; median fluctuation, 89 (79-95)%. Umbilical/maternal metformin plasma concentration ratios were 0.7 (0.4-1.3). Metformin oral clearance (Cl/f) had increased in our patients relative to nonpregnant healthy volunteers or diabetic patients. Therefore, lower plasma metformin concentrations were observed for nondiabetic pregnant women with PCOS. Future studies should be conducted to demonstrate the therapeutic efficacy of metformin during pregnancy. Caution is warranted as umbilical/maternal metformin plasma concentrations ratios of around 0.7 require metformin dosage adjustment.

The relationship between multiple birth children's early phonological skills and later literacy

Previous studies have shown that multiple ; birth children (MBC) are prone to early phonological ;difficulties and later literacy problems. However, to date, ;there has been no systematic long-term follow-up of MBC with phonological difficulties in the preschool years to determine whether these difficulties predict later literacy problems. In this study, 20 MBC whose early speech and language skills had been previously documented were compared to normative data and 20 singleton controls on tasks assessing phonological ; processing and literacy. The major findings indicated that MBC performed significantly more poorly on some tasks :df phonological processing than singleton controls did. Further, the early phonological skills of MBC (i.e., the number of inappropriate phonological processes used) correlated with poor performance on visual rhyme recognition, word repetition, and phoneme detection tasks 5 years later. There was no significant relationship between early biological factors (birth weight and gestation period) and performance on the phonological processing and literacy-related subtests. These results cl-support the hypothesis that MBC's early speech and language difficulties are not merely a transient phase;of; development, but a real disorder, with consequences for later academic achievement.

Administration of growth hormone or IGF-I to pregnant rats on a reduced diet throughout pregnancy does not prevent fetal intrauterine growth retardation and elevated blood pressure in adult offspring

Increasing evidence from human epidemiological studies suggests that poor growth before birth is associated with postnatal growth retardation and the development of cardiovascular disease in adulthood. We have shown previously that nutritional deprivation in the pregnant rat leads to intrauterine growth retardation (IUGR), postnatal growth failure, changes in the endocrine parameters of the somatotrophic axis, and to increased blood pressure in later life. In the present study, we investigated whether administration of insulin-like growth factor-I (IGF-I) or bovine growth hormone (GH) during pregnancy could prevent IUGR and/or alter long-term outcome. Dams h-om day 1 of pregnancy throughout gestation received a diet of nd libitum available food or a restricted dietary intake of 30% of ad libitum fed dams. From day 10 of gestation, dams were treated for 10 days with three times daily subcutaneous injections of saline (100 mu l), IGF-I (2 mu g/g body weight) or GH (2 mu g/g body weight). Maternal weight gain was significantly increased (P