Adriamycin-induced Fetal Hydronephrosis

Introduction: At the end of pregnancy, the amniotic fluid (AF) depends basically on renal function, corresponding to fetal urine. Changes in AF, especially oligohydramnios, are reported in association with fetal hydronephrosis (FH). The experimental model using adriamycin in pregnant female rats has a teratogenic effect and has been classically employed to study esophageal atresia. Nevertheless, adriamycin promotes FH with high frequency as well. In the present study, using this animal model, we tried to identify the incidence and microscopic changes of FH, as well as its correlation with AF weight. Materials and Methods: Eight Spreague-Dawley pregnant female rats received adriamycin 2.2 mg/kg on the 8th and 9th gestational days (considering term gestation = 22 days). Those fetuses that received adriamycin (Adriamycin Group) were compared with fetuses from 2 female rats (Control Group), which received 0.9% saline solution. On the 21.5 gestational day, the fetuses were collected by cesarean incision, sacrificed, and examined for macro and microscopic changes in kidneys and ureters. Fetuses with bilateral hydronephrosis formed the Hydronephrosis Group. AF weight was determined as well. Results: Hydronephrosis occurred in 70 (95%) of the 74 fetuses in the adriamycin group against none of the 21 fetuses from the control group. The amniotic fluid weight was increased in the adriamycin group in relation to the control group (p < 0.001). The histomorphometric study revealed dilation of the renal pelvis and reduction of renal parenchyma in the hydronephrosis group in relation to the control group. Severe cortical atrophy, cortical tubular atrophy and medullar atrophy were observed in the hydronephrosis group. Conclusions: Slight renal lesions were in agreement with changes in AF weight, since they suggest that there was production of urine with the maintenance of AF.306508513Brace, R.A., Physiology of amniotic fluid volume regulation (1997) Clin. Obstet. Gynecol., 40, pp. 280-289Harrison, M.R., Nakayama, D.K., Noall, R., de Lorimier, A.A., Correction of congenital hydronephrosis in utero II. Decompression reverses the effects of obstruction on the fetal lung and urinary tract (1982) J. Pediatr. Surg., 17, pp. 965-974Chevalier, R.L., Thornhill, B.A., Chang, A.Y., Unilateral ureteral obstruction in neonatal rats leads to renal insufficiency in adulthood (2000) Kidney Int., 58, pp. 1987-1995Seseke, F., Thelen, P., Hemmerlein, B., Kliese, D., Zoller, G., Ringert, R.H., Histologic and molecular evidence of obstructive uropathy in rats with hereditary congenital hydronephrosis (2000) Urol. Res., 28, pp. 104-109Freedman, A.L., Bukowski, T.P., Smith, C.A., Evans, M.I., Johnson, M.P., Gonzalez, R., Fetal therapy for obstructive uropathy: Diagnosis specific outcomes (1996) J. Urol., 156 (2 PART 2), pp. 720-723. , [corrected]. discussion 723-4Erratum in: J Urol. 1996156: 1786Bernstein, J., Risdon, R.A., Gilbert-Barness, E., Renal System (1997) Potter's, Pathology of the Fetus and Infant, pp. 863-903. , Gilbert-Barness E (ed.), St Louis, MosbyBastide, A., Manning, F., Harman, C., Lange, I., Morrison, I., Ultrasound evaluation of amniotic fluid: Outcome of pregnancies with severe oligohydramnios (1986) Am. J. Obstet. Gynecol., 154, pp. 895-900Reddy, P.P., Mandell, J., Prenatal diagnosis. Therapeutic implications (1998) Urol. Clin. North Amer., 25, pp. 171-180Beasley, S.W., Diez Pardo, J., Qi, B.Q., Tovar, J.A., Xia, H.M., The contribution of the adriamycin-induced rat model of the VATER association to our understanding of congenital abnormalities and their embryogenesis (2000) Pediatr. Surg. Int., 16, pp. 465-472Merei, J., Hasthorpe, S., Farmer, P., Hutson, J.M., Visceral anomalies in prenatally adriamycin-exposed rat fetuses: A model for the VATER association (1999) Pediatr. Surg. Int., 15, pp. 11-16Merei, J., Batiha, A., Hani, I.B., El-Qudah, M., Renal anomalies in the VATER animal model (2001) J. Pediatr. Surg., 36, pp. 1693-1697Franca, W.M., Goncalves, A., Moraes, S.G., Pereira, L.A., Sbragia, L., Esophageal atresia and other visceral anomalies in a modified Adriamycin rat model and their correlations with amniotic fluid volume variations (2004) Pediatr. Surg. Int., 20, pp. 602-608Steinhardt, G.F., Liapis, H., Phillips, B., Vogler, G., Nag, M., Yoon, K.W., Insulin-like growth factor improves renal architecture of fetal kidneys with complete ureteral obstruction (1995) J. Urol., 154, pp. 690-693Steinhardt, G.F., Salinas-Madrigal, L., deMello, D., Farber, R., Phillips, B., Vogler, G., Experimental ureteral obstruction in the fetal Opossum: Histologic assessment (1994) J. Urol., 152, pp. 2133-2138Tewey, K.M., Rowe, T.C., Yang, L., Halligan, B.D., Liu, L.F., Adriamycin-induced DNA damage mediated by mammalian DNA topoisomerase II (1984) Science, 226 (4673), pp. 466-468Orford, J.E., Cass, D.T., Dose response relationship between adriamycin and birth defects in a rat model of VATER association (1999) J. Pediatr. Surg., 34, pp. 392-398Beasley, S.W., Diez Pardo, J., Qi, B.Q., Tovar, J.A., Xia, H.M., The contribution of the adriamycin-induced rat model of the VATER association to our understanding of congenital abnormalities and their embryogenesis (2000) Pediatr. Surg. Int., 16, pp. 465-472Kimble, R.M., Harding, J.E., Kolbe, A., Does gut atresia cause polyhydramnios? (1998) Pediatr. Surg. Int., 13, pp. 115-117Liu, M.I., Hutson, J.M., Cloacal and urogenital malformations in adriamycin-exposed rat fetuses (2000) BJU Int., 86, pp. 107-112Liu, M.I., Hutson, J.M., Zhou, B., Critical timing of bladder embryogenesis in an adriamycin-exposed rat fetal model: A clue to the origin of the bladder (1999) J. Pediatr. Surg., 34, pp. 1647-165

Erica Jong : 04-04-1974

In an interview recorded April 4, 1974, Erica Jong reads two poems, Becoming a Nun and Man on the Moon ; discusses her training as a writer, and women\u27s sexual repression and struggle for equal rights; and reads from her novel Fear of Flying.https://digitalcommons.brockport.edu/writers_videos/1047/thumbnail.jp

Corticosteroid effect upon intestinal and hepatic interleukin profile in a gastroschisis rat model

PURPOSE: To evaluate the effect of corticosteroids on intestinal and liver interleukin profile in an experimental model of gastroschisis in fetal rats. METHODS: Sprague-Dawley rats at 19.5 days of gestation had its fetuses operated for the creation of gastroschisis. Two groups of fetuses were studied with and without maternal administration of dexamethasone. Each group was composed of fetuses who underwent gastroschisis (G), control fetuses without manipulation (C) and sham fetuses (S). A dosage of the following interleukins was carried out in fetal intestinal and liver tissues: IL-1, IL-6, IL-10, tumor necrosis factor-alpha (TNF-&#945;) and interferon-gamma (IFN-&#947;). The differences between the groups and subgroups were tested by ANOVA with Tukey post-test, with significant values of p<0.05. RESULTS: Dexamethasone led to an increase in intestinal and liver IL-6 (p<0.05) and a decrease in intestinal TNF-&#945; (p<0.001) in fetuses with gastroschisis. CONCLUSION: Corticosteroids had an effect on the intestinal interleukin profile and a small effect on the liver interleukin profile due to immunological immaturity of the fetus, and also of fetuses with gastroschisis. The steroid action may not be exclusively anti-inflammatory, but also pro-inflammatory, varying with time of pregnancy

Cell necrosis, intrinsic apoptosis and senescence contribute to the progression of exencephaly to anencephaly in a mice model of congenital chranioschisis

Exencephaly/anencephaly is one of the leading causes of neonatal mortality and the most extreme open neural tube defect with no current treatments and limited mechanistic understanding. We hypothesized that exencephaly leads to a local neurodegenerative process in the brain exposed to the amniotic fluid as well as diffuse degeneration in other encephalic areas and the spinal cord. To evaluate the consequences of in utero neural tissue exposure, brain and spinal cord samples from E17 exencephalic murine fetuses (maternal intraperitoneal administration of valproic acid at E8) were analyzed and compared to controls and saline-injected shams (n = 11/group). Expression of apoptosis and senescence genes (p53, p21, p16, Rbl2, Casp3, Casp9) was determined by qRT-PCR and protein expression analyzed by western blot. Apoptosis was measured by TUNEL assay and PI/AV flow cytometry. Valproic acid at E8 induced exencephaly in 22% of fetuses. At E17 the fetuses exhibited the characteristic absence of cranial bones. The brain structures from exencephalic fetuses demonstrated a loss of layers in cortical regions and a complete loss of structural organization in the olfactory bulb, hippocampus, dental gyrus and septal cortex. E17 fetuses had reduced expression of NeuN, GFAP and Oligodendrocytes in the brain with primed microglia. Intrinsic apoptotic activation (p53, Caspase9 and 3) was upregulated and active Caspase3 localized to the layer of brain exposed to the amniotic fluid. Senescence via p21-Rbl2 was increased in the brain and in the spinal cord at the lamina I-II of the somatosensory dorsal horn. The current study characterizes CNS alterations in murine exencephaly and demonstrates that degeneration due to intrinsic apoptosis and senescence occurs in the directly exposed brain but also remotely in the spinal cord

BABIES WITH BRAIN DAMAGE WHO CAN NOT SWALLOW Surgical management

Background: Neonates with severe neurological impairment are often unable to swallow, necessitating gastrostomy for feeding. Because of the risk of developing severe reflux, this procedure is often associated with fundoplication. Objective: To assess the safety and efficacy of gastrostomy and Nissen fundoplication in 22 neonates with swallowing difficulties due to serious neurological impairment. Method: All children underwent an initial period of nasogastric feeding and after informed consent underwent gastrostomy and Nissen fundoplication. Results: There were no significant intraoperative complications. There were two cases of postoperative periostomy leakage. Of the 22 neonates 16 were alive four months after surgery. Six neonates died of complications due to underlying disease. Conclusion: We concluded that gastrostomy and Nissen fundoplication are safe procedures and help parents give a better care to these children.663B64164

The role of gut-liver axis in the restriction of intrauterine growth in a model of experimental gastroschisis

PURPOSE: To evaluate the intrauterine growth restriction (IUGR) by the expression of IR-&#946;, IRS-1, IRS-2, IGF-IR&#946; and Ikappa&#946; in experimental model of gastroschisis. METHODS: Pregnant rats at 18.5 days of gestation were submitted to surgery to create experimental fetal gastroschisis (term = 22 days) were divided in three groups: gastroschisis (G), control (C) and sham (S). Fetuses were evaluated for body weight (BW), intestinal (IW), liver (LW) and their relations IW/BW and LW/BW. IR-&#946; and IGF-IR&#946; receptors, IRS-1 and IRS-2 substrates and Ikappa&#946; protein were analyzed by western blotting. RESULTS: BW was lower in G, the IW and IW / BW were greater than C and S (p<0.05) groups. The liver showed no differences between groups. In fetuses with gastroschisis, compared with control fetuses, the expression of IGF-IR&#946; (p<0.001) and Ikappa&#946; (p<0.001) increased in the liver and intestine, as well as IR-&#946; (p<0.001) which decreased in both. In contrast to the intestine, IRS-1 (p<0.001) increased in the liver and IRS-2 decreased (p<0.01). CONCLUSION: The axis of the intestine liver has an important role in inflammation, with consequent changes in the metabolic pathway of glucose can contribute to the IUGR in fetuses with gastroschisis

Fetal lung underdevelopment is rescued by administration of amniotic fluid stem cell extracellular vesicles in rodents

Fetal lung underdevelopment, also known as pulmonary hypoplasia, is characterized by decreased lung growth and maturation. The most common birth defect found in babies with pulmonary hypoplasia is congenital diaphragmatic hernia (CDH). Despite research and clinical advances, babies with CDH still have high morbidity and mortality rates, which are directly related to the severity of lung underdevelopment. To date, there is no effective treatment that promotes fetal lung growth and maturation. Here, we describe a stem cell–based approach in rodents that enhances fetal lung development via the administration of extracellular vesicles (EVs) derived from amniotic fluid stem cells (AFSCs). Using fetal rodent models of pulmonary hypoplasia (primary epithelial cells, organoids, explants, and in vivo), we demonstrated that AFSC-EV administration promoted branching morphogenesis and alveolarization, rescued tissue homeostasis, and stimulated epithelial cell and fibroblast differentiation. We confirmed this regenerative ability in in vitro models of lung injury using human material, where human AFSC-EVs obtained following good manufacturing practices restored pulmonary epithelial homeostasis. Investigating EV mechanism of action, we found that AFSC-EV beneficial effects were exerted via the release of RNA cargo. MicroRNAs regulating the expression of genes involved in lung development, such as the miR17–92 cluster and its paralogs, were highly enriched in AFSC-EVs and were increased in AFSC-EV–treated primary lung epithelial cells compared to untreated cells. Our findings suggest that AFSC-EVs hold regenerative ability for underdeveloped fetal lungs, demonstrating potential for therapeutic application in patients with pulmonary hypoplasia

Maturity of the myenteric plexus is decreased in the gastroschisis rat model

Background: Amniotic fluid ( AF) and its components, such as fetal urine and meconium, may lead to intestinal alterations in gastroschisis, which cause immaturity of the myenteric plexus and consequent intestinal hypomotility and malabsorption. In this study we identified morphological and histological alterations of the intestine and the myenteric plexus with two different times of exposure to AF. Methods: The experimental gastroschisis was achieved at two different gestational ages, on day 18.5 ( E18.5) and day 19.5 (E19.5) of gestation, in fetal rats which were divided into 3 subgroups: control, sham and gastroschisis. We measured fetal body weight ( BW), intestinal weight ( IW) and intestinal length ( IL). The layers of intestinal wall and myenteric plexus were evaluated by hematoxylin and eosin staining ( HE staining) and immunofluorescence (alpha-internexin), respectively. Results: BW was not significantly different among the control, sham and gastroschisis groups at both ages. IW and IL were larger and shorter, respectively, in the gastroschisis fetuses (p<0.001) at both ages. Intestinal diameters and wall layers presented significant differences among control, sham and gastroschisis fetuses at both ages (p<0.001), but the time of exposure to AF compromised the serous membrane, D-II ( diameter II, p<0.001) and IL (p = 0.001). alpha-Internexin presented more intensive immunoreactivity in gastroschisis fetuses at E18.5. Conclusions: In gastroschisis, the longer the time of exposure to AF, the more severe bowel impairment will be, especially with regard to IL and the serous layer, and the more immature the myenteric plexus will be. Copyright (C) 2007 S. Karger AG, Basel.231606

Instances and connectors : issues for a second generation process language

This work is supported by UK EPSRC grants GR/L34433 and GR/L32699Over the past decade a variety of process languages have been defined, used and evaluated. It is now possible to consider second generation languages based on this experience. Rather than develop a second generation wish list this position paper explores two issues: instances and connectors. Instances relate to the relationship between a process model as a description and the, possibly multiple, enacting instances which are created from it. Connectors refers to the issue of concurrency control and achieving a higher level of abstraction in how parts of a model interact. We believe that these issues are key to developing systems which can effectively support business processes, and that they have not received sufficient attention within the process modelling community. Through exploring these issues we also illustrate our approach to designing a second generation process language.Postprin