Fetal Bladder Wall Regeneration with a Collagen Biomatrix and Histological Evaluation of Bladder Exstrophy in a Fetal Sheep Model

Successful primary closure of classic bladder exstrophy (BE) is crucial for development of bladder capacity and voided continence. It is universally agreed that an intensive pain management including the use of caudal epidural anesthesia is an essential cornerstone for the outcome of this complex surgery. Whether and to what extent pain is caused by structural or functional changes is not yet known. The nerve growth factor (NGF) is regarded as a marker for pain in different bladder disorders. This prospective study investigated the role of histological alterations and NGF in patients with BE including 34 patients with BE and 6 patients with congenital vesicoureterorenal reflux (VUR) who served as controls. Between January 2015 and April 2020 transmural bladder biopsies were taken from the posterior bladder wall during delayed primary bladder closure. The samples were stained for histological evaluation and subjected to immunohistochemistry to analyze NGFR p75. Differences in histological alterations were examined with Fisher's exact test, and Mann-Whitney-U-test was used to compare the NGFR p75 staining intensity between patients with BE and controls. Patients with BE showed significantly more often acute inflammation (p < 0.001), squamous metaplasia (p = 0.002), and cystitis glandularis (p = 0.005) as well as NGFR p75 in the urothelium (p = 0.003) than patients with VUR. A limitation of this study is the small number of participants due to the rare disease entity. Similar to other painful bladder disorders, pain transmission in BE after intitial closure may in part be facilitated by elevated NGF signaling through its receptor.

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Bladder Reconstruction and Regeneration of a Bladder Exstrophy in a Fetal Sheep Model

Journal of Pediatric Urology ◽

10.1016/j.jpurol.2009.02.020 ◽

2009 ◽

Vol 5 ◽

pp. S25-S26

Author(s):

Barbara Kortmann ◽

Paul Geutjes ◽

Jane Crevels ◽

Rene Wijnen ◽

Alex Eggink ◽

...

Keyword(s):

Bladder Exstrophy ◽

Sheep Model ◽

Fetal Sheep ◽

Bladder Reconstruction

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Local and systemic inflammation after implantation of a novel iron based porous degradable bone replacement material in sheep model

Scientific Reports ◽

10.1038/s41598-021-91296-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Bernd Wegener ◽

Maik Behnke ◽

Stefan Milz ◽

Volkmar Jansson ◽

Christian Redlich ◽

...

Keyword(s):

Mechanical Stability ◽

Bone Substitutes ◽

Histological Evaluation ◽

Control Group ◽

Blood Levels ◽

Porous Iron ◽

Sheep Model ◽

Bone Replacement ◽

Alloy Particles ◽

Iron Based

AbstractDespite the high potential of healthy bone to regenerate, the reconstruction of large bone defects remains a challenge. Due to the lack of mechanical stability of existing bone substitutes, recently developed degradable metallic alloys are an interesting alternative providing higher load-bearing capabilities. Degradable iron-based alloys therefore might be an attractive innovation. To test the suitability of a newly-designed iron-based alloy for such applications, an animal experiment was performed. Porous iron-based degradable implants with two different densities and a control group were tested. The implants were positioned in the proximal tibia of Merino sheep. Over a period of 6 and 12 months, blood and histological parameters were monitored for signs of inflammation and degradation. In the histological evaluation of the implants` environment we found degraded alloy particles, but no inflammatory reaction. Iron particles were also found within the popliteal lymph nodes on both sides. The serum blood levels of phosphorus, iron and ferritin in the long term groups were elevated. Other parameters did not show any changes. Iron-based degradable porous bone replacement implants showed a good biocompatibility in this experiment. For a clinical application, however, the rate of degradation would have to be significantly increased. Biocompatibility would then have to be re-evaluated.

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Airway inflammatory cell responses to intra-amniotic lipopolysaccharide in a sheep model of chorioamnionitis

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.90547.2008 ◽

2009 ◽

Vol 296 (3) ◽

pp. L384-L393 ◽

Cited By ~ 19

Author(s):

Fook-Choe Cheah ◽

J. Jane Pillow ◽

Boris W. Kramer ◽

Graeme R. Polglase ◽

Ilias Nitsos ◽

...

Keyword(s):

Time Course ◽

Fetal Lung ◽

Inflammatory Cells ◽

Lavage Fluid ◽

Protein Carbonyls ◽

Sheep Model ◽

Fetal Sheep ◽

Nitrative Stress ◽

Maturation Factor ◽

Oxidative Burst Activity

Chorioamnionitis, a risk factor for bronchopulmonary dysplasia in preterm infants, causes an influx of inflammatory cells into the fetal lung. Using a fetal sheep model, we evaluated the time course of activation, functional maturity, and apoptosis of the leukocytes recruited to the fetal air spaces by lipopolysaccharide (LPS). Time-mated sheep were given intra-amniotic injections with 10 mg of Escherichia coli LPS or saline 2 or 7 days before preterm delivery at 124 days of gestation (term is 150 days). Both neutrophils and monocytes in bronchoalveolar lavage fluid (BALF) had activated NF-κB after 2- and 7-day LPS exposures. These neutrophils and monocytes expressed the activation factor CD11b and the maturation factor PU.1 at 2 days, and increased PU.1 expression was detected in macrophages at 7 days. Leukocyte oxidative burst activity was greatest at 7 days. BALF lipid peroxidation increased fivefold at 2 days, while protein carbonyls increased eightfold at 7 days. Nitrative stress was not detected in the BALF, but leukocytes in the lung expressed nitric oxide synthase (NOS)II (inducible NOS). BALF leukocytes expressed the antioxidant peroxiredoxin V. Lung glutathione peroxidase was also increased with LPS exposure. There was minimal apoptosis of airway and lung leukocytes assessed by caspase-3 activation. Intra-amniotic LPS recruits leukocytes to the fetal air space that have a persistent activation. These results have implications for the pathogenesis of lung inflammatory disorders in the preterm.

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Does heart rate variability reflect the systemic inflammatory response in a fetal sheep model of lipopolysaccharide-induced sepsis?

Physiological Measurement ◽

10.1088/0967-3334/36/10/2089 ◽

2015 ◽

Vol 36 (10) ◽

pp. 2089-2102 ◽

Cited By ~ 28

Author(s):

Lucien D Durosier ◽

Christophe L Herry ◽

Marina Cortes ◽

Mingju Cao ◽

Patrick Burns ◽

...

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Inflammatory Response ◽

Systemic Inflammatory Response ◽

Sheep Model ◽

Fetal Sheep

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Left-right difference in fetal liver oxygenation during hypoxia estimated by BOLD MRI in a fetal sheep model

Ultrasound in Obstetrics and Gynecology ◽

10.1002/uog.9044 ◽

2011 ◽

Vol 38 (6) ◽

pp. 665-672 ◽

Cited By ~ 13

Author(s):

A. Sørensen ◽

D. Holm ◽

M. Pedersen ◽

A. Tietze ◽

B. Stausbøl-Grøn ◽

...

Keyword(s):

Fetal Liver ◽

Sheep Model ◽

Fetal Sheep ◽

Bold Mri

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A new analysis of heart rate variability in the assessment of fetal parasympathetic activity: An experimental study in a fetal sheep model

PLoS ONE ◽

10.1371/journal.pone.0180653 ◽

2017 ◽

Vol 12 (7) ◽

pp. e0180653 ◽

Cited By ~ 11

Author(s):

C. Garabedian ◽

C. Champion ◽

E. Servan-Schreiber ◽

L. Butruille ◽

E. Aubry ◽

...

Keyword(s):

Heart Rate ◽

Experimental Study ◽

Heart Rate Variability ◽

Parasympathetic Activity ◽

Sheep Model ◽

Fetal Sheep

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Serotonin contributes to high pulmonary vascular tone in a sheep model of persistent pulmonary hypertension of the newborn

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00043.2013 ◽

2013 ◽

Vol 304 (12) ◽

pp. L894-L901 ◽

Cited By ~ 25

Author(s):

Cassidy Delaney ◽

Jason Gien ◽

Gates Roe ◽

Nicole Isenberg ◽

Jenai Kailey ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Pulmonary Artery ◽

Tryptophan Hydroxylase ◽

Late Gestation ◽

Persistent Pulmonary Hypertension ◽

Sheep Model ◽

Pulmonary Hemodynamics ◽

Fetal Sheep ◽

Pulmonary Arterial

Although past studies demonstrate that altered serotonin (5-HT) signaling is present in adults with idiopathic pulmonary arterial hypertension, whether serotonin contributes to the pathogenesis of persistent pulmonary hypertension of the newborn (PPHN) is unknown. We hypothesized that 5-HT contributes to increased pulmonary vascular resistance (PVR) in a sheep model of PPHN and that selective 5-HT reuptake inhibitor (SSRI) treatment increases PVR in this model. We studied the hemodynamic effects of 5-HT, ketanserin (5-HT2A receptor antagonist), and sertraline, an SSRI, on pulmonary hemodynamics of the late gestation fetal sheep with PPHN caused by prolonged constriction of the ductus arteriosis. Brief intrapulmonary infusions of 5-HT increased PVR from 1.0 ± 0.07 (baseline) to 1.4 ± 0.22 mmHg/ml per minute of treatment ( P < 0.05). Ketanserin decreased PVR from 1.1 ± 0.15 (baseline) to 0.82 ± 0.09 mmHg/ml per minute of treatment ( P < 0.05). Sertraline increased PVR from 1.1 ± 0.17 (baseline) to 1.4 ± 0.17 mmHg/ml per minute of treatment ( P = 0.01). In addition, we studied 5-HT production and activity in vitro in experimental PPHN. Compared with controls, pulmonary artery endothelial cells from fetal sheep with PPHN exhibited increased expression of tryptophan hydroxylase 1 and 5-HT production by twofold and 56%, respectively. Compared with controls, 5-HT2A R expression was increased in lung homogenates and pulmonary artery smooth muscle cell lysates by 35% and 32%, respectively. We concluded that increased 5-HT contributes to high PVR in experimental PPHN through activation of the 5-HT2A receptor and that SSRI infusion further increases PVR in this model.

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Fetoscopic abdominal decompression of congenital diaphragmatic hernia – preliminary results of a fetal sheep model

10.14293/p2199-8442.1.sop-med.pmrxpi.v1 ◽

2014 ◽

Author(s):

Felipe Fromm ◽

Katharina Wenke ◽

Thomas Krebs ◽

Michael Boettcher ◽

Georg Eschenburg ◽

...

Keyword(s):

Animal Model ◽

Congenital Diaphragmatic Hernia ◽

Diaphragmatic Hernia ◽

Fetal Surgery ◽

Amniotic Cavity ◽

Sheep Model ◽

Fetal Sheep ◽

Tracheal Occlusion ◽

Animal Trials ◽

Abdominal Decompression

Background Severe congenital diaphragmatic hernia (CDH) is prenatally managed by fetoscopic tracheal occlusion (FETO) to improve lung growth and maturation. As FETO is not able to reduce the pressure onto the developing lungs originating from the intestine growing into the thoracic cavity, fetal abdominal decompression may alleviate this pressure effect by directing the growing intestine into the amniotic cavity away from the lungs. Therefore, aim of this study was to establish an animal model for fetoscopic abdominal decompression in fetal sheep with CDH. Methods CDH was created surgically on day 75 of 145 day gestation in eight fetuses. 2-3 weeks later, an opening was created in the fetal abdomen by fetoscopic surgery. The fetuses were retrieved by cesarean section at the end of pregnancy and evaluated. Results Five fetuses with CDH were treated with fetoscopic abdominal decompression. Three fetuses with CDH were taken as controls. One fetus was lost after creation of the CDH and two other after creation of the abdominal defect. Preliminary sterological results showed that the septal thickness of the experimental group was smaller than in the CDH group. Conclusion This study demonstrates the general feasibility of fetoscopic abdominal decompression for diaphragmatic hernia in our new animal model. Although not statistically significant, the lungs of treated fetuses were larger and heavier than those of untreated controls. Our findings support the hypothesis of palliative fetal surgery for severe CDH compared to tracheal occlusion. More controlled animal trials are needed.

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