Anti-inflammatory therapy in an ovine model of fetal hypoxia induced by single umbilical artery ligation

2011 ◽  
Vol 23 (2) ◽  
pp. 346 ◽  
Author(s):  
Micka C. Bertucci ◽  
Jan M. Loose ◽  
Euan M. Wallace ◽  
Graham Jenkin ◽  
Suzanne L. Miller
Keyword(s):  
Inflammatory Response ◽  
Intrauterine Growth Restriction ◽  
Umbilical Artery ◽  
Blood Gases ◽  
Fetal Hypoxia ◽  
Single Umbilical Artery ◽  
Artery Ligation ◽  
Pregnant Sheep ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Perinatal morbidity and mortality are significantly higher in pregnancies complicated by chronic hypoxia and intrauterine growth restriction (IUGR). Clinically, placental insufficiency and IUGR are strongly associated with a fetoplacental inflammatory response. To explore this further, hypoxia was induced in one fetus in twin-bearing pregnant sheep (n = 9) by performing single umbilical artery ligation (SUAL) at 110 days gestation. Five ewes were administered the anti-inflammatory drug sulfasalazine (SSZ) daily, beginning 24 h before surgery. Fetal blood gases and inflammatory markers were examined. In both SSZ- and placebo-treated ewes, SUAL fetuses were hypoxic and growth-restricted at 1 week (P < 0.05). A fetoplacental inflammatory response was observed in SUAL pregnancies, with elevated pro-inflammatory cytokines, activin A and prostaglandin E2. SSZ did not mitigate this inflammatory response. It is concluded that SUAL induces fetal hypoxia and a fetoplacental inflammatory response and that SSZ does not improve oxygenation or reduce inflammation. Further studies to explore whether alternative anti-inflammatory treatments may improve IUGR outcomes are warranted.

scholarly journals Focal intra-colon cooling reduces organ injury and systemic inflammation after REBOA management of lethal hemorrhage in rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Awadhesh K. Arya ◽  
Kurt Hu ◽  
Lalita Subedi ◽  
Tieluo Li ◽  
Bingren Hu
Keyword(s):  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Troponin I ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Balloon Catheter ◽  
Organ Injury ◽  
Upper Body ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

AbstractResuscitative endovascular balloon occlusion of the aorta (REBOA) is a lifesaving maneuver for the management of lethal torso hemorrhage. However, its prolonged use leads to distal organ ischemia–reperfusion injury (IRI) and systemic inflammatory response syndrome (SIRS). The objective of this study is to investigate the blood-based biomarkers of IRI and SIRS and the efficacy of direct intestinal cooling in the prevention of IRI and SIRS. A rat lethal hemorrhage model was produced by bleeding 50% of the total blood volume. A balloon catheter was inserted into the aorta for the implementation of REBOA. A novel TransRectal Intra-Colon (TRIC) device was placed in the descending colon and activated from 10 min after the bleeding to maintain the intra-colon temperature at 37 °C (TRIC37°C group) or 12 °C (TRIC12°C group) for 270 min. The upper body temperature was maintained at as close to 37 °C as possible in both groups. Blood samples were collected before hemorrhage and after REBOA. The organ injury biomarkers and inflammatory cytokines were evaluated by ELISA method. Blood based organ injury biomarkers (endotoxin, creatinine, AST, FABP1/L-FABP, cardiac troponin I, and FABP2/I-FABP) were all drastically increased in TRIC37°C group after REBOA. TRIC12°C significantly downregulated these increased organ injury biomarkers. Plasma levels of pro-inflammatory cytokines TNF-α, IL-1b, and IL-17F were also drastically increased in TRIC37°C group after REBOA. TRIC12°C significantly downregulated the pro-inflammatory cytokines. In contrast, TRIC12°C significantly upregulated the levels of anti-inflammatory cytokines IL-4 and IL-10 after REBOA. Amazingly, the mortality rate was 100% in TRIC37°C group whereas 0% in TRIC12°C group after REBOA. Directly cooling the intestine offered exceptional protection of the abdominal organs from IRI and SIRS, switched from a harmful pro-inflammatory to a reparative anti-inflammatory response, and mitigated mortality in the rat model of REBOA management of lethal hemorrhage.

EFFECTS OF SINGLE UMBILICAL ARTERY LIGATION IN THE LAMB FETUS

1969 ◽  
Vol 24 (8) ◽  
pp. 1068-1070 ◽  
Author(s):  
GEORGE C. EMMANOUILIDES ◽  
DUANE E. TOWNSEND ◽  
ROBERT A. BAUER
Keyword(s):  
Umbilical Artery ◽  
Single Umbilical Artery ◽  
Artery Ligation

EFFECTS OF SINGLE UMBILICAL ARTERY LIGATION IN THE LAMB FETUS

PEDIATRICS ◽  
1968 ◽  
Vol 42 (6) ◽  
pp. 919-927
Author(s):  
George C. Emmanouilides ◽  
Duane E. Townsend ◽  
Robert A. Bauer
Keyword(s):  
Hydrogen Exchange ◽  
Umbilical Artery ◽  
Initial Period ◽  
Fetal Distress ◽  
Single Umbilical Artery ◽  
Artery Ligation ◽  
Term Survival ◽  
Indwelling Catheters ◽  
Fetal Survival ◽  
Arterial Blood

The effects of single umbilical artery ligation have been studied in 20 lamb fetuses, using chronic indwelling catheters placed in a retrograde fashion via the ligated umbilical artery in the fetal aorta. Fetal arterial blood pressure, heart rate, blood pH, PCO2 and PO2 were monitored at various intervals until the end of the gestation. The results indicate that prolonged fetal survival is possible. Although fetuses near term did not survive this insult, long-term survival (3 to 56 days) was observed in nine animals of earlier gestational age. After an initial period of hypoxia, acidosis, and hypercapnia, stabilization occurred and "normal" values for these parameters were observed. In spite of the apparently normal gas and hydrogen exchange between mother and fetus, profound fetal malnutrition was observed in two animals who survived 26 and 56 days, respectively. The possible mechanisms of fetal adaptation to this acute change in intra-uterine environment and the potential value of this "experimental model" for studying chronic fetal distress due to placental insufficiency are discussed.

Antenatal glucocorticoids reduce growth in appropriately grown and growth-restricted ovine fetuses in a sex-specific manner

2012 ◽  
Vol 24 (5) ◽  
pp. 753 ◽  
Author(s):  
Suzanne L. Miller ◽  
Amy E. Sutherland ◽  
Veena G. Supramaniam ◽  
David W. Walker ◽  
Graham Jenkin ◽  
...  
Keyword(s):  
Umbilical Artery ◽  
Specific Effect ◽  
Single Umbilical Artery ◽  
Artery Ligation ◽  
Fetal Sheep ◽  
Control Male ◽  
Male And Female ◽  
Intrauterine Growth ◽  
Specific Manner ◽  
Maternal Administration

Antenatal glucocorticoids are administered to mature the fetal lungs before preterm birth. Glucocorticoids also have non-pulmonary effects, including reducing fetal body and brain growth. The present study examined whether glucocorticoid administration has a sex-specific effect on growth in appropriately grown (control) and intrauterine growth-restricted (IUGR) fetal sheep. IUGR was induced at 0.7 gestation in fetal sheep by single umbilical artery ligation. On Days 5 and 6 after surgery, IUGR or control fetuses were exposed to the synthetic glucocorticoid betamethasone (BM; 11.4 mg) or saline via intramuscular maternal administration. On Day 7, a postmortem was conducted to determine fetal sex and weight. Compared with control fetuses, the birthweight of male and female IUGR fetuses was significantly reduced (by 18.5 ± 4.4% (P = 0.002) and 21.7 ± 6.0% (P = 0.001), respectively). Maternal administration of BM significantly reduced bodyweight in both control and IUGR fetuses (by 11.3 ± 2.8% and 20.5 ± 3.6% in control male and female fetuses, respectively; and by 22.9 ± 3.1% and 38.3 ± 3.4% in IUGR male and female fetuses, respectively; P < 0.001 for all, versus control + saline) fetuses. In control and IUGR animals the degree of growth restriction was greater in females than males (P < 0.05) following administration of BM. These data suggest that antenatal glucocorticoids reduce fetal growth in a sex-specific manner, with females more growth restricted than males.

Umbilical Blood Flow and Glucose Uptake in Lamb Fetus Following Single Umbilical Artery Ligation

Neonatology ◽  
1975 ◽  
Vol 26 (3-4) ◽  
pp. 291-299 ◽  
Author(s):  
William Oh ◽  
Keiichiro Omori ◽  
Calvin J. Hobel ◽  
Allen Erenberg ◽  
George C. Emmanouilides
Keyword(s):  
Blood Flow ◽  
Glucose Uptake ◽  
Umbilical Artery ◽  
Single Umbilical Artery ◽  
Artery Ligation ◽  
Umbilical Blood ◽  
Umbilical Blood Flow

scholarly journals Cytokines-Biogenesis and Their Role in Human Breast Milk and Determination

2021 ◽  
Vol 22 (12) ◽  
pp. 6238
Author(s):  
Anna Kiełbasa ◽  
Renata Gadzała-Kopciuch ◽  
Bogusław Buszewski
Keyword(s):  
Inflammatory Response ◽  
Mrna Level ◽  
Endocrine System ◽  
Human Breast Milk ◽  
Cytokine Inhibition ◽  
The Central Nervous System ◽  
Anti Inflammatory ◽  
Aggregation Activity ◽  
Activity Induction ◽  
Pro Inflammatory Cytokines

Cytokines play a huge role in many biological processes. Their production, release and interactions are subject to a very complex mechanism. Cytokines are produced by all types of cells, they function very differently and they are characterized by synergism in action, antagonism, and aggregation activity, opposing action of one cytokine, overlapping activity, induction of another cytokine, inhibition of cytokine synthesis at the mRNA level as well as autoregulation-stimulation or inhibition of own production. The predominance of pro-inflammatory cytokines leads to a systemic inflammatory response, and anti-inflammatory-to an anti-inflammatory response. They regulate the organism’s immune response and protect it against sudden disturbances in homeostasis. The synthesis and activity of cytokines are influenced by the central nervous system through the endocrine system (pituitary gland, adrenal glands).

scholarly journals Electroacupuncture Improves M2 Microglia Polarization and Glia Anti-inflammation of Hippocampus in Alzheimer’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Lushuang Xie ◽  
Yi Liu ◽  
Ning Zhang ◽  
Chenyu Li ◽  
Aaron F. Sandhu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Cytokine Expression ◽  
Tnf Α ◽  
Microglia Polarization ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Background: Alzheimer’s disease (AD) is a neurodegenerative disease characterized by loss of recognition and memory. Neuroinflammation plays pivotal roles in the pathology of AD and affects the progression of the disease. Astrocyte and microglia, as main immune executors in the central nervous system (CNS), participate into the inflammatory response in AD. Glia polarize into different phenotypes during neurodegeneration. Pro-inflammatory glia produce cytokines (IL-1β, TNF-α, and IL-6) resulting into debris aggregates and neurotoxicity. Anti-inflammatory phenotypes produce cytokines (IL-4 and IL-10) to release the inflammation. Electroacupuncture is a useful treatment that has been found to slow the neurodegeneration in animals through experimentation and in humans through clinical trials. The aim of this study was to uncover the mechanisms of glia activation, microglia polarization, and cytokine secretion regulated by electroacupuncture as a treatment for AD.Methods: Twenty male Sprague–Dawley (SD) rats were randomly divided into four groups: Control group (Control), Normal saline group (NS), AD group (AD), and Electroacupuncture group (Acupuncture). The AD and Acupuncture groups were bilaterally injected with Aβ1–42 into the CA1 field of the hippocampus. The Acupuncture group received electroacupuncture stimulation on the acupoint “Baihui” (GV20) for 6 days per week for a total of 3 weeks. The Morris Water Maze (MWM) was used to evaluate learning and memory capacity. Immunofluorescence was used to stain GFAP and Iba1 of the DG and CA1 in the hippocampus, which, respectively, expressed the activation of astrocyte and microglia. The M1 microglia marker, inducible nitric oxide synthase (iNOS), and M2 marker Arginase 1 (Arg1) were used to analyze the polarization of microglia. The pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6), anti-inflammatory cytokines (IL-4 and IL-10), and pathway-molecules (p65 and Stat6) were tested to analyze the glia inflammatory response by immunofluorescence and polymerase chain reaction (PCR).Results: The MWM results showed that electroacupuncture improves the escape latency time and the swimming distance of AD rats. The number of GFAP and Iba1 cells significantly increased in AD rats, but electroacupuncture decreased the cells. The iNOS-positive cells were significantly increased in AD, and electroacupuncture decreased the positive cells. Electroacupuncture elevated Arg1-positive cells in AD rats. Electroacupuncture decreased the glia pro-inflammatory cytokine expression and increased the anti-inflammatory cytokine expression in AD rats. Furthermore, electroacupuncture inhibited the NF-κB pathway molecule (p65) while raising the Stat6 pathway molecule (Stat6).Conclusion: These results provide evidence that electroacupuncture improves the recognition abilities and memory of AD rats. Electroacupuncture inhibits the activation of glia and polarizes microglia toward the M2 phenotype. Electroacupuncture decreased the pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6) and increased the anti-inflammatory cytokines (IL-4 and IL-10). Furthermore, electroacupuncture affects the immune responses through inhibition of NF-κB pathway but activation of Stat6 pathway.

Single umbilical artery ligation-induced fetal growth retardation: effect on postnatal adaptation

1992 ◽  
Vol 263 (3) ◽  
pp. E575-E583 ◽  
Author(s):  
K. Oyama ◽  
J. Padbury ◽  
B. Chappell ◽  
A. Martinez ◽  
H. Stein ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Fetal Growth ◽  
Growth Retardation ◽  
Umbilical Artery ◽  
Physiological Stress ◽  
Fetal Growth Retardation ◽  
Signal Transduction System ◽  
Single Umbilical Artery ◽  
Artery Ligation ◽  
Beta Adrenergic

To assess whether prolonged intrauterine stress and resultant fetal growth retardation result in depletion of adrenal catecholamines and alter the adrenergic signal transduction system, we studied newborn sheep after single umbilical artery ligation (SUAL)-induced growth retardation. The animals were delivered at term, and postnatal cardiovascular, pulmonary, endocrine, and metabolic responses were measured. We also evaluated the status of myocardial and pulmonary beta-adrenergic receptor number and function. SUAL caused significant growth retardation but relative preservation of brain and adrenal gland weight and adrenal catecholamine content. Blood pressure, plasma free fatty acid, and glucose responses at birth were blunted in SUAL animals. The plasma epinephrine (Epi) and norepinephrine levels were comparable in both groups for the first 2 h of age. By 4 h, both plasma concentration and plasma appearance rate of Epi were reduced to 40% of control in SUAL animals (P less than 0.05). Neither beta-receptor density, affinity, nor adenylate cyclase activity were altered by SUAL in either cardiac or pulmonary membranes. These results suggest that, rather than overt depletion, there is relative sparing of initial adrenal medullary function that later waned. This response and preservation of the beta-adrenergic signal transduction system may represent partial compensation for the physiological stress induced by SUAL.

scholarly journals Sirenomelia, the mermaid baby: a case report

2019 ◽  
Vol 8 (11) ◽  
pp. 4609
Author(s):  
Reetika Joshi ◽  
Veino Kuveio Duomai ◽  
Bianchi Sangma
Keyword(s):  
Intrauterine Growth Restriction ◽  
Umbilical Artery ◽  
External Genitalia ◽  
Lower Limbs ◽  
Single Umbilical Artery ◽  
Female Ratio ◽  
Fetal Movements ◽  
Anorectal Atresia ◽  
Male To Female ◽  
Live Baby

Sirenomelia sequence or mermaid syndrome is a rare congenital structural anomaly characterized by different degrees of fusion of lower limbs, thoracolumbar spinal anomalies, sacrococcygeal agenesis, genitourinary and anorectal atresia. The incidence of sirenomelia is 0.8-1 cases/ 105 births with male to female ratio being 3:1. A malformations patient with 40 weeks of gestation admitted with complaints of decreased fetal movements for one week. An emergency C-section was done in view of term pregnancy with severe oligohydramnios and intrauterine growth restriction with poor bishop’s score. A 1.9 kg live baby with fused lower limbs was delivered. The new born baby had narrow chest, fused both lower limbs and feet with 11 toes, small rudimentary external genitalia, imperforate anus and single umbilical artery. The baby also had features of potter’s facies including low set large ears, receding chin and prominent infraorbital folds. Sirenomelia is a rare fatal congenital anomaly. Early detection by prenatal ultrasound will help in timely termination of pregnancy.

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