Neonates undergoing surgery are at higher risk than older children for anesthesia-related adverse events. During the perioperative period, the maintenance of optimal hemodynamics in these patients is challenging and requires a thorough understanding of neonatal physiology and pharmacology. Data from animals and human cohort studies have shown relation of the currently used anesthetics may associate with neurotoxic brain injury that lead to later neurodevelopmental impairment in the developing brain. In this review, the unique neonatal physiologic and pharmacologic features and anesthesia-related neurotoxicity will be discussed.
Anesthesia* ; Anesthetics ; Animals ; Brain ; Brain Injuries ; Child ; Cohort Studies ; Hemodynamics ; Humans ; Infant, Newborn ; Neurotoxicity Syndromes ; Parental Consent ; Perioperative Period ; Pharmacology ; Physiology

Chronic enteritis can produce an excess of reactive oxygen species resulting in cellular damage. Stanniocalcin-1(STC-1) reportedly possesses anti-oxidative activity, the aim of this study was to define more clearly the direct contribution of STC-1 to anti-oxidative stress in cattle. In this study, primary intestinal epithelial cells (IECs) were exposed to hydrogen peroxide (H2O2) for different time intervals to mimic chronic enteritis-induced cellular damage. Prior to treatment with 200 microM H2O2, the cells were transfected with a recombinant plasmid for 48 h to over-express STC-1. Acridine orange/ethidium bromide (AO/EB) double staining and trypan blue exclusion assays were then performed to measure cell viability and apoptosis of the cells, respectively. The expression of STC-1 and apoptosis-related proteins in the cells was monitored by real-time PCR and Western blotting. The results indicated that both STC-1 mRNA and protein expression levels positively correlated with the duration of H2O2 treatment. H2O2 damaged the bovine IECs in a time-dependent manner, and this effect was attenuated by STC-1 over-expression. Furthermore, over-expression of STC-1 up-regulated Bcl-2 protein expression and slightly down-regulated caspase-3 production in the damaged cells. Findings from this study suggested that STC-1 plays a protective role in intestinal cells through an antioxidant mechanism.
Animals ; Animals, Newborn ; Blotting, Western/veterinary ; Caspase 3/*genetics/metabolism ; Cattle ; Cattle Diseases/etiology/*genetics/metabolism ; Duodenum/metabolism ; Enteritis/etiology/genetics/metabolism/*veterinary ; Epithelial Cells/metabolism ; *Gene Expression Regulation ; Glycoproteins/*genetics/metabolism ; Hydrogen Peroxide/pharmacology ; Male ; Proto-Oncogene Proteins c-bcl-2/*genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Real-Time Polymerase Chain Reaction/veterinary

PURPOSE: Cell transplantation of myelin-producing exogenous cells is being extensively explored as a means of remyelinating axons in X-linked adrenoleukodystrophy. We determined whether 3,3',5-Triiodo-L-thyronine (T3) overexpresses the ABCD2 gene in the polysialylated (PSA) form of neural cell adhesion molecule (NCAM)-positive cells and promotes cell proliferation and favors oligodendrocyte lineage differentiation. MATERIALS AND METHODS: PSA-NCAM+ cells from newborn Sprague-Dawley rats were grown for five days on uncoated dishes in defined medium with or without supplementation of basic fibroblast growth factor (bFGF) and/or T3. Then, PSA-NCAM+ spheres were prepared in single cells and transferred to polyornithine/fibronectin-coated glass coverslips for five days to determine the fate of the cells according to the supplementation of these molecules. T3 responsiveness of ABCD2 was analyzed using real-time quantitative polymerase chain reaction, the growth and fate of cells were determined using 5-bromo-2-deoxyuridine incorporation and immunocytochemistry, respectively. RESULTS: Results demonstrated that T3 induces overexpression of the ABCD2 gene in PSA-NCAM+ cells, and can enhance PSA-NCAM+ cell growth in the presence of bFGF, favoring an oligodendrocyte fate. CONCLUSION: These results may provide new insights into investigation of PSA-NCAM+ cells for therapeutic application to X-linked adrenoleukodystrophy.
ATP-Binding Cassette Transporters/*metabolism ; Adrenoleukodystrophy/genetics/*therapy ; Animals ; Animals, Newborn ; Bromodeoxyuridine ; Cell Differentiation ; Fibroblast Growth Factor 2/pharmacology ; Fibronectins/metabolism ; Immunohistochemistry ; Neural Cell Adhesion Molecules/*genetics ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Sialic Acids/metabolism ; Stem Cells ; Thyroid Hormones/*metabolism ; Triiodothyronine/pharmacology

This study was done after identifying animals with a twisted carpal joint in goat herd. These included a kid goat walking on its articulus carpii and a newborn goat with a stiff leg. Necropsies of the diseased goats revealed swollen carpal joints that were twisted backwards. Arthritis was observed during microscopic examination of the carpal joints. Very low levels of eosinophil, leucocyte, and lymphocyte cell infiltration were found in the central nervous system and meninges. Serum copper levels were significantly decreased in most of the animals. All of these results led us to diagnose the animals with swayback disease.
Animals ; Animals, Newborn ; Carpal Joints/metabolism/*pathology ; Copper/blood/*deficiency/metabolism ; Female ; Goat Diseases/*congenital/metabolism/pathology ; Goats ; Joint Diseases/congenital/metabolism/pathology/*veterinary ; Male ; Pregnancy

The aim of our study was to investigate the differential effects of dexamethasone (DXM) and hydrocortisone (HCS) on somatic growth and postnatal lung development in a rat model of bronchopulmonary dysplasia (BPD). A rat model of BPD was induced by administering intra-amniotic lipopolysaccharide (LPS) and postnatal hyperoxia. The rats were treated with a 6-day (D1-D6) tapering course of DXM (starting dose 0.5 mg/kg/day), HCS (starting dose 2 mg/kg/day), or an equivalent volume of normal saline. DXM treatment in a rat model of BPD induced by LPS and hyperoxia was also associated with a more profound weight loss compared to control and LPS + O2 groups not exposed to corticosteroid, whereas HCS treatment affected body weight only slightly. Examination of lung morphology showed worse mean cord length in both LPS + O2 + DXM and LPS + O2 + HCS groups as compared to the LPS + O2 alone group, and the LPS + O2 + DXM group had thicker alveolar walls than the LPS + O2 group at day 14. The HCS treatment was not significantly associated with aberrant alveolar wall thickening and retarded somatic growth. The use of postnatal DXM or HCS in a rat model of BPD induced by intra-amniotic LPS and postnatal hyperoxia appeared detrimental to lung growth, but there was less effect in the case of HCS. These findings suggest that effect of HCS on somatic growth and pulmonary outcome may be better tolerated in neonates for preventing and/or treating BPD.
Amnion/drug effects ; Animals ; Animals, Newborn ; Anti-Inflammatory Agents/*pharmacology ; Dexamethasone/*pharmacology ; Disease Models, Animal ; Female ; Hydrocortisone/*pharmacology ; *Hyperoxia ; Lipopolysaccharides/toxicity ; Lung Diseases/*pathology ; Oxygen/metabolism ; Pulmonary Alveoli/*drug effects/growth & development/pathology ; Rats ; Rats, Sprague-Dawley

Supernumerary ectopic limb(s) (SEL) is a congenital anomaly defined as the presence of accessory limb(s) attached to various body regions. This paper describes a case of SEL with ectopic lung and ectopia cordis in a newborn calf, based on macroscopic, microscopic and radiographic findings. External features of multiple congenital anomalies included an ectopic lung growing over the middle of the backbone and covered with normal haired skin. Ectopia cordis was found in the abdominal cavity and attached to the liver. Two extra abnormal limbs originated separately from within the ectopic lung. Most of the abdominal organs were exposed to the outside through the opened abdominal cavity. Microscopically the ectopic lung tissue had edema in the connective tissue around the bronchus and artery. Changes in other organs included congestion of the renal medulla, infiltration of inflammatory cells (lymphocytes and eosinophils) around the hepatic portal tract, and edema surrounding blood vessels and neurons in the brain. The rudimentary humerus of the forelimb was attached to the thoracic spine, as viewed radiographically. The hindlimb was consisted of an irregularly shaped femur, short tibia and fibula, two tarsal bones, one metatarsal bone, and three phalanges. This is the first description of congenital anomalies involving the SEL, ectopic lung and ectopia cordis in a calf.
Abdominal Cavity ; Animals ; Arteries ; Blood Vessels ; Body Regions ; Brain ; Bronchi ; Connective Tissue ; Ectopia Cordis ; Edema ; Estrogens, Conjugated (USP) ; Extremities ; Femur ; Fibula ; Forelimb ; Hair ; Hindlimb ; Humans ; Humerus ; Infant, Newborn ; Liver ; Lung ; Metatarsal Bones ; Neurons ; Skin ; Spine ; Tarsal Bones ; Tibia

Lack of hygiene and puerperal mastitis are common causes of bacterial diseases in nursing neonates. The aim of this study was to isolate microorganisms from milk samples of healthy female Jindo dogs with suckling puppies and to investigate antimicrobial susceptibility against the isolated bacteria. Milk samples were collected from 120 udders of 12 lactating Jindo dogs that were 2~4 years old without any clinical diseases including mastitis. Bacteria were isolated from 64 milk samples (53.3%), either singly (76.6%) or in combination (23.4%). Staphylococcus (S.) spp. was the most common microorganisms (74.7%) isolated from canine milk, followed by Haemophillus spp. (10.9%), Streptococcus spp. (9.6%), Gardnerella spp. (2.4%) and Moraxella spp. (2.4%). The most frequently isolated organism was S. warneri (31.3%). Antimicrobial susceptibility of these bacteria was tested with 17 antimicrobial agents by Kirbyand Bauer standardized disc diffusion method. Results indicated that bacteria isolated from healthy canine milk were mostly susceptible to amoxicillin-clavulanic acid, cephalothin and ceftiofur, but were resistant to erythromycin, neomycin and tetracycline.
Amoxicillin-Potassium Clavulanate Combination ; Animals ; Anti-Infective Agents ; Bacteria ; Cephalosporins ; Cephalothin ; Diffusion ; Dogs ; Erythromycin ; Female ; Gardnerella ; Humans ; Hygiene ; Infant, Newborn ; Mammary Glands, Animal ; Mastitis ; Milk ; Moraxella ; Neomycin ; Staphylococcus ; Streptococcus ; Tetracycline

PURPOSE: Retinopathy of prematurity (ROP) is a leading cause of blindness with retinal detachment due to oxygen toxicity in preterm infants. Recently advances in neonatal care had to led improved survival rates in premature infants and ROP re-emerged as a significant clinical problem. In the present study, we aimed to determine the protective abilities of minocycline in a animal model of ROP and a primary retinal cell cultures of neonatal rat via anti-apoptotic actions using Western blotting and real-time PCR with Bcl-2, Bax and caspase-3 antibodies and mRNAs. METHODS: In the in vivo oxygen-induced retinopathy (OIR), the cyclic hyperoxia was performed that 80% O2 for 1 day and 21% O2 for 1 day from P1-14 of newborn rats. Minocycline was injected intravitreously for 7 days and sacrificed at P21. In the in vitro OIR, primary retinal cell culture was done using P0-P2 SD rats. Hyperoxia injury was done for 100% O2 exposure for 6 hours. Western blotting and real-time PCR using Bcl-2, Bax and caspase-3 antibody and primer were done in the rat model of ROP and the dispersed retinal cell culture. To identify photoreceptors of retinal cells the immunofluorescence assay photoreceptor marker, IRBP, was used. RESULTS: In the in vivo OIR, the expression of Bcl-2 antibody and mRNA was increased and those of Bax and caspase-3 were reduced in the minocycline-treated group. In the in vitro OIR, the result was the same as above. CONCLUSION: In conclusion, minocycline was suggested to have retinal protective effects for hyperoxic injury via anti-apoptotic mechanism.
Animals ; Antibodies ; Apoptosis ; Blindness ; Blotting, Western ; Caspase 3 ; Cell Culture Techniques ; Diterpenes ; Fluorescent Antibody Technique ; Humans ; Hyperoxia ; Infant, Newborn ; Infant, Premature ; Minocycline ; Models, Animal ; Oxygen ; Rats ; Real-Time Polymerase Chain Reaction ; Retinal Detachment ; Retinaldehyde ; Retinopathy of Prematurity ; RNA, Messenger ; Survival Rate

Neonatologists are deeply concerned with the concept of ventilator-induced lung injury (VILI) and they are greatly careful in the neonatal intensive care unit to apply positive-pressure ventilation (PPV) strategies that are gentle to the lungs. To achieve adequate gas exchange after delivery, lung fluid should be cleared and replaced with air, and functional residual capacity (FRC) should be established. However preterm newborns have difficulties establishing FRC and maintaining upper airway patency at birth. Hence majority of preterm newborns need some assistance to initiate breathing after birth and some require extensive resuscitation. PPV is therefore commonly used in the delivery room, however most clinicians including neonatologists or obstetricians appear less aware that the gentle approach as in NICU should be applied to prevent lung injury during the first few minutes of life. PPV may cause lung injury through various mechanisms such as high Vt (tidal volume) and overdistension (volutrauma), repeated alveolar collapse and re-expansion (atelect-trauma), and infection and inflammation (biotrauma), through which leads to epithelial cell injury, leakage of proteinaceous fluid into the lungs, inhibiting surfactant function and interfering lung mechanics, and consequently generating lung injury. In this review, I describe briefly what causes preterm lung injury during PPV based on animal and human researches, and I suggest some strategies to help minimize lung injury during resuscitation of preterm newborns in the delivery room.
Animals ; Delivery Rooms ; Epithelial Cells ; Functional Residual Capacity ; Humans ; Infant, Newborn ; Inflammation ; Intensive Care, Neonatal ; Lung ; Lung Injury ; Mechanics ; Parturition ; Positive-Pressure Respiration ; Respiration ; Resuscitation ; Ventilator-Induced Lung Injury

TNF-alpha, a proinflammatory cytokine, inhibits osteoblast differentiation under diverse inflammatory conditions; however, the underlying mechanisms in terms of the TNF-alpha signaling pathway remain unclear. In this study, we examined the role of Msx2 in TNF-alpha-mediated inhibition of alkaline phosphatase (ALP) expression and the signaling pathways involved. TNF-alpha down-regulated ALP expression induced by bone morphogenetic protein 2 (BMP2) in C2C12 and Runx2-/- calvarial cells. Over-expression of Msx2 suppressed BMP2-induced ALP expression. Furthermore, TNF-alpha induced Msx2 expression, and the knockdown of Msx2 by small interfering RNAs rescued ALP expression, which was inhibited by TNF-alpha. TNF-alpha activated the NF-kappaB and the JNK pathways. Inhibition of NF-kappaB or JNK activation reduced the inhibitory effect of TNF-alpha on ALP expression, whereas TNF-alpha-induced Msx2 expression was only suppressed by the inhibition of the NF-kappaB pathway. Taken together, these results indicate that Msx2 mediates the inhibitory action of TNF-alpha on BMP2-regulated osteoblast differentiation and that the TNF-alpha-activated NF-kappaB pathway is responsible for Msx2 induction.
Alkaline Phosphatase/genetics/metabolism ; Animals ; Animals, Newborn ; Bone Morphogenetic Protein 2/pharmacology ; Cell Culture Techniques ; Cell Differentiation/*drug effects/genetics ; Cell Proliferation/drug effects ; Cells, Cultured ; Core Binding Factor Alpha 1 Subunit/genetics ; Down-Regulation/drug effects ; Gene Expression Regulation/drug effects ; Homeodomain Proteins/antagonists & inhibitors/genetics/*physiology ; Mice ; Mice, Inbred ICR ; Mice, Transgenic ; Osteoblasts/*drug effects/metabolism/physiology ; RNA, Small Interfering/pharmacology ; Tumor Necrosis Factor-alpha/*pharmacology