摘要:

To study whether room air is as effective as 100% O2in resuscitation after hypoxia, hypoxemia (Pao22.3–4.3 kPa) was induced in newborn pigs (2–5 d old) by ventilation with 8% O2in nitrogen. When systolic blood pressure had fallen to 20 mm Hg, animals were randomly reoxygenated with either 21% O2(group 1, n - 9) or 100% O2(group 2, n = 11) for 20 min followed by 21% O2in both groups. Controls (group 3, n = 5) were ventilated with 21% O2throughout the experiment. Base deficit peaked at 31 ± 5 mmol/L (mean ± SD) for both hypoxic groups at 5 min of reoxygenation and then normalized over the following 3 h. There were no statistically significant differences between the two groups during reoxygenation concerning blood pressure, heart rate, base deficit, or plasma hypoxanthine. Hypoxanthine peaked at 165 ± 40 and 143 ± 42 μmol/L in group 1 and 2 (NS), respectively, and was eliminated monoexponentially in both groups with an initial half-life for excess hypoxanthine of 48 ± 21 and 51 ± 27 min (NS), respectively. Blinded pathologic examination of cerebral cortex, cerebellum, and hippocampus after 4 d showed no statistically significant differences with regard to brain damage. We conclude that 21% O2is as effective as 100% O2for normalizing blood pressure, heart rate, base deficit, and plasma hypoxanthine after severe neonatal hypoxemia in piglets and that the extent of the hypoxic brain damage is similar in the two groups.

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Pressure ventilation of the newborn can adversely affect the cardiovascular system. Increasing airway pressure increases cerebral venous pressure, thus stressing brain vasculature. To test the hypothesis that cerebral venous distension caused by mechanical ventilation alters cerebral microvascular responses, we studied cerebrovascular responses before, during, and after positive pressure ventilation. Anesthetized newborn pigs were ventilated with a standard time-cycled, pressure-limited infant respirator. Pial arterioles were measured in response to hypercapnia, topical isoproterenol, and topical norepinephrine during control [mean airway pressure (Paw) = 0.9 ± 0.05 kPa (4.8 ± 0.3 cm H2O)] conditions, during 40–60 min of increased Paw [2.5 ± 0.2 kPa (13.9 ± 1.3 cm H2O)], and when the Paw was lowered again. Pial arteriolar dilation in response to hypercapnia was not changed by increasing Paw. Similarly, responses to isoproterenol and norepinephrine were unaltered during raised Paw. However, a significant decrease in responses to topical isoproterenol and norepinephrine was observed after increased Paw. These experiments show that specific prostanoid-independent cerebrovascular responses are altered subsequent to pressure ventilation, whereas prostanoid-dependent dilation to hypercapnia was not affected. These changes suggest that the newborn cerebral vasculature is affected by positive pressure ventilation, further raising the possibility that ventilation-induced alterations in microvascular responses could make the brain more vulnerable to added stresses after pressure ventilation.

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Taurine is an organic osmolyte in brain cells. We studied whether cerebral taurine transport is enhanced as part of the cell volume regulatory adaptation to hypernatremia. Hypernatremic dehydration was induced for 48 h. Synaptosomes, metabolically active nerve terminal vesicles, were isolated by homogenization of brain and purification on a discontinuous Ficoll gradient. Taurine transport was evaluated in vitro using a rapid filtration assay. After 48 h of hypernatremia, there was a 22.4% increment in Na+-specific taurine transport from 2.99 ± 0.16 to 3.66 ± 0.13 μmol/mg protein/30 min (p < 0.001). Dehydration for 48 h without hypertonic saline loading had no effect on taurine uptake. Glycine transport was unaltered by hypernatremia. The adaptation in taurine uptake resulted from an enhanced Vmaxof the high affinity-low capacity transport system [265 ±17, control versus 337 ±19 nmol/min/ mg protein, experimental (p < 0.03)] without a change in the Km (≈60 μM). Under both control and hypernatremic conditions, Na+and Cl−were required for maximal total Na+-mediated taurine uptake. Oubain (1 mM) decreased taurine uptake by 25%, whereas addition of β-alanine or hypotaurine (500 μM) to the external media reduced taurine transport by 45–65% in both control and experimental conditions (p < 0.01). Synaptosomal taurine uptake in hypernatremic rats was inhibited by 15–20% (p < 0.01) after addition of 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (0.1 mM) or 4,4'-diisothiocyanostiIbene-2,2'-disulfonic acid (0.1 mM) to the external medium. We conclude that hypernatremic dehydration of moderate severity and duration results in stimulation of brain taurine uptake, mediated by increased activity of the β-amino acid carrier. An intact anionic binding site is required for maximal taurine uptake during hypernatremia.

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

We investigated, using a human placental choriocarcinoma cell line as a model, the effects of the immunosuppressive drug cyclosporin A on several placental transport systems mediating the transfer of glucose and amino acids from mother to fetus. The results of the investigation show that the transport system responsible for the transfer of taarine is selectively impaired by the drug, whereas the other transport systems are either stimulated or not affected. The inhibitory effect of the drug on taurine transport appears to be due to interference with calmodulin-dependent processes because calmodulin antagonists such as W-7, calmidazolium, and CGS 9343B mimic the effects of cyclosporin A. FK506, another immunosuppressive drug that is currently undergoing clinical trials, does not have this inhibitory effect.

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The mdx mouse has been used for the development of cellular and gene therapies for Duchenne muscular dystrophy. The relatively frequent occurrence of dystrophin-positive muscle cells called revertants has hampered these efforts by interfering with data interpretation. The mdx4cvand mdx5cvdystrophin mouse mutants have approximately 10-fold fewer revertants than the mdx mutant at both 2 and 6 mo. The mdx3cvdystrophin mouse mutant may be a useful model for some types of human dystrophin deficiencies in which the levels of dystrophin are low but not completely absent.

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

We examined the ability of severe combined immunodeficient (SCID) mice-human peripheral blood leukocyte (PBL) chimeras to respond to immunization with Haemophilus influenzae b polysaccharide (Hib PS) vaccines. Two to 3 wk after PBL engraftment, human-PBL-SCID mice, prepared with PBL from one of five adult donors, were immunized with free or protein-conjugated Hib PS. Antibody to Hib PS was quantitated in preimmunization and postimmunization sera. Before immunization, anti-Hib PS antibody was detectable (>10 ng/mL) in three of 40 mice. Of the 37 human-PBL-SCID mice not having detectable serum antibody before immunization, 31 produced ≥20 ng/mL (≥2-fold increase) anti-Hib PS antibody 2 to 3 wk after immunization. Both free and protein-conjugated forms of Hib PS were immunogenic. Geometric mean anti-Hib PS antibody levels ranged from 50 to 139 ng/mL. Vaccine-induced anti-Hib PS antibodies frequently expressed Hibld-1, a cross-reactive idiotype that predominates the in vivo human antibody response to Hib PS. However, among mice engrafted with PBL from a single donor, the Hibld-1 distribution was highly skewed, suggesting that clonally distinct B cells were being stimulated in individual mice. These findings indicate that human PBL transplanted into SCID mice are functionally responsive to Hib PS antigenic challenge. This system may serve as a useful model for studying the regulation and cellular requirements for human polysaccharide immunity.

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID