摘要:

We examined the ontogeny of relaxation responses to three categories of calcium channel antagonists, represented by verapamil, diltiazem, and nifedipine, for both potential-operated (KCl-mediated) and receptor-operated channels [norepinephrine (NE)-mediated] in rat thoracic aorta. Aortic rings from 2− to 3-d, 1-wk, and 12-wk-old Sprague Dawley rats were mounted in an organ bath, bathed in Krebs' solution, and connected to a force-displacement transducer to measure isometric tension. Endothelium intact vessels at optimal passive force were exposed to a single ED50of isotonic KCl or NE, equilibrium contraction was measured, then vessels were washed and exposed for 30 min to 1 $mUM verapamil, 1 $mUM diltiazem, or 0.1 $mUM nifedipine, followed by another dose of KCl or NE. Verapamil and diltiazem demonstrated significant (p< 0.05) age-related increases in effectiveness for blocking KCl-mediated contraction [(% reduction of control contraction $$ SEM) (Verapamil: 2–3 d, 67.7 $$ 4.2; 1 wk, 72.5 $$ 1.8; 12 wk, 89.5 $$ 1.0. Diltiazem: 2–3 d, 64.6 $$ 2.9; 1 wk, 73.5 $$ 3.0; 12 wk, 83.1 $$ 1.8]. Nifedipine was equally effective at all ages: 2–3 d, 85.6 $$ 1 1.3; wk, 90.0 $$ 1.6; and 12 wk, 91.3 $$ 1.4. Verapamil and diltiazem also showed significant age-related increases in effectiveness for blocking NE-mediated contraction (Verapamil: 2–3 d, 6.2 $$ 3.9; 1 wk, 28.0 $$ 4.8; 12 wk, 44.1 $$ 6.0. Diltiazem: 2–3 d, 8.0 $$ 3.1; 1 wk, 20.5 $$ 3.9; 12 wk, 46.5 $$ 4.8). Again, nifedipine was equally effective at all ages: 2–3 d, 42.0 $$ 6.8; 1 wk, 35.8 $$ 3.9; and 12 wk, 37.5 $$ 3.2. In summary, for the categories of calcium channel antagonists that interact at the phenylalkytomine (verapamil) and benzothiazepine (diltiazem) binding sites, there were age-related increases in effectiveness for blocking both potential-operated and receptor-operated channels. However, for nifedipine, which binds to the 1,4-dihydropyridine binding site, no maturational change was observed. These results suggest that the ontogeny of calcium channel antagonists' function may vary depending on the site of binding within the calcium channel. (Pediatr Res29: 278–281, 1991)

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Prostacyclin is released during hyperventilation (HV); however, its role as mediator of HV-induced pulmonary vasodilation remains controversial. We have investigated this by studying the effects of HV on pulmonary artery pressure (PAP) in otherwise normal lungsversuslungs vasoconstricted with group B streptococci (GBS), with and without prior prostacyclin synthesis inhibition. Two-to 3-wk-old piglets were given tranylcypromine, a prostacyclin synthetase inhibitor (n= 6), or placebo (n= 6). Animals were mechanically ventilated normally, then hyperventilated (PCO21.5 $$ 0.2 kPa) and then returned to normal ventilation. After each 30-min segment, plasma 6-keto-prostaglaiidin F1a(6-keto-PGF1a) (prostacyclin hydrolysis product) levels and PAP were measured. Then GBS infusions were administered to both groups to induce pulmonary hypertension. With GBS, the normal ventilation/hyperventilation/normal ventilation protocol was repeated as above. Results are as follows:1) HV of normal lungs caused release of 6-keto-PGF1a(351 $$ 234 to 873 $$ 310 pg/mL;p< 0.05), but PAP was unaffected (1.4 $$ 0.2 kPa);2) HV of lungs vasoconstricted with GBS caused a similar release of 6-keto-PGF1a(595 $$ 112 to 977 $$ 216 pg/mL;p< 0.05), this time accompanied by a significant decrease in PAP (3.1 $$ 0.5 to 2.3 $$ 0.5 kPa;p< 0.05);3) HV of normal lungs pretreated with tranylcypromine produced neither an increase in 6-keto-PGF1a(400 $$ 24 to 436 $$ 33 pg/mL) nor a decrease in PAP (1.3 $$ 0.2 to 1.4 $$ 0.2 kPa; and4) HV after tranylcypromine pretreatment and GBS-induced pulmonary hypertension also produced no change (6-keto-PGF1a:527 $$ 54 to 556 $$ 93 pg/mL and PAP; 39.5 $$ 6.2 to 37.6 $$ 6.7 kPa). In conclusion, prostacyclin may mediate HV-induced pulmonary vasodilation after GBS-induced pulmonary hypertension, (Pediatr Res29: 282–287, 1991)

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Prenatal caloric restriction in guinea pigs causes intrauterine growth retardation and reduced neonatal viability and surfactant phosopholipid (PL). We report here fetal surfactant levels in this model, and correlate total lung PL with ultrastructural maturation of surfactant type II cells and lamellar bodies (LB). Pregnant guinea pigs were fedad libitumthroughout their 68-d gestation (control), or fed 50% rations from d 45 until term (starved). Fetal lungs were examined at d 55, 60, and 65 for PL content and composition, including disaturated phosphati-dylcholine (DPC), and compared with neonates for both groups. Lung lobes were analyzed ultrastructurally in d 65 fetuses for the numerical, volume, and surface densities of type II cells and the volume densities of LB. Prenatal starvation caused significant intrauterine growth retardation at all ages; body and dry lung weights were reduced on d 65 by 26 and 23%, respectively. By d 55 and thereafter, starvation decreased total lung PL by 43–45% but did not alter PL composition. On d 65, the total lung volumes and relative numbers, surface densities, and volumes of type II cells in tissue and the relative volumes of LB within type II cells did not differ by caloric regimen. Thus, starved and control fetuses had similar total volumes of LB per lung (13–15 $mUL), although starved animals had significantly less lung DPC. Although the total volume of LB per lung correlated well with total lung DPC from d 55 through birth in controls, starvation led to a significant departure from this relationship. These results suggest that the concentration of DPC within LB can vary markedly without changing the size and appearance of the LB, or that the reduced amounts of DPC in starved fetuses represent deficiencies of surfactant from non-LB compartments. (Pediatr Res29: 288–291, 1991)

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Although the prematurely born are known to have decreased baseline levels of protective antioxidant enzymes (Frank L, Sosenko IRS: J Pediatr 110:9 and 106, 1987), the ability to augment the baseline values during high O2exposure is the key factor determining O2toleranceversusO2susceptibility. We have compared the pulmonary antioxidant enzyme responses of prematurely delivered rabbits (gestational d 29 of 32) and full-term rabbits to 48–72 h of hyperoxic exposure. We found that although full-term newborns exposed to >90% O2consistently showed elevated superoxide dismutase, catalase, glutathione peroxidase, and glucose-6-phosphate dehydrogenase activities, the premature animals repeatedly failed to respond to hyperoxia with increased antioxidant enzyme activity levels. Consistent with the comparative antioxidant enzyme responses were the evidences of O2toxicity in the two age groups. The prematurely born rabbits had significantly increased lung lavage protein content, lung conjugated diene levels, and more severe light microscopic lung pathology compared with the full-term animals during equal O2exposure time. This first reported comparison of prematurely bornversusfull-term animal responses to hyperoxia might help to explain the clinical observation that the very prematurely born infant is excessively prone to the development of O2-induced lung injury and the progressive development of bronchopulmonary dysplasia. (Pediatr Res29: 292–296, 1991)

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Erythrocyte superoxide dismutase (ESOD) activity reflects copper utilization and the risk of copper deficiency. To investigate the possible effects of inorganic iron on the metabolism of copper in low birth weight infants, we have measured ESOD activities in three groups of infants receiving different iron supplements. Fifty-five low birth weight infants were randomly assigned to receive daily from 28 d either 13.8 mg (HiFe), 7 mg (MidFe), or no elemental iron (NatFe) as iron edetate. At 27 d, 8, 12, and 20 wk postnatal age, infants were weighed and measured and hematologic indices, plasma ferritin, zinc, and copper concentrations, and ESOD activities were assayed. Anthropometrical and hematologic indices and plasma copper and zinc concentrations did not differ among treatment groups at any time, but at 20 wk, plasma ferritin concentrations $$($mUg/L) mean; SD$$ were lower in the NatFe group (17; 2.0) than in the HiFe group (32; 1.9: 95% confidence interval for mean difference 6.6 to 22.0, p < 0.01). ESOD activities (U/g Hb) were similar in HiFe (1447; 263), MidFe (1552; 322), and NatFe (1538; 382) groups at 27 d, but by 20 wk activities in the HiFe group (1537; 211) were lower than in the MidFe (1789; 403:95% confidence interval 38 to 466,p< 0.05) and NatFe (1858; 304: 95% confidence interval 150 to 492,p< 0.01) groups. The lower ESOD activities found in the HiFe group at 20 wk may reflect altered copper metabolism induced by the iron supplement, but the clinical importance of this observation is unknown. (Pediatr Res29: 297–301, 1991)

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

We evaluated the effectiveness of administration of high-dose busulfan (BU), an alkylating agent with substantial myeloablative but negligible immunosuppressive properties, on the engraftment of congenic normal bone marrow and spleen cells (hematopoietic cell transplantation; HCT) in murine galactosylceramidase deficiency (the twitcher mouse), a model of human sphingolipid storage disease. Untreated mice died with extensive demyelbtatioa and failure to thrive at a median age of 40 d (range, 28–47;n= 51). The life-span of twitcher mice given HCT at age 10 d after 100 mg/kg BU was significantly prolonged (median, 94 d; range, 55–140;n= 17); these animals did not develop the hindlimb paralysis seen in untreated twitchers. Histologic examination of twitcher sciatic nerves after HCT showed remyelinated areas and decreased globoid cell inclusions. Animals given HCT after conditioning with BU had both lymphoid and hematopoietic repopulation with donor cells by 90 d after HCT, as documented by presence of donor glucose phosphate isomerase-1A activity in blood, bone marrow, spleen, and lymph nodes. After BU and HCT, galactosylceramidase activity in livers and spleens of twitcher mice reached 45 and 80% of control, respectively; only modest elevations were observed in kidneys and lymph nodes. Hydrolase activity rose to 20% in the brains and exceeded control values in the sciatic nerves of transplanted twitcher mice, indicating entry of at least some donor-derived cells and/ or hydrolase across the blood-brain and blood-nerve barriers after BU and HCT. These observations suggest that, in gene-replacement therapy for human lysosomal storage diseases, administration of BU alone may be sufficient for sustained engraftment of autologous marrow cells into which the specific hydrolase gene has been inserted. (Pediatr Res29: 302–305, 1991)

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

We have studied an 8-yr-old male patient with adenosine deaminase-positive severe combined immunodeficiency disease with a normal number of peripheral CD3+, T cell receptor-αβ+T cells. The majority of these T cells expressed the CD8 molecule and were oligoclonal in nature as proven by Southern blot analysis of the T cell receptor genes. T cells failed to proliferatein vitroeither upon stimulation with T cell mitogens or when stimulated with a combination of the phorbol ester phorbol myristate acetate and the Ca-ionophore ionomycin. High doses of recombinant IL-2, when added toin vitrocultures, were able to restore proliferation induced by phorbol myristate acetate and ionomycin but the response to concanavalin A remained severely defective. However, activation of the patient's T cells with phytohemagglutinin or concanavalin A induced an increase of free cytoplasmic Ca++, which was 2− to 5-fold higher than in normal CD8+T cells. Furthermore, phorbol myristate acetate or phytohemagglutinin induced the translocation of protein kinase C from cytosol to plasma membrane. Analysis of membrane phospholipid composition of the patient's T cells disclosed that the ratio of phosphatidylcholine to phosphatidylserine was 5-fold higher than in normal T cells. The abnormal Ca++response after activation with T cell raitogens as well as the high phosphatidylcholine/phosphatidylserine ratio may be causally linked to the defectivein vitroT cell proliferation. Because the capacity of T lymphocytes to produce or respond to IL-2 may vary, the oligoclonality of the T cells of the patient should be considered as well in the explanation of defective cell proliferation. (Pediatr Res29: 306–309, 1991)

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

We have developed a human MAb that opsonizes group B streptococci, the major cause of gram-positive bacterial sepsis in newborns. It is an IgM class human MAb that possesses unique protective activity against experimental infections caused by the predominant group B capsule serotypes III and I. Preliminary preclinical studies with the IgM human MAb were designed to provide initial information useful for predicting its safety and pharmacokinetic properties. Two neonatalMacaca fascicularismonkeys were infused with the human MAb at either 17.8 or 230 mg/kg. Safety was evaluated by visually monitoring postinfusion clinical status and by standard clinical chemistry analyses and quantitative hematology on blood samples collected for 30 d. The serum antibody levels were determined by ELISA and antibody functional activity in serum samples by opsonophagocytic assays. The IgM human MAb appeared safe (normal laboratory values and clinical status) with a half-life of 2.5 d, a period compatible with the 5-d half-life reported for human IgM in adult serum. In addition, the human MAb retained functional opsonic activity for at least 30 d. Human MAb may offer a safe alternative for treating severe bacterial infections.

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The purpose of this study was to examine sex- and age-related differences in the concentration and composition of lipoprotein particles containing apoA-I (LP-A-I) and those containing apoA-I and apoA-II (LP-I:A-II), the main HDL as defined by their apolipoprotein composition. Lipoproteins were isolated by immunoaffinity chromatography of whole plasma from 16 normal prepubertal children and 15 normal male and female adults using “pan”-MAb to apoA-I and apoA-II. Although there was no difference between children and adults in the concentration of LP-A-I:A-II, adult females had significantly higher levels of LP-A-I than either children or adult males. Main differences between children and adults as well as between adult males and females were in the apolipoprotein composition of the lipoprotein particles; children had the highest content of minor apolipoproteins (apoC and apoE) in LP-A-I but the lowest in LP-A-I:A-II. The lipid/apolipo-protein ratios of LP-A-I and LP-A-I:A-II were significantly higher in children and women than in men. The LP-A-I and LP-A-I:A-II contained 75% of the total plasma apoC and apoE in women and children but only 50% in men. However, in all three groups, 70–90% of the minor HDL apolipoproteins were associated with LP-A-I:A-II. The nonmolar ratios of minor apolipoproteins in LP-A-I and LP-A-I:A-II and the sex- and age-related differences in apoA-I/apoA-II ratios of LP-A-I:A-II suggest that both lipoproteins may consist of a spectrum of lipoprotein subfamilies differing in their apolipoprotein composition. Results of this study indicate that the age- and sex-related differences in the levels and composition of LP-A-I and LP-A-I:A-II relate primarily to changes in the protein moieties of these particles. (Pediatr Res 29: 315–321, 1991)

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID