Objective: Oxidative stress, a common feature in cardiovascular and renal disease is associated with the causes and consequences of fetal growth restriction. Hence, renal redox status is likely an early determinant of morbidity in small-for-gestational-age (SGA) infants. In this study, we examined renal oxidative stress in naturally-farrowed SGA newborn pigs.
Methods: We studied SGA newborn pigs with 52% less body weight and 59% higher brain/liver weight ratio compared with their appropriate-for-gestational-age (AGA) counterparts.
Results: The kidneys of the SGA newborn pigs weighed 56% less than the AGA group. The glomerular cross-sectional area was also smaller in the SGA group. SGA newborn pigs exhibited increased renal lipid peroxidation, reduced kidney and urine total antioxidant capacity, and increased renal nitrotyrosine immunostaining. Whereas the protein expression level of NADPH oxidase (NOX)2 was unchanged, NOX4 expression was significantly higher in SGA kidneys. The level of serum potassium was lower, but serum sodium and creatinine were similar in SGA compared with AGA newborn pigs. The serum concentrations of C‐reactive protein and NGAL, the biomarkers of inflammation and early acute kidney injury were significantly elevated in the SGA group.
Conclusion: Early induction of oxidative stress may contribute to the onset of kidney injury in growth-restricted infants. 相似文献
A few thienyl substituted pyrazole derivatives were synthesized to aid in the characterization of the cannabinoid receptor antagonist and also to serve as potentially useful antiobesity agent. Structural requirements for selective CB1 receptor antagonistic activity of 5-thienyl pyrazole derivatives included the structural similarity with potent, specific antagonist rimonabant 1. Compound 3 has been identified as a hair growth stimulator and an antiobesity agent in animal models. 相似文献
The purpose of this research was to generate, characterize, and investigate the in vivo efficacy of budesonide (BUD) microparticles prepared by spray-drying technology with a potential application as carriers
for pulmonary administration with sustained-release profile and improved respirable fraction. Microspheres and porous particles
of chitosan (drug/chitosan, 1:2) were prepared by spray drying using optimized process parameters and were characterized for
different physicochemical parameters. Mass median aerodynamic diameter and geometric standard deviation for conventional,
microspheres, and porous particles formulations were 2.75, 4.60, and 4.30 μm and 2.56, 1.75, and 2.54, respectively. Pharmacokinetic
study was performed in rats by intratracheal administration of either placebo or developed dry powder inhalation (DPI) formulation.
Pharmacokinetic parameters were calculated (Ka, Ke, Tmax, Cmax, AUC, and Vd) and these results indicated that developed formulations extended half life compared to conventional formulation
with onefold to fourfold improved local and systemic bioavailability. Estimates of relative bioavailability suggested that
developed formulations have excellent lung deposition characteristics with extended T1/2 from 9.4 to 14 h compared to conventional formulation. Anti-inflammatory activity of BUD and developed formulations was compared
and found to be similar. Cytotoxicity was determined in A549 alveolar epithelial cell line and found to be not toxic. In vivo pulmonary deposition of developed conventional formulation was studied using gamma scintigraphy and results indicated potential
in vitro–in vivo correlation in performance of conventional BUD DPI formulation. From the DPI formulation prepared with porous particles,
the concentration of BUD increased fourfold in the lungs, indicating pulmonary targeting potential of developed formulations. 相似文献
Using simple, inexpensive equipment, we have used solution-phase parallel synthesis to rapidly prepare hundreds of sulfonamide- and urea-containing FKBP inhibitors, resulting in rapid identification of extremely potent compounds in these series. 相似文献
We evaluated the hypothesis that photosynthetic traits differ between leaves produced at the beginning (May) and the end
(November–December) of the rainy season in the canopy of a seasonally dry forest in Panama. Leaves produced at the end of
the wet season were predicted to have higher photosynthetic capacities and higher water-use efficiencies than leaves produced
during the early rainy season. Such seasonal phenotypic differentiation may be adaptive, since leaves produced immediately
preceding the dry season are likely to experience greater light availability during their lifetime due to reduced cloud cover
during the dry season. We used a construction crane for access to the upper canopy and sampled 1- to 2-month-old leaves marked
in monthly censuses for six common tree species with various ecological habits and leaf phenologies. Photosynthetic capacity
was quantified as light- and CO2-saturated oxygen evolution rates with a leaf-disk oxygen electrode in the laboratory (O2max) and as light-saturated CO2 assimilation rates of intact leaves under ambient CO2 (Amax). In four species, pre-dry season leaves had significantly higher leaf mass per unit area. In these four species, O2max and Amax per unit area and maximum stomatal conductances were significantly greater in pre-dry season leaves than in early wet season
leaves. In two species, Amax for a given stomatal conductance was greater in pre-dry season leaves than in early wet season leaves, suggesting a higher
photosynthetic water-use efficiency in the former. Photosynthetic capacity per unit mass was not significantly different between
seasons of leaf production in any species. In both early wet season and pre-dry season leaves, mean photosynthetic capacity
per unit mass was positively correlated with nitrogen content per unit mass both within and among species. Seasonal phenotypic
differentiation observed in canopy tree species is achieved through changes in leaf mass per unit area and increased maximum
stomatal conductance rather than by changes in nitrogen allocation patterns.
Received: 7 March 1996 / Accepted: 1 August 1996 相似文献
A chitinase producing bacterium Enterobacter sp. NRG4, previously isolated in our laboratory, has been reported to have a wide range of applications such as anti-fungal
activity, generation of fungal protoplasts and production of chitobiose and N-acetyl D-glucosamine from swollen chitin. In
this paper, the gene coding for Enterobacter chitinase has been cloned and expressed in Escherichia coli BL21(DE3). The structural portion of the chitinase gene comprised of 1686 bp. The deduced amino acid sequence of chitinase
has high degree of homology (99.0%) with chitinase from Serratia marcescens. The recombinant chitinase was purified to near homogeneity using His-Tag affinity chromatography. The purified recombinant
chitinase had a specific activity of 2041.6 U mg−1. It exhibited similar properties pH and temperature optima of 5.5 and 45°C respectively as that of native chitinase. Using
swollen chitin as a substrate, the Km, kcat and catalytic efficiency (kcat/Km) values of recombinant chitinase were found to be 1.27 mg ml−1, 0.69 s−1 and 0.54 s−1M−1 respectively. Like native chitinase, the recombinant chitinase produced medicinally important N-acetyl D-glucosamine and
chitobiose from swollen chitin and also inhibited the growth of many fungi. 相似文献
The bacterium Francisella tularensis (Ft) is a potential weapon of bioterrorism when aerosolized. Macrophage infection is necessary for disease progression and efficient phagocytosis by human macrophages requires serum opsonization by complement. Microbial complement activation leads to surface deposition of a highly regulated protein complex resulting in opsonization or membrane lysis. The nature of complement component C3 deposition, i.e., C3b (opsonization and lysis) or C3bi (opsonization only) fragment deposition, is central to the outcome of activation. In this study, we examine the mechanisms of Ft resistance to complement-mediated lysis, C3 component deposition on the Ft surface, and complement activation. Upon incubation in fresh nonimmune human serum, Schu S4 (Ft subsp. tularensis), Fn (Ft subsp. novicida), and LVS (Ft subsp. holarctica live vaccine strain) were resistant to complement-mediated lysis, but LVSG and LVSR (LVS strains altered in surface carbohydrate structures) were susceptible. C3 deposition, however, occurred on all strains. Complement-susceptible strains had markedly increased C3 fragment deposition, including the persistent presence of C3b compared with C3bi, which indicates that C3b inactivation results in survival of complement-resistant strains. C1q, an essential component of the classical activation pathway, was necessary for lysis of complement-susceptible strains and optimal C3 deposition on all strains. Finally, use of Francisella LPS mutants confirmed O Ag as a major regulator of complement resistance. These data provide evidence that pathogenic Francisella activate complement, but are resistant to complement-mediated lysis in part due to limited C3 deposition, rapid conversion of surface-bound C3b to C3bi, and the presence of LPS O Ag. 相似文献