摘要:

The role of type IV collagenases during rat bladder development and in response to partial bladder outlet obstruction was evaluated. Gelatinase gel zymography was performed on developing rat bladders (gestation d 16 and 19, at birth, 5, 10, 15, 20, 30, and 75 d postnatally), after partial obstruction of the bladder outlet in young adults and after separation of the epithelium from the mesenchyme in young adults. Bladder function was assessed by cystometry in obstructed animals. During development, the 72-kD type-IV collagenase [matrix metalloproteinase (MMP)-2, both latent and activated] was maximally expressed in the fetal period and decreased with age; whereas the 92-kD gelatinase(MMP-9) was not expressed in developing or adult bladders. MMP-2 was localized to the bladder mesenchyme and was undetectable in isolated epithelium. In 46 obstructed rats, there was an 8-fold increase in bladder volume and weight along with smooth muscle hypertrophy (mean smooth muscle cell diameter 7.09± 0.11 μmversus4.65 ± 0.05 μm in normal animals,p< 0.001). Obstructed rats had increased quantities of latent and activated MMP-2 and MMP-9 compared with sham-operated and normal controls. These findings suggest that expression and activation of type IV collagenases (MMP-2 and 9) are developmentally regulated and play a role in bladder remodeling during developmental morphogenesis and after partial outlet obstruction.Abbreviations: ECM,extracellular matrix;MMP,matrix metalloproteinases

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The XRCC1 (X-RayRepairCrossComplementing) gene was described to play a role for the sensitivity of mammalian cell lines toward ionizing irradiation. Cells with a mutation of this gene present with decreased single strand break repair and reduced recombination repair, they show increased double strand breaks, and sister chromatid exchange is increased up to 10-fold. The goal of our study was to investigate the transcription of this gene in the heart after ionizing irradiation in the mouse. Furthermore, we intended to examine whether radiation-sensitive mice would show a transcriptional pattern different from radiation-resistant mice. Radiation-sensitive BALB/c/J Him mice and radiation-resistant C3H He/Him mice were whole body irradiated with x-ray at 2, 4, and 6 Gy and killed 5, 15, and 30 min after irradiation. mRNA was isolated from the heart and hybridized with probes for XRCC1 and β-actin as a housekeeping gene control. Irradiation at 2 Gy showed increased transcription of XRCC1 at 5 min in the C3H He/Him group, approached XRCC1 transcription of BALB/c J/Him mice at 15 min, and was lower in the latter at 30 min after irradiation. Irradiation at 4 Gy showed double the transcription at 5 min and an about 3-fold rapid increase of mRNA XRCC1 in the radiation-resistant group at 15 min after irradiation, returning to the transcriptional level of sensitive animals at 30 min. Irradiation at 6 Gy seemed to overwhelm the system in both groups, but resistant mice still showed higher levels of XRCC1 transcription. We conclude that radiation-resistant mice show a higher transcription level for the XRCC1 gene in the heart early after x-ray whole body irradiation. This finding is the firstin vivostudy on XRCC1 of this kind and may in part explain the differences in the radiation sensitivity between the two strains studied.Abbreviations: XRCC1,x-ray repair cross complementing;RS,radiation sensitive;RR,radiation resistant;CHO,Chinese hamster ovary

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Dehydroepiandrosterone sulfate (DHEAS) is prenatally secreted by the fetal adrenal, is an indicator of adrenarche from late childhood onward and is a marker of the individual hormonal milieu in the adult. The regulation of DHEAS secretion is still poorly understood. We postulated that serum DHEAS concentrations in children may be related to fetal growth. To test this hypothesis, serum DHEAS was measured at a median age of 8.2 y (range 5.8-16.0 y) in 13 pairs of discordant siblings after twin (n= 8), triplet(n= 4), or quadruplet (n= 1) pregnancy. At birth, one of each pair was small for gestational age (SGA) and the other had an appropriate weight (AGA); weight of the smallest infant was a median 67% (range 33-80%) of that of the largest sibling. In all 10 pairs with similar weight (≤ 1 SD difference) at the time of sampling, serum DHEAS concentration in the SGA child was higher (median 2-fold increase; range 1.1-7;p= 0.002) than in the AGA sibling. Conversely, in the 3 pairs with still discordant weight (>2 SD difference), serum DHEAS levels in SGA children were lower than in AGA children. In conclusion, the presented findings, which account for both prenatal and postnatal weight gain, unmask a link between adrenarche and fetal growth. This relationship further supports the concept of early endocrine “programming” and extends this principle to adrenarche.Abbreviations: AGA,appropriate for gestational age;SGA,small for gestational age;DHEAS,dehydroepiandrosterone sulfate;DHEA,dehydroepiandrosterone

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Severely birth-asphyxiated human infants develop delayed(“secondary”) cerebral energy failure, which carries a poor prognosis, during the first few days of life. This study tested the hypothesis that i.v. magnesium sulfate (MgSO4) after severe transient cerebral hypoxia-ischemia decreases the severity of delayed energy failure in the newborn piglet. Twelve piglets underwent temporary occlusion of the common carotid arteries and hypoxemia. Resuscitation was started when cerebral[phosphocreatine (PCr)]/[inorganic phosphate (Pi)], as determined by phosphorus magnetic resonance spectroscopy, had fallen virtually to zero, and nucleotide triphosphate (NTP) had fallen below a third of baseline. The piglets were randomized to receive, blind, either:1) three i.v. infusions of 12.5% MgSO4heptahydrate solution: 400 mg·kg-1MgSO4·7H2O starting 1 h after resuscitation, and 200 mg·kg-112 and 24 h later (n= 6); or2) three infusions of placebo, 0.9% NaCl (n= 6). Phosphorus and proton spectroscopy were continued until 48 h after resuscitation, and values were compared between the two groups. Mean plasma magnesium levels, 1 h after each of the three doses of MgSO4, were 2.1, 2.0, and 1.9 mmol·L-1, respectively. The severity of the primary insult, determined by the time-integral of depletion of cerebral[NTP]/[exchangeable phosphate pool (EPP)], was similar in the MgSO4-treated and placebo groups. After resuscitation, there was no difference in the progression or severity of delayed energy failure between the two groups, as judged by cerebral [PCr]/[Pi], [NTP]/[EPP], or lactate/creatine andN-acetylaspartate/creatine peak-area ratios. We conclude that MgSO4did not decrease the severity of delayed cerebral energy failure.Abbreviations: Cr,creatine;EPP,exchangeable phosphate pool;Lac,lactate;MABP,mean arterial blood pressure;MRS,magnetic resonance spectroscopy;Naa,N-acetylaspartate;NMDA,N-methyl-D-aspartate;PCr,phosphocreatine;Pi,inorganic phosphate

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID