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Activity Dependent (activity + dependent)

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Medical Sciences	75%

Selected Abstracts

Effect of Osteoblast-Targeted Expression of Bcl-2 in Bone: Differential Response in Male and Female Mice,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2005
Alexander G Pantschenko
Abstract Transgenic mice (Col2.3Bcl-2) with osteoblast-targeted human Bcl-2 expression were established. Phenotypically, these mice were smaller than their wildtype littermates and showed differential effects of the transgene on bone parameters and osteoblast activity dependent on sex. The net effect was an abrogation of sex differences normally observed in wildtype mice and an inhibition of bone loss with age. Ex vivo osteoblast cultures showed that the transgene had no effect on osteoblast proliferation, but decreased bone formation. Estrogen was shown to stimulate endogenous Bcl-2 message levels. These studies suggest a link between Bcl-2 and sex regulation of bone development and age-related bone loss. Introduction: Whereas Bcl-2 has been shown to be an important regulator of apoptosis in development, differentiation, and disease, its role in bone homeostasis and development is not well understood. We have previously showed that the induction of glucocorticoid-induced apoptosis occurred through a dose-dependent decrease in Bcl-2. Estrogen prevented glucocorticoid-induced osteoblast apoptosis in vivo and in vitro by preventing the decrease in Bcl-2 in osteoblasts. Therefore, Bcl-2 may be an important regulator of bone growth through mechanisms that control osteoblast longevity and function. Materials and Methods: Col2.3Bcl-2 mice were developed carrying a 2.3-kb region of the type I collagen promoter driving 1.8 kb of human Bcl-2 (hBcl-2). Tissue specific expression of hBcl-2 in immunoassays validated the transgenic animal model. Histomorphometry and DXA were performed. Proliferation, mineralization, and glucocorticoid-induced apoptosis were examined in ex vivo cultures of osteoblasts. The effect of estrogen on mouse Bcl-2 in ex vivo osteoblast cultures was assayed by RT-PCR and Q-PCR. Results and Conclusions: Two Col2.3Bcl-2 (tg/+) founder lines were established and appeared normal except that they were smaller than their nontransgenic wildtype (+/+) littermates at 1, 2, and 6 months of age, with the greatest differences at 2 months. Immunohistochemistry showed hBcl-2 in osteoblasts at the growth plate and cortical surfaces. Nontransgenic littermates were negative. Western blots revealed hBcl-2 only in type I collagen-expressing tissues. Histomorphometry of 2-month-old mice showed a significant decrease in tg/+ calvaria width with no significant differences in femoral trabecular area or cortical width compared with +/+. However, tg/+ males had significantly more trabecular bone than tg/+ females. Female +/+ mice showed increased bone turnover with elevated osteoblast and osteoclast parameters compared with +/+ males. Col2.3Bcl-2 mice did not show such significant differences between sexes. Male tg/+ mice had a 76.5 ± 1.5% increase in ObS/BS with no significant differences in bone formation rate (BFR) or mineral apposition rate (MAR) compared with male +/+ mice. Transgenic females had a significant 48.4 ± 0.1% and 20.1 ± 5.8% decrease in BFR and MAR, respectively, compared with +/+ females. Osteoclast and osteocyte parameters were unchanged. By 6 months, femurs from female and male +/+ mice had lost a significant amount of their percent of trabecular bone compared with 2-month-old mice. There was little to no change in femoral bone in the tg/+ mice with age. Ex vivo cultures of osteoblasts from +/+ and Col2.3Bcl-2 mice showed a decrease in mineralization, no effect on proliferation, and an inhibition of glucocorticoid-induced apoptosis in Col2.3Bcl-2 cultures. Estrogen was shown to increase mouse Bcl-2 transcript levels in osteoblast cultures of wildtype mice, supporting a role for Bcl-2 in the sex-related differences in bone phenotype regulated by estrogen. Therefore, Bcl-2 differentially affected bone phenotype in male and female transgenic mice, altered bone cell activity associated with sex-related differences, and decreased bone formation, suggesting that apoptosis is necessary for mineralization. In addition, Bcl-2 targeted to mature osteoblasts seemed to delay bone development, producing a smaller transgenic mouse compared with wildtype littermates. These studies suggest that expression of Bcl-2 in osteoblasts is important in regulating bone mass in development and in the normal aging process of bone. [source]

Severe withdrawal syndrome in three newborns subjected to continuous opioid infusion and seizure activity dependent on brain hypoxia , ischemia.

PEDIATRIC ANESTHESIA, Issue 10 2006
A possible link
Summary Background :,The aim of this investigation was to verify whether brain hypoxia represented a risk factor for the occurrence and severity of opioid abstinence syndrome. Methods :,Three newborns who manifested seizure activity as a result of hypoxia, focal brain ischemia, and hypoxia and sepsis, respectively, were compared with 17 neonates who suffered from hypoxia without developing seizure activity. Results :,The first three neonates suffered a severe withdrawal syndrome (a rating on the neonatal abstinence score >17), the others did not. Conclusions :,It is hypothesized that brain hypoxia facilitated the occurrence and severity of the withdrawal syndrome because some key neurochemical processes (such as N -methyl- d -aspartate activation, protein kinase C activation and nitric oxide production) are common to both phenomena. [source]

In vitro antiproliferative effect of six Salvia species on human tumor cell lines

PHYTOTHERAPY RESEARCH, Issue 8 2006
Giovina Fiore
Abstract This study was designed to examine the in vitro antiproliferative activity of the methanol crude extracts of six Salvia species: Salvia dominica L. leaves, Salvia lanigera Desf. aerial parts, Salvia menthaefolia Ten. roots, Salvia palaestina Benth. aerial parts, Salvia sclarea L. roots and Salvia spinosa L. aerial parts. Extracts were screened for their possible antitumoral activity by MTT test on nine human cancer cell lines: glioblastoma (DBTRG-05MG, T98G, U-87MG), colorectal adenocarcinoma (WiDr and HT-29), prostate adenocarcinoma (MDA Pca2b), choriocarcinoma (JEG-3), endometrium adenocarcinoma (HEC-1A) and B lymphoblast (CIR). IC50 values were determined for only five extracts and ranged from 90 to 400 mg/mL approximately. Salvia menthaefolia extract exhibited marked antiproliferative activity against all tumor cell lines showing lower IC50 values, while S. spinosa, S. sclarea and S. dominica extracts showed a degree cytotoxic activity dependent on the cell line type. Finally S. palaestina extract revealed a moderate antiproliferative effect only against three cell lines. Salvia lanigera extract displayed toxic activity at all concentrations tested. The results strengthen the evidence that the genus Salvia could be considered a natural resource of potential antitumor agents. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Effect of sandy and muddy substrates on the growth and survival of the freshwater clam Galatea paradoxa (Born 1778)

AQUACULTURE RESEARCH, Issue 9 2010
Daniel Adjei-Boateng
This study was conducted to determine the effect of a sandy and muddy substrate on the growth and survival of three size-classes of Galatea paradoxa (Born 1778). The experiment was conducted over a 6-month period in a 1000 m2 pond at the research farm of the Faculty of Renewable Natural Resources. Three size classes (shell length) of G. paradoxa categorized as small (20,30 mm), medium (31,40 mm) and large (>40 mm) were used to ascertain the effect of a sandy and muddy substrate on growth performance. Growth in general was very slow, between 1.4 and 2.4 mm over the 6-month experimental period. The lengths measured at the end of the experiment were also significantly different. However, the mean length gained and the specific growth rate for the three size classes in the two substrates (sandy and muddy) were not significantly different (P>0.05). The results of this study indicate that the pond environment is not suitable for the culture G. paradoxa as the species is adapted to life in a river with its filter-feeding activity dependent on the water current. The effect of the substrate type on growth was not significant. However, the substrate type did affect survival, with sandy substrates yielding in better survival than muddy ones. [source]