• Title/Summary/Keyword: GCS

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Evidence for adverse effect of perinatal glucocorticoid use on the developing brain

  • Chang, Young Pyo
    • Clinical and Experimental Pediatrics
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    • v.57 no.3
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    • pp.101-109
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    • 2014
  • The use of glucocorticoids (GCs) in the perinatal period is suspected of being associated with adverse effects on long-term neurodevelopmental outcomes for preterm infants. Repeated administration of antenatal GCs to mothers at risk of preterm birth may adversely affect fetal growth and head circumference. Fetal exposure to excess GCs during critical periods of brain development may profoundly modify the limbic system (primarily the hippocampus), resulting in long-term effects on cognition, behavior, memory, co-ordination of the autonomic nervous system, and regulation of the endocrine system later in adult life. Postnatal GC treatment for chronic lung disease in premature infants, particularly involving the use of dexamethasone, has been shown to induce neurodevelopmental impairment and increases the risk of cerebral palsy. In contrast to studies involving postnatal dexamethasone, long-term follow-up studies for hydrocortisone therapy have not revealed adverse effects on neurodevelopmental outcomes. In experimental studies on animals, GCs has been shown to impair neurogenesis, and induce neuronal apoptosis in the immature brains of newborn animals. A recent study has demonstrated that dexamethasone-induced hypomyelination may result from the apoptotic degeneration of oligodendrocyte progenitors in the immature brain. Thus, based on clinical and experimental studies, there is enough evidence to advice caution regarding the use of GCs in the perinatal period; and moreover, the potential long-term effects of GCs on brain development need to be determined.

The Predictors of Survival and Functional Outcome in Patients with Pontine Hemorrhage

  • Jung, Dae-Sung;Jeon, Byung-Chan;Park, Yong-Sook;Oh, Hyung-Suk;Chun, Tae-Sang;Kim, Nam-Kyu
    • Journal of Korean Neurosurgical Society
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    • v.41 no.2
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    • pp.82-87
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    • 2007
  • Objective : Pontine hemorrhages usually result in a much higher morbidity and mortality than any other intracranial vascular lesion. The purpose of this study was to evaluate survival and the contributing factors for patients with pontine hemorrhage. Methods : Of the 41 patients who were admitted to our hospital with their first acute pontine hemorrhage from 1997 to 2005, 35 patients were included in this study. Medical records were reviewed to confirm the accuracy of diagnosis and collect demographic, clinical and radiological data. The patients were divided into two groups, survivors and deceased patients; then the survivors were divided again into a group of patient with good results and those with poor results. The location of the hematoma, maximum anteroposterior [AP] diameter, maximum transverse diameter, hematoma volume, ventricular extension, extension into the midbrain, hydrocephalus and initial Glasgow coma scale [GCS] were evaluated. Results : The two year survival rate was 58.5%. The survival of patients with pontine hemorrhage was affected by initial GCS score and transverse hematoma dimeter. Functional outcome of patients who survived was affected by initial GCS, maximum transverse diameter, maximum AP diameter and hematoma volume. Conclusion : The rate of survival after pontine hemorrhage is associated with the transverse diameter of the hematoma and more importantly the initial GCS. Long-term outcome of survivors is influenced by the initial GCS, transverse diameter, AP diameter and volume. Through the multivariate analysis, initial GCS is the only significant factor on survival. Strictly speaking, initial GCS is not modifiable. However, surgical reduction may be considered to amend theses decisive factors. Additional study for indication, timing and method of surgical management is needed.

Transcriptional Regulation of the Gene Encoding ${\gamma}$-Glutamylcysteine Synthetase from the Fission Yeast Schizosaccharomyces pombe

  • Kim, Su-Jung;Kim, Hong-Gyum;Kim, Byung-Chul;Kim, Kyunghoon;Park, Eun-Hee;Lim, Chang-Jin
    • Journal of Microbiology
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    • v.42 no.3
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    • pp.233-238
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    • 2004
  • Transcriptional regulation of the Schizosaccharomyces pombe y-glutamylcysteine synthetase (GCS) gene was examined using the two GCS-lacZ fusion plasmids pUGCS101 and pUGCS102, which harbor 607 bp and 447 bp upstream regions, respectively. The negatively-acting sequence was located in the -607 - -447 bp upstream region of the GCS gene. The upstream sequence responsible for induction by menadione(MD) and L-buthionine-(S, R)-sulfoximine (BSO) resides in the -607 - -447 bp region, whereas the sequence which codes for nitric oxide induction is located within the -447 bp region, measured from the translational initiation point. Carbon source-dependent regulation of the GCS gene appeared to be dependent on the nucleotide sequence within -447 bp region. The transcription factor Papl is involved in the induction of the GCS gene by MD and BSO, but not by nitric oxide. Induction of the GCS gene occurring due to low glucose concentration does not depend on the presence of Pap1. These data imply that induction by MD and BSO may be mediated by the Pap1 binding site, probably located in the -607 - -447 region, and also that the nitric oxide-mediated regulation of the S. pombe GCS gene may share a similar mechanism with its carbon-dependent induction.

Influence of Nitric Oxide on Steroid Synthesis, Growth and Apoptosis of Buffalo (Bubalus bubalis) Granulosa Cells In vitro

  • Dubey, Pawan K.;Tripathi, Vrajesh;Singh, Ram Pratap;Sastry, K.V.H.;Sharma, G.Taru
    • Asian-Australasian Journal of Animal Sciences
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    • v.24 no.9
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    • pp.1204-1210
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    • 2011
  • Objective of this study was to examine the effect of sodium nitroprusside (SNP), a nitric oxide (NO) donor on steroid synthesis, growth and apoptosis of buffalo granulosa cells (GCs) in vitro. Follicular fluid of antral follicles (3-5 mm diameter) was aspirated and GCs were cultured in 0 (control), $10^{-3}$, $10^{-5}$, $10^{-7}$, $10^{-9}\;M$ of SNP for 48 h. To evaluate whether this effect was reversible, GCs were cultured in presence of $10^{-5}\;M$ SNP+1.0 mM $N^{\omega}$-nitro-L-arginine methyl ester (L-NAME) a NO synthase (NOS) inhibitor or hemoglobin (Hb, $1.0{\mu}g$) as NO scavenger. Nitrate/nitrite concentration was evaluated by Griess method, progesterone and estradiol concentrations by RIA and apoptosis by TUNEL assay. SNP ($10^{-3}$, $10^{-5}$, $10^{-7}\;M$) significantly (p<0.05) inhibited estradiol and progesterone synthesis, growth, disorganized GCs aggregates and induced apoptosis in a dose dependent manner. However, $10^{-9}\;M$ SNP induced the progesterone synthesis and stimulated GCs to develop into a uniform monolayer. Combination of SNP $10^{-5}$ M+L-NAME strengthened the inhibitory effect while, SNP+Hb together reversed these inhibitory effects. In conclusion, SNP at greater concentrations ($10^{-3}$, $10^{-5}$ and $10^{-7}\;M$) has a cytotoxic effect and it may lead to cell death whereas, at a lower concentration ($10^{-9}\;M$) induced progesterone synthesis and growth of GCs. These findings have important implications that NOS derived NO are involved at physiological level during growth and development of buffalo GCs which regulates the steroidogenesis, growth and apoptosis.

Production of Transgenic Granulosa Cells after Retrovirus Vector Injection into Follicle in Mouse

  • Ju, Jin-Young;Chi, Hee-Jun;Koo, Jung-Jin;Kim, Teoan;Lee, Hoon-Taek;Chung, Kil-Saeng
    • Proceedings of the KSAR Conference
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    • 2001.03a
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    • pp.62-62
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    • 2001
  • Recently, production of transgenic animal by nuclear transfer has been known as a useful method. The production of cloned offspring derived from nuclear transfer depends upon a variety of factors such as species, donor cells type and cell cycle, and source of recipient ova. Therefore, we attempted a different transgenic methods using follicular granulosa cells (GCs). In general, ovulated GCs undergoes lutenization and transformation in vitro which might defective effects on developmental potential. In order to avoid the GCs transformation in vitro culture system, we introduced a direct injection of retrovirus into the follicles and then collected them mechanically from ovaries of 6-8 week-old ICR mice. Retrovirus vector constructed with pLN $\beta$ EGFP was injected into the follicles. The follicles are cultured in $\alpha$ -MEM supplemented with human FSH, LH and ITS in Costar Transwell dish for 4 days. Survival rate of virus injected follicles was 52.1% (12/23) and expression rate of EGPP gene was 33.3% (4/12). In this study, we found GCs performed transgenesis in our culture system. In addition, the GCs in follicle may be developed in vivo like environment rather than in vitro environment. Thus, the use of GCs as donor cells may be useful in the nuclear transfer for cloning of genetic modification. Therefore, these results suggest that follicular GCs can be transfected by viral vector during folliculogenesis in vitro.

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Evaluation of Clinical Usefulness of Critical Patient Severity Classification System(CPSCS) and Glasgow coma scale(GCS) for Neurological Patients in Intensive care units(ICU) (신경계 중환자에게 적용한 중환자 중증도 분류도구와 Glasgow coma scale의 임상적 유용성 평가)

  • Kim, Hee-Jeong;Kim, Jee-Hee
    • Proceedings of the KAIS Fall Conference
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    • 2012.05a
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    • pp.22-24
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    • 2012
  • The tools that classify the severity of patients based on the prediction of mortality include APACHE, SAPS, and MPM. Theses tools rely crucially on the evaluation of patients' general clinical status on the first date of their admission to ICU. Nursing activities are one of the most crucial factors influencing on the quality of treatment that patients receive and one of the contributing factors for their prognosis and safety. The purpose of this study was to identify the goodness-of-fit of CPSCS of critical patient severity classification system(CPSCS) and Glasgow coma scale(GCS) and the clinical usefulness of its death rate prediction. Data were collected from the medical records of 187 neurological patients who were admitted to the ICU of C University Hospital. The data were analyzed through $x^2$ test, t-test, Mann-Whitney, Kruskal-Wallis, goodness-of-fit test, and ROC curve. In accordance with patients' general and clinical characteristics, patient mortality turned out to be statistically different depending on ICU stay, endotracheal intubation, central venous catheter, and severity by CPSCS. Homer-Lemeshow goodness-of-fit tests were CPSCS and GCS and the results of the discrimination test using the ROC curve were $CPSCS_0$, .734, $GCS_0$,.583, $CPSCS_{24}$,.734, $GCS_{24}$, .612, $CPSCS_{48}$,.591, $GCS_{48}$,.646, $CPSCS_{72}$,.622, and $GCS_{72}$,.623. Logistic regression analysis showed that each point on the CPSCS score signifies1.034 higher likelihood of dying. Applied to neurologically ill patients, early CPSCS scores can be regarded as a useful tool.

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The Prognostic Factors Related to Traumatic Brain Stem Injury

  • Kim, Hun-Joo
    • Journal of Korean Neurosurgical Society
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    • v.51 no.1
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    • pp.24-30
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    • 2012
  • Objective : This study was conducted to assess the clinical significance of traumatic brain stem injury (TBSI) reflected on Glasgow Coma Score (GCS) and Glasgow Outcome Score (GOS) by various clinical variables. Methods : A total of 136 TBSI patients were selected out of 2695 head-injured patients. All initial computerized tomography and/or magnetic resonance imaging studies were retrospectively analyzed according to demographic- and injury variables which result in GCS and GOS. Results : In univariate analysis, mode of injury showed a significant effect on combined injury (p<0.001), as were the cases with skull fracture on radiologic finding (p<0.000). The GCS showed a various correlation with radiologic finding (p<0.000), mode of injury (p<0.002), but less favorably with impact site (p<0.052), age (p<0.054) and skull fracture (p<0.057), in order of statistical significances. However, only GOS showed a definite correlation to radiologic finding (p<0.000). In multivariate analysis, the individual variables to enhance an unfavorable effect on GCS were radiologic finding [odds ratio (OR) 7.327, 95% confidence interval (CI)], mode of injury (OR; 4.499, 95% CI) and age (OR; 3.141, 95% CI). Those which influence an unfavorable effect on GOS were radiologic finding (OR; 25.420, 95% CI) and age (OR; 2.674, 95% CI). Conclusion : In evaluation of TBSI on outcome, the variables such as radiological finding, mode of injury, and age were revealed as three important ones to have an unfavorable effect on early stage outcome expressed as GCS. However, mode of injury was shown not to have an unfavorable effect on late stage outcome as GOS. Among all unfavorable variables, radiological finding was confirmed as the only powerful prognostic variable both on GCS and GOS.

Clinical Usefulness of Critical Patient Severity Classification System(CPSCS) and Glasgow coma scale(GCS) for Neurological Patients in Intensive care units(ICU) (Glasgow coma scale의 임상적 유용성 평가 - 중환자 중증도 분류도구 -)

  • Kim, Hee-Jeong;Kim, Jee-Hee;Roh, Sang-Gyun
    • Proceedings of the Korea Institute of Fire Science and Engineering Conference
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    • 2012.04a
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    • pp.190-193
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    • 2012
  • The tools that classify the severity of patients based on the prediction of mortality include APACHE, SAPS, and MPM. Theses tools rely crucially on the evaluation of patients' general clinical status on the first date of their admission to ICU. Nursing activities are one of the most crucial factors influencing on the quality of treatment that patients receive and one of the contributing factors for their prognosis and safety. The purpose of this study was to identify the goodness-of-fit of CPSCS of critical patient severity classification system(CPSCS) and Glasgow coma scale(GCS) and the clinical usefulness of its death rate prediction. Data were collected from the medical records of 187 neurological patients who were admitted to the ICU of C University Hospital. The data were analyzed through $x^2$ test, t-test, Mann-Whitney, Kruskal-Wallis, goodness-of-fit test, and ROC curve. In accordance with patients' general and clinical characteristics, patient mortality turned out to be statistically different depending on ICU stay, endotracheal intubation, central venous catheter, and severity by CPSCS. Homer-Lemeshow goodness-of-fit tests were CPSCS and GCS and the results of the discrimination test using the ROC curve were $CPSCS_0$,.734, $GCS_0$,.583, $CPSCS_{24}$,.734, $GCS_{24}$,.612, $CPSCS_{48}$,.591, $GCS_{48}$,.646, $CPSCS_{72}$,.622, and $GCS_{72}$,.623. Logistic regression analysis showed that each point on the CPSCS score signifies1.034 higher likelihood of dying. Applied to neurologically ill patients, early CPSCS scores can be regarded as a useful tool.

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EFFECT OF SECOND GENERATION POPULATIONS ON THE INTEGRATED COLOR OF METAL-RICH GLOBULAR CLUSTERS IN EARLY-TYPE GALAXIES

  • Chung, Chul;Lee, Sang-Yoon;Yoon, Suk-Jin;Lee, Young-Wook
    • The Bulletin of The Korean Astronomical Society
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    • v.38 no.1
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    • pp.30.2-30.2
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    • 2013
  • The mean color of globular cluster (GCs) systems in early-type galaxies (ETGs) is, in general, bluer than the integrated color of field stars in their host galaxies. Recently, Goudfrooij & Kruijssen (2013) reported that even red GCs in the ETGs show bluer colors than their host field stars and suggested the different initial mass function (IMF) for red GCs and field stars to explain the observed offset in color. Here we suggest an alternative scenario that explains the observed color offsets between red GCs in ETGs and the field stars in the parent galaxies without invoking to the variation of the IMF. We find that the inclusion of second-generation (SG) helium-enhanced populations in the model fully explains the observed color offset between red GCs and field stars in the host galaxies. We have also tested the effect of the IMF slope on our models, but the effect is relatively small compared to the effect of the SG population. Our new model suggests that, in order to explain far-UV strong metal-rich GCs in M87 and the observed color offset between metal-rich GCs and the field stars in ETGs simultaneously, the inclusion of the SG populations with enhanced helium abundance is a more natural solution than the model that only adopted variations in the IMF.

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Development of a Label-Free LC-MS/MS-Based Glucosylceramide Synthase Assay and Its Application to Inhibitors Screening for Ceramide-Related Diseases

  • Fu, Zhicheng;Yun, So Yoon;Won, Jong Hoon;Back, Moon Jung;Jang, Ji Min;Ha, Hae Chan;Lee, Hae Kyung;Shin, In Chul;Kim, Ju Yeun;Kim, Hee Soo;Kim, Dae Kyong
    • Biomolecules & Therapeutics
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    • v.27 no.2
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    • pp.193-200
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    • 2019
  • Ceramide metabolism is known to be an essential etiology for various diseases, such as atopic dermatitis and Gaucher disease. Glucosylceramide synthase (GCS) is a key enzyme for the synthesis of glucosylceramide (GlcCer), which is a main ceramide metabolism pathway in mammalian cells. In this article, we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to determine GCS activity using synthetic non-natural sphingolipid C8-ceramide as a substrate. The reaction products, C8-GlcCer for GCS, could be separated on a C18 column by reverse-phase high-performance liquid chromatography (HPLC). Quantification was conducted using the multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z $588.6{\rightarrow}264.4$ for C8-GlcCer at positive ionization mode. The calibration curve was established over the range of 0.625-160 ng/mL, and the correlation coefficient was larger than 0.999. This method was successfully applied to detect GCS in the human hepatocellular carcinoma cell line (HepG2 cells) and mouse peripheral blood mononuclear cells. We also evaluated the inhibition degree of a known GCS inhibitor 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) on GCS enzymatic activity and proved that this method could be successfully applied to GCS inhibitor screening of preventive and therapeutic drugs for ceramide metabolism diseases, such as atopic dermatitis and Gaucher disease.