Displaying publications 1 - 20 of 78 in total

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  1. Mohamad M, Mitchell SJ, Wu LE, White MY, Cordwell SJ, Mach J, et al.
    Aging Cell, 2016 08;15(4):706-15.
    PMID: 27095270 DOI: 10.1111/acel.12481
    While age-related insulin resistance and hyperinsulinemia are usually considered to be secondary to changes in muscle, the liver also plays a key role in whole-body insulin handling and its role in age-related changes in insulin homeostasis is largely unknown. Here, we show that patent pores called 'fenestrations' are essential for insulin transfer across the liver sinusoidal endothelium and that age-related loss of fenestrations causes an impaired insulin clearance and hyperinsulinemia, induces hepatic insulin resistance, impairs hepatic insulin signaling, and deranges glucose homeostasis. To further define the role of fenestrations in hepatic insulin signaling without any of the long-term adaptive responses that occur with aging, we induced acute defenestration using poloxamer 407 (P407), and this replicated many of the age-related changes in hepatic glucose and insulin handling. Loss of fenestrations in the liver sinusoidal endothelium is a hallmark of aging that has previously been shown to cause deficits in hepatic drug and lipoprotein metabolism and now insulin. Liver defenestration thus provides a new mechanism that potentially contributes to age-related insulin resistance.
    Matched MeSH terms: Glycogen/metabolism
  2. Mohktar RA, Montgomery MK, Murphy RM, Watt MJ
    Am J Physiol Endocrinol Metab, 2016 07 01;311(1):E128-37.
    PMID: 27189934 DOI: 10.1152/ajpendo.00084.2016
    Cytoplasmic lipid droplets provide a reservoir for triglyceride storage and are a central hub for fatty acid trafficking in cells. The protein perilipin 5 (PLIN5) is highly expressed in oxidative tissues such as skeletal muscle and regulates lipid metabolism by coordinating the trafficking and the reversible interactions of effector proteins at the lipid droplet. PLIN5 may also regulate mitochondrial function, although this remains unsubstantiated. Hence, the aims of this study were to examine the role of PLIN5 in the regulation of skeletal muscle substrate metabolism during acute exercise and to determine whether PLIN5 is required for the metabolic adaptations and enhancement in exercise tolerance following endurance exercise training. Using muscle-specific Plin5 knockout mice (Plin5(MKO)), we show that PLIN5 is dispensable for normal substrate metabolism during exercise, as reflected by levels of blood metabolites and rates of glycogen and triglyceride depletion that were indistinguishable from control (lox/lox) mice. Plin5(MKO) mice exhibited a functional impairment in their response to endurance exercise training, as reflected by reduced maximal running capacity (20%) and reduced time to fatigue during prolonged submaximal exercise (15%). The reduction in exercise performance was not accompanied by alterations in carbohydrate and fatty acid metabolism during submaximal exercise. Similarly, mitochondrial capacity (mtDNA, respiratory complex proteins, citrate synthase activity) and mitochondrial function (oxygen consumption rate in muscle fiber bundles) were not different between lox/lox and Plin5(MKO) mice. Thus, PLIN5 is dispensable for normal substrate metabolism during exercise and is not required to promote mitochondrial biogenesis or enhance the cellular adaptations to endurance exercise training.
    Matched MeSH terms: Glycogen/metabolism
  3. Chan KH, Lee CH, Sharif SZ, Hayati F, Sallapan S
    Ann Med Surg (Lond), 2020 Dec;60:438-441.
    PMID: 33251002 DOI: 10.1016/j.amsu.2020.11.035
    Background: Metastatic neuroendocrine tumours (NETs) to the breast are very rare entities.

    Case presentation: A 26-year-old lady presented with anterior neck swelling with symptoms of superior vena cava syndrome for 6 months. Imaging study revealed a mediastinal mass which was preceded with core biopsy which was consistent with high-grade small cell NETs. Despite second-line adjuvant chemotherapy and radiotherapy, her disease became advanced which was confirmed via restaging scan. There were bilateral breast lesions discovered during the scan which was deemed to be metastatic NETs histologically. Despite prompt initiation of treatment, she succumbed 1 year after the radiotherapy due to disease progression.

    Conclusion: High suspicion of an index is needed for diagnosis when patients with known primary NETs present with suspicious breast lesions. Triple assessment is mandatory, however histopathology assessment and immunohistochemistry staining are the mainstay of diagnosis.

    Matched MeSH terms: Glycogen Storage Disease Type VI
  4. Norlina R, Norashikin MN, Loh SH, Aziz A, Cha TS
    Appl Biochem Biotechnol, 2020 Aug;191(4):1653-1669.
    PMID: 32198601 DOI: 10.1007/s12010-020-03312-y
    Abscisic acid (ABA) has been known to exist in a microalgal system and serves as one of the chemical stimuli in various biological pathways. Nonetheless, the involvement of ABA in fatty acid biosynthesis, particularly at the transcription level in microalgae is poorly understood. The objective of this study was to determine the effects of exogenous ABA on growth, total oil content, fatty acid composition, and the expression level of beta ketoacyl-ACP synthase I (KAS I) and omega-3 fatty acid desaturase (ω-3 FAD) genes in Chlorella vulgaris UMT-M1. ABA was applied to early stationary C. vulgaris cultures at concentrations of 0, 10, 20, and 80 μM for 48 h. The results showed that ABA significantly increased biomass production and total oil content. The increment of palmitic (C16:0) and stearic (C18:0) acids was coupled by decrement in linoleic (C18:2) and α-linolenic (C18:3n3) acids. Both KAS I and ω-3 FAD gene expression were downregulated, which was negatively correlated to saturated fatty acid (SFAs), but positively correlated to polyunsaturated fatty acid (PUFA) accumulations. Further analysis of both KAS I and ω-3 FAD promoters revealed the presence of multiple ABA-responsive elements (ABREs) in addition to other phytohormone-responsive elements. However, the role of these phytohormone-responsive elements in regulating KAS I and ω-3 FAD gene expression still remains elusive. This revelation might suggest that phytohormone-responsive gene regulation in C. vulgaris and microalgae as a whole might diverge from higher plants which deserve further scientific research to elucidate its functional roles.
    Matched MeSH terms: Glycogen Synthase
  5. Wee LH, Morad NA, Aan GJ, Makpol S, Wan Ngah WZ, Mohd Yusof YA
    Asian Pac J Cancer Prev, 2015;16(15):6549-56.
    PMID: 26434873
    The PI3K-Akt-mTOR, Wnt/β-catenin and apoptosis signaling pathways have been shown to be involved in genesis of colorectal cancer (CRC). The aim of this study was to elucidate whether combination of Gelam honey and ginger might have chemopreventive properties in HT29 colon cancer cells by modulating the mTOR, Wnt/β-catenin and apoptosis signaling pathways. Treatment with Gelam honey and ginger reduced the viability of the HT29 cells dose dependently with IC50 values of 88 mg/ml and 2.15 mg/ml respectively, their while the combined treatment of 2 mg/ml of ginger with 31 mg/ml of Gelam honey inhibited growth of most HT29 cells. Gelam honey, ginger and combination induced apoptosis in a dose dependent manner with the combined treatment exhibiting the highest apoptosis rate. The combined treatment downregulated the gene expressions of Akt, mTOR, Raptor, Rictor, β-catenin, Gsk3β, Tcf4 and cyclin D1 while cytochrome C and caspase 3 genes were shown to be upregulated. In conclusion, the combination of Gelam honey and ginger may serve as a potential therapy in the treatment of colorectal cancer through inhibiton of mTOR, Wnt/β catenin signaling pathways and induction of apoptosis pathway.
    Matched MeSH terms: Glycogen Synthase Kinase 3/genetics; Glycogen Synthase Kinase 3 beta
  6. Chong ZX, Ho WY, Yeap SK
    Biochem Pharmacol, 2023 Apr;210:115466.
    PMID: 36849065 DOI: 10.1016/j.bcp.2023.115466
    Eyes absent homolog 4 (EYA4) is a protein that regulates many vital cellular processes and organogenesis pathways. It possesses phosphatase, hydrolase, and transcriptional activation functions. Mutations in the Eya4 gene can cause sensorineural hearing loss and heart disease. In most non-nervous system cancers such as those of the gastrointestinal tract (GIT), hematological and respiratory systems, EYA4 acts as a putative tumor suppressor. However, in nervous system tumors such as glioma, astrocytoma, and malignant peripheral nerve sheath tumor (MPNST), it plays a putative tumor-promoting role. EYA4 interacts with various signaling proteins of the PI3K/AKT, JNK/cJUN, Wnt/GSK-3β, and cell cycle pathways to exert its tumor-promoting or tumor-suppressing effect. The tissue expression level and methylation profiles of Eya4 can help predict the prognosis and anti-cancer treatment response among cancer patients. Targeting and altering Eya4 expression and activity could be a potential therapeutic strategy to suppress carcinogenesis. In conclusion, EYA4 may have both putative tumor-promoting and tumor-suppressing roles in different human cancers and has the potential to serve as a prognostic biomarker and therapeutic agent in various cancer types.
    Matched MeSH terms: Glycogen Synthase Kinase 3 beta/genetics
  7. Tan BL, Norhaizan ME
    Biomed Pharmacother, 2019 Feb;110:748-757.
    PMID: 30554113 DOI: 10.1016/j.biopha.2018.12.027
    Manilkara zapota (L.) P. Royen (Family: Sapotaceae), commonly called as sapodilla, has been applied as traditional folk medicine for diarrhea and pulmonary infections. Conventional therapy in colorectal cancer is not likely effective due to undesirable outcomes. The anti-colon cancer properties of Manilkara zapota leaf water extract have yet to be investigated thus far. Therefore, our present study aimed to evaluate the ability to induce apoptosis and the underlying mechanisms of Manilkara zapota leaf water extract against human colorectal cancer (HT-29) cells. The cytotoxicity of Manilkara zapota leaf water extract was screened in different cancer cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) analyses. The morphological changes in HT-29 cell lines after exposure to Manilkara zapota leaf water extract were viewed under fluorescence and inverted light microscope. The apoptotic cell was measured by Annexin V-propidium iodide staining. The caspase-3 and -8 activities were assessed by colorimetric assay. Overall analyses revealed that treatment with Manilkara zapota leaf water extract for 72 h can inhibit the viability of HT-29 cells. Incubation with Manilkara zapota leaf water extract for 24, 48, and 72 h significantly increased (p < 0.05) the total apoptotic cells compared to the control. Treatment with 21, 42, and 84 μg/mL of Manilkara zapota leaf water extract for 72 h triggered both caspase-3 and -8 activities in a concentration-dependent pattern. We also found that the catalase level in the two treatment groups (21 and 42 μg/mL) was significantly elevated after 24 h incubation. Incubation with Manilkara zapota leaf water extract for 72 h triggered the transcriptional elevation of the adenomatous polyposis coli (APC), glycogen synthase kinase 3β (GSK3β), AXIN1, and casein kinase 1 (CK1). The β-catenin mRNA levels were reduced accordingly when the concentration of the Manilkara zapota leaf water extract was increased. Our results suggested that Manilkara zapota leaf water extract offer great potential against colorectal cancer through modulation of Wnt/β-catenin signaling pathway, caspase-dependent pathway, and antioxidant enzyme.
    Matched MeSH terms: Glycogen Synthase Kinase 3 beta
  8. Gopinath V, Saravanan S, Al-Maleki AR, Ramesh M, Vadivelu J
    Biomed Pharmacother, 2018 Nov;107:96-108.
    PMID: 30086465 DOI: 10.1016/j.biopha.2018.07.136
    Natural polysaccharides are renewable with a high degree of biocompatibility, biodegradability, and ability to mimic the natural extracellular matrix (ECM) microenvironment. Comprehensive investigations of polysaccharides are essential for our fundamental understanding of exploiting its potential as bio-composite, nano-conjugate and in pharmaceutical sectors. Polysaccharides are considered to be superior to other polymers, for its ease in tailoring, bio-compatibility, bio-activity, homogeneity and bio-adhesive properties. The main focus of this review is to spotlight the new advancements and challenges concerned with surface modification, binding domains, biological interaction with the conjugate including stability, polydispersity, and biodegradability. In this review, we have limited our survey to three essential polysaccharides including cellulose, starch, and glycogen that are sourced from plants, microbes, and animals respectively are reviewed. We also present the polysaccharides which have been extensively modified with the various types of conjugates for combating last-ditch pharmaceutical challenges.
    Matched MeSH terms: Glycogen/pharmacology*
  9. Liau KF, Shoji T, Ong YH, Chua AS, Yeoh HK, Ho PY
    Bioprocess Biosyst Eng, 2015 Apr;38(4):729-37.
    PMID: 25381606 DOI: 10.1007/s00449-014-1313-3
    A recently reported stable and efficient EBPR system at high temperatures around 30 °C has led to characterization of kinetic and stoichiometric parameters of the Activated Sludge Model no. 2d (ASM2d). Firstly, suitable model parameters were selected by identifiability analysis. Next, the model was calibrated and validated. ASM2d was found to represent the processes well at 28 and 32 °C except in polyhyroxyalkanoate (PHA) accumulation of the latter. The values of the kinetic parameters for PHA storage (q PHA), polyphosphate storage (q PP) and growth (μ PAO) of polyphosphate-accumulating organisms (PAOs) at 28 and 32 °C were found to be much higher than those reported by previous studies. Besides, the value of the stoichiometric parameter for the requirement of polyphosphate for PHA storage (Y PO4) was found to decrease as temperature rose from 28 to 32 °C. Values of two other stoichiometric parameters, i.e. the growth yield of heterotrophic organisms (Y H) and PAOs (Y PAO), were high at both temperatures. These calibrated parameters imply that the extremely active PAOs of the study were able to store PHA, store polyphosphate and even utilize PHA for cell growth. Besides, the parameters do not follow the Arrhenius correlation due to the previously reported unique microbial clade at 28 and 32 °C, which actively performs EBPR at high temperatures.
    Matched MeSH terms: Glycogen/chemistry
  10. Lim WY, Goh CH, Thevarajah TM, Goh BT, Khor SM
    Biosens Bioelectron, 2020 Jan 01;147:111792.
    PMID: 31678828 DOI: 10.1016/j.bios.2019.111792
    Recently, surface enhanced Raman scattering (SERS) has attracted much attention in medical diagnosis applications owing to better detection sensitivity and lower limit of detection (LOD) than colorimetric detection. In this paper, a novel calibration-free SERS-based μPAD with multi-reaction zones for simultaneous quantitative detection of multiple cardiac biomarkers - GPBB, CK-MB and cTnT for early diagnosis and prognosis of acute myocardial infarction (AMI) are presented. Three distinct Raman probes were synthesised, subsequently conjugated with respective detecting antibodies and used as SERS nanotags for cardiac biomarker detection. Using a conventional calibration curve, quantitative simultaneous measurement of multiple cardiac biomarkers on SERS-based μPAD was performed based on the characteristic Raman spectral features of each reporter used in different nanotags. However, a calibration free point-of-care testing device is required for fast screening to rule-in and rule-out AMI patients. Partial least squares predictive models were developed and incorporated into the immunosensing system, to accurately quantify the three unknown cardiac biomarkers levels in serum based on the previously obtained Raman spectral data. This method allows absolute quantitative measurement when conventional calibration curve fails to provide accurate estimation of cardiac biomarkers, especially at low and high concentration ranges. Under an optimised condition, the LOD of our SERS-based μPAD was identified at 8, 10, and 1 pg mL-1, for GPBB, CK-MB and cTnT, respectively, which is well below the clinical cutoff values. Therefore, this proof-of-concept technique shows significant potential for highly sensitive quantitative detection of multiplex cardiac biomarkers in human serum to expedite medical decisions for enhanced patient care.
    Matched MeSH terms: Glycogen Phosphorylase/blood*
  11. Manoharan SD, Abdul Hamid H, Md Hashim NF, Cheema MS, Chiroma SM, Mustapha M, et al.
    Brain Res, 2024 Apr 15;1829:148793.
    PMID: 38309553 DOI: 10.1016/j.brainres.2024.148793
    Alzheimer's disease (AD) is a progressive neurological disorder that impairs memory and cognitive abilities, primarily in the elderly. The burden of AD extends beyond patients, impacting families and caregivers due to the patients' reliance on assistance for daily tasks. The main features of the pathogenesis of AD are beta-amyloid plaques and neurofibrillary tangles (NFTs), that strongly correlate with oxidative stress and inflammation. NFTs result from misfolded and hyperphosphorylated tau proteins. Various studies have focused on tau phosphorylation, indicating protein phosphatase 2A (PP2A) as the primary tau phosphatase and glycogen synthase kinase-3 beta (GSK-3β) as the leading tau kinase. Experimental evidence suggests that inhibition of PP2A and increased GSK-3β activity contribute to neuroinflammation, oxidative stress, and cognitive impairment. Hence, targeting PP2A and GSK-3β with pharmacological approaches shows promise in treating AD. The use of natural compounds in the drug development for AD have been extensively studied for their antioxidant, anti-inflammatory, anti-cholinesterase, and neuroprotective properties, demonstrating therapeutic advantages in neurological diseases. Alongside the development of PP2A activator and GSK-3β inhibitor drugs, natural compounds are likely to have neuroprotective effects by increasing PP2A activity and decreasing GSK-3β levels. Therefore, based on the preclinical and clinical studies, the potential of PP2A and GSK-3β as therapeutic targets of natural compounds are highlighted in this review.
    Matched MeSH terms: Glycogen Synthase Kinase 3 beta/metabolism
  12. Norlia B., Norwati M., Norwati A., Mohd Rosli H., Norihan M. S.
    MyJurnal
    This study was part of the larger studies to isolate and characterize gene related to flowering in teak. This study isolated differentially expressed genes of teak flowering tissues. One of the genes encodes plant protein kinases highly homologous to the AtSK-II of Arabidopsis GSK3/SHAGGY subfamily. The gene was named as Tectona grandis SHAGGY kinase (Tg-SK). The protein sequence of this gene contained the characteristic catalytic domain of GSK-3/SHAGGY protein kinase. The gene also shows the same genomic organization of 11 introns and 12 exons. Although the size of the introns varies, the positions of exon/intron boundaries are very similar to AtSK-II. The discovery of this gene in teak, which is a forest tree species, supports the hypothesis, which suggested the gene is found in all eukaryotes.
    Matched MeSH terms: Glycogen Synthase Kinase 3
  13. Khor TO, Gul YA, Ithnin H, Seow HF
    Cancer Lett, 2004 Jul 16;210(2):139-50.
    PMID: 15183529
    The enhancement of cell proliferation and promotion of cell survival via the inhibition of apoptosis is thought to be the key to the initiation and progression of cancers. The phosphatidylinositol-3 kinase (PI3K)/Akt is an important survival signal pathway that has been shown to be crucial in the regulation of balance between pro-apoptotic and survival (anti-apoptotic) signal. In this study, the expression of phosphorylated Akt at Thr308 and Ser473, BCL-2-antagonist of cell death (BAD) at Ser136 and glycogen synthase kinase-3beta (GSK-3beta) at Ser9 in 47 paraffin-embedded human colorectal carcinoma (CRC) tissues were determined by immunohistochemical staining in order to dissect the alterations in the signal transduction pathways in CRC. Our results showed that there was a significant increase in the expression of these biomolecules in CRC tissues compared to the apparently normal adjacent tissues. The frequency of increased expression in tumor colonic mucosa were as follows: p-Akt1/2/3 (Thr308) = 16/47 (34%); p-Akt1 (Ser473) = 21/47 (44.7%); phospho-BAD (p-BAD) Ser136 = 27/47 (57.4%) and phospho-GSK-3beta (p-GSK-3beta) = 21/47 (44.7%). Analysis of the total p-Akt1 (Ser473), p-Akt1/2/3 (Thr308), p-GSK-3beta (Ser9) and p-BAD (Ser136) score found that there was a statistically significant relationship with each other. A statistically significant positive linear relationship was found between total p-Akt (Ser473) score and total p-GSK-3beta (Ser9) score as well as with total p-BAD (Ser136) score. On the other hand, total p-Akt1/2/3 (Thr308) scores had a statistically significant positive linear relationship with p-GSK-3beta (Ser9) only. The Akt targets, p-GSK-3beta (Ser9) and p-BAD (Ser136) were positively correlated to each other. There was no significant correlation between clinico-pathological data with total p-Akt1 (Ser473), p-Akt1/2/3 (Thr308), p-GSK-3beta (Ser9) and p-BAD (Ser136) score except for age. The total scores of p-GSK-3beta were found to be higher in patients in the age group of greater than 60. This is the first report of p-Akt1/2/3 (Thr308) and p-BAD (Ser136) expression in primary colorectal tumor tissue. Our data further supports the role of PI3K/Akt signaling pathways in the pathogenesis of CRC and contributes to the identification of target molecules in the signal transduction pathway for cancer therapy.
    Matched MeSH terms: Glycogen Synthase Kinase 3/biosynthesis*; Glycogen Synthase Kinase 3/genetics
  14. Ban KC, Singh H, Krishnan R, Seow HF
    Cancer Lett, 2003 Sep 25;199(2):201-8.
    PMID: 12969793
    The aim of this study is to investigate the potential correlation between the expression of phosphorylated glycogen synthase kinase-3beta (phospho-GSK-3beta) and beta-catenin, and the mutations of beta-catenin gene at the consensus GSK-3beta phosphorylation site. The reason for this approach is to gain a better understanding of the molecular mechanisms of hepatocarcinogenesis in Malaysia. The expression of phospho-GSK-3beta and beta-catenin by immunohistochemistry and the mutations of beta-catenin were studied in 23 hepatocellular carcinoma (HCC) and surrounding tissues. Overexpression of phospho-GSK-3beta and beta-catenin was found in 12/23 (52.2%) and 13/23 (56.5%) in HCC tissues, 6/23 (26.1%) and 9/23 (39.1%) in surrounding tissues, respectively. Overexpression of beta-catenin in HCC tissues compared to the surrounding liver tissue was found to be higher in HCC tissues (p=0.015). In addition, we found that the expression of phospho-GSK-3beta was related with the accumulation of beta-catenin in surrounding tissues (p<0.05). The expression of phospho-GSK-3beta and its association with the development of HCC is reported for the first time. In addition, this is the first report from Malaysia which shows that there are no mutations at the GSK-3beta consensus phosphorylation sites on beta-catenin gene in all 23 paired HCC and surrounding tissues. This result differed from HCC in geographical areas with high aflatoxin exposure.
    Matched MeSH terms: Glycogen Synthase Kinase 3/metabolism*
  15. Abu NA, Lim CB, Nor NSM
    Clin Pediatr Endocrinol, 2021;30(2):93-97.
    PMID: 33867669 DOI: 10.1297/cpe.30.93
    Mauriac syndrome is a rare and underdiagnosed complication of type 1 diabetes mellitus (T1DM). It is characterized by growth retardation, delayed puberty, Cushingoid features, hepatomegaly, and increased transaminase levels. The term glycogenic hepatopathy has been used to describe patients with poorly controlled T1DM and glycogen overload in the hepatocytes but without all the features of Mauriac syndrome. Although rare, glycogenic hepatopathy is reported to be the main cause of hepatomegaly in young patients with T1DM. We report two cases of glycogenic hepatopathy in children with poorly controlled T1DM. Both children had hepatomegaly, elevated liver enzyme levels, and elevated lactate levels. A liver biopsy confirmed the diagnosis of glycogenic hepatopathy in both patients. In conclusion, hepatomegaly with elevated liver enzymes, negative infective and metabolic screenings and persistently elevated plasma lactate levels should raise the suspicion of glycogenic hepatopathy in poorly controlled T1DM. Early diagnosis and improvement in glycemic control are the mainstays of treatment, which can prevent long-term complications.
    Matched MeSH terms: Glycogen
  16. Aung YN, Nur AM, Ismail A, Aljunid SM
    Clinicoecon Outcomes Res, 2019;11:505-513.
    PMID: 31447570 DOI: 10.2147/CEOR.S209108
    Purpose: Care at ICUs is expensive and variable depending on the type of care that the patients received. Knowing the characteristics of the patient and his or her disease is always useful for improving health services and cost containment.

    Patients and methods: An observational study was conducted at four different intensive care units of an academic medical institution. Demographic characteristics, disease-management casemix information, cost and outcome of the high costing decile, and the rest of the cases were compared.

    Results: A total of 3,220 discharges were included in the study. The high-cost group contributed 35.4% of the ICU stays and 38.8% of the total ICU expenditure. Diseases of the central nervous system had higher odds to be in the top decile of costly patients whereas the cardiovascular system was more likely to be in the non-high cost category. The high-cost patients were more likely to have death as an outcome (19.2% vs 9.3%; p<0.001). The most common conditions that were in the high-cost groups were craniotomy, other ear, nose, mouth, and throat operations, simple respiratory system operations, complex intestinal operations, and septicemia. These five diagnostic groups made up 43% of the high-cost decile.

    Conclusion: High-cost patients utilized almost 40% of the ICU cost although they were only 10% of the ICU patients. The chances of admission to the ICU increased with older age and severity level of the disease. Central nervous system diseases were the major problem of patients aged 46-69 years old. In addition to cost reduction strategies at the treatment level, detailed analysis of these cases was needed to explore and identify pre-event stage prevention strategies.

    Matched MeSH terms: Glycogen Storage Disease Type VI
  17. Liew HJ, Fazio A, Faggio C, Blust R, De Boeck G
    PMID: 26219478 DOI: 10.1016/j.cbpa.2015.07.011
    Interacting effects of feeding and stress on corticoid responses in fish were investigated in common carp fed 3.0% or 0.5% body mass (BM) which received no implant, a sham or a cortisol implant (250 mg/kg BM) throughout a 168 hour post-implant period (168 h-PI). At 12h-PI, cortisol implants elevated plasma cortisol, glucose and lactate. Plasma osmolality and ions remained stable, but cortisol increased gill and kidney Na(+)/K(+) ATPase (NKA) and H(+) ATPase activities. Gill NKA activities were higher at 3%-BM, whereas kidney H(+) ATPase activity was greater at 0.5%-BM. Cortisol induced liver protein mobilization and repartitioned liver and muscle glycogen. At 3%-BM, this did not increase plasma ammonia, reflecting improved excretion efficiency concomitant with upregulation of Rhesus glycoprotein Rhcg-1 in gill. Responses in glucocorticoid receptors (GR1/GR2) and mineralocorticoid receptor (MR) to cortisol elevation were most prominent in kidney with increased expression of all receptors at 24 h-PI at 0.5%-BM, but only GR2 and MR at 0.5%-BM. In the liver, upregulation of all receptors occurred at 24 h-PI at 3%-BM, whilst only GR2 and MR were upregulated at 0.5%-BM. In the gill, there was a limited upregulation: GR2 and MR at 72 h-PI and GR1 at 168 h-PI at 3%-BM but only GR2 at 72 h-PI at 0.5%-BM. Thus cortisol elevation led to similar expression patterns of cortisol receptors in both feeding regimes, while feeding affected the type of receptor that was induced. Induction of corticoid receptors occurred simultaneously with increases in Rhcg-1 mRNA expression (gill) but well after NKA and H(+) ATPase activities increased (gill/kidney).
    Matched MeSH terms: Glycogen/metabolism
  18. Moyson S, Liew HJ, Diricx M, Sinha AK, Blust R, De Boeck G
    PMID: 25263807 DOI: 10.1016/j.cbpa.2014.09.017
    In the present study, the combined effects of hypoxia and nutritional status were examined in common carp (Cyprinus carpio), a relatively hypoxia tolerant cyprinid. Fish were either fed or fasted and were exposed to hypoxia (1.5-1.8mg O2L(-1)) at or slightly above their critical oxygen concentration during 1, 3 or 7days followed by a 7day recovery period. Ventilation initially increased during hypoxia, but fasted fish had lower ventilation frequencies than fed fish. In fed fish, ventilation returned to control levels during hypoxia, while in fasted fish recovery only occurred after reoxygenation. Due to this, C. carpio managed, at least in part, to maintain aerobic metabolism during hypoxia: muscle and plasma lactate levels remained relatively stable although they tended to be higher in fed fish (despite higher ventilation rates). However, during recovery, compensatory responses differed greatly between both feeding regimes: plasma lactate in fed fish increased with a simultaneous breakdown of liver glycogen indicating increased energy use, while fasted fish seemed to economize energy and recycle decreasing plasma lactate levels into increasing liver glycogen levels. Protein was used under both feeding regimes during hypoxia and subsequent recovery: protein levels reduced mainly in liver for fed fish and in muscle for fasted fish. Overall, nutritional status had a greater impact on energy reserves than the lack of oxygen with a lower hepatosomatic index and lower glycogen stores in fasted fish. Fasted fish transiently increased Na(+)/K(+)-ATPase activity under hypoxia, but in general ionoregulatory balance proved to be only slightly disturbed, showing that sufficient energy was left for ion regulation.
    Matched MeSH terms: Glycogen/metabolism
  19. Liew HJ, Chiarella D, Pelle A, Faggio C, Blust R, De Boeck G
    PMID: 23921225 DOI: 10.1016/j.cbpa.2013.07.029
    The objective of this study was to investigate the interaction between feeding, exercise and cortisol on metabolic strategies of common carp over a 168h post-implant period. Feeding provided readily available energy and clearly increased muscle and liver protein and glycogen stores. Swimming, feeding and cortisol all induced aerobic metabolism by increasing oxygen consumption, and stimulated protein metabolism as demonstrated by the increased ammonia and urea excretion and ammonia quotient. Hypercortisol stimulated ammonia self-detoxifying mechanisms by enhancing ammonia and urea excretion, especially during severe exercise. At high swimming level, higher branchial clearance rates in cortisol treated fish succeeded in eliminating the elevation of endogenous ammonia, resulting in reduced plasma Tamm levels compared to control and sham implanted fish. Carp easily induced anaerobic metabolism, both during routine and active swimming, with elevated lactate levels as a consequence. Both feeding and cortisol treatment increased this dependence on anaerobic metabolism. Hypercortisol induced both glycogenesis and gluconeogenesis resulting in hyperglycemia and muscle and liver glycogen deposition, most likely as a protective mechanism for prolonged stress situations and primarily fuelled by protein mobilization.
    Matched MeSH terms: Glycogen/metabolism
  20. Kamarudin MN, Mohd Raflee NA, Hussein SS, Lo JY, Supriady H, Abdul Kadir H
    Drug Des Devel Ther, 2014;8:1765-80.
    PMID: 25336920 DOI: 10.2147/DDDT.S67980
    Alpha-lipoic acid, a potent antioxidant with multifarious pharmacological benefits has been reported to be neuroprotective in several neuronal models and used to treat neurological disorders such as Alzheimer's disease. Nonetheless, conclusive mechanisms of alpha-lipoic acid for its protective effects particularly in NG108-15 cells have never been investigated. In this study, the intricate neuroprotective molecular mechanisms by (R)-(+)-alpha-lipoic acid (R-LA) against H2O2-induced cell death in an in vitro model of neurodegeneration were elucidated. Pretreatment with R-LA (2 hours) significantly increased NG108-15 cell viability as compared to H2O2-treated cells and mitigated the induction of apoptosis as evidenced by Hoechst 33342/propidium iodide staining. R-LA (12.5-50 μM) aggrandized the reduced glutathione over glutathione disulfide ratio followed by a reduction in the intracellular reactive oxygen species level and an increase in mitochondrial membrane potential following H2O2 exposure. Moreover, pretreatment with R-LA stimulated the activation of PI3K-Akt through mTORC1 and mTORC2 components (mTOR, rictor and raptor) and production of antiinflammatory cytokine, IL-10 which led to the inactivation of glycogen synthase kinase-3β (GSK-3β) and reduction of both Bax/Bcl2 and Bax/Bcl-xL ratios, accompanied by inhibition of the cleaved caspase-3. Additionally, this observation was preceded by the suppression of NF-κβ p65 translocation and production of proinflammatory cytokines (IL-6 and TNF-α). The current findings accentuate new mechanistic insight of R-LA against apoptogenic and brain inflammatory factors in a neuronal model. These results further advocate the therapeutic potential of R-LA for the treatment of neurodegenerative diseases.
    Matched MeSH terms: Glycogen Synthase Kinase 3/metabolism*
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