BACKGROUND: Pancreatic β-cells elevate insulin production and secretion through a compensatory mechanism to override insulin resistance under metabolic stress conditions. Deficits in β-cell compensatory capacity result in hyperglycemia and type 2 diabetes (T2D). However, the mechanism in the regulation of β-cell compensative capacity remains elusive. Nuclear factor-Y (NF-Y) is critical for pancreatic islets' homeostasis under physiological conditions, but its role in β-cell compensatory response to insulin resistance in obesity is unclear. METHODS: In this study, using obese ( ob/ob ) mice with an absence of NF-Y subunit A (NF-YA) in β-cells ( ob , Nf-ya βKO) as well as rat insulinoma cell line (INS1)-based models, we determined whether NF-Y-mediated apoptosis makes an essential contribution to β-cell compensation upon metabolic stress. RESULTS: Obese animals had markedly augmented NF-Y expression in pancreatic islets. Deletion of β-cell Nf-ya in obese mice worsened glucose intolerance and resulted in β-cell dysfunction, which was attributable to augmented β-cell apoptosis and reactive oxygen species (ROS). Furthermore, primary pancreatic islets from Nf-ya βKO mice were sensitive to palmitate-induced β-cell apoptosis due to mitochondrial impairment and the attenuated antioxidant response, which resulted in the aggravation of phosphorylated c-Jun N-terminal kinase (JNK) and cleaved caspase-3. These detrimental effects were completely relieved by ROS scavenger. Ultimately, forced overexpression of NF-Y in INS1 β-cell line could rescue palmitate-induced β-cell apoptosis, dysfunction, and mitochondrial impairment. CONCLUSION Pancreatic NF-Y might be an essential regulator of β-cell compensation under metabolic stress.
Rats ; Mice ; Animals ; Reactive Oxygen Species/metabolism* ; Diabetes Mellitus, Type 2/metabolism* ; Insulin Resistance ; Insulin ; Insulin-Secreting Cells/metabolism* ; Apoptosis ; Stress, Physiological ; Transcription Factors/metabolism* ; Palmitates/pharmacology* ; Obesity/metabolism*

OBJECTIVE: To investigate the causes, clinical manifestation and treatment principles of frontal sinus tract after the frontal approach craniotomy. METHOD: The clinic data of 13 patients with frontal skin sinus tract after the frontal approach craniotomy were retrospectively analyzed. All of them were described in the clinical record to have undergone frontal sinus mucosa pushing down or shaving and bone wax filling in the frontal sinus during the surgery, of whom 3 cases had history of frontal abscess incision drainage. All patients were performed endoscopic frontal sinus surgery and forehead skin sinus tract excision and suture. RESULT: All of the patients successfully recovered after one-stage operation, and the frontal skin sinus tract was healed. CONCLUSION The frontal approach craniotomy with postoperative frontal sinus tract was related with the improper use of bone wax tamponade and sealing of frontal sinus. The treatment principles were to remove bone wax, remove inflammatory granulation tissue around the sinus tract, and to open frontal sinus and promote frontal sinus drainage.
Craniotomy ; methods ; Drainage ; Endoscopy ; Forehead ; Frontal Sinus ; surgery ; Granulation Tissue ; surgery ; Humans ; Palmitates ; Retrospective Studies ; Waxes

The saturated free fatty acid (FFA), palmitate, could induce apoptosis in various cell types, but little is known about its effects on human umbilical cord-derived mesenchymal stem cells (hUC-MSCs). Here, we investigated whether palmitate induced apoptosis and endoplasmic reticulum (ER) stress in hUC-MSCs. hUC-MSCs were stained by labeled antibodies and identified by flow cytometry. After administration with palmitate, apoptotic cell was assessed by flow cytometry using the Annexin V-FITC/7-AAD apoptosis detection kit. Relative spliced XBP1 levels were analyzed using semi-quantitative RT-PCR. The mRNA of BiP, GRP94, ATF4 and CHOP were analyzed by real-time PCR. Relative BiP and CHOP protein were analyzed using Western blot analysis. The results showed that hUC-MSCs were homogeneously positive for MSC markers; palmitate increased apoptosis of hUC-MSCs and activated XBP1 splicing, BiP, GRP94, ATF4 and CHOP transcription. These findings suggest that palmitate induces apoptosis and ER stress in hUC-MSCs.
Activating Transcription Factor 4 ; metabolism ; Apoptosis ; DNA-Binding Proteins ; metabolism ; Endoplasmic Reticulum Stress ; Heat-Shock Proteins ; metabolism ; Humans ; Membrane Glycoproteins ; metabolism ; Mesenchymal Stromal Cells ; cytology ; drug effects ; Palmitates ; pharmacology ; Regulatory Factor X Transcription Factors ; Transcription Factor CHOP ; metabolism ; Transcription Factors ; metabolism ; Umbilical Cord ; cytology ; X-Box Binding Protein 1

OBJECTIVETo study the effect of palmitate on toll-like receptor 4 (TLR4) expression and signaling in vascular endothelial cells.

METHODSPig iliac endothelial cells (PIECs) were incubated with palmitate. TLR4 gene expression levels were measured by quantitative real-time PCR, and TLR4 and IκBα protein expressions by Western blotting. The expression levels of TLR4 protein on the surface of PIECs were quantified using flow cytometry. ELISA was employed to detect tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) concentrations in the cell medium.

RESULTSPalmitate treatment significantly increased TLR4 mRNA and protein expression levels in PIECs compared with those in the control cells (4.73∓0.61 vs 1.25∓0.90, P<0.05; 5.79∓0.05 vs 4.07∓0.31, P<0.05). The expression levels of TLR4 on the cell surface significantly increased (38.070∓3.907 vs 29.390∓1.072, P<0.05), while IκBα protein level was significantly lowered in PIECs after palmitate treatment as compared with those in the control cells (2.04∓0.22 vs 3.98∓0.18, P<0.05). Palmitate treatment significantly elevated TNF-α (2.52∓0.30 vs 1.38∓0.26, P<0.05) and IL-6 (IL-6: 3.28∓0.32 vs 1.44∓0.28, P<0.05) concentrations in the cell culture medium.

CONCLUSIONPalmitate can enhance TLR4 expression and signaling in porcine vascular endothelial cells.

Animals ; Blotting, Western ; Endothelial Cells ; drug effects ; metabolism ; I-kappa B Proteins ; metabolism ; Interleukin-6 ; metabolism ; NF-KappaB Inhibitor alpha ; Palmitates ; pharmacology ; RNA, Messenger ; Real-Time Polymerase Chain Reaction ; Signal Transduction ; Swine ; Toll-Like Receptor 4 ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVE: Schizophrenia is a chronic and persistent mental illness and requires continuous treatment. Nevertheless, a majority of schizophrenia subjects show non-adherence to oral antipsychotics due to many factors including a lack of insight and a decline in their cognitive function. Medication non-adherence is associated with an increase in relapse and hospitalization and incurs a heavy burden not only to subjects and caregivers, but also to society. Treatment with antipsychotic long acting injection can maintain a consistent plasma drug concentration and has been shown to prevent relapse and re-hospitalization. This study aims to assess the cost-effectiveness of paliperidone palmitate long acting injection (PLAI) compared with atypical oral antipsychotics (risperidone, olanzapine, aripiprazole and paliperidone) in schizophrenia subjects who are non-adherent to oral atypical antipsychotics. METHODS: A decision-tree model was constructed to compare the clinical and economic outcomes of PLAI and oral comparator over 1 year in schizophrenia subjects who are non-adherent to oral atypical antipsychotics. Clinical data such as relapse rate, extra pyramidal symptoms (EPS) rate, suicide rate and non-adherence rate were obtained from published literature. Utility values for each schizophrenia health state were calculated based on an Australian study to measure the utility values for schizophrenia patients. Direct medical cost data were obtained from domestic literature. Sensitivity analyses were performed on major variables. RESULTS: Based on model estimates, PLAI can increase quality-adjusted life years (QALY) per patient by 0.39 and is associated with a 2.93-fold lower probability of relapse compared with the weighted average of the oral treatments (0.2204 vs 0.6462). The total annual medical costs per patient (including medication, inpatient and outpatient cost) were 4.51 million Korean Won for PLAI, and 5.19 million Korean Won for the weighted average of oral atypical antipsychotics, leading to a cost reduction of 0.68 million Korean Won with PLAI. CONCLUSION: With lower total medical cost and improved treatment outcomes compared to oral treatments, PLAI was assessed to be a dominant treatment option for schizophrenia patients who are non-adherent to oral atypical antipsychotics.
Antipsychotic Agents ; Benzodiazepines ; Caregivers ; Hospitalization ; Humans ; Inpatients ; Isoxazoles ; Medication Adherence ; Outpatients ; Palmitates ; Piperazines ; Plasma ; Pyrimidines ; Quality-Adjusted Life Years ; Quinolones ; Recurrence ; Republic of Korea ; Schizophrenia ; Suicide ; Aripiprazole ; Paliperidone Palmitate

BACKGROUNDGlucolipotoxicity might play an important role in the β cell decompensation stage during the development of obesity-associated type 2 diabetes. Tissue inhibitor of metalloproteinase-1 (TIMP-1) inhibits matrix metalloproteinase (MMP) activity and regulates proliferation and apoptosis of a variety of cell types, including pancreatic β-cells. In the present study, we investigated whether TIMP-1 counteracts glucolipotoxicity in the pancreatic β-cell line INS-1.

METHODSINS-1 cells were incubated in normal or high glucose, with or without palmitate (0.4 mmol/L), in the presence of TIMP-1 or MMP inhibitor GM60001. In some experiments, cells were pretreated with phosphatidylinositol-3 (PI-3) kinase inhibitor, LY294002 or wortmannin. The amount of dead INS-1 cells was determined by HO342 and propidium iodide staining. Akt phosphorylation was evaluated by Western blotting analysis to investigate a possible mechanism of TIMP-1's action.

RESULTSTIMP-1 protected INS-1 cells from glucolipotoxicity independent of MMP inhibition. TIMP-1 stimulated Akt phosphorylation. Inhibition of the PI-3 kinase pathway abolished the survival effect of TIMP-1.

CONCLUSIONTIMP-1 may counteract glucolipotoxicity induced β-cell death via a PI-3 kinase pathway.

Animals ; Cell Line ; Glucose ; pharmacology ; Insulin-Secreting Cells ; drug effects ; metabolism ; Palmitates ; pharmacology ; Phosphatidylinositol 3-Kinases ; Phosphorylation ; drug effects ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Signal Transduction ; Tissue Inhibitor of Metalloproteinase-1 ; pharmacology

Ischemia and reperfusion (I/R) injury is a major cause of hepatic failure after liver surgery, but no method could monitor or predict it real-time during surgery. We measured bioelectrical impedance (BEI) and cell viability to assess the usefulness of BEI during I/R in rat liver. A 70% partial liver ischemia model was used. BEI was measured at various frequencies. Adenosine triphosphate (ATP) content, and palmitic acid oxidation rate were measured, and histological changes were observed in order to quantify liver cell viability. BEI changed significantly during ischemia at low frequency. In the ischemia group, BEI increased gradually during 60 min of ischemia and had a tendency to plateau thereafter. The ATP content decreased below 20% of the baseline level. In the I/R group, BEI recovered to near baseline level. After 24 hr of reperfusion, the ATP contents decreased to below 50% in 30, 60 and 120 min of ischemia and the palmitic acid metabolic rates decreased to 91%, 78%, and 74%, respectively, compared with normal liver. BEI may be a good tool for monitoring I/R during liver surgery. The liver is relatively tolerant to ischemia, however after reperfusion, liver cells may be damaged depending upon the duration of ischemia.
Adenosine Triphosphate/metabolism ; Animals ; *Cell Survival ; Electric Impedance ; Energy Metabolism ; Ischemia/*metabolism ; Liver/*metabolism/pathology ; Male ; Palmitates/metabolism ; Rats ; Rats, Sprague-Dawley ; *Reperfusion ; Reperfusion Injury/metabolism/pathology

A case of delayed progressive extradural pneumatocele after microvascular decompression (MVD) is presented. A 60-year-old male underwent MVD for hemifacial spasm; the mastoid air cell was opened and sealed with bone wax during surgery. One month after surgery, the patient complained of tinnitus, and progressive extradural pneumatoceles without cerebrospinal fluid (CSF) leakage was observed. Revision surgery was performed and the opened mastoid air cell was completely sealed with muscle patch and glue. The patient's symptoms were resolved, with no recurrence of pneumatoceles at 6 month follow up. Progressive extradural pneumatocele without CSF leakage after posterior fossa surgery is a very rare complication. Previous reports and surgical management of this rare complication are discussed.
Adhesives ; Decompression ; Follow-Up Studies ; Humans ; Male ; Mastoid ; Microvascular Decompression Surgery ; Middle Aged ; Muscles ; Palmitates ; Recurrence ; Tinnitus ; Waxes

OBJECTIVETo investigate the attenuating effect of curcumin, an anti-inflammatory compound derived from dietary spice turmeric (Curcuma longa) on the pro-inflammatory insulin-resistant state in 3T3-L1 adipocytes.

METHODSGlucose uptake rate was determined with the [3H] 2-deoxyglucose uptake method. Expressions of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were measured by quantitative RT-PCR analysis and ELISA. Nuclear transcription factor kappaB p65 (NF-kappa p65) and mitogen-activated protein kinase (MAPKs) were detected by Western blot assay.

RESULTSThe basal glucose uptake was not altered, and curcumin increased the insulin-stimulated glucose uptake in 3T3-L1 cells. Curcumin suppressed the transcription and secretion of TNF-alpha and IL-6 induced by palmitate in a concentration-dependent manner. Palmitate induced nuclear translocation of NF-kappaB. The activities of Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase1/2 (ERK1/2) and p38MAPK decreased in the presence of curcumin. Moreover, pretreatment with SP600125 (inhibitor of JNK) instead of PD98059 or SB203580 (inhibitor of ERK1/2 or p38MAPK, respectively) decreased the up-regulation of TNF-alpha induced by palmitate.

CONCLUSIONCurcumin reverses palmitate-induced insulin resistance state in 3T3-L1 adipocytes through the NF-kappaB and JNK pathway.

3T3-L1 Cells ; Animals ; Anthracenes ; pharmacology ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Curcumin ; pharmacology ; Glucose ; metabolism ; Insulin ; pharmacology ; Insulin Resistance ; Interleukin-6 ; genetics ; metabolism ; JNK Mitogen-Activated Protein Kinases ; metabolism ; MAP Kinase Signaling System ; Mice ; NF-kappa B ; metabolism ; Palmitates ; pharmacology ; Protein Kinase Inhibitors ; pharmacology ; Tumor Necrosis Factor-alpha ; genetics ; metabolism ; Up-Regulation

OBJECTIVETo establish an in vitro cell model to investigate hepatic steatosis of non-alcoholic fatty liver disease.

METHODSHepG2 cells cultured in MEM containing 10 % fetal bovine serum were divided into control group and model group. At 7 0%-80 % confluency, HepG2 cells in model group were exposed to a long-chain mixture of free fatty acids (oleate and palmitate) for 24 h, cells in control group were subject to fresh medium. Lipid droplets were observed with oil red O stain and electron microscope, triglyceride and malonaldehyde were detected by respective assay kits.

RESULTA large number of lipid droplet were detected in model HepG2 cells; the level of triglyceride increased. However,malonaldehyde did not increase significantly compared with control group.

CONCLUSIONA large number of lipid droplet were detected in model HepG2 cells; the level of triglyceride increased. However, malonaldehyde did not increase significantly compared with control group.

Culture Media ; pharmacology ; Fatty Acids, Nonesterified ; pharmacology ; Fatty Liver ; Hep G2 Cells ; Humans ; Models, Biological ; Non-alcoholic Fatty Liver Disease ; Oleic Acid ; pharmacology ; Palmitates ; pharmacology