Triple combination of palliative oral metronomic chemotherapy in recurrent and metastatic epithelial ovarian cancer: A retrospective study

Background: Ovarian cancer is a leading cause of death from gynecological cancer in the world and in India. This study aims to evaluate the efficacy and toxicity profile of oral metronomic chemotherapy (MCT) in the form of etoposide, cyclophosphamide, and tamoxifen in recurrent and metastatic ovarian cancer. Methods: This was a retrospective observational study that included those post?treatment patients who had the recurrent or metastatic disease after completion of treatment in 2018 at Regional Cancer Centre, Bikaner, Rajasthan. Forty patients who were unfit for further intensive intravenous chemotherapy were included. The oral MCT constituted etoposide, cyclophosphamide, and tamoxifen. Descriptive statistics and Kaplan?Meier analyses were performed. Progression?free survival (PFS) and overall survival (OS) were assessed. Results: Forty women with a median age of 62 (range: 35?80) years were enrolled in the study to receive oral MCT. The Eastern Cooperative Oncology Group?Performance Status (ECOG?PS) was 0�in 28 patients and 2�in 12 patients. The best clinical response rate post?oral MCT was seen in the first 4 months. Objective response was observed in 24 (60%) of patients in the form of stable disease (19, 47.5%) and partial response (5, 12.5%). Disease progression was observed in 10 (25%) of patients. The median follow?up was 6.4 months (4.5�2 months). The median estimated OS was 6.5 months. The median estimated PFS was 3.7 months. Nineteen (47.5%) patients had grade?I/II mucositis. Grade?III/IV mucositis were observed in 9 (22.5%) patients. Thirty?seven (92.5%) patients died at the end of the study at 1 year. Dose reduction was required in 15 (37.5%) patients. Conclusion: Oral MCT was found to be an effective and well?tolerated regime with good symptomatic control and low?moderate toxicity profile in patients with relapsed and metastatic ovarian cancer. However, 22% of patients showed grade?III/IV thrombocytopenia.

Pyruvate Supplementation Can Prevent HIIE-induced Metabolic Acidosis and Increase the Expression of MCT1/MCT4 in Skeletal Muscles of Rats / 中国生物化学与分子生物学报

As one of the causes of exercise-induced fatigue, exercise-induced metabolic acidosis has attracted much attention. The effect of pyruvate supplementation on exercise-induced metabolic acidosis is rarely reported, and its mechanism has not been fully elucidated. Monocarboxylate transporters (MCTs) play an important role in the maintenance of the acid-base balance, but it is not clear whether pyruvate can alleviate acidosis by increasing the expression of MCTs. In this study, pyruvate (616 mg/kg/day) was supplemented to rats for one week, and then acute HIIE was performed. The HIIE protocol comprised 13 repeats of a 60 s sprint session at 110% VO

Construction of Stable MCT1-Knockout RKO Cell Line Based on CRISPR/Cas9 Technology and Its Biological Function Detection / 华中科技大学学报(医学版)

@#Objective To precisely knock out MCT1in humancolorectalcancercellline RKO by using CRISPR/Cas9 gene editingtechnique,and to detect its biological function. Methods CRISPRv2-MCT1-KO # 1 and CRISPRv2-MCT1-KO # 2 plasmids weretransfected into RKO cells. The monoclonal cells were selected by the medium containing puromycin after 48 h. The expression of MCT1 was detected by Western blotting and DNA sequencing. The change of expression and distribution of MCT1 protein were detected by immunofluorescence.Intracellular lactic acid level was detected by lactic acid detection kits. Colonyformation assayand CCK-8 assay were performed to detect cell proliferation ability. The potential signaling pathways of MCT1 in colorectal cancer were explored by GSEA software. Results CRISPRv2-MCT1-KO plasmid was well constructed. Western blottingand DNAsequencingresults showedthat MCT1 was successfully knocked outinthe humancolorectal cancer RKOcells. Compared withthecontrol group, MCT1 protein was notobserved onthecell membraneof MCT1-nockoutcells,andtheintracellularlactatelevel was significantlyreduced(P <0.05). The proliferation ability of RKO cells was significantly decreased after MCT1 knockout(P <0.05). GSEA analysis showedthat MCT1 may promotethe occurrence and development ofcolorectal cancerthrough oxidative phosphorylation and MYC signaling pathway. Conclusion The stable MCT1-knockout human colorectal cancer RKO cell line was successfully constructed by applying CRISPR/Cas9 technology, which might become an ffectivetoolforstudyingtherole of MCT1 inthe occurrence and development ofcolorectal cancer.

Explore Mechanism of Modified Si Junzitang in Improving Acidic Microenvironment and Reversing Gastric Precancerous Lesions Based on MCT4/CD147 / 中国实验方剂学杂志

Objective:To observe the effect of modified Si Junzitang on the level of lactic acid in gastric mucosa and the expression of Carboxylic acid transporter 1（MCT1）， monocarboxylic acid transporter 4（MCT4）， and extracellular matrix metalloproteinase inducer （CD147）in rats with gastric precancerous lesions（GPL）. Method:Seventy-four SD male rats were randomly divided into normal group （12 rats） and model group （62 rats）. <italic>N</italic>-methyl-<italic>N'</italic>-nitro-<italic>N</italic>-nitrosoguanidine（MNNG）-ammonia compound method was used to establish GPL rat models， and at the 9^th week， the model rats were randomly divided into model group， folic acid group（2.7 mg·kg^-1）， modified Si Junzitang high， medium and low dose groups（12.6， 6.3， 3.15 g·kg^-1）， with 12 rats in each group. After intragastric administration for 12 weeks， the general conditions of the rats were observed. Hematoxylin-eosin（HE）staining was used to observe the histopathological changes of gastric mucosa in rats， chemical colorimetry was used to detect the content of lactic acid in gastric mucosa； immunohistochemistry and real-time polymerase chain reaction（Real-time PCR）were used to detect MCT1， MCT4， CD147 protein and mRNA expression in gastric mucosal tissues. Result:Modified Si Junzitang significantly improved the pathological manifestations in GPL rats such as gastric mucosal epithelial gland structure， disorder of arrangement and cell atypia. Compared with the normal group， the lactic acid content of the gastric mucosa tissue in the model group increased significantly（<italic>P</italic><0.01）， and the protein and mRNA expressions of MCT1， MCT4， CD147 significantly increased（<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the model group， the lactic acid content in each dose group of modified Si Junzitang was significantly reduced（<italic>P</italic><0.05， <italic>P</italic><0.01）， and the protein expression levels of MCT4 and CD147 were also significantly reduced in each dose group of modified Si Junzitang（<italic>P</italic><0.05， <italic>P</italic><0.01）. The mRNA expression of MCT4 was significantly reduced in the middle and high dose groups（<italic>P</italic><0.05， <italic>P</italic><0.01）， and the mRNA expression of CD147 was significantly reduced in the high dose group（<italic>P</italic><0.05）. Modified Si Junzitang showed no significant regulatory effect on MCT1. Conclusion:Modified Si Junzitang can significantly improve the abnormal histopathology of gastric mucosal epithelium in GPL model rats. Its mechanism may be related to down-regulating the overexpression of MCT4 and CD147， inhibiting lactic acid outflow， and improving the acidic microenvironment of gastric mucosal epithelium.

MicroRNAs miR-1 and miR-206 Regulate Monocarboxylate Transporter-4 and Vascular Endothelial Growth Factor Gene Expression in Colorectal Cancer

Background: Colorectal cancer (CRC) is currently the third most common cancer type in males and the second most occurring in females. The role of microRNA (miRNA) in the development of colorectal cancer is notfully elucidated. Therefore, understanding the mechanistic interaction between miRNA and their target oncogenes may hold great importance as a possible target for interventional anticancer therapy Aims:To identify miRNAs that are part of the regulating pathway of Monocarboxylate Transporter-4 (MCT4) and Vascular Endothelial Growth Factor (VEGF) oncogenes.Study Design:We used publicly available prediction tools (e.g. TargetScan, MicroCosm, PicTar, and DIANA-microT-CDS) to identify the possible miRNA that target the two oncogenes. Methodology:We used the GeneMania database to visualize the network and verify gene names and remove ambiguity and duplications. Furthermore, we used miRTarBase database to identify experimentally validated targets which we used to further confirm miRNA-oncogene relationships. Finally, we utilized miR-Mfold web-tool to further visualize the circular structures and the simulated miR-1 and miR-206 targeting arrangements.Results:We found two putative miRNA (miR-1 and miR-206) that may downregulate MCT4 coded by SLC16A3gene and VEGF which is coded by VEGF gene. We found relationships between the validated target genes of miR-1 and miR-206 through GeneMania which we extracted from the literature. And we elucidated the proposed structure of these two miRNAs through miR-Mfold web-tool.Conclusion: Our results elucidated a novel regulation pathway in CRC cells and may suggest a potential therapeutic approach for CRC therapy. MiR-1 and miR-206 may help cells go to apoptosis and inhibit the angiogenesis of colorectal cancer cells by down-regulation of MCT4 and VEGF proteins in tumor tissues.

Comparison of Pain on Injection of Propofol MCT with Propofol LCT.

Propofol is one of the safest drugs for induction of general anaesthesia. Routinely available preparation in the market being propofol LCT (long chain triglycerides) has the disadvantage of pain on injection. This pain is very discomforting for the patient and also to the anaesthesiologist. So, they are coming up with a new preparation propofol MCT (medium chain triglycerides) which causes less pain on injection. We wanted to compare the occurrence of pain on injection of Propofol MCT with Propofol LCT.METHODSAfter obtaining institutional ethical committee approval, 150 patients undergoing various elective surgeries under general anaesthesia where propofol was used as an induction agent, aged between 18 and 65 years of ASA I & II were enrolled in the study. The study patients were divided into two groups. Group M, who received Propofol MCT and group L, who received Propofol LCT as an induction drug. The intensity of pain was evaluated by using Visual Analogue Score (VAS). Similarly change of triglyceride levels after single induction dose of Propofol MCT and Propofol LCT were observed.RESULTSGroup M showed reduced pain score (4.15±1.90) after injection along with less incidence of pain compared to Group L (6.37±2.49). Serum triglyceride levels had no significant difference in preoperative and postoperative values.CONCLUSIONSPain on injection with Propofol MCT (4.15 ± 1.90) is less compared to Propofol LCT (6.37± 2.49) & no evidence of change of triglyceride levels was seen after a single induction dose in the study.

Effect of silencing monocarboxylate transporter 4 on the malignant biological behaviors of prostate cancer PC3 cells / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate the effects of silencing monocarboxylate transporter 4 (MCT4) on the proliferation, migration and invasion of prostate cancer PC3 cells and its possible molecular mechanism. Methods: RNA interference technology was used to transfect siRNA-MCT4 (si-MCT4) and negative control plasmid (si-NC) into PC3 cells, respectively. The content of lactic acid in the cell culture medium of transfected PC3 cells was detected by lactic acid assay after culturing for 96 h. The proliferation, migration and invasion ability of PC3 cells were detected by CCK-8 and Transwell assay, respectively. Western blotting was used to detect the silencing effect and the expressions of integrin β 4-FAK-SRC-MEK-ERK signaling pathway associated proteins (integrin β4, p-FAK, p-SRC, p-ERK1/2, p-MEK1/2) and EMT associated proteins (E-cadherin and N-cadherin). Results: PC3 cell line with silenced MCT4 was successfully constructed. Compared with the control group, the content of extracellular lactic acid in the PC3 cell culture medium of the si-MCT4 group was significantly decreased (P<0.01), and the proliferation, migration and invasion of cells were significantly decreased (P<0.05 or P<0.01). Compared with the control group, the protein expressions of integrin β4, p-FAK, p-SRC, p-MEK1/2, p-ERK1/2 and N-cadherin were significantly decreased (all P<0.01), while the protein expression of E-cadherin was significantly increased (P<0.01). Conclusion: Silencing MCT4 can significantly inhibit the proliferation, migration and invasion of PC3 cells, the mechanism of which may be related to the inhibition of lactic acid level in cell culture medium and suppression of integrin β4-FAK-SRC-MEKERK signaling pathway associated proteins as well as EMT associated proteins.

The effect of downregulation of MCT1 on the proliferation of glioma cells / 中华肿瘤杂志

Objective@#To investigate the molecular mechanism of down-regulation of monocarboxylic acid transporter 1 (MCT1) on the proliferation inhibition of glioma cell.@*Methods@#siMCT1, siMCT4 and negative control siRNA were transfected into glioma cell lines including U-251 and U-87. The proliferation activities of U-251 and U-87 cells were detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay and clonogenic assay. Glucose consumption and lactic acid efflux of U-251 and U-87 cells were determined by spectrophotometry.Western blot was used to detect the expressions of MCT1, MCT4, human glucose transporter 1 (GLUT1), GLUT4, tuberous sclerosis associated protein (TSC2), p-TSC2, 4E binding protein 1 (4EBP1), p-4EBP1, ribosomal S6 protein kinase (S6) and p-S6 protein in U-251 and U-87 cells.@*Results@#Compared with negative control group, siMCT1 and siMCT4 significantly inhibited the expressions of MCT1 and MCT4 protein in U-251 and U-87 cells (both P<0.05). However, only knockdown of MCT1, the proliferation activities of U-251 and U-87 cells significantly decreased (P<0.05). The clone formation rates of U-251 and U-87 cells decreased to (55.20±3.27)% and (68.33±4.58) %, respectively (P<0.05). The glucose consumption of U-251 and U-87 cells in the negative control group at 72 hours were (82.65±6.66) pmol/L and (63.33±5.27) pmol/L, respectively, significantly higher than (31.70±3.17) pmol/L and (26.41±3.19) pmol/L of the siMCT1 transfected group (P<0.05). The extracellular lactate flow of U-251 and U-87 cells in negative control group at 72 h were (155.49±8.15) mmol/L and (135.37±8.21) mmol/L, respectively, significantly higher than (42.69±4.66) mmol/L and (38.91±4.83) mmol/L of the siMCT1 transfected group (P<0.05). Western blot analysis showed that knockdown of MCT1 significantly decreased the protein levels of GLUT1 p-TSC2, p-4EBP1 and p-S6 in U-251 and U-87 cells.@*Conclusions@#Downregulation of MCT1 expression can inhibit the proliferation of glioma cells. Deletion of MCT1 inhibits the glycolysis and metabolism of glioma cells through regulating the mTOR signaling pathway.

Very-long chain acyl coenzyme A dehydrogenase deficiency / 中国实用儿科杂志

Very long chain acyl-CoA dehydrogenase deficiency(VLCADD)is a disorder involving the initial step of fatty acid beta-oxidation in the mitochondrial matrix. VLCADD can present at various ages,from the neonatal period to adulthood,with symptoms including hypoglycemia,rhabdomyolysis,skeletal muscle weakness and cardiomyopathy,and poses the greatest risk of complications during intercurrent illness or after prolonged fasting. Early diagnosis,treatment,and surveillance can reduce mortality. The most common diagnostic evaluation methods are plasma acylcarnitine profiles and ACADVL gene molecular testing. Functional testing,including white blood cell or fibroblast enzyme assay,is a useful diagnostic adjunct if molecular sequencing alone is insufficient to deter-mine the diagnosis or uncharacterized mutations are identified. Treatment emphasizes the avoidance of fasting and often includes a specialized diet that is high carbohydrate/low longchain fat which is supplemented by medium chain triglycerides(MCT).very-long chain acyl coenzyme A dehydrogenase

Study of acupuncture combined with rat nerve growth factor on neurobehavioral ability of cerebral palsy infant rats and its brain tissue growth and metabolism associated proteins / 中国针灸

<p><b>OBJECTIVE</b>To study the effects of acupuncture combined with rat nerve growth factor (NGF) on the cerebral palsy infant rats and the proteins which associated with growth, apoptosis and metabolism.</p><p><b>METHODS</b>Seventy infant rats were selected, Fifty infant rats of which were made the cerebral palsy infant model by the ligation of unilateral carotid artery for cerebral ischemia and oxygen-deficient environment, then the 30 model rats were randomly divided into a model group, a NGF group and a combined group, 10 rats in each group. Twenty infant rats were used in the sham-operated group and the blank control group, 10 rats in each group. The treatment was not given in the blank control group. The rats in the sham-operated group were cut the neck skin and separated the left carotid artery, and then sutured and disinfected the wound. The intraperitoneal injection of NGF (2000 U•kg•d) was used in the NGF group. Based on the injection in the NGF group, acupuncture was used in the combined group, once a day, and the acupoints were "Baihui" (GV 20), left "nieⅠ" (extra), "Dazhui" (GV 14), "Jizhong" (extra), "Quchi" (LI 11), "Yongquan" (KI 1), "Hegu" (LI 4), "Zhoujie" (extra) and "Xiqianxue" (extra). The same volume of saline was intraperitoneally injected in the model group for continuous 14 days. Neurobehavioral ability score was evaluated after treatment. TUNEL were conducted to detect the brain cell apoptosis rate and the expressions of apoptosis associated gene Bax, Bcl-2 and Casp3 were detected by PCR. The level of nerve growth associated protein (GAP-43) and energy metabolism-related protein monocarboxylate transporter protien 1(MCT 1) were detected by Western blot.</p><p><b>RESULTS</b>After intervention, the neurobehavioral ability of baby rats in the blank control and sham-operated group was normal, but there was various degrees of abnormity in the model group, NGF group and combined group. The scores of neurobehavioral ability of the combined group and NGF group were better than those of the model control (all <0.05), and the scores in the combined group was better than those in the NGF group (all <0.05). The left brain cell apoptosis rate, expressions of Bax and Casp3 in the combined group and NGF group were lower and the expressions of Bcl-2 were higher than those of the model group (all <0.05), with more obvious results of Bax and Gasp3 in the combined group than those in the NGF group (all <0.05). The protein levels of GAP-43 and MCT 1 in the combined group and NGF group were higher than those in the model group (all <0.05), with higher expressions in the combined group compared with those in the NGF group (both <0.05).</p><p><b>CONCLUSION</b>Acupuncture combined with NGF could improve the neurobehavioral ability of cerebral palsy infant rats, inhibit the nerve cell apoptosis and improve the brain tissue injure and energy metabolism by up-regulating the expressions of GAP-43 and MCT 1.</p>

Molecular docking studies of human MCT8 protein with soy isoflavones in Allan-Herndon-Dudley syndrome (AHDS) / 药物分析学报

Monocarboxylate transporter-8 (MCT8) is a specific thyroid hormone transporter, essential for the uptake of thyroid hormone into target tissues. Mutations in the MCT8 gene have been identified as the cause of Allan-Herndon-Dudley syndrome (AHDS). It has been reported that soy isoflavones influence thyroid hormone system and can interact with thyroid hormone transporter proteins. Therefore, the present study aimed to find out whether soy isoflavones (genistein, daidzein and glycitein) can be used as a natural inhibitor to target MCT8 in AHDS. Docking studies were performed for soy isoflavones in order to evaluate their binding affinity to MCT8 protein using AutoDock4 (version 4.2.6) and AutoDock Vina. After docking, the ligands were ranked according to their binding energy and the best lead compound was selected based on the least binding energy. The docking results indicated that daidzein possesses the lowest binding energy against MCT8. Moreover, it was found that the residues PRO-338, HIS-341, and GLU-348 were involved in hydrogen bond interactions with genistein and daidzein. This study suggests that daidzein is a promising natural inhibitor to target MCT8 in AHDS.

Inborn Errors of Ketone Body Metabolism and Transport: An Update for the Clinic and for Clinical Laboratories

Abstract Major progress occurred in understanding inborn errors of ketone body transport and metabolism between the International Congresses on Inborn Errors of Metabolism in Barcelona (2013) and Rio de Janeiro (2017). These conditions impair either ketogenesis (presenting as episodes of hypoketotic hypoglycemia) or ketolysis (presenting as ketoacidotic episodes); for both groups, immediate intravenous glucose administration is the most critical and (mHGGCS, HMGCS2) effective treatment measure. Ketogenesis Deficiencies: New biomarkers were described for mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mHGGCS, HMGCS2) deficiency. New patient series refined clinical knowledge of 3-hydroxy-3-methylglutaryl-CoA lyase (HGGCL, HMGCL) deficiency. Although affected humans have not been described, two animal model phenotypes are pertinent: zebrafish deficient in monocarboxylate transporter 7 (MCT7, slc16a6) (decreased ketone body exit from hepatocytes) or mice lacking D-3-hydroxy-n-butyrate dehydrogenase (BDH1, BDH1) (isolated hyperacetoacetatemia; fatty liver). Ketolysis Deficiencies: Monocarboxylate transporter 1 (MCT1, SLC16A1) deficiency is a newly described defect of ketone body transport, joining deficiencies of succinyl-CoA:3-oxoacid CoA transferase (SCOT, OXCT1) and methylacetoacetyl-CoA thiolase (MAT, ACAT1). Some heterozygotes for MCT1 or SCOT deficiency develop ketoacidosis.

A Novel c.826G>A Mutation in a Boy with Allan-Herndon-Dudley Syndrome: Clinical Significance of Thyroid Function Tests in Developmental Delay of Unknown Origin / 대한소아신경학회지

Allan-Herndon-Dudley syndrome (AHDS) is an X-linked intellectual disability caused by monocarboxylate transporter 8 (MCT8) deficiency. AHDS manifests in global developmental delay, axial hypotonia, quadriplegia, movement disorders in male patients, and most of them show the delayed or hypomyelination on brain magnetic resonance images. Typically, Triiodothyronine (T3) levels are markedly elevated, thyroid stimulating hormone (TSH) levels are normal or elevated, and free thyroxine (T4) levels are normal or decreased. In AHDS patients, early neurological manifestations are easily mistaken as cerebral palsy with unknown origin. Here, we present a novel c.826G>A mutation in a boy with severe axial hypotonia, limb dystonia and developmental delay. Thyroid function test including TSH, T3, and free T4 levels was the important clue for the diagnosis of AHDS of the patient.

Preparation and evaluation of a phospholipid-based injectable gel for the long term delivery of leuprolide acetaterrh

A phospholipid-based injectable gel was developed for the sustained delivery of leuprolide acetate (LA). The gel system was prepared using biocompatible materials (SPME), including soya phosphatidyl choline (SPC), medium chain triglyceride (MCT) and ethanol. The system displayed a sol state with low viscosity in vitro and underwent in situ gelation in vivo after subcutaneous injection. An in vitro release study was performed using a dialysis setup with different release media containing different percentages of ethanol. The stability of LA in the SPME system was investigated under different temperatures and in the presence of various antioxidants. In vivo studies in male rats were performed to elucidate the pharmacokinetic profiles and pharmacodynamic efficacy. A sustained release of LA for 28 days was observed without obvious initial burst in vivo. The pharmacodynamic study showed that once-a-month injection of LA-loaded SPME (SPME-LA) led to comparable suppression effects on the serum testosterone level as observed in LA solution except for the onset time. These findings demonstrate excellent potential for this novel SPME system as a sustained release delivery system for LA.

TORC2 and eisosomes are spatially interdependent, requiring optimal level of phosphatidylinositol 4, 5-bisphosphate for their integrity.

The elucidation of the organization and maintenance of the plasma membrane has been sought due to its numerous roles in cellular function. In the budding yeast Saccharomyces cerevisiae, a novel paradigm has begun to emerge in the understanding of the distribution of plasma membrane microdomains and how they are regulated. We aimed to investigate the dynamic interdependence between the protein complexes eisosome and TORC2, representing microdomains MCC and MCT, respectively. In this study, we reveal that the eisosome organizer Pil1 colocalizes with the MCT marker Avo2. Furthermore, we provide evidence that the formation of MCT is dependent on both eisosome integrity and adequate levels of the plasma membrane phosphoinositide PI(4,5)P2. Taken together, our findings indicate that TORC2, eisosomes, and PI(4,5)P2 exist in an interconnected relationship, which supports the emerging model of the plasma membrane.

MCT oil-based diet reverses hypertrophic cardiomyopathy in a patient with very long chain acyl-coA dehydrogenase deficiency.

Very long chain acyl-CoA dehydrogenase (VLCAD) deficiency is one of the genetic defects of mitochondrial fatty acid beta-oxidation presenting in early infancy or childhood. If undiagnosed and untreated, VLCAD deficiency may be fatal, secondary to cardiac involvement. We assessed the effect of replacing part of the fat in the diet of a 2 ½-month-old male infant, who was diagnosed with VLCAD deficiency,with medium-chain triglyceride (MCT) oil and essential fats. The patient presented with vomiting, dehydration, and was found to have persistent elevation of liver function tests, hepatomegaly, pericardial and pleural effusion, right bundle branch block, and biventricular hypertrophy. Because of the cardiomyopathy, hepatomegaly, and an abnormal acylcarnitine profile and urine organic acids, he was suspected of having VLCAD deficiency. This was confirmed on acyl-coA dehydrogenase, very long chain (ACADVL) gene analysis. He was begun on an MCT oil-based formula with added essential fatty acids, uncooked cornstarch (around 1 year of age), and frequent feeds. By 7 months of age, cardiomyopathy had reversed and by 18 months of age, all cardiac medications were discontinued and hypotonia had improved such that physical therapy was no longer required. At 5 years of age, he is at the 50th percentile for height and weight along with normal development. Pediatricians need to be aware about the basic pathophysiology of the disease and the rationale behind its treatment as more patients are being diagnosed because of expansion of newborn screen. The use of MCT oil as a medical intervention for treatment of VLCAD deficiency remains controversial mostly because of lack of clear phenotype-genotype correlations, secondary to the genetic heterogeneity of the mutations. Our case demonstrated the medical necessity of MCT oil-based nutritional intervention and the need for the further research for the development of specific guidelines to improve the care of these patients.

Exercise training and selenium or a combined treatment ameliorates aberrant expression of glucose and lactate metabolic proteins in skeletal muscle in a rodent model of diabetes

Exercise training (ET) and selenium (SEL) were evaluated either individually or in combination (COMBI) for their effects on expression of glucose (AMPK, PGC-1alpha, GLUT-4) and lactate metabolic proteins (LDH, MCT-1, MCT-4, COX-IV) in heart and skeletal muscles in a rodent model (Goto-Kakisaki, GK) of diabetes. Forty GK rats either remained sedentary (SED), performed ET, received SEL, (5 micromol/kg body wt(-1)/day(-1)) or underwent both ET and SEL treatment for 6 wk. ET alone, SEL alone, or COMBI resulted in a significant lowering of lactate, glucose, and insulin levels as well as a reduction in HOMA-IR and AUC for glucose relative to SED. Additionally, ET alone, SEL alone, or COMBI increased glycogen content and citrate synthase (CS) activities in liver and muscles. However, their effects on glycogen content and CS activity were tissue-specific. In particular, ET alone, SEL alone, or COMBI induced upregulation of glucose (AMPK, PGC-1alpha, GLUT-4) and lactate (LDH, MCT-1, MCT-4, COX-IV) metabolic proteins relative to SED. However, their effects on glucose and lactate metabolic proteins also appeared to be tissue-specific. It seemed that glucose and lactate metabolic protein expression was not further enhanced with COMBI compared to that of ET alone or SEL alone. These data suggest that ET alone or SEL alone or COMBI represent a practical strategy for ameliorating aberrant expression of glucose and lactate metabolic proteins in diabetic GK rats.

Advances in thyroid hormone transporters / 中华内分泌代谢杂志

Thyroid hormones play important roles in growth, development, and metabolism of various cells and tissues. It has been assumed for a long time that thyroid hormones are lipophilic and enter cells by passive diffusion, but it has become increasingly clear that cellular uptake and efflux of thyroid hormones are mediated by transporters. The discovery of these thyroid hormone transporters will lead to a better understanding of the tissuespecific regulation of thyroid hormones.

A Case of Intestinal Type Mucinous Adenocarcinoma and Strumal Carcinoid Tumor arising in One of Bilateral Mature Cystic Teratoma of the Ovary / 대한산부인과학회잡지

Malignant transformation of mature cystic teratoma (MCT) is an uncommon complication occuring in approximately 1-3%. Any of the constituent tissues of a teratoma has the potential to undergo malignant transformation; squamous cell carcinoma is the most commonly associated cancer, however, adenocarcinomas or carcinoid tumors arising in mature cystic teratoma are uncommon, especially simultaneously. We present an unusual case of postmenopausal women having mucinous adenocarcinoma and strumal carcinoid tumor simultaneously arising in one of bilateral mature cystic teratoma of the ovary. We suggest malignant transformation of MCT should be treated according to the management of the worst histologic diagnosis of the transformations if there are 2 or more malignancies are arised in MCT of the ovary.

The Effect of Alcohol on Dynamic Posturography / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The acute effect of alcohol is well known. However, although many authors have studied the effect of alcohol on equilibrium and found a deteriorated balancing capacity, objective studies of deteriorated balancing capacity have rarely been reported. The object of this study is to assess the effect of alcohol on vestibular function impairment by dynamic posturography. MAERIALS AND METHODS: Twelve healthy male volunteers aged 23-27 years (mean 25years) were assessed by dynamic posturography 30 min, 60 min and 90 min before and after the ingestion of alcohol. Alcohol levels were measured by blood samples 30, 60 and 90 min before, at and after ingestion. The samples were analyzed for alcohol by chromatography (SIGMA diagnostics). Each condition in SOT and latencies in MCT were used to estimate the effect of alcohol. RESULTS: The obtained results were as follows: 1) The time when serum alcohol concentration reach the maximum was 60 minute (50%). 2) Conditions 4, 5, 6 and composite scores showed statistically significant lower equilibrium scores (p0.05). CONCLUSION: Acute alcohol ingestion influences impairment of vestibular and visual input on equilibrium.