tCho Levels Research Articles

Preparation and characterization of D. opposita Thunb polysaccharide-zinc inclusion complex and evaluation of anti-diabetic activities

In the present work, Dioscorea opposita Thunb polysaccharide-zinc (DPS-zinc) inclusion complex was synthesized for the first time and its anti-diabetes activities against Streptozotocin (STZ)-induced diabetic rats were assayed. The detail structural and morphological analysis of as-prepared DPS-zinc complex was done by using different spectroscopic and microscopic methods. The pharmacological study revealed that DPS-zinc presented a potent hypoglycemic effect on STZ-induced diabetic rats, decreased the glucose and insulin levels, reduced malondialdehyde (MDA) contents and increased SOD and T-AOC activities significantly in liver. The levels of T-CHO, TG and LDL-C in serum were dramatically decreased while HDL-C level was increased with the treatment of proposed inclusion complex. In brief, DPS-zinc could be considered as a potential candidate for developing an ingredient of functional foods for zinc supplements with the hypoglycemic action.

Antidiabetic Effects of the Auricularia auricular Polysaccharides Simulated Hydrolysates in Experimental Type-2 Diabetic Rats

A model of type-2 diabetes mellitus (T2DM) using high-fat diet and low-dose STZ was established to assess the antidiabetic effects of Auricularia auricular polysaccharides simulated hydrolysates (AAPHs) obtained from the dried fruiting body of A. auricular. AAPHs were administered intragastrically (i.g.) at the dose of 0.15 g/kg b. W. to diabetic Wistar rats for 4 weeks. Results show that AAPHs was demonstrated to exhibit significant diminution in T-CHO and LDL-C levels (P < 0.05 or P < 0.01) compared to the diabetic control group. In addition, the secretion level of GLP-1 were different with the diabetes model group from 0 to 30 min, and had a tendency to alleviate weight loss. The current study suggests that AAPHs might be incorporated as a supplement in diabetic agents or combined with other health-care foods.

Assessment of Anterior Cingulate Cortex (ACC) and Left Cerebellar Metabolism in Asperger's Syndrome with Proton Magnetic Resonance Spectroscopy (MRS).

PurposeProton magnetic resonance spectroscopy (1H MRS) is a noninvasive neuroimaging method to quantify biochemical metabolites in vivo and it can serve as a powerful tool to monitor neurobiochemical profiles in the brain. Asperger’s syndrome (AS) is a type of autism spectrum disorder, which is characterized by impaired social skills and restrictive, repetitive patterns of interest and activities, while intellectual levels and language skills are relatively preserved. Despite clinical aspects have been well-characterized, neurometabolic profiling in the brain of AS remains to be clear. The present study used proton magnetic resonance spectroscopy (1H MRS) to investigate whether pediatric AS is associated with measurable neurometabolic abnormalities that can contribute new information on the neurobiological underpinnings of the disorder.MethodsStudy participants consisted of 34 children with AS (2–12 years old; mean age 5.2 (±2.0); 28 boys) and 19 typically developed children (2–11 years old; mean age 5.6 (±2.6); 12 boys) who served as the normal control group. The 1H MRS data were obtained from two regions of interest: the anterior cingulate cortex (ACC) and left cerebellum.ResultsIn the ACC, levels of N-acetylaspartate (NAA), total creatine (tCr), total choline-containing compounds (tCho) and myo-Inositol (mI) were significantly decreased in children with AS compared to controls. On the other hand, no significant group differences in any of the metabolites were found in the left cerebellum. Neither age nor sex accounted for the metabolic findings in the regions.ConclusionThe finding of decreased levels of NAA, tCr, tCho, and mI in the ACC but not in left cerebellar voxels in the AS, suggests a lower ACC neuronal density in the present AS cohort compared to controls.

The Effect of Trigonella Foenum Graceum L. (Fenugreek) on Metabolic Syndrome: An Accidental Finding

Objectives: The global prevalence of Helicobacter pylori (H. pylori) infection remains high. Recent studies demonstrated the potential relationship among H. pylori-induced chronic inflammation, insulin resistance and metabolic disorders. The aim of this study was to investigate the association between H. pylori infection and metabolic syndrome (MetS).Methods: This cross-sectional study enrolled 4,232 health examination participants aged from 30 to 65-year-old in the northern Taiwan in 10 years. The general information and blood tests of all subjects were collected from the health examination center. H. pylori infection was diagnosed via 13C-urea breath test. The log-transformed (log) serum high sensitivity C-reactive protein (hs-CRP) was used as the inflammatory parameter. MetS was defined according to the revised National Cholesterol Educational Program Adult Treatment Panel III (Revised NCEP ATP III) criteria. Subjects were divided into two groups based on their H. pylori infectious status. The association between H. pylori infection and metabolic parameters was assessed with multivariate logistic regression analysis.Results: A total of 4,232 subjects (2,641 males and 1,591 females, aged 47.0 years ± 8.2 years) were enrolled for the analysis. H. pylori infection presented in 44.8% of all subjects. MetS presented in 27.6% of all subjects. Participants with H. pylori infection showed higher proportion of MetS, higher body mass index(BMI) and higher serum cholesterol(T-CHO) levels with statistical significance (p<0.001). There was no significant difference in the log serum hs-CRP between subjects with and without H. pylori infection. H. pylori infection increased the risk of large waist circumference component [OR=1.26 (1.10-1.43)] and high fasting plasma glucose component [OR=1.18 (1.04-1.34)], and contributed significantly to the presence of MetS with adjusted OR 1.23 (1.03-1.46).Conclusions: Adults with H. pylori infection was associated with higher prevalence of MetS, higher BMI and higher mean serum T-CHO levels. Furthermore, H. pylori infection was identified as a risk factor for MetS.

On the Effect of Sex on Prefrontal and Cerebellar Neurometabolites in Healthy Adults: An MRS Study.

In neuropsychiatric research, the aspects of sex have received increasing attention over the past decade. With regard to the neurometabolic differences in the prefrontal cortex and the cerebellum of both men and women, we performed a magnetic resonance spectroscopic (MRS) study of a large group of healthy subjects. For neurometabolic measurements, we used single-voxel proton MRS. The voxels of interest (VOI) were placed in the pregenual anterior cingulate cortex (pACC) and the left cerebellar hemisphere. Absolute quantification of creatine (Cre), total choline (t-Cho), glutamate and glutamine (Glx), N-acetylaspartate, and myo-inositol (mI) was performed. Thirty-three automatically matched ACCs and 31 cerebellar male–female pairs were statistically analyzed. We found no significant neurometabolic differences in the pACC region (Wilks' lambda: p = 0.657). In the left cerebellar region, we detected significant variations between the male and female groups (p = 0.001). Specifically, we detected significantly higher Cre (p = 0.005) and t-Cho (p = 0.000) levels in men. Additionally, males tended to have higher Glx and mI concentrations. This is the first study to report neurometabolic sex differences in the cerebellum. The effects of sexual hormones might have influenced our findings. Our data indicates the importance of adjusting for the confounding effects of sex in MRS studies.

Age- and sex-related changes in fasting plasma glucose and lipoprotein in cynomolgus monkeys.

BackgroundThe age-related dysfunction of glucose and lipid metabolism has a long-standing relationship with cardiovascular and neurodegenerative disease. However, the effects of metabolic dysfunction on men and women are different. Reasons for these sex differences remains unclear. Cynomolgus monkeys have been used, in the past, for the study of human metabolic diseases due to their biologically proximity to humans. Nevertheless, few studies to date have focused on both age- and sex-related differences in glucose and lipid metabolism. The present study was designed to specifically address these questions by using a large cohort of cynomolgus monkeys (N = 1,399) including 433 males and 966 females with ages ranging 4 to 24 years old.MethodsFasting plasma glucose (FPG) and lipid parameters including total cholesterol (T-Cho), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured. All these parameters were compared between ages and sexes.ResultsAmong the entire cohort, age was strongly correlated with levels of FPG, TG and HDL. Consequently, sex-related analysis revealed that females had significantly higher average levels of FPG, T-Cho, TG, HDL-C and LDL-C than their male counterparts. In addition, more female (28.5 %) than male (16 %) monkeys qualified for impaired fasting plasma glucose (IFPG). In those IFPG animals, sex-related differences were also detected i.e. females had significantly increased levels of T-Cho, TG and LDL-C.ConclusionsThe result, for the first time, demonstrated the similarities and differences in detail between male and female cynomolgus monkeys in relationship to age-related glucose and lipoprotein metabolisms, and differences under various physiological conditions. The detailed glucose and lipoprotein profiling should provide additional and important insights for prediabetic conditions. Cynomolgus monkeys appear to be an excellent model for translational research of diabetes and for novel therapeutic strategies testing to overt diabetes.

Nutritional parameters affecting severity of pneumonia and length of hospital stay in patients with pneumococcal pneumonia: a retrospective cross-sectional study.

BackgroundPneumococcal pneumonia is the most common form of community-acquired pneumonia (CAP). Although a pneumococcal conjugate vaccine has contributed to a reduction in the incidence of pneumococcal pneumonia among older children and adults, no significant decrease in the incidence has been observed among persons aged ≥65 years. A low body mass index and hypoalbuminemia are common in Japanese patients with CAP, but the association of other nutritional parameters with the severity of pneumonia or length of hospital stay in patients with pneumococcal pneumonia is unclear.MethodsFifty-seven previously healthy inpatients who presented with pneumococcal pneumonia were divided into two groups: those aged ≥65 years (n = 36) and those aged <65 years (n = 21). Patients’ characteristics (the Confusion, Urea, Respiratory rate, Blood pressure, age >65 years (CURB-65) score), the pneumonia severity index (PSI), and inflammatory and metabolic nutritional parameters were compared between the two groups.ResultsThe older group showed significantly lower serum albumin and cholinesterase (ChE) levels. Multivariate linear regression analysis revealed that the PSI was positively correlated with age in both groups. In the younger age group, both the CURB-65 score and PSI showed significant negative correlations with the serum ChE level, and there was a significant negative correlation between the length of stay and serum total cholesterol (T-cho) level. In the older group, the fasting period, lymphocyte count, and age showed significant positive correlations with the length of stay. There was a significant negative correlation between the length of stay and serum albumin level, but no correlation with the serum ChE or T-cho levels, in the older patients.ConclusionsOur findings suggest that in patients aged <65 years, age and serum ChE and T-cho levels were associated with both the severity of pneumococcal pneumonia and length of stay. In contrast, the length of stay in older patients was associated with multiple factors that differed from those in younger patients. These differences may reflect age-related immunosenescence in older patients and a greater effect of serum ChE and T-cho levels on immunity in younger patients.

Global metabolic profiling for the study of Rhizoma Paridis saponins-induced hepatotoxicity in rats.

Rhizoma Paridis saponins (RPS) is a traditional Chinese medicine (TCM) from the plant Paris polyphylla var. yunnanensis (Fr.) Hand.-Mazz. Despite its potentially clinical utility such as anticancer and anti-inflammation, it has slight side effects and toxicity as previous report. In this work, 90-day administration of RPS induced liver injury. 1 H-NMR- and GC/MS-based metabonomic analyses in conjunction with histopathological examinations, blood biochemistry and hepatic phase I and II enzymes assays were performed to evaluate the toxic mechanisms of RPS induced in rats. As a result, oral administration of RPS possessed certain liver toxicity in SD rats. 1 H-NMR and GC/MS data indicated that RPS inhibited the oxidation of fatty acids, glycolysis, and TCA cycle pathway, and disturbed glycine, serine, and threonine metabolism. Low expression of TG, T-CHO, and LDL-C and high levels of ALT and AST indicated that chronic exposure to RPS caused hepatocyte damage, synthesis dysfunction, and transportation failure of lipoproteins. In addition, RPS downregulated the mRNA levels of CYP1A2, CYP2E1, and UGTs. In conclusion, we used metabonomics approach to study the toxicity of RPS for the first time. This research demonstrated that metabonomics method was a promising tool to study and diagnose TCM-induced toxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 99-108, 2017.

Abstract 1484: Pancreatic cancer and normal pancreas water content and its impact in metabolite quantification

Abstract The absence of early symptoms in pancreatic cancer creates a critical need for identifying new noninvasive biomarkers. Magnetic resonance spectroscopy (MRS) and spectroscopic imaging (MRSI) are being evaluated in the diagnosis of several solid malignancies. A hallmark of most solid tumors is the detection of elevated phosphocholine (PC) and total choline (tCho). We previously observed elevated levels of tCho in several pancreatic cancer cell lines and tumor xenografts (1). Initial single voxel studies performed in humans suggest that the tCho signal normalized to water may be relatively high in normal pancreas compared to pancreatic tumor (2). Since metabolites are normalized to the water signal it is important to determine differences in its content for accurate quantification. Here, we quantified tCho in orthotopic and subcutaneous Panc1 pancreatic xenografts, and in normal pancreas. 1H MRSI acquired on a 9.4T spectrometer showed heterogeneous tCho signal in orthotopic tumors. To further determine differences in tCho, tumor tissues and pancreas were embedded in agarose and imaged ex vivo with 1H MRSI. Concentration of tCho was 3.38 ± 0.95 mM in orthotopic tumors, 1.32 ± 0.59 mM in subcutaneous tumors, and 1.27 ± 0.52 mM in normal pancreas (n = 2), when using the uncorrected water signal for normalization. Despite a much higher tCho signal in the subcutaneous tumors, tCho concentrations were comparable to the pancreas. We next estimated the water content of the tumors and the pancreas as a ratio of wet weight to dry weight (measured after 72h of lyophilization) and confirmed a significantly higher water content in tumors compared to the pancreas (wet to dry weight ratio of ∼ 6 vs ∼ 4). A separate set of tumors were freeze-clamped and used for high-resolution 1H MRS. Tumor and pancreas extracts were obtained using a dual-phase extraction method and 1H MR spectra were acquired as previously described (3). To determine the tCho concentration, peak integrations from spectra for choline, PC and glycerophosphocholine were compared to an internal standard. Integrals of the metabolites of interest were determined and normalized first to the tissue wet weight. Once the tCho concentration in tumors and pancreas was corrected for differences in water content, a two-fold higher tCho concentration was observed in tumor tissue compared to normal pancreas. These data support the use of 1H MRSI that provides a tCho map rather than the placement of single voxels to address heterogeneities in the pancreas and in pancreatic cancers. The results highlight the importance of quantifying water content in the calculation of metabolite concentration when comparing different tissues. Work supported by NIH P50CA103175. (1) Penet et al., Clin Cancer Res (2014). (2) Ma et al., Journal of computer assisted tomography (2011). (3) Shah et al., NMR Biomed (2012). Citation Format: Marie-France Penet, Balaji Krishnamachary, Tariq Shah, Yelena Mironchik, Anirban Maitra, Zaver M. Bhujwalla. Pancreatic cancer and normal pancreas water content and its impact in metabolite quantification. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1484. doi:10.1158/1538-7445.AM2015-1484

In vivo proton MR spectroscopy of pancreatic neuroendocrine tumors in a multiple endocrine neoplasia type 1 conditional knockout mouse model.

MR spectroscopy (MRS) can improve diagnosis and follow treatment in cancer. However, no study has yet reported application of in vivo (1)H-MRS in malignant pancreatic lesions. This study quantitatively determined whether in vivo (1)H-MRS on multiple endocrine neoplasia type 1 (Men1) conditional knockout (KO) mice and their wild type (WT) littermates could detect differences in total choline (tCho) levels between tumor and control pancreas. Relative tCho levels in pancreatic tumors or pancreata from KO and WT mice were determined using in vivo (1)H-MRS at 9.4 T. The levels of Cho-containing compounds were also quantified using in vitro (1)H-NMR on extracts of pancreatic tissues from KO and WT mice, respectively, and on extracts of pancreatic tissues from patients with pancreatic neuroendocrine tumors (PNETs). tCho levels measured by in vivo (1)H-MRS were significantly higher in PNETs from KO mice compared to the normal pancreas from WT mice. The elevated choline-containing compounds were also identified in pancreatic tumors from KO mice and tissues from patients with PNETs via in vitro (1)H-NMR. These results indicate the potential use of tCho levels estimated via in vivo (1)H-MRS in differentiating malignant pancreatic tumors from benign tumors.

Abstract 1185: Altered choline metabolism in pancreatic cancer cells and tumor xenografts

Abstract Early-stage pancreatic cancer is usually clinically silent, and most patients presenting symptoms attributable to pancreatic cancer have advanced disease. Better understanding of the disease, effective detection methods, and new therapeutic targets are urgently needed to improve its outcome. Magnetic resonance spectroscopy (MRS) is being evaluated in the diagnosis of several solid malignancies (1). A hallmark of most solid tumors is the detection of elevated levels of phosphocholine (PC) and total choline (tCho) (1). The increase in PC levels in solid tumors has been attributed to high level of choline kinase (Chk)-alpha (2). Here, we characterized the metabolism of multiple pancreatic ductal adenocarcinoma cell lines and tumors with in vitro high resolution MRS and in vivo 1H magnetic resonance spectroscopic imaging (MRSI). We also characterized the expression of Chk-alpha in the cells and tumor extracts. Eight pancreatic adenocarcinoma cell lines (Panc1, BxPC3, Pa04C, Pa02C, Pa20C, Pa28C, Pa03C, and Pa09C) and one immortalized pancreatic cell line (human pancreatic nestin expressing (HPNE)) were investigated. For the in vivo experiments, cells were inoculated subcutaneously in male SCID mice. Once tumors reached 500 mm3, the mice were scanned on a 4.7T spectrometer for 1H MRSI, after which the tumors excised for immunoblot analysis, and high-resolution 1H MRS. Cells and tumor extracts were carried out as previously described (3). Fully relaxed 1H MR spectra of the extracts were acquired on a Bruker Avance 500 spectrometer at 11.7 T. Integrals of the metabolites of interest were determined and normalized to the number of cells and to the tumor weight respectively. Significant differences in tCho were identified in pancreatic cell lines and the tumor xenografts. In the panel of cell lines, the differences in tCho levels were associated with differences in Chk-alpha expression. PC and tCho levels were significantly elevated in the pancreatic cancer cell lines compared to the immortalized pancreatic cell line, and Chk-alpha was overexpressed in the cancer cell lines. In vivo studies revealed that elevated tCho was detected in tumors derived from the 4 cell lines tested, with higher levels of tCho in Panc1 tumors. These in vivo results were confirmed by ex vivo MRS analysis of the tumor extracts. The high level of tCho observed in Panc1 tumors was mainly due to increased PC, and correlated with high Chk-alpha expression observed in the immunoblots. These data support the use of 1H MRS to noninvasively detect pancreatic cancer. Moreover, the aberrant choline metabolism may provide novel targets in the treatment of pancreatic cancer. Acknowledgement: This work was supported by NIH P50CA103175. *Equal contribution.

Abstract 509: Hypoxia and HIF silencing mediated dysregulation of total choline, CD44 expression, and metastatic burden in MDA-MB-231 human breast cancers

Abstract Hypoxic tumors frequently exhibit an aggressive phenotype due to dysregulated gene expression and metabolic changes. Hypoxia results in the stabilization of hypoxia inducible factors (HIF-1/2) that transcriptionally activate genes involved in invasion, metastasis, metabolism, and in the adaptation of cancer cells to their microenvironment. In breast cancer, stem-like breast cancer cells that survive, repopulate and metastasize to distant locations, have elevated expression of CD44. In a previous study, we observed elevated expression of CD44 in hypoxic tumor regions, and identified HIF-1α as a regulator of CD44 expression in breast cancer cells under hypoxic conditions [1]. Hypoxia has also been implicated in increasing the activity of choline kinase (Chk)-alpha, the enzyme responsible for elevated phosphocholine (PC) and total choline (tCho) consistently observed in cancers [2]. In previous studies, lentiviral transduction of MDA-MB-231 breast cancer cells (231 cells) with shRNA against Chk-alpha and the in vivo delivery of the Chk-shRNA virus into tumor bearing mice resulted in decreased CD44 message and expression together with effective silencing of Chk message and expression [3]. Here, using non-invasive proton magnetic resonance spectroscopic imaging (1H MRSI), we have established the importance of HIF in reducing total choline and metastatic tumor burden, and have identified a role for CD44 in establishing lung metastasis. HIF silencing in MDA-MB-231 cells significantly delayed tumor growth in mice. Both, the in vitro 1H and 31P MR spectra and in vivo 1H MRS images of tumors derived from engineered cells showed decreased tCho levels and distribution. This decrease of tCho was statistically significant in tumors derived from double silenced cells. Western blot analysis of tumors detected a decrease in Chk expression in double silenced (HIF-1 and 2) tumors. Silencing HIF-1α, -2α or both resulted in a significant reduction of metastatic lung burden in mice. Additionally, HIF-2α silencing was more effective at reducing lung colonization than HIF-1α, while silencing both was the most effective. Although metastatic burden decreased in HIF-1α silenced cells, the percentage of cells with high CD44 expression in the metastatic foci was comparable to that in the wild type or empty vector foci. These data identify the importance of targeting HIF and CD44 to prevent lung colonization and disrupt the metastatic cascade. This work was supported by NIH R01CA136576 and P50 CA103175. We thank Mr. Gary Cromwell for valuable technical assistance.

Lactate and choline metabolites detected in vitro by nuclear magnetic resonance spectroscopy are potential metabolic biomarkers for PI3K inhibition in pediatric glioblastoma.

The phosphoinositide 3-kinase (PI3K) pathway is believed to be of key importance in pediatric glioblastoma. Novel inhibitors of the PI3K pathway are being developed and are entering clinical trials. Our aim is to identify potential non-invasive biomarkers of PI3K signaling pathway inhibition in pediatric glioblastoma using in vitro nuclear magnetic resonance (NMR) spectroscopy, to aid identification of target inhibition and therapeutic response in early phase clinical trials of PI3K inhibitors in childhood cancer. Treatment of SF188 and KNS42 human pediatric glioblastoma cell lines with the dual pan-Class I PI3K/mTOR inhibitor PI-103, inhibited the PI3K signaling pathway and resulted in a decrease in phosphocholine (PC), total choline (tCho) and lactate levels (p<0.02) as detected by phosphorus (31P)- and proton (1H)-NMR. Similar changes were also detected using the pan–Class I PI3K inhibitor GDC-0941 which lacks significant mTOR activity and is entering Phase II clinical trials. In contrast, the DNA damaging agent temozolomide (TMZ), which is used as current frontline therapy in the treatment of glioblastoma postoperatively (in combination with radiotherapy), increased PC, glycerophosphocholine (GPC) and tCho levels (p<0.04). PI-103-induced NMR changes were associated with alterations in protein expression levels of regulatory enzymes involved in glucose and choline metabolism including GLUT1, HK2, LDHA and CHKA. Our results show that by using NMR we can detect distinct biomarkers following PI3K pathway inhibition compared to treatment with the DNA-damaging anti-cancer agent TMZ. This is the first study reporting that lactate and choline metabolites are potential non-invasive biomarkers for monitoring response to PI3K pathway inhibitors in pediatric glioblastoma.

AB0929 The Serum Levels of Cholinesterase and Total Cholesterol PREDICT the Existence or Latency of Multiple Organs' Involvements in Japanese Patients with Igg4-Related Disease

BackgroundIgG4-related disease (IgG4-RD) is the new entity, which is a multisystem and fibroinflammatory condition. It is characterized by progressive scarring and dysfunction of affected organs and tissues including the pancreas,...

Progressive decrease of N-acetylaspartate to total creatine ratio in the pregenual anterior cingulate cortex in patients with major depressive disorder: longitudinal 1H-MR spectroscopy study

Longitudinal metabolic changes of total choline (tCho), creatine+phosphocreatine (total creatine, tCr), and N-acetylaspartate (NAA) in the pregenual anterior cingulate cortex (pACC) of patients with major depressive disorder (MDD) have not been well evaluated. To evaluate the longitudinal changes of the metabolic levels of tCho, tCr, and NAA in the pACC of MDD patients and normal controls with the use of Single-voxel (1)HMRS. Single-voxel (1)HMRS was acquired in the pACC of 21 female patients with MDD and 26 age- and gender-matched controls. Follow-up scans were acquired in 10 patients with MDD and 15 controls after 9-10 months from baseline scans. Absolute concentrations of tCho, tCr, and NAA, and the ratios of NAA/tCr and tCho/tCr were calculated and compared between and within groups. The patient group showed slightly improved clinical symptoms, as measured by Beck's Depression Inventory (P=0.035), after treatment with antidepressants. Comparison of baseline scans between the groups showed no differences in any of the absolute metabolite concentrations or ratios. The NAA/tCr ratio in the pACC of patients with MDD showed a significant decrease in the follow-up scan (P=0.032), and the NAA/tCr ratio of the baseline scan showed logarithmic negative association with illness duration (P=0.024). A progressive decrease in the NAA/tCr ratio in the pACC of patients with MDD was demonstrated and the decrease in this ratio was at the highest rate in the early period after illness onset. These findings indicate the neuronal degeneration and dysfunction of the pACC, and the importance of early clinical intervention in female patients with MDD.

Catechin-rich green tea extract increases the expression of genes of the cholesterol synthetic pathways in livers of normal diet- and high-fat diet-fed rats

Background In vivo studies using rodents have shown that green tea extract (GT) and catechins isolated from green tea can induce a variety of health effects, including antiobesity, hypoglycemic and hypolipidemic activities. However, we and others observed that serum cholesterol levels were increased by GT and tea catechins in rats and mice [1]. In this study, we examined whether dietary GT affects the expression of genes involved in cholesterol synthesis. Materials and methods Catechin-rich (30% catechin) GT was used for the in vivo studies. Male Sprague-Dawley rats (average weight 237.7 g) were divided into six groups. The first group was fed a normal diet (ND, 10% calories from fat); the second group a high-fat diet (HFD, 40% calories from fat); the third group a ND containing 1% GT (ND + 1% GT); the fourth group a HFD + 1% GT; the fifth group a ND + 3% GT; and the sixth group a HFD + 3% GT. After 4 weeks of feeding, rats were euthanized by whole blood collection under anesthesia. Serum metabolites were determined using a dry chemistry analyzer. Total RNA samples extracted from the liver were used for microarray and quantitative real-time PCR (qPCR) analyses. Hepatic lipids were extracted with chloroform-methanol 2:1, and liver triglyceride (TG) and cholesterol (Cho) levels were determined. Results As reported previously, GT increased the serum levels of total cholesterol (T-Cho) and high-density lipoprotein cholesterol (HDL-Cho) in a concentration-dependent manner in both ND- and HFD-fed rats. Conversely, GT lowered hepatic TG and T-cho levels. Microarray analysis data suggested that GT increased more than two-fold the mRNA expression of nine hepatic genes involved in cholesterol synthesis out of 21 analyzed in ND-fed rats. qPCR analysis revealed that GT significantly increased the mRNA levels of six genes involved in cholesterol synthesis in ND-fed rats. Similar but smaller effects of GT also were observed in HFD-fed rats. Conclusions The results suggested that GT increased serum cholesterol levels, at least in part, through the increased expression of genes in the cholesterol synthetic pathways in the liver. GT also increased the mRNA levels of Srebf2 and Insig1, which are positively regulated by SREBP2. Therefore, dietary GT may increase expression of these genes by SREBP2 activation.

Cerebral metabolic abnormalities in A3243G mitochondrial DNA mutation carriers

To establish cerebral metabolic features associated with the A3243G mitochondrial DNA mutation with proton magnetic resonance spectroscopic imaging ((1)H MRSI) and to assess their potential as prognostic biomarkers. In this prospective cohort study, we investigated 135 clinically heterogeneous A3243G mutation carriers and 30 healthy volunteers (HVs) with (1)H MRSI. Mutation carriers included 45 patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS); 11 participants who would develop the MELAS syndrome during follow-up (converters); and 79 participants who would not develop the MELAS syndrome during follow-up (nonconverters). The groups were compared with respect to MRSI metabolic indices of 1) anaerobic energy metabolism (lactate), 2) neuronal integrity (N-acetyl-l-aspartate [NAA]), 3) mitochondrial function (NAA; lactate), 4) cell energetics (total creatine), and 5) membrane biosynthesis and turnover (total choline [tCho]). Consistent with prior studies, the patients with MELAS had higher lactate (p < 0.001) and lower NAA levels (p = 0.01) than HVs. Unexpectedly, converters showed higher NAA (p = 0.042), tCho (p = 0.004), and total creatine (p = 0.002), in addition to higher lactate levels (p = 0.032), compared with HVs. Compared with nonconverters, converters had higher tCho (p = 0.015). Clinically, converters and nonconverters did not differ at baseline. Lactate and tCho levels were reliable biomarkers for predicting the risk of individual mutation carriers to develop the MELAS phenotype. (1)H MRSI assessment of cerebral metabolism in A3243G mutation carriers shows promise in identifying disease biomarkers as well as individuals at risk of developing the MELAS phenotype.

Feasibility of MR spectroscopy for characterizing malignant breast lesions using a clinical 3-T scanner

To investigate the feasibility of in vivo proton magnetic resonance spectroscopy ((1)H-MRS) for characterizing malignant breast lesions using a clinical 3-T scanner, and to compare the measured total choline-containing compound (tCho) levels in this work with the previously published results at 1.5T and 4T. Twenty-six patients (35-72years old, mean age 53 years), with biopsy-confirmed breast cancer, underwent anatomical imaging, dynamic contrast-enhanced MR imaging, and single-voxel (1)H-MRS. The absolute tCho concentration in malignant tumors was calculated and was expressed as a concentration unit in mmol/kg. All lesions were divided into two groups (mass- and non-mass-type lesions), based on the morphological pattern of enhancement, and analyzed. The measured tCho levels had a range of 0.10-10.1 (mean±SD, 1.62±2.29mmol/kg) in 15 (58%) of 26 malignant breast spectra, which was consistent with the previous in vivo estimates at 1.5T and 4.0T. There were 11 (42%) false-negative cases, which resulted in 58% sensitivity. The sensitivity of the (1)H-MRS in size-dependent subgroups (e.g., <2.0 and ≥2.0cm) increased from 14 to 66%, in a statistically significant manner (P=0.019). In addition, the tCho detection rate was higher in mass-type lesions (14/21, 66%) than in non-mass-type lesions (1/5, 20%), reaching a significant level (P=0.03). The sensitivity based on the dynamic contrast-enhanced kinetics was 100%. Quantitative in vivo (1)H-MRS at 3T may provide useful information for quantifying tCho concentration levels and characterizing tumor types (e.g., mass vs diffuse) of breast cancer. However, its limitation in characterizing small lesions has to be considered.

해상가두리 양식장에서 배합사료 및 생사료 투여에 의한 조피볼락, Sebastes schlegeli 건강도

The purpose of this research is to evaluate the effects of a commercial mixed extruded pellet(EP) and raw fish moist pellet(MP) diet on diseases prevalence and serological constituents and HSI of korean rockfish, Sebastes schlegeli grown in two commercial-scale aquaculture farms from June to December in 2009. The growth of MP-fed rockfish was slightly faster than EP-fed rockfish during experimental period, but did not show significant differences. The levels of TCHO, TG, Glucose and TP in the MP-fed rockfish group were higher than those of EP-fed group, whereas there was no significant difference in other biochemical factors of blood between two groups. In addition, bacteria and virus were not detected in both MP- and EP-fed rockfish groups, and the infection rates of gill fluke between two groups did not show clear difference. In conclusion, there was no comparable difference in growth and the health extents of one year rockfish by administration of the commercial mixed extruded pellet(EP) and raw fish moist pellet(MP) diets.

Relationship Between Fertility at Foal Heat and Blood Biochemistry Parameters Monitored During the Peripartum Period in Thoroughbred Mares

This study aimed to examine fertility at foal heat and its relevance to body condition score (BCS) and blood nutritional metabolites in Thoroughbred mares. Thoroughbred mares foaled from 2006 to 2009 were included and classified into two groups: group C (conception; n = 34), which included mares that conceived during foal heat (within 3 weeks after foaling), and group NC (nonconception; n = 39), which included mares that did not conceive despite mating during their foal heat. BCS and blood samples were obtained 1 month before the expected foaling date and 1, 2, 3, and 4 weeks after foaling. Total protein (TP), albumin (Alb), blood urea nitrogen (BUN), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), total cholesterol (T-Cho), triglyceride (TG), nonesterified fatty acid (NEFA), calcium (Ca), inorganic phosphate (iP), and magnesium (Mg) levels were measured using an automatic clinical chemistry analyzer. Repeated measures analysis of variance (ANOVA) and Student t-test were used to examine the differences between the two groups. No significant differences were observed between the two groups in any of the above-mentioned parameters at 1 month before the expected foaling date (Student t-test). Furthermore, no significant differences were observed between the two groups in serum levels of TP, Alb, AST, GGT, T-Cho, NEFA, Ca, and Mg and BCS at postpartum periods (repeated measures ANOVA). Serum TG, BUN, and iP levels remained lower in group NC than in group C after foaling (P < .05, repeated measures ANOVA). Although the mechanism by which these nutritional factors affect a decline in reproductive performance remains unclear, our results suggest that blood biochemical tests can detect potential imbalances in nutrition and metabolism, even if there is no difference in BCS.