Evaluation Of Metabolic Changes Research Articles

Evaluation of metabolic changes in clinic attendees with therapeutic carbohydrate restriction

Background: Obesity and related metabolic health disorders are major clinical problems that have become increasingly prevalent worldwide.Aim: This before-after study examined the impact of therapeutic carbohydrate restriction (TCR) in managing metabolic health and promoting weight loss in a clinical setting using indirect calorimetry (IC).Setting: Data were collected from medical records obtained from a specialised allied health clinic focusing on metabolic health.Methods: The study analysed retrospective data from 202 overweight or obese participants (77% female, mean age 47.3) who received TCR as part of a behavioural modification programme involving multiple visits where their lifestyle, body composition and respiratory quotient (RQ), a key indicator of fat oxidation were recorded.Results: The study found that TCR improved fat oxidation in 84% of participants at short term visit (around 2 weeks), with an average weight loss of 1.8 kg. At medium term visit (around 12 weeks), 82% of participants maintained an increase in fat oxidation rate, with an average weight loss of 3.9 kg. In addition, among those with recorded body composition and waist circumference, 71% of weight lost was from fat, with an average reduction of 4.9 cm in waist measurements.Conclusion: This real-world study suggests that personalised TCR guided by IC can be an effective strategy for improving metabolic flexibility to help manage excess weight and related co-morbidities in a free-living population. Further research is needed to examine the long-term effects of TCR using this approach.Contribution: The utilisation of IC allows for the examination of individual shifts and improvements in metabolism among patients undergoing TCR.

Quantitative evaluation of radiation-induced metabolic changes in the ipsilateral breast by FDG-PET/CT

AbstractBackground and aimThere are no reports of quantitative evaluation of metabolic changes in the mammary gland after radiation therapy. The purpose of this study was to investigate metabolic changes in the ipsilateral mammary gland after radiation therapy and to evaluate the late radiation effects.Patients and methodsMetabolic changes of the ipsilateral and contralateral mammary glands were retrospectively evaluated by F-18 fluorodeoxyglucose (FDG) PET/CT after whole breast irradiation following lumpectomy in five breast cancer patients. The maximum standardized uptake values (SUVmax) of the ipsilateral mammary gland (S1) and the contralateral mammary gland (S0) were measured. The relative SUVmax (= S1/S0) was measured immediately before, one year after, three years after, and five years after radiation therapy.ResultsThe SUVmax of the ipsilateral mammary gland decreased gradually, but there was no decrease in the SUVmax of the contralateral mammary gland. Relative SUVmax values before, 1, 3, and 5 years after radiation therapy were 1.33 ± 0.20, 1.13 ± 0.35, 0.99 ± 0.26 and 0.62 ± 0.10, respectively. Relative SUVmax value at 5 years was significantly lower than before radiation therapy (P < 0.01).Conclusions18F-FDG PET/CT may be useful in assessing mammary gland function and predict lactation disorders in advance.

BIOCHEMICAL AND MOLECULAR BIOLOGICAL CHARACTERIZATION OF RAT'S DERMAL FIBROBLAST CULTURE IN HYPOXIA

Dermal fibroblast cell culture is a convenient model for studying various effects on cells, including hypoxia. Fibroblasts, in addition to collagen production, are able to synthesize biogenic amines, hormones, neuropeptides, and neurotransmitters identical to those in the central nervous and endocrine systems, which allows them to be used to study cellular disorders in various diseases. The purpose of the study was to evaluate the functional changes in the culture of dermal fibroblasts under hypoxic conditions using biochemical and molecular biological methods. In cells of fibroblast culture under normoxia (air and 5% CO2 in an incubator) and hypoxic exposure (a mixture of gases - 95% N2 and 5% CO2) at 1 and 3 hours, biochemical methods were used to determine the activity of aspartate aminotransferase (AsAT), alanine aminotransferase (AlAT), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), glucose levels, concentrations of ATP, ADP, AMP, as well as the level of mRNA expression of the hypoxia-induced factor Hif-1a and the nuclear factor Nf-κb by polymerase chain reaction. It was shown that under hypoxic exposure at 1 hour in fibroblast culture, cell viability, glucose levels and activity of LDH, AlAT, AsAT decrease, the amount of ATP decreases, after 3 hours there is a tendency to normalize all indicators. Adaptive mechanisms make it possible to normalize the functioning of cells under hypoxic conditions from 1 to 3 hours. The results obtained in the evaluation of metabolic changes at different times of hypoxic exposure (1 and 3 hours) in the culture of rat fibroblasts indicate a high adaptive capacity of connective tissue cells - fibroblasts at a lack of oxygen. The study of intracellular parameters during hypoxia, the determination of critical points depending on the time of exposure will determine the directions for further study of the mechanisms of cell adaptation, which, perhaps, will complement the tactics of compensatory effects in ischemia of tissues of various genesis. The revealed changes reflect the adaptive response of the fibroblast culture in response to hypoxic exposure.

Evaluation of Metabolic Changes in Acute Intermittent Porphyria Patients by Targeted Metabolomics.

Acute intermittent porphyria (AIP) is an inherited rare hepatic disorder due to mutations within the hydroxymethylbilane gene. AIP patients with active disease overproduce aminolevulinic acid (ALA) and porphobilinogen (PBG) in the liver which are exported inducing severe neurological attacks. Different hepatic metabolic abnormalities have been described to be associated with this condition. The goal of this research was to explore the metabolome of symptomatic AIP patients by state-of-the art liquid chromatography-tandem mass spectrometry (LC-MS/MS). A case versus control study including 18 symptomatic AIP patients and 33 healthy controls was performed. Plasmatic levels of 51 metabolites and 16 ratios belonging to four metabolic pathways were determined. The results showed that the AIP patients presented significant changes in the two main areas of the metabolome under study: (a) the tryptophan/kynurenine pathway with an increase of tryptophan in plasma together with increase of the kynurenine/tryptophan ratio; and (b) changes in the tricarboxylic acid cycle (TCA) including increase of succinic acid and decrease of the fumaric acid/succinic acid ratio. We performed a complementary in vitro study adding ALA to hepatocytes media that showed some of the effects on the TCA cycle were parallel to those observed in vivo. Our study confirms in plasma previous results obtained in urine showing that AIP patients present a moderate increase of the kynurenine/tryptophan ratio possibly associated with inflammation. In addition, it also reports changes in the mitochondrial TCA cycle that, despite requiring further research, could be associated with an energy misbalance due to sustained overproduction of heme-precursors in the liver.

Pre- and Post-Resection Urine Metabolic Profiles of Bladder Cancer Patients: Results of Preliminary Studies on Time Series Metabolomics Analysis.

Simple SummaryBladder cancer is one of the most frequently diagnosed cancers worldwide and due to non-specific symptoms, it is often detected at a late stage. For this reason, possible diagnostic alternatives that could be used for non-invasive screening are still being sought. In recent years, metabolomics approach has been frequently used for this type of research, using urine or blood collected from two groups: patients with a given disease and healthy volunteers. Usually, to minimize the impact of between-subject differences, participants of the study are matched in terms of age, gender, or BMI. Another way to rule out the impact of this variability is to analyze samples taken at intervals from the same patient. Therefore, the aim of our study was to validate results obtained using the traditional approach on a small group of patients, from whom samples were taken before and after resection of the bladder tumor, in a given time frame.The incidence of bladder cancer (BCa) has remained high for many years. Nevertheless, its pathomechanism has not yet been fully understood and is still being studied. Therefore, multiplatform untargeted urinary metabolomics analysis has been performed in order to study differences in the metabolic profiles of urine samples collected at three time points: before transurethral resection of bladder tumor (TURBT), the day after the procedure and two weeks after TURBT. Collected samples were analyzed with the use of high-performance liquid chromatography hyphenated with time-of-flight mass spectrometry detection (HPLC-TOF/MS) and gas chromatography coupled with triple quadrupole mass spectrometry detection (GC-QqQ/MS, in a scan mode). Levels of metabolites selected in our previous study were assessed in order to confirm their potential to differentiate the healthy and diseased samples, regardless of the risk factors and individual characteristics. Hippuric acid, pentanedioic acid and uridine confirmed their potential for sample differentiation. Based on the results of statistical analysis for the paired samples (comparison of metabolic profiles of samples collected before TURBT and two weeks after), a set of metabolites belonging to nucleotide metabolism and methylation processes was also selected. Longitudinal studies proved to be useful for the evaluation of metabolic changes in bladder cancer.

Evaluation of Metabolic Changes in HCV Diabetic Patients Treated With Direct Acting Antiviral Agents

Abstract Background Viral hepatitis is a major public health problem in need of urgent response. The prevalence of hepatitis C virus (HCV) infection in Egypt is the highest in the world. Seroprevalence was modeled to 10.6% and viraemic prevalence to 7.3% in 2014. The association between hepatitis C virus (HCV) infection and diabetes has been widely postulated. Prospective studies have demonstrated a higher risk of developing type 2 diabetes mellitus (T2DM) and insulin resistance in the HCV population. Objective to evaluate metabolic changes in HCV-positive diabetic patients following combination therapy of hepatitis C, clarifying the role of DAAs in these changes. Patients and Methods This study was conducted in Ain Shams University Hospital outpatient clinics who attended from March to December 2018. our study included 70 patients, and were subdivided into the following two groups: Group I: Easy to treat group. Contains 35 diabetic patients with HCV related chronic liver disease treated with sofosbuvir, daclatasvir. Group II: Difficult to treat group. Contains 35 diabetic patients with HCV related chronic liver disease treated with sofosbuvir and daclatasvir and ribavirin. Results Treatment was considered successful when patients became non-viraemic as identified by negative HCV RNA serum PCR at 12 weeks from the end of the treatment regimens (SVR). It was found that diabetic patients treated with DAAs achieved reduction of HbA1C by mean of (0.724±0.3%). The mean increase of serum uric acid level was (0.607±0.4 mg/dL). There were increases in Cholesterol (by mean of 16.85±3.4), HDL (by mean of 5.34±2.1) and LDL (by mean of 13.91±4.2) as well as a decrease in TG (by mean of 13.56±5.1). Conclusion Our study concludes that HCV eradication in diabetic patients leads to various metabolic changes in the form of: Reduction of serum HbA1c level. Elevation of serum uric acid. Elevation of serum cholesterol, HDL, LDL as well as a decrease in TG. Further and larger studies are needed to evaluate the full magnitude of RBV effects on the patients’ metabolism.

Metabolic flux of Bacillus subtilis under poised potential in electrofermentation system: Gene expression vs product formation

The role of poised (negative/positive) potential (0.2/0.4/0.6/0.8 V vs Ag/AgCl at anode) was studied in electrofermentation system (EF) to understand the metabolic flux of Bacillus subtilis with pyruvate as a carbon source. The relative expression of genes encoding pyruvate dehydrogenase (pdhA), lactate dehydrogenase (lctE), acetate kinase (ackA), pyruvate carboxylase (pycA), adenylosuccinate lyase (purB), acylCoA dehydrogenase (acdA) and NADH dehydrogenase (ndh) allowed evaluation of metabolic changes in correlation to product formation and bioelectrochemical analysis. In comparison to control, poised circumstances showed marked influence on product profile with up-regulation of key enzymes involved in pyruvate metabolism. EF poised with − 0.8 V and −0.6 V enhanced bio-hydrogen production by 6 folds and 4 folds respectively. Concomitantly, −0.8 V resulted in maximum ethanol and acetic acid production whilst, −0.6 V and + 0.6 V resulted in maximum lactic acid and succinic acid production respectively. The transcripts for genes associated synthesis were upregulated in the respected poised reactors.

Gas chromatography/mass spectrometry analysis of organic acid profiles in human serum: A protocol of direct ultrasound-assisted derivatization.

Low-molecular-weight organic acids that generally contain one to three carboxyl groups are involved in many important biological processes; therefore, it is important to develop a quantitative method for analyzing organic acids in serum in order to allow an evaluation of metabolic changes. In this study, we evaluated a protocol for detecting 26 organic acids in serum based on ultrasound-assisted derivatization by gas chromatography/mass spectrometry (GC/MS). Serum samples were prepared using ultrasound-assisted silane derivatization before GC/MS analysis to quantify concentrations of organic acids. Additionally, we investigated the variables affecting derivatization yields, including the extraction solvent, derivatization reagents, and derivatization conditions (reaction temperature, duration, and sonication parameters). The protocol was ultimately applied to detect organic acid profiles related to obesity. We used acetone as the extraction solvent and determined suitable derivatization conditions, as follows: BSTFA + 1% TMCS, 50°C, 10min, and 100% ultrasound power. The protocol showed satisfactory linearity (r = 0.9958-0.9996), a low limit of detection (0.04-0.42 μmol/L), good reproducibility (coefficient of variation (CV) %: 0.32-13.76%), acceptable accuracy (recovery: 82.97-114.96%), and good stability within 5days (CV%: 1.35-12.01% at room temperature, 1.24-14.09% at 4°C, and 1.01-11.67% at -20°C). Moreover, the protocol was successfully applied to obtain the organic acid profiles from obese and healthy control subjects. We identified and validated a protocol for ultrasound-assisted derivatization prior to GC/MS analysis for detecting 26 kinds of organic acids in serum. The results suggest the efficacy of this protocol for clinical applications to determine metabolic changes related to fluctuations in organic acid profiles.

Serum metabolomic patterns in young patients with ischemic stroke: a case study.

Ischemic stroke is one of the leading causes of death and adult disability. The incidence of ischemic stroke continues to rise in young adults. This study aimed to provide a comprehensive evaluation of metabolic changes and explore possible mechanisms in young ischemic stroke patients without common risk factors. This study investigated serum metabolomics in 50 young patients with newly suffered ischemic stroke and 50 age-, sex-, and body mass index-matched healthy controls. Liquid chromatography coupled with a Waters Xevo TQ-S mass spectrometer with an electrospray ionization (ESI) source was used to analyze amino acid or bile acid, and free fatty acid or lipid was analyzed by liquid chromatography coupled with a Qtrap5500 mass spectrometer with an ESI source. The metabolomic data were analyzed by performing a multivariate statistical analysis. A total of 197 metabolites, including amino acids, bile acids, free fatty acids, and lipids, were identified in all participants. Multivariate models showed significant differences in serum metabolomic patterns between young patients with ischemic stroke and healthy controls. The stroke patients had increased L-methionine, homocysteine, glutamine, uric acid, GCDCA, and PE (18:0/20:4, 16:0/22:5), and decreased levels of L-citrulline, taurine, PC (16:2/22:6, 16:2/20:5, 15:0/18:2), and SM (d18:1/23:0, d20:0/19:1, d18:1/22:0, d16:0/26:1, d16:0/18:0, d16:0/22:1, d18:1/19:1, d16:0/17:1, d16:1/24:1, d18:1/19:0). Based on the identified metabolites, the metabolic pathways of arginine biosynthesis, glycerophospholipid metabolism, and taurine and hypotaurine metabolism were significantly enriched in the young patients with ischemic stroke. Serum metabolomic patterns were significantly different between young patients with ischemic stroke and healthy controls. Our study is beneficial in providing a further view into the pathophysiology of young patients with ischemic stroke.

Evaluation of metabolic changes in liver and serum of streptozotocin-induced diabetic rats after Mango diet supplementation

Abstract Mango consumption has shown bioactive properties against several diseases like diabetes, therefore, we evaluated how a mango-supplemented diet affects metabolic pathways in diabetic rats. Serum and liver samples were collected from 26 rats divided into 3 groups (healthy, untreated diabetic and mango-treated diabetic) after dietary intervention and analysed using an LC-MS untargeted metabolomic strategy. Twenty-six and 29 metabolites in serum and liver were potentially annotated, showing significant differences among groups. Several affected pathways were due to the disease state [fatty acids (i.e. palmitoleic, linolenic, stearidonic, eicosapentaenoic, docosahexaenoic acids and others), bile acids (i.e. glycocholic acid) and amino acids (i.e. leucine, isoleucine and valine)], and others due to mango supplementation (increased hepatic bioaccumulation of euxanthone, a mangiferin metabolite, and increased glutathione concentration). These results suggest that a mango-supplemented diet exerted a significant antioxidant effect in the liver of diabetic rats, likely due to its phenolic compounds, like mangiferin and its metabolites.

Evaluation of metabolic changes induced by polyphenols in the crayfish Astacus leptodactylus by metabolomics using Fourier transformed infrared spectroscopy

In the present study, the effects of polyphenols on the chemical composition of the hepatopancreas of the Astacus leptodactylus, a highly sought farmed crayfish, have been investigated by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy. The hepatopancreas spectrum was quite complex and contained several peaks arising from the contribution of different functional groups belonging to protein, lipids and carbohydrates. The PCA statistical analysis revealed that there were significant differences between crayfish fed a diet without polyphenols and crayfish fed a diet containing polyphenols. Such differences indicated an increase in lipids and proteins in the hepatopancreas of polyphenol-fed crayfish. In conclusion, the analysis of the infrared spectral profile of the hepatopancreas of Astacus leptodactylus, allowed us to elucidate the changes in different biomolecules in response to polyphenol treatment, and confirms the suitability of ATR-FTIR spectral data to analyze diet-induced metabolic effects. These considerations, coupled with the small amount of sample and no preparation needed, make ATR-FTIR a useful tool for routine analyses where the metabolic impact of substances is investigated, especially with a large number of samples.

“Gear mechanism” of bariatric interventions revealed by untargeted metabolomics

Mechanisms responsible for metabolic gains after bariatric surgery are not entirely clear. The purpose of this study was evaluation of metabolic changes after laparoscopic Roux-en-Y gastric bypass or laparoscopic sleeve gastrectomy in semi-annual follow up.The study participants were selected from obese patients with T2DM who underwent one of the mentioned bariatric procedures. Serum metabolic fingerprinting by use of liquid and gas chromatography with mass spectrometry detection was performed on samples obtained from studied patients before, one, and six months post-surgery.Performed analyses resulted in 49 significant and identified metabolites. Comparison of the two described procedures has allowed to detect metabolites linked with numerous pathways, processes and diseases. Based on the metabolites detected and pathways affected, we propose a “gear mechanism” showing molecular changes evoked by both bariatric procedures. Critical evaluation of clinical data and obtained metabolomics results enables us to conclude that both procedures are very similar in terms of general clinical outcome, but they strongly differ from each other in molecular mechanisms leading to the final effect.For the first time general metabolic effect of bariatric procedures is described. New hypotheses concerning molecular mechanisms induced by bariatric surgeries and new gut microbiota modulations are presented.

THE EFFECT OF APPLICATION OF ANTIOXIDANT THERAPY IN THE TREATMENT OF NON-ALKOHOLIC STEATOHEPATATIS IN CHORNOBYL NPP ACCIDENT SUFFERERS IN THE REMOTE PERIOD AFTER IRRADIATION.

to determine the effectiveness of combined treatment with hepatoprotectors and antioxidant a complexpreparation of vitamins A and E (I) in patients with non-alcoholic steatohepatitis (NASH) who suffered from theChornobyl NPP accident based on the results of evaluation of metabolic changes. The state of the hepatobiliary system of 72 patients with NASH suffered as a result of theChornobyl accident was studied based on the results of the biochemical analysis of blood, indicators characterizingthe processes of oxidative modification of macromolecules and the state of the antioxidant system (AOS), as well asstructural changes in the liver according to ultrasound investigations in the course of the examination before andafter treatment. The treatment of NASH with hepatoprotectors and antioxidant I in the sufferers of the Chornobyl accidentincreased the level of antioxidant defense products (catalase and superoxide dismutase) with the normalization ofthe integral index of the AOS, and a significant decrease in the number of patients with reduced AOS status (from42.6% to 24, 2%, p <0.05), positive dynamics of biochemical parameters of blood with decreasing frequency ofdetection of cholestasis syndrome, hypercholesterolemia and hyperglycemia were established as well as the positivedynamics of structural changes in the liver according to ultrasound data. Combined therapy of NASH with hepatoprotectors and antioxidant I in patients who suffered from theChornobyl NPP accident contributes to the restoration of the prooxidant-antioxidant balance, decreases cholestasis,hypercholesterolemia and hyperglycemia, and promotes positive dynamics of structural changes in the liver.

Evaluation of metabolic changes in oxalate-rich plant Rumex obtusifolius L. caused by ion beam irradiation

Some Rumex species such as sorrel are edible as baby leaf salad greens. On the other hand, Rumex plants accumulate soluble oxalate, a toxic metabolite which causes serious diseases such as renal syndrome. We attempted to produce low-oxalate plants of R. obtusifolius, a perennial weed which has higher vitamin C and amino acid content and higher tolerance to stress than many other Rumex species. Ion beams are ionising radiation with high linear energy transfer that causes a wide spectrum of mutations. Thus, in the present study we evaluated the effects of ion beams on oxalate and other primary metabolites in leaves of R. obtusifolius using CE-MS. The results showed that oxalate content was increased by irradiation with carbon ion beams. Metabolome analysis revealed that ion beams affected carbon flow to the isocitrate pathway, which is involved in oxalate synthesis. These observations suggested that modulation of carbon flow to the isocitrate pathway is important to regulate oxalate levels in plants.

The predictive value of 18F-FDG PET-CT for assessing the clinical outcomes in locally advanced NSCLC patients after a new induction treatment: low-dose fractionated radiotherapy with concurrent chemotherapy

BackgroundPatients with locally advanced non-small-cell lung cancer (LA-NSCLC) have poor prognosis despite several multimodal approaches. Recently, low-dose fractionated radiotherapy concurrent to the induction chemotherapy (IC-LDRT) has been proposed to further improve the effects of chemotherapy and prognosis. Until now, the predictive value of metabolic response after IC-LDRT has not yet been investigated. Aim: to evaluate whether the early metabolic response, assessed by 18F-fluoro-deoxyglucose positron emission-computed tomography (18F-FDG PET-CT), could predict the prognosis in LA-NSCLC patients treated with a multimodal approach, including IC-LDRT.MethodsForty-four consecutive patients (35males, mean age: 66 ± 7.8 years) with stage IIIA/IIIB NSCLC were retrospectively evaluated. Forty-four patients underwent IC-LDRT (2 cycles of chemotherapy, 40 cGy twice daily), 26/44 neo-adjuvant chemo-radiotherapy (CCRT: 50.4Gy), and 20/44 surgery. 18F-FDG PET-CT was performed before (baseline), after IC-LDRT (early) and after CCRT (final), applying PET response criteria in solid tumours (PERCIST). Patients with complete/partial metabolic response were classified as responders; patients with stable/progressive disease as non-responders. Progression free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meyer analysis; the relationship between clinical factors and survivals were assessed using uni-multivariate regression analysis.ResultsForty-four out of 44, 42/44 and 23/42 patients underwent baseline, early and final PET-CT, respectively. SULpeak of primary tumour and lymph-node significantly (p = 0.004, p = 0.0002, respectively) decreased after IC-LDRT with a further reduction after CCRT (p = 0.0006, p = 0.02, respectively). At early PET-CT, 20/42 (47.6%) patients were classified as responders, 22/42 (52.3%) as non-responders. At final PET-CT, 19/23 patients were classified as responders (12 responders and 7 non-responders at early PET-CT), and 4/23 as non-responders (all non-responders at early PET-CT). Early responders had better PFS and OS than early non-responders (p ≤ 0.01). Early metabolic response was predictive factor for loco-regional, distant and global PFS (p = 0.02, p = 0.01, p = 0.005, respectively); surgery for loco-regional and global PFS (p = 0.03, p = 0.009, respectively).ConclusionsIn LA-NSCLC patients, 18F-FDG metabolic response assessed after only two cycles of IC-LDRT predicts the prognosis. The early evaluation of metabolic changes could allow to personalize therapy. This multimodality approach, including both low-dose radiotherapy that increases the effects of induction chemotherapy, and surgery that removes the disease, improved clinical outcomes. Further prospective investigation of this new induction approach is warranted.

Evaluation of metabolic changes in Parkinson's disease patients with different severities of cognitive impairments by 18F-FDG PET/CT brain imaging

Objective To investigate the characteristics of cerebral glucose metabolism (CGM) in PD patients with cognitive impairment (PD-CI) using 18F-FDG PET/CT, and to analyze the correlation between the progress of PD-CI and CGM changes. Methods A total of 31 idiopathic PD patients (14 males, 17 females, aged 37-77 years) from May 2013 to February 2014 were divided into 3 groups based on Montreal cognitive assessment (MOCA): none CI in PD (PD-NC) group (MOCA>26 scores), mild CI in PD (PD-MCI) group (MOCA 21-26 scores), PD with dementia (PDD) group (MOCA<21 scores). The normal controls (NC) group included 12 age- and gender-matched healthy adults (7 males, 5 females, aged 40-76 years). All subjects underwent PET/CT imaging after intravenous injection of 18F-FDG(5.55 MBq/kg). MIMneuro software was used to analyze the data. The correlation between the CGM and cognitive function was analyzed using Pearson or Spearman correlation analysis. Results (1) Compared with NC group, PDD group presented a widespread cortical metabolism decrease in frontal, parietal, temporal, occipital lobes and the limbic lobe; PD-MCI group showed hypometabolic areas in the parietal and occipital lobes, and with less extent in the frontal and temporal lobes; PD-NC group showed no significant cerebral hypometabolism. (2) Compared with PD-NC group, PDD group showed widespread cortical metabolism decrease in occipital lobe, temporal lobe, partial parietal cortex and the posterior cingulated cortex. Compared with PD-MCI group, PDD group had lower metabolism, mainly in posterior brain areas (parietal, occipital and temporal lobes). Compared with PD-NC group, PD-MCI group showed hypometabolism in right supramarginal gyrus and the left parahippocampal gyrus. (3) There were positive correlations between visuospatial/executive function and visual cortex metabolism, angular gyrus metabolism or superior parietal lobule metabolism (r=0.535, 0.443, 0.395; all P<0.05). A positive correlation was also found between delayed memory and heschl's gyrus metabolism (r=0.337, P<0.05). Conclusions The cerebral glucose metabolism detected with 18F-FDG PET/CT is well correlated with MOCA assessments. Thus it may be helpful in evaluation of the progress of cognitive impairments in PD. Key words: Parkinson disease; Cognition disorders; Tomography, emission-computed; Tomography, X-ray computed; Deoxyglucose

Clinical Relevance of Single-Voxel (1)H MRS Metabolites in Discriminating Suprasellar Tumors.

Spatially resolved metabolic data obtained from Proton Magnetic Resonance Spectroscopy ((1)H MRS) provides information which increases the diagnostic accuracy of imaging sequences in predicting the histology of suprasellar tumors. To evaluate the role of (1)H MRS in the diagnosis of various suprasellar tumors. Sixty cases of various suprasellar, hypothalamic and third ventricular neoplasms were investigated with long-echo single voxel (1)H -MRS using 1.5 Tesla clinical imager. Single-voxel spectroscopic examinations were guided by T1-weighted or T2-weighted images. Statistical analysis was carried out using IBM SPSS software version 19. We observed that whenever brain tissue was damaged or replaced by any process, NAA was markedly reduced. Extra-axial lesions which do not infiltrate brain or contain neuroglial tissue, didn't demonstrate any NAA resonances. Cr was used as an internal standard for semi-quantitative evaluation of metabolic changes of other brain metabolites. Increased Cho was seen in processes with elevated cell-membrane turnover. Spectra obtained from different tumors exhibit reproducible differences while histologically similar tumors yield characteristic spectra with only minor differences. Pituitary tumors were typically characterized by significant reduction of NAA, Cr peak and moderate elevation of Cho peak. Gliomas were typically characterized by decrease of NAA and Cr peaks and increase of Cho peak. Craniopharyngiomas were typically characterized by significant decrease of all metabolites.

Physiological and biochemical measurements before, during and after pregnancy of healthy rats.

To analyze the physiological and biochemical measurements before, during and after pregnancy of healthy rats. Wistar adult females rats (n=8) were weighed and blood samples were obtained before, during and after pregnancy for biochemical determinations, chow intake, water consumption and milk production were evaluated. At day 10 postpartum, the rats were killed for weighing of organs and adipose tissues. The results showed increase in body weight, serum insulin and ingestion of water and chow. At day 17 pregnancy, presented normal values in the OGTT. At days 7, 14 and 20 of pregnancy, there was increase in triglyceride levels. At term pregnancy, there was weight gain due to fetal growth. In the postpartum period presented reduced blood glucose levels. The glycemic means were reduced during and after pregnancy compared to after pregnancy. The triglyceride concentrations were increased before and during pregnancy in relation to after pregnancy. The total cholesterol levels presented no changes. The use of experimental animals is suitable for evaluation of metabolic changes because the profile of answers found in this study was similar to human profile, showing the relevance of translational research to better understand the pathophysiological mechanisms and possible treatment for diseases.

Patterns of metabolite changes identified from large-scale gene perturbations in Arabidopsis using a genome-scale metabolic network.

Metabolomics enables quantitative evaluation of metabolic changes caused by genetic or environmental perturbations. However, little is known about how perturbing a single gene changes the metabolic system as a whole and which network and functional properties are involved in this response. To answer this question, we investigated the metabolite profiles from 136 mutants with single gene perturbations of functionally diverse Arabidopsis (Arabidopsis thaliana) genes. Fewer than 10 metabolites were changed significantly relative to the wild type in most of the mutants, indicating that the metabolic network was robust to perturbations of single metabolic genes. These changed metabolites were closer to each other in a genome-scale metabolic network than expected by chance, supporting the notion that the genetic perturbations changed the network more locally than globally. Surprisingly, the changed metabolites were close to the perturbed reactions in only 30% of the mutants of the well-characterized genes. To determine the factors that contributed to the distance between the observed metabolic changes and the perturbation site in the network, we examined nine network and functional properties of the perturbed genes. Only the isozyme number affected the distance between the perturbed reactions and changed metabolites. This study revealed patterns of metabolic changes from large-scale gene perturbations and relationships between characteristics of the perturbed genes and metabolic changes.

Evaluation of metabolic changes within the normal appearing gray and white matters in neurologically asymptomatic HIV-1-positive and HCV-positive patients: Magnetic resonance spectroscopy and immunologic correlation

ObjectiveThe aim of the study was to evaluate early metabolic changes using proton MR spectroscopy (MRS) in asymptomatic HIV-1-positive and HCV-positive patients without abnormalities in the structural MR examination. MethodsSixty-five asymptomatic patients: 21 HIV-1-positive naive, 20 HIV-1-positive with combination antiretroviral therapy (cART), 9 HIV-1/HCV-positive naive, 15 HCV-positive naive and 18 normal subjects were enrolled in the study. The MRS examinations were performed with a 1.5T MR scanner. Voxels were located in the following regions: posterior cingulate gyrus (PCG), anterior cingulate gyrus (ACG), parietal white matter (PWM), left basal ganglia (BG) and frontal white matter (FWM). The NAA/Cr, Cho/Cr, mI/Cr ratios and correlations of MRS measurements with the immunologic data were analyzed. ResultsThere was a significant decrease (p<0.05) of the NAA/Cr ratios in PCG, ACG and PWM regions in HIV-1-positive cART treated patients compared to the normal subjects. The significantly decreased NAA/Cr ratios in PWM and FWM were observed in HCV infected patients. The subjects with HIV-1/HCV co-infection revealed significantly lower NAA/Cr ratios in the ACG area. Other metabolite ratios in all analyzed regions, as well as the NAA/Cr ratios in BG showed no significant differences. The decrease of CD4n T cell count was associated with the decease of the NAA/Cr ratio in the PCG area and the increase of Cho/Cr ratio in the FWM region. ConclusionsThe metabolic changes – reduction of NAA/Cr ratios are most pronounced in HIV-1-positive patients using cART. The low CD4n T cell count is a risk factor for neurocognitive impairment in HIV-1-positive patients.