Cingulate biochemistry in heroin users on substitution pharmacotherapy

2012 ◽  
Vol 47 (3) ◽  
pp. 244-249 ◽  
Author(s):  
Antonio Verdejo-García ◽  
Dan I Lubman ◽  
Kim Roffel ◽  
Raquel Vilar-López ◽  
Emre Bora ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Anterior Cingulate ◽  
Resonance Spectroscopy ◽  
High Dose ◽  
Dependent Manner ◽  
Heroin Users ◽  
Addiction Severity ◽  
Beneficial Effects ◽  
High Doses ◽  
The Right

Objective: High doses of opiate substitution pharmacotherapy are associated with greater treatment retention and lower illicit drug consumption, although the neurobiological bases of these benefits are poorly understood. Dysfunction of the anterior cingulate cortex (ACC) is associated with greater addiction severity and mood dysregulation in opiate users, such that the beneficial effects of substitution pharmacotherapy may relate to normalisation of ACC function. This study aimed to investigate the differential impact of methadone compared with buprenorphine on dorsal ACC biochemistry. A secondary aim was to explore the differential effects of methadone and buprenorphine on dorsal ACC biochemistry in relation to depressive symptoms. Methods: Twenty-four heroin-dependent individuals stabilised on methadone ( n=10) or buprenorphine ( n=14) and 24 healthy controls were scanned using proton Magnetic Resonance Spectroscopy and compared for metabolite concentrations of N-acetylaspartate, glutamate/glutamine, and myo-inositol. Results: (1) Methadone was associated with normalisation of dorsal ACC biochemistry (increased N-acetylaspartate and glutamate/glutamine levels, and decreased myo-inositol levels) in a dose-dependent manner; (2) buprenorphine-treated individuals had higher myo-inositol and glutamate/glutamine levels than methadone-treated patients in the right dorsal ACC; and (3) myo-inositol levels were positively correlated with depressive symptoms in participants stabilised on buprenorphine. Conclusions: These findings point to a beneficial role of high-dose methadone on dorsal ACC biochemistry, and suggest a link between elevated myo-inositol levels and depressive symptoms in the context of buprenorphine treatment.

scholarly journals Neurochemical Correlates of Brain Atrophy in Fibromyalgia Syndrome: A Magnetic Resonance Spectroscopy and Cortical Thickness Study

2020 ◽  
Vol 10 (6) ◽  
pp. 395
Author(s):  
Paola Feraco ◽  
Salvatore Nigro ◽  
Luca Passamonti ◽  
Alessandro Grecucci ◽  
Maria Eugenia Caligiuri ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Cortical Thickness ◽  
Inferior Frontal Gyrus ◽  
Pain Modulation ◽  
Anterior Cingulate ◽  
Resonance Spectroscopy ◽  
Dependent Manner ◽  
Cingulate Gyrus ◽  
Concentration Dependent Manner ◽  
The Right

(1) Background: Recently, a series of clinical neuroimaging studies on fibromyalgia (FM) have shown a reduction in cortical volume and abnormally high glutamate (Glu) and glutamate + glutamine (Glx) levels in regions associated with pain modulation. However, it remains unclear whether the volumetric decreases and increased Glu levels in FM are related each other. We hypothesized that higher Glu levels are related to decreases in cortical thickness (CT) and volume in FM patients. (2) Methods: Twelve females with FM and 12 matched healthy controls participated in a session of combined 3.0 Tesla structural magnetic resonance imaging (MRI) and single-voxel MR spectroscopy focused on the thalami and ventrolateral prefrontal cortices (VLPFC). The thickness of the cortical and subcortical gray matter structures and the Glu/Cr and Glx/Cr ratios were estimated. Statistics included an independent t-test and Spearman’s test. (3) Results: The Glu/Cr ratio of the left VLPFC was negatively related to the CT of the left inferior frontal gyrus (pars opercularis (p = 0.01; r = −0.75) and triangularis (p = 0.01; r = −0.70)). Moreover, the Glx/Cr ratio of the left VLPFC was negatively related to the CT of the left middle anterior cingulate gyrus (p = 0.003; r = −0.81). Significantly lower CTs in FM were detected in subparts of the cingulate gyrus on both sides and in the right inferior occipital gyrus (p < 0.001). (4) Conclusions: Our findings are in line with previous observations that high glutamate levels can be related, in a concentration-dependent manner, to the morphological atrophy described in FM patients.

scholarly journals High-dose vitamin C enhances cancer immunotherapy

2020 ◽  
Vol 12 (532) ◽  
pp. eaay8707 ◽  
Author(s):  
Alessandro Magrì ◽  
Giovanni Germano ◽  
Annalisa Lorenzato ◽  
Simona Lamba ◽  
Rosaria Chilà ◽  
...  
Keyword(s):  
Immune System ◽  
Vitamin C ◽  
Clinical Evidence ◽  
High Dose ◽  
Dependent Manner ◽  
Cancer Cell Growth ◽  
Mutational Burden ◽  
Cancer Types ◽  
High Doses ◽  
High Dose Vitamin

Vitamin C (VitC) is known to directly impair cancer cell growth in preclinical models, but there is little clinical evidence on its antitumoral efficacy. In addition, whether and how VitC modulates anticancer immune responses is mostly unknown. Here, we show that a fully competent immune system is required to maximize the antiproliferative effect of VitC in breast, colorectal, melanoma, and pancreatic murine tumors. High-dose VitC modulates infiltration of the tumor microenvironment by cells of the immune system and delays cancer growth in a T cell–dependent manner. VitC not only enhances the cytotoxic activity of adoptively transferred CD8 T cells but also cooperates with immune checkpoint therapy (ICT) in several cancer types. Combination of VitC and ICT can be curative in models of mismatch repair–deficient tumors with high mutational burden. This work provides a rationale for clinical trials combining ICT with high doses of VitC.

scholarly journals Poor outcome with anti-programmed death-ligand 1 (PD-L1) antibody due to poor pharmacokinetic properties in PD-1/PD-L1 blockade-sensitive mouse models

2020 ◽  
Vol 8 (1) ◽  
pp. e000400 ◽  
Author(s):  
Taiki Kurino ◽  
Reiko Matsuda ◽  
Ayu Terui ◽  
Hiroyuki Suzuki ◽  
Tomomi Kokubo ◽  
...  
Keyword(s):  
Mouse Models ◽  
Pharmacological Activity ◽  
Tumor Model ◽  
High Dose ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Poor Outcome ◽  
Liver And Kidney ◽  
High Doses

BackgroundRecently, antiprogrammed cell death protein 1 (aPD-1) and antiprogrammed death-ligand 1 (aPD-L1) monoclonal antibodies (mAbs) have been approved. Even though aPD-1 and aPD-L1 mAbs target the same PD-1/PD-L1 axis, it is still unclear whether both mAbs exert equivalent pharmacological activity in patients who are sensitive to PD-1/PD-L1 blockade therapy, as there is no direct comparison of their pharmacokinetics (PK) and antitumor effects. Therefore, we evaluated the differences between both mAbs in PK and therapeutic effects in PD-1/PD-L1 blockade-sensitive mouse models.MethodsHerein, murine breast MM48 and colon MC38 xenografts were used to analyze the pharmacological activity of aPD-1 and aPD-L1 mAbs. The PK of the mAbs in the tumor-bearing mice was investigated at low and high doses using two radioisotopes (Indium-111 and Iodine-125) to evaluate the accumulation and degradation of the mAbs.ResultsaPD-1 mAb showed antitumor effect in a dose-dependent manner, indicating that the tumor model was sensitive to PD-1/PD-L1 blockade therapy, whereas aPD-L1 mAb failed to suppress tumor growth. The PK study showed that aPD-L1 mAb was accumulated largely in normal organs such as the spleen, liver, and kidney, resulting in low blood concentration and low distributions to tumors at a low dose, even though the tumors expressed PD-L1. Sufficient accumulation of aPD-L1 mAb in tumors was achieved by administration at a high dose owing to the saturation of target-mediated binding in healthy organs. However, degradation of aPD-L1 mAb in tumors was greater than that of aPD-1 mAb, which resulted in poor outcome presumably due to less inhibition of PD-L1 by aPD-L1 mAb than that of PD-1 by aPD-1 mAb.ConclusionAccording to the PK studies, aPD-1 mAb showed linear PK, whereas aPD-L1 mAb showed non-linear PK between low and high doses. Collectively, the poor PK characteristics of aPD-L1 mAb caused lower antitumor activity than of aPD-1 mAb. These results clearly indicated that aPD-L1 mAb required higher doses than aPD-1 mAb in clinical setting. Thus, targeting of PD-1 would be more advantageous than PD-L1 in terms of PK.

scholarly journals Resting-state functional connectivity, cortical GABA and neuroactive steroids in peripartum and peripartum depressed women: a functional magnetic imaging and resonance study

2018 ◽  
Author(s):  
Kristina M. Deligiannidis ◽  
Christina L. Fales ◽  
Aimee R. Kroll-Desrosiers ◽  
Scott A. Shaffer ◽  
Vanessa Villamarin ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Resting State ◽  
Neuroactive Steroids ◽  
Anterior Cingulate ◽  
Resonance Spectroscopy ◽  
Resting State Functional Connectivity ◽  
Magnetic Imaging ◽  
Temporal Pole ◽  
The Right ◽  
The Relationship

ABSTRACTPostpartum depression (PPD) is associated with abnormalities in resting-state functional connectivity (RSFC) but the underlying neurochemistry is unclear. We hypothesized that peripartum GABAergic neuroactive steroids (NAS) are related to cortical GABA concentrations and RSFC in PPD as compared to healthy comparison women (HCW). To test this, we measured RSFC with fMRI and GABA+/Creatine (Cr) concentrations with proton magnetic resonance spectroscopy (1H MRS) in the pregenual anterior cingulate (pgACC) and occipital cortices (OCC) and quantified peripartum plasma NAS. We examined between-group differences in RSFC and the relationship between cortical GABA+/Cr concentrations with RSFC. We investigated the relationship between NAS, RSFC and cortical GABA+/Cr concentrations. Within the default mode network (DMN) an area of the dorsomedial prefrontal cortex (DMPFC) had greater connectivity with the rest of the DMN in PPD (peak voxel: MNI coordinates (2, 58, 32), p=0.002) and was correlated to depression scores (peak HAM-D17 voxel: MNI coordinates (0, 60, 34), p=0.008). pgACC GABA+/Cr correlated positively with DMPFC RSFC in a region spanning the right anterior/posterior insula and right temporal pole (r=+0.661, p=0.000). OCC GABA+/Cr correlated positively with regions spanning both amygdalae (right amygdala: r=+0.522, p=0.000; left amygdala: r=+0.651, p=0.000) as well as superior parietal areas. Plasma allopregnanolone was higher in PPD (p=0.03) and positively correlated with intra DMPFC connectivity (r=+0.548, p=0.000) but not GABA+/Cr. These results provide initial evidence that PPD is associated with altered DMN connectivity; cortical GABA+/Cr concentrations are associated with postpartum RSFC and allopregnanolone is associated with postpartum intra-DMPFC connectivity.

A magnetic resonance spectroscopy study of antisocial behaviour disorder, psychopathy and violent crime among military conscripts

2008 ◽  
Vol 20 (2) ◽  
pp. 72-77 ◽  
Author(s):  
Cengiz Basoglu ◽  
Umit Semiz ◽  
Ozgur Oner ◽  
Huseyin Gunay ◽  
Servet Ebrinc ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Antisocial Behaviour ◽  
Anterior Cingulate ◽  
Resonance Spectroscopy ◽  
Violent Crimes ◽  
Magnetic Resonance Spectroscopy Study ◽  
Dorsolateral Prefrontal ◽  
Psychopathy Checklist Revised ◽  
The Right

Background:Prefrontal and/or temporo-limbic abnormalities associated with antisocial personality disorder (APD), high psychopathy scores and violent behaviours can readily be evaluated by neuroimaging methods.Objectives:In this study, we compared the brain metabolites in adult male military conscripts with APD, high psychopathy scores and serious violent crimes (n = 15) with age- and educational-level-matched healthy controls (n = 15) by means of magnetic resonance spectroscopy.Methods:All cases were diagnosed by means of the Diagnostic Statistical Manual-IV APD module of the Structured Clinical Interview for DSM III-R Axis II Disorders (SCID-II) semistructured questionnaire in Turkish. The psychopathy scores were evaluated by means of the Hare Psychopathy Checklist-Revised translated into Turkish (PCL-R). PCL-R is a 20-item, reliable and valid instrument for assessment of psychopathy, both in categorical and dimensional natures. All patients had a total score of 29 (of possible 40) or higher from PCL-R, indicating a high degree of psychopathy.Results:Our results showed no significant differences in ratio of N-acetyl aspartate (NAA), creatine (Cr) and choline-related compounds in the right dorsolateral prefrontal cortex, anterior cingulate cortex (ACC) and amygdala–hippocampus regions of cases compared with controls. ACC NAA/Cr was significantly negatively correlated with both the PCL-R total score and the PCL-R factor I score (interpersonal/affective problems) among the cases.Conclusion:As ACC plays an important role in decision-making and emotional information processing, we postulate that the lower NAA/Cr ratio, suggesting impaired neural integrity, may increase the severity of interpersonal/affective problems of the psychopathy factor in male subjects exhibiting APD, high psychopathy overall scores and violent crimes.

scholarly journals Dysfunctional energy metabolisms in fibromyalgia compared with healthy subjects

2021 ◽  
Vol 17 ◽  
pp. 174480692110128
Author(s):  
Ye-Ha Jung ◽  
Hyeonjin Kim ◽  
Dasom Lee ◽  
Jae-Yeon Lee ◽  
Jee Youn Moon ◽  
...  
Keyword(s):  
Anterior Cingulate ◽  
Mcgill Pain Questionnaire ◽  
Resonance Spectroscopy ◽  
Healthy Controls ◽  
Post Traumatic Stress ◽  
Pain Questionnaire ◽  
Total Pain ◽  
Post Traumatic ◽  
Left Thalamus ◽  
The Right

This study aimed to investigate the levels of creatine (Cr) metabolites in the anterior cingulate cortex (ACC), thalamus, and insula of patients with fibromyalgia (FM) using proton magnetic resonance spectroscopy (MRS). The levels of Cr and phosphocreatine (PCr) relative to total Cr (tCr), which includes Cr and PCr, in the ACC, thalamus, and insula were determined using MRS in 12 patients with FM and in 13 healthy controls. The FM group had lower levels of PCr/tCr in the ACC and right insula compared to healthy controls. There was a negative correlation between Cr/tCr in the ACC and total pain levels (McGill Pain Questionnaire-Total; r = −0.579, p = 0.049) and between Cr/tCr in the left insula and affective pain levels (McGill Pain Questionnaire-Affective; r = −0.638, p = 0.047) in patients with FM. In addition, there were negative correlations between stress levels (Stress Response Inventory) and Cr/tCr in the right (r = −0.780, p = 0.005) and left thalamus (r = −0.740, p = 0.006), as well as in the right insula (r = −0.631, p = 0.028) in patients with FM. There were negative correlations between symptom levels of post-traumatic stress disorder (PTSD; PTSD checklist) and Cr/tCr in the right (r = −0.783, p = 0.004) and left thalamus (r = −0.642, p = 0.024) of patients with FM. These findings are paramount to understanding the decisive pathologies related to brain energy metabolism in patients with FM.

scholarly journals Effects of Alpha-Tocopherol on Biochemical Parameters in Adult Mice

2021 ◽  
Vol 11 (12) ◽  
pp. 83-90
Author(s):  
Franck Arnaud Moukobolo Kinsangou ◽  
Henriette Poaty ◽  
Dimitry Moudiongui Mboungou
Keyword(s):  
Vitamin E ◽  
Biochemical Parameters ◽  
Blood Lipid ◽  
Alpha Tocopherol ◽  
High Dose ◽  
Beneficial Effects ◽  
Adult Mice ◽  
Blood Biochemical ◽  
High Dietary Intake ◽  
High Doses

Background: Numerous reviews report the beneficial effects of alpha tocopherol in preventive supplementation and also as an adjuvant in the treatment of some pathologies (cardiovascular, cancers). In this work, we analyzed the effects of vitamin E at high doses on some biochemical parameters. Methods: Thirty-two adult male and female mice (CD1 albino mice) were randomly selected for a 4-week experiment. The mice were supplemented with alpha tocopherol at doses of 150, 400 and 750mg/day. With a high dietary intake of vitamin E Results: According to our analyses, we can note Excess weight predominated in groups 4 to 7. All the blood lipid parameters showed an abnormal concentration, as of the 400 mg dose of α-T-acetate. Hyperglycemia and hyperlipidemia were observed. These variations were more pronounced for total cholesterol and triglycerides than for HDL and LDL fractions. Conclusion: The study showed significant effects of high-dose α-T supplementation on biochemical parameters, mainly hyperglycemia and dyslipidemia. Key words: Vitamin E, Alpha-tocopherol, blood biochemical parameters.

Association between altered neurochemical metabolites and apathy in patients with Alzheimer's disease

2017 ◽  
Vol 30 (5) ◽  
pp. 761-768 ◽  
Author(s):  
Yi-Chun Yeh ◽  
Chun-Wei Li ◽  
Yu-Ting Kuo ◽  
Mei-Feng Huang ◽  
Tai-Ling Liu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Anterior Cingulate ◽  
Resonance Spectroscopy ◽  
Depression Severity ◽  
Cognitive Domains ◽  
Neurochemical Changes ◽  
The Right ◽  
Frontal Lesions

ABSTRACTBackground:Apathy is a condition characterized by a lack of motivation that manifests in emotional, behavioral, and cognitive domains. Although previous studies have indicated that apathy is associated with frontal lesions, few studies have focused on the different subdomains of apathy, and no in vivo human biochemical data have been obtained to examine the neurochemical changes related to apathy in patients with Alzheimer's disease (AD). Thus, we investigated the frontal neurochemical alterations related to apathy among patients with AD using proton magnetic resonance spectroscopy (1H MRS).Methods:Apathy was assessed through the Apathy Evaluation Scale (AES). 1H MRS was performed to measure neurochemical metabolite levels in the anterior cingulate region and right orbitofrontal region. Associations between neurochemical metabolites and the total score and subscores of each domain of the AES were analyzed.Results:Altogether, 36 patients completed the study. Patients with lower N-acetylaspartate/creatine ratios (NAA/Cr) in the anterior cingulate region demonstrated higher total apathy scores (β = −0.56, p = 0.003) with adjustments for age, gender, educational level, dementia severity, and depression severity. In a further analysis, a lower NAA/Cr in the anterior cingulate region was associated with all subdomains of apathy, including cognition (β = −0.43, p = 0.028), behavior (β = −0.55, p = 0.002), and emotion (β = −0.50, p = 0.005). No statistically significant associations were discovered in the right orbitofrontal region.Conclusions:Our results suggest that apathy, in each of its cognitive, behavioral, or emotional subdomains is associated with brain neurochemical alterations in the anterior cingulate region. Abnormal neuronal integrity over the anterior cingulate cortex may exhibit a central role in causing all aspects of apathy in patients with AD.

scholarly journals Report of the Pilot Study Done for the Proposed Investigation on the Possible Synergic Effect between High-Dose Ascorbic Acid Application and Oncothermia Treatment

2013 ◽  
Vol 2013 ◽  
pp. 1-2
Author(s):  
Csaba Kovago ◽  
Nora Meggyeshazi ◽  
Gabor Andocs ◽  
Andras Szasz
Keyword(s):  
Ascorbic Acid ◽  
Vitamin C ◽  
Internal Control ◽  
Remission Rate ◽  
Treatment Method ◽  
High Dose ◽  
Main Question ◽  
High Doses ◽  
The Right

According to recent investigations, the parenteral application of ascorbic acid (vitamin C) at high doses has significant antitumor activity in in vitro assays. The goal of our experiment was to determine the possible potentiating effect of application of high dose pH-neutralized ascorbic acid to the normal oncothermia treatment method. The NMRI mice were inoculated with C26 murine colon carcinoma cell line subcutaneously at both of their femoral regions and were kept till the tumors reached symmetrically 10 mm in diameter. We created four experimental groups, containing 5 male and 5 female animals in each. Both vitamin-C and oncothermia treatments were applied once; ascorbic acid was applied intra-peritoneally. Oncothermia treatment was applied only to the right limb tumor; the other side will be used as internal control. After the treatment, the animals were sacrificed, and all tumors were removed and analyzed histopathologically. Our main question centers on the comparison of the cell destruction ratio of the various applied treatment regimes, and studies the possible synergy or additive cross-potentiating of the methods. The results of this experiment turned out to be controversial, since the ascorbic acid did not change the remission rate of the allografts and showed no synergy with oncothermia.

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