scholarly journals Nocturnal Gamma-Hydroxybutyrate Reduces Cortisol-Awakening Response and Morning Kynurenine Pathway Metabolites in Healthy Volunteers

2019 ◽  
Vol 22 (10) ◽  
pp. 631-639
Author(s):  
D A Dornbierer ◽  
M Boxler ◽  
C D Voegel ◽  
B Stucky ◽  
A E Steuer ◽  
...  
Keyword(s):  
Quinolinic Acid ◽  
Kynurenic Acid ◽  
Killer Cell ◽  
Affective State ◽  
Neuropsychiatric Disorders ◽  
Cortisol Awakening Response ◽  
Therapeutic Effects ◽  
Cell Counts ◽  
Acid Ratio ◽  
Gamma Hydroxybutyrate

Abstract Background Gamma-hydroxybutyrate (GHB; or sodium oxybate) is an endogenous GHB-/gamma-aminobutyric acid B receptor agonist. It is approved for application in narcolepsy and has been proposed for the potential treatment of Alzheimer’s disease, Parkinson’s disease, fibromyalgia, and depression, all of which involve neuro-immunological processes. Tryptophan catabolites (TRYCATs), the cortisol-awakening response (CAR), and brain-derived neurotrophic factor (BDNF) have been suggested as peripheral biomarkers of neuropsychiatric disorders. GHB has been shown to induce a delayed reduction of T helper and natural killer cell counts and alter basal cortisol levels, but GHB’s effects on TRYCATs, CAR, and BDNF are unknown. Methods Therefore, TRYCAT and BDNF serum levels, as well as CAR and the affective state (Positive and Negative Affect Schedule [PANAS]) were measured in the morning after a single nocturnal dose of GHB (50 mg/kg body weight) in 20 healthy male volunteers in a placebo-controlled, balanced, randomized, double-blind, cross-over design. Results In the morning after nocturnal GHB administration, the TRYCATs indolelactic acid, kynurenine, kynurenic acid, 3-hydroxykynurenine, and quinolinic acid; the 3-hydroxykynurenine to kynurenic acid ratio; and the CAR were significantly reduced (P < 0.05–0.001, Benjamini-Hochberg corrected). The quinolinic acid to kynurenic acid ratio was reduced by trend. Serotonin, tryptophan, and BDNF levels, as well as PANAS scores in the morning, remained unchanged after a nocturnal GHB challenge. Conclusions GHB has post-acute effects on peripheral biomarkers of neuropsychiatric disorders, which might be a model to explain some of its therapeutic effects in disorders involving neuro-immunological pathologies. This study was registered at ClinicalTrials.gov as NCT02342366.

scholarly journals A minimal dose of unmanipulated bone marrow infusion without conditioning for T-B+NK- severe combined immunodeficiency

2021 ◽  
Author(s):  
Eun Sang Yi ◽  
Hee Young Ju ◽  
Hee Won Cho ◽  
Ji Won Lee ◽  
Ki Woong Sung ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Killer Cell ◽  
Severe Combined Immunodeficiency ◽  
Therapeutic Effects ◽  
Combined Immunodeficiency ◽  
Hematopoietic Stem ◽  
Cell Counts ◽  
Minimal Dose ◽  
Marrow Infusion ◽  
Bone Marrow Infusion

Abstract Hematopoietic stem cell transplantation (HSCT) is the standard method of reconstituting immune function in severe combined immunodeficiency (SCID); however, there is no consensus about optimal cell doses. In this study, we investigated HSCT outcomes and immune reconstitution, following minimal dose (MD) HSCT in T cell-negative (T-), B cell-positive (B+), natural killer cell-negative (NK-) SCID patients. We retrospectively reviewed patients with SCID who received HSCT between 2002–2018. Standard dose (SD) and MD were classified based on a total nucleated cell count (TNC) of 1.0 × 108/kg or more and less. Total seven patients with SCID received HSCT. MD group (n = 4) were administered 5 mL or less of bone marrow without conditioning, with median TNC and CD34+ cell counts of 0.49 × 108/kg and 0.62 × 106/kg, respectively. T cells recovered within a year, and immunoglobulin supplementation was discontinued at median 3.5 months after HSCT in all MD recipients. All MD recipients were alive without disease recurrence at a median of 126.9 months after HSCT, exhibiting donor chimerism in the range of 10.1–100%. In patients with T-B + NK- SCID, sufficient therapeutic effects were safely obtained with minimal dose of bone marrow infusion without conditioning.

scholarly journals Reduction of kynurenic acid to quinolinic acid ratio in both the depressed and remitted phases of major depressive disorder

2015 ◽  
Vol 46 ◽  
pp. 55-59 ◽  
Author(s):  
Jonathan Savitz ◽  
Wayne C. Drevets ◽  
Brent E. Wurfel ◽  
Bart N. Ford ◽  
Patrick S.F. Bellgowan ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Quinolinic Acid ◽  
Kynurenic Acid ◽  
Major Depressive ◽  
Acid Ratio

scholarly journals A minimal dose of unmanipulated bone marrow infusion without conditioning for T-B+NK- severe combined immunodeficiency

2021 ◽  
Author(s):  
Eun Sang Yi ◽  
Hee Young Ju ◽  
Hee Won Cho ◽  
Ji Won Lee ◽  
Ki Woong Sung ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Killer Cell ◽  
Severe Combined Immunodeficiency ◽  
Therapeutic Effects ◽  
Combined Immunodeficiency ◽  
Hematopoietic Stem ◽  
Cell Counts ◽  
Minimal Dose ◽  
Marrow Infusion ◽  
Bone Marrow Infusion

Abstract Purpose Hematopoietic stem cell transplantation (HSCT) is the standard method of reconstituting immune function in severe combined immunodeficiency (SCID); however, current conditioning recommendations and optimal cell doses lack consensus. In this study, we investigated HSCT outcomes and immune reconstitution, following minimal dose (MD) HSCT in T cell-negative (T-), B cell-positive (B+), natural killer-cell negative (NK-) SCID patients. Methods We retrospectively reviewed patients with SCID who received HSCT between 2002–2018. Standard dose (SD) and MD were classified based on a total nucleated cell count (TNC) of 1.0 × 10 8 /kg or more and less. Results Seven patients with SCID received HSCT, of which four belonged to the MD group. Patients in the MD group were administered 5 mL or less of bone marrow without conditioning, with median TNC and CD34+ cell counts of 0.49 × 10 8 /kg and 0.62 × 10 6 /kg, respectively. T cells recovered within a year after HSCT, and immunoglobulin supplementation was discontinued at a median of 3.5 months after HSCT in all MD recipients. All MD recipients were alive without disease recurrence at a median of 126.9 months after HSCT, exhibiting donor chimerism in the range of 10.1%–100%. Although grade II–III graft-versus-host diseases occurred, these were manageable in all patients. One of the three patients in the SD group died of cytomegalovirus infection, while another was dependent on intravenous immunoglobulin until 41 months after HSCT. Conclusion In patients with T-B+NK- SCID, sufficient therapeutic effects were safely obtained with minimal dose of bone marrow infusion without conditioning.

Kynurenic Acid in Synovial Fluid and Serum of Patients with Rheumatoid Arthritis, Spondyloarthropathy, and Osteoarthritis

2013 ◽  
Vol 40 (6) ◽  
pp. 903-909 ◽  
Author(s):  
Jolanta Parada-Turska ◽  
Wojciech Zgrajka ◽  
Maria Majdan
Keyword(s):  
Rheumatoid Arthritis ◽  
Regression Analysis ◽  
Synovial Fluid ◽  
Blood Cell ◽  
Red Blood Cell ◽  
High Performance ◽  
Kynurenic Acid ◽  
Linear Regression Analysis ◽  
Cell Counts

Objective.Previously we demonstrated that kynurenic acid (KYNA), an endogenous metabolite of kynurenine, is present in the synovial fluid of patients with rheumatoid arthritis (RA). KYNA inhibits proliferation of synoviocytesin vitro. The goal of our study was to compare KYNA concentrations in synovial fluid and blood of patients with RA, inflammatory spondyloarthropathies (SpA), and osteoarthritis (OA).Methods.Serum and synovial fluid samples were obtained from 189 patients with RA, 56 patients with SpA, and 32 patients with OA. KYNA was separated using a high-performance liquid chromatography system and measured fluorometrically.Results.KYNA concentration in synovial fluid obtained from patients with RA and SpA was significantly lower than that in patients with OA (p < 0.05). The concentration of KYNA in serum of patients with RA, SpA, and OA did not differ among all groups studied. The positive correlation between KYNA content in synovial fluid and serum was found in patients with RA (p < 0.05). Univariate linear regression analysis demonstrated that fibrinogen was significantly associated with KYNA in synovial fluid (p < 0.05), and red blood cell counts, morning stiffness, and pain scores were significantly associated with KYNA level in serum (all p < 0.05). Multivariate regression analysis revealed correlation between the following independent variables: hemoglobin level, hematocrit, red blood cell count in conjunction with age and KYNA content in synovial fluid. A lack of correlation was observed between KYNA content in synovial fluid of patients with RA and other clinical and laboratory measures of disease activity.Conclusion.Our data show a local deficit of KYNA in inflammatory states.

β-Endorphin and natural killer cell cytolytic activity during prolonged exercise. Is there a connection?

1998 ◽  
Vol 275 (6) ◽  
pp. R1725-R1734 ◽  
Author(s):  
G. A. Gannon ◽  
S. G. Rhind ◽  
M. Suzui ◽  
J. Zamecnik ◽  
B. H. Sabiston ◽  
...  
Keyword(s):  
Natural Killer Cell ◽  
Natural Killer ◽  
Nk Cell ◽  
Block Design ◽  
Killer Cell ◽  
Cytolytic Activity ◽  
Opioid Antagonist ◽  
Moderate Intensity ◽  
Moderate Intensity Exercise ◽  
Cell Counts

This study was designed to test whether a single 50-mg dose of the opioid antagonist naltrexone hydrochloride, ingested 60 min before 2 h of moderate-intensity exercise (i.e., 65% peak O2consumption), influenced the exercise-induced augmentation of peripheral blood natural killer cell cytolytic activity (NKCA). Ten healthy male subjects were tested on four occasions separated by intervals of at least 14 days. A rested-state control trial was followed by three double-blind exercise trials [placebo (P), naltrexone (N), and indomethacin] arranged according to a random block design. The indomethacin exercise trial is discussed elsewhere (S. G. Rhind, G. A. Gannon, P. N. Shek, and R. J. Shepherd. Med. Sci. Sports Exerc. 30: S20, 1998). For both the P and N trials, plasma levels of β-endorphin were increased ( P < 0.05) at 90 and 120 min of exercise but returned to resting (preexercise) levels 2 h postexercise. CD3−CD16+CD56+NK cell counts and NKCA were significantly ( P < 0.05) elevated at each 30-min interval of exercise compared with correspondingly timed resting control values. However, there were no differences in NK cell counts or NKCA between P and N trials at any time point during the two trials. Changes in NKCA reflected mainly changes in NK cell count ( r = 0.72; P < 0.001). The results do not support the hypothesis that the enhancement of NKCA during prolonged submaximal aerobic exercise is mediated by β-endorphin.

scholarly journals Involvement of Interleukin-10 in the Anti-Inflammatory Effect of Sanyinjiao (SP6) Acupuncture in a Mouse Model of Peritonitis

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Morgana Duarte da Silva ◽  
Giselle Guginski ◽  
Maria Fernanda de Paula Werner ◽  
Cristiane Hatsuko Baggio ◽  
Rodrigo Marcon ◽  
...  
Keyword(s):  
Vascular Permeability ◽  
Interleukin 10 ◽  
Sham Acupuncture ◽  
Therapeutic Effects ◽  
Plasma Extravasation ◽  
Sterile Saline ◽  
Cell Counts ◽  
Cytokine Levels ◽  
Anti Inflammatory ◽  
Inflammatory Effect

In this study, we determined the anti-inflammatory effect of manual acupuncture at the Sanyinjiao or Spleen 6 (SP6) point on carrageenan-induced peritonitis in mice and investigated mechanisms that may underlie this effect. In the first set of experiments, male Swiss mice were allocated into five groups: the control (sterile saline), dexamethasone (DEXA), invasive sham-acupuncture (non-acupoint), SP6 acupuncture and carrageenan-treated groups. Ten minutes after needle retention or 30 min after DEXA treatment, mice received an intraperitoneal injection of carrageenan (750 μg/mouse). After 4 h, total leukocyte and differential cell counts (neutrophils and mononuclear), myeloperoxidase (MPO) activity, vascular permeability and cytokine levels were evaluated. In another set of experiments, adrenalectomized (ADX) mice were used to study the involvement of the adrenal gland on the therapeutic effects of acupuncture. Mice were allocated into two groups: the ADX and sham-operated animals (Sham ADX) that were subdivided into four subgroups each: the control (sterile saline), DEXA, SP6 acupuncture and carrageenan-treated groups. The SP6 and DEXA treatments inhibited the inflammatory cell infiltration, vascular permeability and MPO activity in carrageenan-injected mice. In addition, the SP6 treatment also increased interleukin (IL)-10 levels. In contrast, when the animals were adrenalectomized, the SP6 treatment failed to reduce total leukocyte and the plasma extravasation. In conclusion, this study clearly demonstrates the anti-inflammatory effect of SP6 acupuncture in a model of carrageenan-induced peritonitis. Our results demonstrated that SP6 acupuncture depends of the adrenal glands and increased IL-10 levels to produce its anti-inflammatory action.

scholarly journals Association of Anger Expression-Out with NK Cell Counts in Colorectal Cancer Patients

2018 ◽  
Vol 31 (3) ◽  
pp. 152
Author(s):  
Estela Kakoo-Brioso ◽  
Luís Costa ◽  
Sílvia Ouakinin
Keyword(s):  
Colorectal Cancer ◽  
Natural Killer Cell ◽  
Cell Count ◽  
Natural Killer ◽  
Cancer Patients ◽  
Psychological Factors ◽  
Killer Cell ◽  
Anger Expression ◽  
Cell Counts ◽  
Colorectal Cancer Patients

Introduction: There is growing evidence describing the relation between psychological factors and the progression of colorectal cancer. Several mechanisms have been proposed but the one showing more promising evidence relies on the modulation of the antitumoral immune response by psychological factors, particularly through natural killer cells. We aimed to study the relation between natural killer cell count and anxiety, depression and anger state, trait and expression in 54 pre-surgical colorectal cancer patients.Material and Methods: We measured peripheral blood natural killer cell count and applied the State-Trait Anger Expression Inventory and the Hospital Anxiety and Depression Scale to 54 pre-surgical colorectal cancer patients. We used the Mann-Whitney U test and the Kruskal-Wallis test when appropriate to compare independent groups.Results: Patients with higher Anger Expression-Out had lower natural killer cell numbers than patients with lower Anger Expression-Out (p value = 0.008). No relation was found between natural killer cell levels and Anger State, Anger Trait, or Anger Expression-In. No difference in natural killer cell count was found between patients with and without clinical anxiety or depression.Discussion: These results suggest that, in colorectal cancer patients, natural killer cell counts are influenced by Anger Expression-Out, but not by clinical anxiety or depression.Conclusion: The unregulated emotional expression might be a conditioning factor of innate immunity. Additional studies are needed to further investigate this relation and to ascertain the clinical impact of therapeutic interventions regarding emotional regulation on the anti-tumoral immune response.

scholarly journals Early natural killer cell counts in blood predict mortality in severe sepsis

Critical Care ◽  
2011 ◽  
Vol 15 (5) ◽  
pp. R243 ◽  
Author(s):  
David Andaluz-Ojeda ◽  
Verónica Iglesias ◽  
Felipe Bobillo ◽  
Raquel Almansa ◽  
Lucía Rico ◽  
...  
Keyword(s):  
Severe Sepsis ◽  
Natural Killer Cell ◽  
Natural Killer ◽  
Killer Cell ◽  
Cell Counts

scholarly journals Variation in Leukocyte Subset Concentrations Affects Calcineurin Activity Measurement: Implications for Pharmacodynamic Monitoring Strategies

2008 ◽  
Vol 54 (3) ◽  
pp. 517-524 ◽  
Author(s):  
Huub H van Rossum ◽  
Fred P H T M Romijn ◽  
Kathryn J Sellar ◽  
Nico P M Smit ◽  
Paul J M van der Boog ◽  
...  
Keyword(s):  
T Cell ◽  
Renal Transplant ◽  
Killer Cell ◽  
Therapeutic Drug ◽  
Activity Measurement ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Leukocyte Subset ◽  
Cell Counts ◽  
Monitoring Strategies

Abstract Background: In renal transplantation patients, therapeutic drug monitoring of the calcineurin (CN) inhibitor cyclosporin A (CsA) is mandatory because of the drug’s narrow therapeutic index. Pharmacodynamic monitoring of CN inhibition therapy could provide a tool to define and maintain the therapeutic efficacy of CsA therapy. We investigated the effect of variation in cell counts of leukocyte subsets on leukocyte CN activity measurement in renal transplant recipients. Methods: We measured leukocyte CN activity, whole blood CsA concentrations, and leukocyte subset cell counts in 25 renal transplant recipients. Blood was collected before graft implantation and CsA therapy, 1 day before transplantation when CsA therapy was already started, and 5 days after transplantation. Monocyte, granulocyte, CD4+ T-cell, CD8+ T-cell, B-cell, and natural killer–cell CN activities and CsA inhibition sensitivities were determined in vitro by a spectrophotometric CN assay. Results: Leukocyte CN activity was inhibited after drug intake. Inter- and intrapatient variation in leukocyte subset cell counts resulted in variation of sample composition. The mean (SD) CN activity varied among leukocyte cell subsets, ranging from 650 (230) to 166 (26) pmol/min/106 cells for monocytes and CD4+ T cells, respectively. CsA half maximal inhibitory concentration (IC50) values ranged from 15 to 78 μg/L for monocytes and B cells, respectively. Conclusion: Inter- and intraindividual leukocyte subset cell count variation can affect measured CN activity independent of CsA concentration. Cell-specific activity and drug sensitivity should be considered for sample validation to optimize method specificity when pharmacodynamic monitoring strategies are applied in a clinical setting.

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