Anti-inflammatory treatment approaches in major depression

2011 ◽  
Vol 26 (S2) ◽  
pp. 2093-2093 ◽  
Author(s):  
N. Müller ◽  
M.J. Schwarz
Keyword(s):  
Major Depression ◽  
Proinflammatory Cytokines ◽  
Psychiatric Patients ◽  
Double Blind Study ◽  
Double Blind ◽  
Depressed Patients ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Significant Therapeutic Effect

Proinflammatory cytokines, such as IL-6, IL-1 and TNF-a appear to be elevated at least in the peripheral blood of depressed patients. Thus, the activity of the enzyme IDO, which is driven by pro-inflammatory cytokines and regulates the tryptophan/kynurenine metabolism may be enhanced in depressed patients through these cytokines. Although IL-6 does not directly act on IDO, its elevated levels in serum may contribute to IDO activation within the CNS by the stimulatory effect on PGE2, which acts as cofactor in the activation of IDO. This fits with a report on the correlation of increased in vitro IL-6 production with decreased tryptophan levels in depressed. Due to the increase of proinflammatory cytokines and PGE2 in some psychiatric patients, antiinflammatory treatment would be expected to show advantagous effects in schizophrenic and depressed patients. Cyclo-oxygenase-2 inhibitors have been evaluated in major depression. We were able to demonstrate a statistically significant therapeutic effect of the COX-2 inhibitor on depressive symptoms in a randomized double blind pilot add-on study using the selective COX-2 inhibitor celecoxib in MD. Another randomized double-blind study in fifty depressed patients suffering from MD also showed an statistically significant better outcome of the COX-2 inhibitor celecoxib plus fluoxetine compared to fluoxetine alone. Additionally, results of the clinical study of celecoxib add-on to sertraline and the effects of this anti-inflammatory therapy approach to inflammatory markers planned by the MOODINFLAME consortium will be presented as far as available. Further on, alternative therapeutic strategies based on immune-modulatory effects will be discussed.

The Safety Of Ibuprofen In Factor VIII And IX Deficient Hemophiliacs

1981 ◽  
Author(s):  
M J Inwood ◽  
B Killackey ◽  
R B Philp
Keyword(s):  
Factor Viii ◽  
Factor Ix ◽  
Double Blind Study ◽  
Double Blind ◽  
Spontaneous Bleeding ◽  
Hemophilic Arthropathy ◽  
Viii And Ix ◽  
Anti Inflammatory ◽  
Clinically Significant

Most anti-inflammatory analgesics, particularly ASA, are considered contraindicated in the treatment of hemophiliacs because of inhibition of in vitro hemostatic function. Nevertheless, it would appear reasonable to use such agents in the therapy of chronic or acute hemophiliac arthropathy, provided that the anti-inflammatory drug did not increase the incidence of hemorrhage.Using moderately and severely affected factor VIII and IX deficient hemophiliacs, Ibuprofen was given, using a short (24 hrs) and long term (21 days) trial in order to assess the effect on in vitro hemostasis and the incidence of hemorrhagic symptoms compared to a comparable period prior to the ingestion of drug. An initial safety trial used 24 normal subjects and 12 moderately to severely affected factor VIII and factor IX deficient hemophiliacs. Within each group 600 mgs of Ibuprofen or lactose placebo was given in a random double-blind study. Over 24 hours no changes were seen in the bleeding time, peripheral blood counts or spontaneous bleeding patterns. Subsequently a 21 day trial was initiated with 15 moderately to severely affected hemophiliacs, using a dose of 2400 mg per os Ibuprofen per day. At 0,7,14 and 21 days, factor assays, bleeding times, platelet function and cell studies were performed. No clinically significant changes were found in any of the experimental variables, including pattern of spontaneous hemorrhages. Four of the 15 subjects experienced intermittent dyspepsia, controlled by antacids. 7 of 11 individuals with hemophilic arthropathy had a subjective decrease in symptoms from arthropathy.It is concluded that Ibuprofen is not associated with clinically significant changes in vitro or in vivo hemostatic function in factor VIII or IX deficient hemophiliacs, and should be considered in the treatment of hemophilic arthropathy.

The Therapeutic Potential of Non Steroidal Anti-inflammatory Drugs in the Treatment of Depression and Schizophrenia

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
N. Müller ◽  
M. Riedel ◽  
M.J. Schwarz
Keyword(s):  
Therapeutic Effect ◽  
Proinflammatory Cytokines ◽  
Therapeutic Potential ◽  
Disease Process ◽  
Antidepressant Effect ◽  
Double Blind Study ◽  
Double Blind ◽  
Cardiovascular Side Effects ◽  
Cox 2 ◽  
Cox 2 Inhibitors

COX-2 inhibition seems to balance the type-1/type-2 immune response, possibly via inhibition of prostaglandin E2. COX-2 inhibition reduces proinflammatory cytokines. COX-2 inhibition has an impact to the glutamatergic neurotransmission and influences the tryptophan/kynurenine metabolism: all three components seem to be involved in the pathophysiology of psychiatric disorders, particularly in schizophrenia and major depression.Due to the increase of proinflammatory cytokines and PGE2 in depressed patients, antiinflammatory treatment would be expected to show antidepressant effects. An antidepressant effect of rofecoxib was found in patients with osteoarthritis. An own randomized double blind pilot add-on study using the selective COX-2 inhibitor celecoxib in MD showed a significant therapeutic effect of the COX-2 inhibitor on depressive symptoms. Although those preliminary data have to be interpreted cautiously, those results are encouraging for further studies dealing with the inflammatory hypothesis of depression.Secondly, we and other research-groups performed several studies of COX-2 inhibitors in schizophrenia. In a prospective, randomized, double-blind study with the COX-2 inhibitor celecoxib in acute exacerbation of schizophrenia, a therapeutic effect of celecoxib was observed. The finding of a clinical advantage of COX-2 inhibition could not be replicated in a second study. Further analysis of the data revealed that the efficacy of therapy with a COX-2 inhibitor seems most pronounced in the first years of the schizophrenic disease process.It has to be considered, however, that therapy with COX-2 inhibitors is currently under discussion - as therapy with other non-steroidal antiphlogistics - due to cardiovascular side-effects.

The Effect of Warfarin Sodium on the Duration of Platelet Aggregation

1967 ◽  
Vol 18 (03/04) ◽  
pp. 766-778 ◽  
Author(s):  
H. J Knieriem ◽  
A. B Chandler
Keyword(s):  
Platelet Count ◽  
Placebo Group ◽  
Platelet Aggregation ◽  
Prothrombin Time ◽  
Platelet Rich Plasma ◽  
Healthy Adults ◽  
Double Blind Study ◽  
Double Blind ◽  
Warfarin Sodium

SummaryThe effect of the administration of warfarin sodium (Coumadin®) on the duration of platelet aggregation in vitro was studied. Coumadin was given for 4 consecutive days to 10 healthy adults who were followed over a period of 9 days. The duration of adenosine diphosphate-induced platelet aggregation in platelet-rich plasma, the prothrombin time, and the platelet count of platelet-rich plasma were measured. Four other healthy adults received placebos and participated in a double-blind study with those receiving Coumadin.Although administration of Coumadin caused a prolongation of the prothrombin time to 2 or 21/2 times the normal value, a decrease in the duration of platelet aggregation was not observed. In most individuals who received Coumadin an increase in the duration of platelet aggregation occurred. The effect of Coumadin on platelet aggregation was not consistently related to the prothrombin time or to the platelet count. In the placebo group there was a distinct relation between the duration of platelet aggregation and the platelet count in platelet-rich plasma.The mean increase in the duration of platelet aggregation when compared to the control value before medication with Coumadin was 37.7%. In the placebo group there was a mean increase of 8.4%. The difference between the two groups is significant (p <0.001). Increased duration of platelet aggregation also occurred in two individuals who received Coumadin over a period of 10 and 16 days respectively.

scholarly journals Bone Marrow Mesenchymal Stromal Cells on Silk Fibroin Scaffolds to Attenuate Polymicrobial Sepsis Induced by Cecal Ligation and Puncture

Polymers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1433
Author(s):  
Ok-Hyeon Kim ◽  
Jun-Hyung Park ◽  
Jong-In Son ◽  
Ok-Ja Yoon ◽  
Hyun-Jung Lee
Keyword(s):  
Bone Marrow ◽  
Cecal Ligation ◽  
Biological Properties ◽  
Pge2 Production ◽  
Polymicrobial Sepsis ◽  
Control Surface ◽  
Related Factors ◽  
Cox 2 ◽  
Anti Inflammatory

Suitable scaffolds with appropriate mechanical and biological properties can improve mesenchymal stromal cell (MSC) therapy. Because silk fibroins (SFs) are biocompatible materials, they were electrospun and applied as scaffolds for MSC therapy. Consequently, interferon (IFN)-primed human bone marrow MSCs on SF nanofibers were administered into a polymicrobial sepsis murine model. The IL-6 level gradually decreased from 40 ng/mL at 6 h after sepsis to 35 ng/mL at 24 h after sepsis. The IL-6 level was significantly low as 5 ng/mL in primed MSCs on SF nanofibers, and 15 ng/mL in primed MSCs on the control surface. In contrast to the acute response, inflammation-related factors, including HO-1 and COX-2 in chronic liver tissue, were effectively inhibited by MSCs on both SF nanofibers and the control surface at the 5-day mark after sepsis. An in vitro study indicated that the anti-inflammatory function of MSCs on SF nanofibers was mediated through enhanced COX-2-PGE2 production, as indomethacin completely abrogated PGE2 production and decreased the survival rate of septic mice. Thus, SF nanofiber scaffolds potentiated the anti-inflammatory and immunomodulatory functions of MSCs, and were beneficial as a culture platform for the cell therapy of inflammatory disorders.

scholarly journals Mesenchymal Stem Cells (MSCs) Coculture Protects [Ca2+]i Orchestrated Oxidant Mediated Damage in Differentiated Neurons In Vitro

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 250 ◽  
Author(s):  
Adel Alhazzani ◽  
Prasanna Rajagopalan ◽  
Zaher Albarqi ◽  
Anantharam Devaraj ◽  
Mohamed Hessian Mohamed ◽  
...  
Keyword(s):  
Cell Death ◽  
Transforming Growth Factor ◽  
Neuronal Cells ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Apoptotic Cells ◽  
Sequence Of Events ◽  
Cox 2 ◽  
Anti Inflammatory

Cell-therapy modalities using mesenchymal stem (MSCs) in experimental strokes are being investigated due to the role of MSCs in neuroprotection and regeneration. It is necessary to know the sequence of events that occur during stress and how MSCs complement the rescue of neuronal cell death mediated by [Ca2+]i and reactive oxygen species (ROS). In the current study, SH-SY5Y-differentiated neuronal cells were subjected to in vitro cerebral ischemia-like stress and were experimentally rescued from cell death using an MSCs/neuronal cell coculture model. Neuronal cell death was characterized by the induction of proinflammatory tumor necrosis factor (TNF)-α, interleukin (IL)-1β and -12, up to 35-fold with corresponding downregulation of anti-inflammatory cytokine transforming growth factor (TGF)-β, IL-6 and -10 by approximately 1 to 7 fold. Increased intracellular calcium [Ca2+]i and ROS clearly reaffirmed oxidative stress-mediated apoptosis, while upregulation of nuclear factor NF-B and cyclo-oxygenase (COX)-2 expressions, along with ~41% accumulation of early and late phase apoptotic cells, confirmed ischemic stress-mediated cell death. Stressed neuronal cells were rescued from death when cocultured with MSCs via increased expression of anti-inflammatory cytokines (TGF-β, 17%; IL-6, 4%; and IL-10, 13%), significantly downregulated NF-B and proinflammatory COX-2 expression. Further accumulation of early and late apoptotic cells was diminished to 23%, while corresponding cell death decreased from 40% to 17%. Low superoxide dismutase 1 (SOD1) expression at the mRNA level was rescued by MSCs coculture, while no significant changes were observed with catalase (CAT) and glutathione peroxidase (GPx). Interestingly, increased serotonin release into the culture supernatant was proportionate to the elevated [Ca2+]i and corresponding ROS, which were later rescued by the MSCs coculture to near normalcy. Taken together, all of these results primarily support MSCs-mediated modulation of stressed neuronal cell survival in vitro.

1643 – Efficacy of agomelatine in more anxious elderly depressed patients. A randomized, double-blind study vs placebo

2013 ◽  
Vol 28 ◽  
pp. 1 ◽  
Author(s):  
R. Heun ◽  
R.M. Corral ◽  
A. Ahokas ◽  
H. Nicolini ◽  
J.M. Teixeira ◽  
...  
Keyword(s):  
Blind Study ◽  
Double Blind Study ◽  
Double Blind ◽  
Depressed Patients

The Efficacy and Tolerability of Combined Antidepressant Treatment in Different Depressive Subgroups

1993 ◽  
Vol 162 (3) ◽  
pp. 363-368 ◽  
Author(s):  
Sinead O'brien ◽  
Patrick McKeon ◽  
Myra O'regan
Keyword(s):  
Treatment Group ◽  
Side Effects ◽  
Major Depression ◽  
Orthostatic Hypotension ◽  
Antidepressant Treatment ◽  
Combined Treatment ◽  
Endogenous Depression ◽  
Double Blind Study ◽  
Double Blind ◽  
Global Improvement

Eighty patients admitted to hospital with major depression were randomly allocated to six weeks of treatment with tranylcypromine, amitriptyline, or tranylcypromine and amitriptyline in combination, in a double-blind study. Scores on the HRSD improved significantly in all three groups, but there were no differences between the three groups. Patients on tranylcypromine and amitriptyline combined improved more according to their self-ratings after six weeks, and response was earlier as measured by a clinical global improvement scale. Those with endogenous depression improved more than those with neurotic depression, irrespective of treatment group. Combined treatment was less well tolerated than single treatments and gave rise to more side-effects, although there was no serious toxicity. Orthostatic hypotension was observed more frequently in patients on combined treatment. This group also experienced a significant increase in weight and prolongation of the P-R interval on ECG.

Sign in / Sign up

Export Citation Format

Share Document