Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Results of a large therapeutic trial of interferon-gamma in patients with rheumatoid arthritis (RA) are described. Of 110 RA-patients enrolled in this clinical trial, 46 were treated with interferon-gamma for 12 months. During the treatment period, dosage was reduced on an individual basis. There was a correlation between the improvement of clinical parameters, such as pain or morning stiffness, and the improvement of laboratory parameters such as erythrocyte sedimentation rate, anemia, leucocytosis or thrombocytosis. Interferon-gamma was well tolerated, and no organ toxicity was detected.
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PMID:Correlation of clinical and serological findings in patients with rheumatoid arthritis treated for one year with interferon-gamma. 210 38

In a multicenter placebo-controlled double-blind randomized clinical study, 91 patients with rheumatoid arthritis were given 28 days' treatment with recombinant interferon-gamma (50 micrograms daily for 20 days, then 50 micrograms each second day up to day 28, given by subcutaneous injection). The aim of the study was to provide a methodologically clear demonstration of the efficacy of treatment with interferon-gamma, using criteria that could be handled by statistical tests. Evaluatable documentation was available for 79 patients, of whom 40 were treated with the active compound. The principal criterion for the statistical evaluation of the therapeutic success was improvement of the Ritchie "joint pain index" or Lansbury "joint pain index" by at least 30% within 28 days. The chi-square test showed superiority of the interferon arm over the placebo arm with an error probability of alpha less than 1%. In addition, efficacy of interferon-gamma was demonstrated in respect of practically all parameters investigated. The frequency of side-effects, including febrile reactions, was the same for the active compound and the placebo. During interferon treatment the daily maximum body temperature was raised by 0.3 degrees C on average, but was below 37.2 degrees C at all times.
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PMID:Results of a multicenter placebo-controlled double-blind randomized phase III clinical study of treatment of rheumatoid arthritis with recombinant interferon-gamma. 313 72

During the last two years, 80 patients with definite chronic rheumatoid arthritis were treated with interferon-gamma. Considerable improvement in the clinical picture occurred in 58, with pain decreasing rapidly and lastingly or even disappearing. Even in largely immobile patients the ability to walk and general mobility were nearly fully restored. The treatment was well tolerated in 74 patients. As the substance is administered subcutaneously it is suitable for out-patient treatment.
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PMID:[Interferon in chronic polyarthritis. Positive effect in clinical evaluation]. 393 59

The antitumor activity of combination therapy with traditional Chinese medicines and OK432 (Streptococcus pyogenes) for cancer patients was investigated. Excellent antitumor activity of this treatment was achieved in one patient with hepatocellular carcinoma. The present report describes the clinical course of this patient and examines the contribution of production of tumor necrosis factor (TNF) and interferon-gamma (IFN). Endogenous production of TNF could be observed after drip intravenous injection of OK 432 in the serum of patients treated by previous oral administration of traditional Chinese medicines. The serum levels of IFN were very low and remained at almost undetectable levels under these conditions. The selective use of immunostimulants such as traditional Chinese medicines may be of value in combination with other therapies such as drip infusion of OK 432, in the treatment of advanced cancer or of aged patients because of the low toxicity. One patient out of 12 revealed a partial response as assessed by the antitumor activity. However, with this treatment, patients did become free from pain and a good performance status was supported.
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PMID:Combination therapy with traditional Chinese medicines and Streptococcus pyogenes products (OK 432) for endogenous tumor necrosis factor therapy. A preliminary report. 766 72

The effect of intrathecal (i.t.) injection of the cytokine interferon-gamma) (IFN-gamma) on the spinal nociceptive flexor reflex was examined in decerebrate, spinalized, unanesthetized rats. IFN-gamma elicited an initial intense, brief facilitation of the flexor reflex followed by a sustained reflex facilitation lasting 40 +/- 5 min (range 20-65 min). The initial and prolonged reflex facilitations by IFN-gamma were partially and totally blocked, respectively, by i.t. pretreatment with nitro-L-arginine-ester, an inhibitor of nitric oxide synthase, at doses which did not influence spinal cord blood flow. Spinal application of IFN-gamma produced powerful and prolonged facilitation of the flexor reflex, possibly reflecting a hyperalgesic action of this cytokine. The facilitatory effect of IFN-gamma was mediated, at least in part, by the activation of the L-arginine-nitric oxide pathway. Thus, IFN-gamma released in the CNS may participate in eliciting pain and hyperalgesia in infectious or neuroinflammatory diseases where there is increased production of this cytokine.
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PMID:Intrathecal interferon-gamma facilitates the spinal nociceptive flexor reflex in the rat. 771 23

Perhaps as many as 25-50% of adult patients and children with acquired immunodeficiency syndrome (AIDS) eventually suffer from neurological manifestations, including dysfunction of cognition, movement, and sensation. How can human immunodeficiency virus type 1 (HIV-1) result in neuronal damage if neurons themselves are for all intents and purposes not infected by the virus? This article reviews a series of experiments leading to a hypothesis that accounts at least in part for the neurotoxicity observed in the brains of AIDS patients. There is growing support for the existence of HIV- or immune-related toxins that lead indirectly to the injury or demise of neurons via a potentially complex web of interactions among macrophages (or microglia), astrocytes, and neurons. HIV-infected monocytoid cells (macrophages, microglia, or monocytes), after interacting with astrocytes, secrete eicosanoids, i.e., arachidonic acid and its metabolites, including platelet-activating factor. Macrophages activated by HIV-1 envelope protein gp120 also appear to release arachidonic acid and its metabolites. In addition, interferon-gamma (IFN-gamma) stimulation of macrophages induces release of the glutamate-like agonist, quinolinate. Furthermore, HIV-infected macrophage production of cytokines, including TNF-alpha and IL1-beta, contributes to astrogliosis. A final common pathway for neuronal susceptibility appears to be operative, similar to that observed in stroke, trauma, epilepsy, neuropathic pain, and several neurodegenerative diseases, possibly including Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This mechanism involves the activation of voltage-dependent Ca2+ channels and N-methyl-D-aspartate (NMDA) receptor-operated channels, and, therefore, offers hope for future pharmacological intervention. This article focuses on clinically tolerated calcium channel antagonists and NMDA antagonists with the potential for trials in humans with AIDS dementia in the near future.
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PMID:HIV-related neuronal injury. Potential therapeutic intervention with calcium channel antagonists and NMDA antagonists. 799 15

Nitric oxide (NO) is an important inflammatory mediator in nonhuman animal models of rheumatoid arthritis (RA). The purpose of the present study was to determine whether blood mononuclear cells from patients with active RA (as compared to control subjects) have higher levels of NO synthase type 2 (NOS2) and produce more NO in vitro. Leukocytes from 25 RA patients and 20 normal subjects were examined. Arthritis activity was assessed by tender and swollen joint counts, duration of morning stiffness, patient assessment of pain, physician and patient global assessment of disease activity, the modified Stanford Health Assessment Questionnaire, and by blood levels of acute phase reactants. Blood mononuclear cell NOS enzyme activity/antigen content and nitrite/nitrate formation in vitro were measured. Blood mononuclear cells from RA patients had increased NOS activity and increased NOS2 antigen content as compared to those from normal subjects, and responded to interferon-gamma with increased NOS expression and nitrite/nitrate production in vitro. NOS activity of freshly isolated blood mononuclear cells correlated significantly with disease activity, as assessed by render and swollen joint counts. Our results demonstrate that patients with RA have systemic activation for NOS2 expression, and that the degree of activation correlates with disease activity. Increased NOS2 expression and NO generation may be important in the pathogenesis of RA.
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PMID:Increased expression of blood mononuclear cell nitric oxide synthase type 2 in rheumatoid arthritis patients. 906 35

The objective of this study was to determine the effects of castration, with its presumed pain and inflammatory effects, including increased cortisol, and elevated cortisol per se on in vitro interferon-gamma (IFN-gamma) production, ADG, ADFI, and plasma haptoglobin and fibrinogen. Thirty Friesian bull calves (174 +/- 3.8 kg) were assigned to three treatments (given on d 0): 1) control (CON); 2) i.v. cortisol administration to mimic castration-induced increases in cortisol (CORT); and 3) surgical castration (SURG). Blood samples were collected for 12 h on d 0 and at 24 and 72 h after treatment for cortisol determination. Keyhole limpet hemocyanin (KLH)- and concanavalin A (Con A)-induced in vitro IFN-gamma production in blood, and plasma haptoglobin and fibrinogen were measured in blood samples taken before treatment on d 0 and on d 1 and 3. On d 0, CORT and SURG animals had higher peak cortisol (P < .001) and area under the cortisol curve (P < .001) than CON animals. There were no differences (P > .05) between CON, CORT, and SURG animals in cortisol at 24 and 72 h. There were no differences (P > .05) between CON and CORT animals in IFN-gamma production, haptoglobin, fibrinogen, ADG, and ADFI. Compared with CON animals, SURG animals had lower (P < .05) KLH-induced IFN-gamma on d 1 and CON A-induced IFN-gamma on d 1 and 3. Haptoglobin concentrations were greater (P < .05) for SURG than for CON animals on d 1 and 3. Fibrinogen concentrations were greater (P < .001) for SURG than for CON animals on d 3. The SURG animals had lower (P < .01) ADG and ADFI during d 0 to 7 than CON animals. In conclusion, castration decreased IFN-gamma production, ADG, and ADFI and increased haptoglobin and fibrinogen, and these effects seemed to be independent of plasma cortisol concentrations.
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PMID:Effects of cortisol on in vitro interferon-gamma production, acute-phase proteins, growth, and feed intake in a calf castration model. 911 Feb 18

Mycobacterium avium complex infections (MAC) are being reported with increasing frequency in immunocompromised patients. When these infections become resistant to standard antibiotic therapy, treatment with interferon-gamma (IFN-gamma) can be helpful. Pain, fever, splenic enlargement, and cytopenias caused by splenic sequestration developed during IFN-gamma treatment in a 9-year-old boy and were successfully treated by splenectomy. The development of IFN-gamma-induced splenic sequestration and cytopenias in MAC-infected patients represents a new indication for splenectomy.
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PMID:Splenectomy in a child with chronic Mycobacterium avium complex infection and splenic sequestration. 960 93

We investigated the effects of (+)-4-[(alpha R)-alpha-((2S, 5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N, N-diethylbenzamide (SNC 80), a nonpeptidic delta-opioid receptor-selective agonist, on rat leukocyte functions. Intracerebroventricular injection of SNC 80 (20 nmol) in Fischer 344N male rats did not affect splenic natural killer cell activity compared with intracerebroventricular saline-injected controls. SNC 80 also had no effect on concanavalin A-, anti-T cell receptor-, interleukin-2- and anti-T cell receptor + interleukin-2-induced splenic and thymic lymphocyte proliferation in most experiments. In some experiments, however, SNC 80 significantly (P < .01) caused a 41 to 93% increase of concanavalin A-, anti-T cell receptor-, interleukin-2- and anti-T cell receptor + interleukin-2-induced splenic lymphocyte proliferation compared to controls. Additionally, SNC 80 did not significantly affect splenic T cell or natural killer cell populations as measured by the expression of T cell receptoralphabeta, and T helper (CD4), T suppressor/cytotoxic (CD8) and natural killer cell surface markers. Finally, SNC 80 did not affect interferon-gamma- or lipopolysaccharide (LPS)-induced splenic nitric oxide, and LPS-induced tumor necrosis factor-alpha production by splenic macrophages. These results suggest that SNC 80 could be useful in the treatment of pain without suppressing immune function. However, the potential immunoenhancing properties of SNC 80 may be also valuable in immunocompromised individuals.
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PMID:Rat natural killer cell, T cell and macrophage functions after intracerebroventricular injection of SNC 80. 969 52


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