Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the treatment of severe hypertension the choice of vasodilator is limited by side-effects, of which the lupus erythematosus syndrome induced by hydralazine is potentially the most serious, particularly in patients with the slow acetylator phenotype. This study describes the clinical evaluation of a new vasodilator, endralazine, which is related to hydralazine but which is not metabolised to any great extent by acetylation. In 6 essential hypertensives not adequately controlled by combined beta-blocker and diuretic therapy the additional administration of the first dose of 10 mg endralazine resulted in a significant reduction in blood pressure, without orthostatic symptoms, but associated with significant increases in heart rate and plasma noradrenaline concentration. These 6 patients and a further 9 similar hypertensive patients were then prescribed twice daily endralazine for 4 weeks with significant improvement in blood pressure control. During this short period of maintenance treatment with endralazine the single dose observations were repeated and no significant changes in heart rate or plasma noradrenaline concentration were observed. In summary, endralazine is an effective vasodilator/antihypertensive which was well tolerated in a triple therapy regimen in this study.
 ...
PMID:Clinical evaluation of endralazine (BO22708), a new vasodilator, in essential hypertension. 674 47

We routinely measured plasma neurotransmitters and hormone levels in order to investigate the role of stress on many types of diseases. In this study, we present results obtained from patients with severe chronic diseases. The study sample consisted of 88 patients (asthmatics, ulcerative colitis, Crohn's disease, chronic active hepatitis, chronic relapsing hepatitis, multiple sclerosis, trigeminal neuralgia, systemic lupus erithematous, and rheumatoid arthritis), and their respective controls. Noradrenaline (NA), adrenaline (Ad), dopamine (DA), platelet-serotonin (pS), free-serotonin (fS), growth hormone (GH) and cortisol (CRT) were determined during both exacerbation and improvement periods. A profile compatible with uncoping stress disorder (raised NA-Ad-DA + fS + CRT as well as low pS and NA/Ad ratio) was found during exacerbation periods when compared with improvement, as seen in controls. However, during improvement periods the neurochemical profile remained significantly different from that of normal controls. The neurochemical plus hormonal plasma profiles registered in chronic illness, both during exacerbation and improvement periods, strongly suggest that an uncoping stress mechanism underlies diseases of these patients.
 ...
PMID:Plasma neurotransmitters and cortisol in chronic illness: role of stress. 799 62

The sympathetic nervous system is one of the major pathways involved in immune-neuroendocrine interactions. Disturbances in these interactions are likely to have consequences during lymphoproliferative diseases. Work derived from our group as well as from several others led us to the hypothesis that the overstimulation of the immune system that characterizes this type of pathology results in decreased sympathetic nerve activity in lymphoid organs. To explore this possibility, we used as a model lpr/lpr mice, which develop a genetically determined autoimmune, lupus-like lymphoproliferative disease. We show that 18-week-old female C57Bl/6J lpr/lpr mice, which do not show overt symptoms of the disease but already have increased IgM and IgG2a levels in the blood, have decreased noradrenaline (NA) concentration and content in the spleen, but not in the kidney, as compared to normal C57Bl/6J littermates. Lpr/lpr mice do not express normal Fas, and therefore apoptosis cannot be triggered through this receptor. The defects in sympathetic innervation in the spleen of lpr/lpr mice prompted us to evaluate whether NA could influence lymphoid cell mass by inducing apoptosis. We found that NA can directly induce apoptosis in normal lymphoid cells via beta-adrenergic receptors. From the reported results we propose that reduction in sympathetic nerve function in lpr/lpr mice contributes to aggravation of the disease and suggest that in addition to the incapacity to mount Fas-mediated apoptosis, a second proapoptotic mechanism, namely, that triggered by NA, is defective in these animals because of reduced availability of the neurotransmitter.
 ...
PMID:Sympathetic abnormalities during autoimmune processes: potential relevance of noradrenaline-induced apoptosis. 1279 55

Lpr/lpr mice develop a lymphoproliferative, autoimmune, lupus-like disease. These mice lack functional Fas (CD95) expression and are resistant to Fas ligand (CD178)-mediated apoptosis, a critical mechanism for the maintenance of peripheral tolerance. In this study, we show that noradrenaline (NA), the main sympathetic neurotransmitter, can induce apoptosis of lymphoid cells independently of functional Fas. Based on this finding, we used lpr/lpr mice as model to study the role of noradrenergic nerves in the expression of a lymphoproliferative disease. Early in ontogeny, the concentration of NA was significantly increased in the spleen of lpr/lpr mice, compared with normal littermates. However, splenic sympathetic innervation gradually declined as the disease progressed, and IgM blood levels and splenic NA concentration inversely correlated when the disease was overtly manifested. When the loss of noradrenergic fibers that occurred naturally during adult life in lpr/lpr mice was experimentally advanced by neonatal sympathectomy, the concentration of IgM and IgG2a in blood was markedly higher than that of control lpr/lpr mice, and the appearance of lymphadenopathy was accelerated. Furthermore, although neonatal denervation did not affect the life span of normal animals, it shortened significantly the survival time of lpr/lpr mice. These data show that, in addition to defects in the Fas pathway, an altered sympathetic innervation in lpr/lpr mice also contributes to the pathogenesis of the autoimmune disease, and strongly support the hypothesis that the sympathetic nervous system can modulate the expression of lymphoproliferative diseases.
 ...
PMID:The role of noradrenergic nerves in the development of the lymphoproliferative disease in Fas-deficient, lpr/lpr mice. 1670 70