Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042384 (vasculitis)
 20,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Estrogen is known to influence immune responses in healthy subjects in a dichotomous fashion. Thus, in number of previous studies we and others have demonstrated that B cell activities are augmented after exposure to estrogen whereas T cell reactivity is suppressed. Furthermore, it has been shown that this hormone has significant impact on the course of certain human and experimental autoimmune diseases. In this study we report that treatment with physiological doses of estradiol exerts dichotomous effects on different manifestations of the lupus disease in MRL/l mice. On one hand immune complex-mediated glomerulonephritis was significantly accelerated. This outcome was due to polyclonal B cell activation with increased production of antibodies to double-stranded DNA and formation of circulating immune complexes. In contrast, T cell-mediated lesions such as focal sialadenitis, renal vasculitis, and periarticular inflammation were all significantly ameliorated in MRL/l mice exposed to estrogen. Thus, we were able to demonstrate that, within one subject and even within one organ, administration of estrogen leads to differential outcome of SLE morbidity. We propose that the differential effect of estrogen on the manifestations of the autoimmune disease of MRL/l mice is due to its dichotomous effects on B and T cell-mediated immune responses.
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PMID:Estrogen accelerates immune complex glomerulonephritis but ameliorates T cell-mediated vasculitis and sialadenitis in autoimmune MRL lpr/lpr mice. 139 37

Both cigarette smoking and oral contraceptives (OCs) have been shown to exacerbate Crohn's disease. The pathogenic mechanism for Crohn's disease proposed by the authors--multifocal gastrointestinal infarction, mediated by a chronic mesenteric vasculitis--provides a framework for understanding these effects. Smoking induces morphologic injury to endothelial cells, inhibits aortic endothelial prostacyclin synthesis, and leads to elevated levels of plasma fibrinogen and decreased levels of plasminogen and tissue plasminogen activator activity. OCs that contain more than 50 mcg of ethinyl estradiol increase levels of procoagulant substrates and produce decreases in both anticoagulant and fibrinolytic activity. Enhanced expression of both monocyte and vascular endothelial cell procoagulant activity is the initiating event in the fibrin formation that initially characterizes Crohn's disease. Although microvascular changes have been observed in Crohn's disease patients who neither smoke nor use OCs, it appears likely that when further prothrombic stimuli such as OCs and nicotine are superimposed on Crohn's disease, the result is an exacerbation of disease activity.
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PMID:Smoking, the oral contraceptive pill, and Crohn's disease. 186 7

US and British studies have shown significantly higher incidence of strokes due to thromboembolism, subarachnoid hemorrhage, and cerebral venous thrombosis in users of oral contraceptives, particularly high estrogen formulations. Estrogen increases plasma levels of fibrinogen and the clotting factors VII, VIII, IX, X, and XII; enhances platelet aggregation; and suppresses antithrombin III and the fibrinolytic system. Estrogen may also cause immune-mediated vasculitis. The risk of strokes increases for women over 35 and smokers. Estrogen-induced chorea, including chorea of pregnancy, may be due to direct dopaminergic action of estrogens or to an accumulation of dopamine in the brain caused by competitive binding to the dopamine-degrading enzyme catechol-o-methyltransferase. Epileptics taking anticonvulsants and oral contraceptives have 25 times the risk of pill failure as normally expected, due to metabolism of anticonvulsants, such as phenytoin, phenobarbital, primidone, carbamazepine, and ethosuximide, by the hepatic microsomal enzyme system, resulting in a dramatic decrease of circulating ethinyl estradiol. Available options are to increase the estrogen dose to as much as 100 mg, to substitute valproic acid for other anticonvulsants, or to augment ethinyl estradiol levels by oral administration of ascorbic acid, which increases the bioavailability of the steroid. During pregnancy, on the other hand, serum levels of anticonvulsants decrease by 30-40%.
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PMID:Sex hormones in stroke, chorea, and anticonvulsant therapy. 305 49

A 15 year old female began to suffer from a headache 12 hours prior to admission to a hospital in Broken Hill, N.S.W., Australia. Several hours after the onset of the headache, she had a generalized tonic-clonic seizure. Upon arrival at the hospital, she was lethargic, but did respond to commands. Her speech was slurred and the right side of her body was paralyzed. She had no fever and blood pressure was normal. Despite attempts to treat her with intravenous dexamethasone, she slipped into an unconscious state. A CT scan uncovered a left parietal hypodense lesion. Her pupils quickly dilated the next day. The right pupil did respond slightly to light, however. Physicians made a burr hole in the parietal area of her skull which exposed underlying necrotic tissue. After the operation, her brain stem failed to function. She died the following day, 3 days after the symptoms began. Other than a febrile convulsion at 10 months, she had been in good health. She had been taking a combined oral contraceptive (COC) made of 125mcg levonorgestrel and 50mcg ethinyl estradiol for 2 weeks. Pathologists found an area of necrosis in the left temporo-parietal region of the brain and an occlusive thrombosis near the left middle cerebral artery. Further, a pronounced segmental necrotizing vasculitis of the left middle cerebral and right posterior cerebral arteries existed. Based on other documented cases and this case, the physicians point to evidence that vessel size in vasculitis has an effect on the severity of the disease. Vasculitis in small vessels has a tendency to cause a gradual progression of the disease, while this disease in medium and large vessels may cause a rapid progression of the disease, as in this case. The researchers suspect that the COC may have precipitated the disease.
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PMID:Isolated angiitis of the brain in a young female on the contraceptive pill. 345 Dec 35

Estrogen replacement therapy has been demonstrated to shift the lipoprotein profile toward a less atherogenic one with concomitant increases in HDL and reductions in LDL cholesterol and serum triglycerides. Estrogen, however, has also been implicated in playing a significant role in autoimmune disease and may be involved with disease incidence and progression. The MRL/lpr mouse strain represents an autoimmune disease model with features resembling systemic lupus erythematosus including high-titer autoantibodies, glomerulonephritis, and vasculitis. In the present study, the effects of estrogen treatment on serum lipoprotein profiles were investigated by fast protein liquid chromatography in female MRL/lpr mice, in the MRL/++ strain with a milder form of disease, and in control Balb/c mice. Treatment of MRL/lpr mice for periods of 1 week or longer with pharmacologic doses of estrogen resulted in a significant increase in the amount of cholesterol carried on LDL particles. The up to eightfold increase in LDL cholesterol was less significant in the MRL/++ or Balb/c mice. Maximal increases were observed at 1 to 2 mg/kg of estrogen agonists, and the effect on LDL cholesterol increases was inhibited by tamoxifen. The HDL-to-LDL shift in cholesterol observed in estrogen-treated autoimmune mice correlated with an increase in apolipoprotein E, primarily on larger HDL particles. In addition to the increase in LDL cholesterol, hormonal treatment also resulted in a shift in triglycerides from the VLDL to the LDL fraction in both normal and autoimmune mice. These results suggest that pharmacologic doses of estrogen may contribute to cardiovascular disease progression by shifting the relative distribution of cholesterol from HDL to LDL in this murine model of lupus.
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PMID:Estrogen-induced alterations in lipoprotein metabolism in autoimmune MRL/lpr mice. 758 27

Systemic lupus erythematosus (SLE) predominantly affects women (9:1 compared to men) of childbearing age and often decreases its intensity in postmenopausal women, suggesting that sex hormones play a role in its pathogenesis. Comparison of steady-state levels of calcineurin mRNA using RNase protection assays revealed increased calcineurin expression in response to estradiol in cultured T cells from nine female lupus patients. Calcineurin mRNA levels did not increase significantly in T cells from eight age-matched normal control female volunteers. Estrogen-dependent calcineurin mRNA increased in a dose-dependent fashion, while progesterone and dexamethasone did not increase calcineurin mRNA in patient cells. Lupus T cell calcineurin mRNA increased in response to estradiol at 6 h but not at 3 h. Calcineurin phosphatase activity increased in lupus T cell extracts after incubation of cells with estradiol, while phosphatase activity in normal T cells was unaffected by estrogen. Calcineurin expression in T cells from patients with vasculitis and rheumatoid arthritis taking medications similar to those taken by the lupus patients was unaffected by estradiol. This study provides the first evidence for a molecular marker of estrogen action in lupus patients and suggests that estrogen-dependent changes in lupus T cell calcineurin could alter proinflammatory cytokine gene regulation and T-B cell interactions.
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PMID:Gender differences in autoimmune diseases: estrogen increases calcineurin expression in systemic lupus erythematosus. 983 88

The cause or mechanism of the female predisposition in systemic lupus erythematosus and progressive systemic sclerosis is largely unknown. Accumulating evidence shows that dysfunction or activation of endothelial cells plays an important role in these conditions. In this study, we investigated the influence of various steroid hormones on the IL-1beta (50 U/mL)/TNF-alpha (50 U/mL) stimulated human dermal microvascular endothelial cell line (HMEC-1) and human umbilical vein endothelial cells (HUVEC). Dexamethasone showed significant inhibition of cytokine-induced ICAM-1 expression in HMEC-1, and E-selectin, VCAM-1 and ICAM-1 expressions in HUVEC. Androgens, especially dihydrotestosterone had a small, but statistically significant suppressive effect in HMEC-1 only. Estrogen exhibited no regulatory function in either cell line. No obvious expression of estrogen and androgen receptors could be demonstrated in either cell by immunostaining. Our study provided some pharmacological evidence that the superior anti-inflammatory effect of glucocorticoids on vasculitis was partly due to their inhibition of the CAM expression in endothelial cells. More studies are needed to determine if androgens could have a protective effect in vasculitis or vasculopathy associated with connective tissue diseases.
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PMID:Effects of dexamethasone and sex hormones on cytokine-induced cellular adhesion molecule expression in human endothelial cells. 1237 Jan 31

Systemic Lupus Erythematosus (SLE) is a chronic inflammatory rheumatic disease which affects the connective tissue. Its etiology is as yet unknown, while its pathogenesis involves the immune system. Both genetic and environmental and hormonal factors play a key role in the impaired immune regulation. A correlation with estrogens is demonstrated by the fact that the greatest incidence is found in young women, when estrogen secretion is at its highest. The disease is also reported to worsen in women taking oral contraceptives. It is therefore believed that the components of oral contraceptives, estrogens (ethinyl estradiol) and progestins, can affect the immune profile. Of the various complications attributed to systemic lupus erythematosus, gastrointestinal disorders are less common but potentially by far the most serious. We report a case of ischemic necrosis with sigma perforation in a patient with SLE. Signs and symptoms of acute abdomen in patients with SLE are rare (0.2%), but serious. Most patients require an exploratory laparotomy, as the causes are often linked with vasculitis.
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PMID:Ischemic necrosis with sigmoid perforation in a patient with Systemic Lupus Erythematosus (SLE): case report. 2252 51