Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0020538 (hypertension)
170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Perivascular cells are a heterogeneous population found in the central nervous system (CNS) and the peripheral nervous system (PNS). Several terms are used for these cells, including perivascular cells, perivascular macrophages, perivascular microglia, fluorescent granular perithelial cells (FGP), or Mato cells. Different terminology used may reflect subpopulations of perivascular cells within different anatomic regions and experimental paradigms, neuropathological conditions, and species studied. Different terminology also points to the lack of clear consensus of what cells are perivascular cells in different disease states and models, especially with breakdown of the blood-brain barrier (BBB). Despite this, there is consensus that perivascular cells, although a minor component of the CNS, are important immunoregulatory cells. Perivascular cells are bone marrow derived, continuously turn over in the CNS, and are found adjacent to CNS vessels. Thus, they are potential sensors of CNS and peripheral immune system perturbations; are activated in models of CNS inflammation, autoimmune disease, neuronal injury and death; and are implicated as phagocytic and pinocytotic cells in models of stroke and hypertension. Recent evidence from our laboratory implicate perivascular cells as primary targets of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infection in the CNS of humans and macaques. This article reviews current knowledge of perivascular cells, including anatomic location and nomenclature and putative immunoregulatory roles, and discusses new data on the infection of these cells by SIV, their accumulation after SIV infection, and a possible role of the immune system in SIV encephalitis.
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PMID:Central nervous system perivascular cells are immunoregulatory cells that connect the CNS with the peripheral immune system. 1159 24

Insulin-dependent diabetes mellitus (type-1 diabetes) is an inflammatory autoimmune disease associated with vascular permeability changes leading to many complications including nephropathy, retinopathy, hypertension, hyperalgesia and neuropathy. The bradykinin B(1) receptor was recently found to be upregulated during the development of the diabetes and to be involved in its complications. Kinins are known to be important mediators of a variety of biological effects including cardiovascular homeostasis, inflammation and nociception. In the present study, we studied the effect of the selective B(1) receptor agonist, des-Arg(9)-bradykinin, and its specific antagonists, Ac-Lys-[D-beta Nal(7), Ile(8)]des-Arg(9)-bradykinin (R-715) and Ac-Orn-[Oic(2), alphaMe Phe(5), D-beta Nal(7), Ile(8)]des-Arg(9)-bradykinin (R-954), on diabetic hyperalgesia. Diabetes was induced in male CD-1 mice by injecting a single high dose of streptozotocin (200 mg kg(-1), i.p.) and the nociception was assessed using the hot plate and the tail flick tests, 1 week following the injection of streptozotocin. Our results showed that induction of diabetes by streptozotocin provoked a marked hyperalgesia in diabetic mice expressed as about 11% decrease in hot plate reaction time and 26% decrease in tail flick reaction time. Following acute administration of R-715 (200-800 microg kg(-1), i.p.) and R-954 (50-600 microg kg(-1), i.p.), this hyperalgesic activity was blocked and the hot plate and tail flick latencies of diabetic mice returned to normal values observed in control healthy mice. In addition, the acute administration of des-Arg(9)-bradykinin (200-600 microg kg(-1), i.p.) significantly potentiated diabetes-induced hyperalgesia, an effect that was totally reversed by R-715 (1.6-2.4 mg kg(-1), i.p.) and R-954 (0.8-1.6 mg kg(-1), i.p.). These results provide a major evidence for the implication of the bradykinin B(1) receptors in the development of hyperalgesia associated with diabetes and suggest a novel approach to the treatment of this diabetic complication using the bradykinin B(1) receptor antagonists.
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PMID:Role of bradykinin B(1) receptors in diabetes-induced hyperalgesia in streptozotocin-treated mice. 1246 57

Autoimmune diseases characterized by activation of immune effector cells and damage of target organs are currently treated with a combination of several disease-modifying antirheumatic drugs (DMARDs) that preserve different immunomodulatory mechanisms. Such a combination treatment strategy not only provides synergistic effects but also reduces side effects from individual drug. Tetrandrine (Tet), purified from a creeper Stephania tetrandra S Moore, is a bis-benzylisoquinoline alkaloid and has been used to treat patients with silicosis, autoimmune disorders, and hypertension in Mainland China for decades. The accumulated studies both in vitro and in vivo reveal that Tet preserves a wide variety of immunosuppressive effects. Importantly, the Tet-mediated immunosuppressive mechanisms are evidently different from some known DMARDs. The synergistic effects have also been demonstrated between Tet and other DMARDs like FK506 and cyclosporin. These results highlight Tet a very potential candidate to be considered as one of DMARDs in the treatment of autoimmune diseases, especially rheumatoid arthritis. This review summarizes evidence-based in vivo and in vitro studies on this potential Chinese immunosuppressive herb.
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PMID:Immunomodulatory effects and mechanisms of plant alkaloid tetrandrine in autoimmune diseases. 1246 46

Physicians in the United States rarely screen for hypovitaminosis D and rarely prescribe vitamin D, even when medically indicated. This is of particular concern in Minnesota. The sun's intensity at Minnesota's latitudes limits vitamin D production, at best, to March through October. A variety of lifestyle situations, including long work hours, may preclude adequate sun exposure. Additionally, people of Northern European background may avoid sun exposure to reduce risk of skin cancer and premature aging. And people of Asian and African heritage may not have sufficient vitamin D production due to increased skin pigmentation. This brief article summarizes key points regarding the importance of vitamin D, including its action as a steroid hormone and its role in cancer, hypertension, and autoimmune disease as well as in perinatal and prenatal health. The potential benefit of hypovitaminosis D screening and vitamin D supplementation is discussed, as are the populations most likely to need screening and supplementation.
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PMID:Vitamin D--the steroid hormone prescription for every patient. 1258 59

Insulin-dependent diabetes mellitus (type 1 diabetes) is an inflammatory autoimmune disease associated with vascular permeability changes leading to many complications including nephropathy, retinopathy, neuropathy, hypertension and hyperalgesia. The bradykinin B(1) receptors (BKB(1)-R) were recently found to be upregulated alongside the development of type 1 diabetes and to be involved in its complications. Kinins are important mediators of a variety of biological effects including cardiovascular homeostasis, inflammation and nociception. In the present study, we studied the effect of a selective BKB(1)-R agonist desArg(9)-BK (DBK) and two selective receptor antagonists, the R-715 (Ac-Lys-[D-beta Nal(7), Ile(8)] desArg(9)-BK) and the R-954 (Ac-Orn-[Oic(2), alphaMe Phe(5), D-beta Nal(7), Ile(8)] desArg(9)-BK) on diabetic hyperalgesia. Type 1 diabetes was induced in male CD-1 mice via a single injection of streptozotocin (STZ, 200mg/kg, i.p.), one week before the test. Nociception, a measure of hyperalgesia, was assessed using the plantar stimulation (Hargreaves) and the tail-immersion tests. The induction of type 1 diabetes provoked a significant hyperalgesic activity in diabetic mice, causing an 11% decrease in plantar stimulation reaction time and 13% decrease in tail-immersion reaction time, compared to normal mice. Following acute administration of R-715 (100-600 microg/kg, i.p.), or R-954 (50-400 microg/kg, i.p.), the STZ-induced hyperalgesic activity was blocked in a dose-dependent manner and the hot plate and tail-immersion latencies of diabetic mice returned to normal values observed in control healthy mice. In addition, the acute administration of DBK (400 microg/kg, i.p.) significantly potentiated diabetes-induced hyperalgesia, an effect that was totally reversed by R-715 (1.6-2.4 mg/kg, i.p.) and R-954 (0.8-1.2mg/kg, i.p.). These results provide further evidence for the implication of the BKB(1)-R in type 1 diabetic hyperalgesia and suggest a novel approach in the treatment of this complication using the BKB(1)-R antagonists.
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PMID:Kinin B1 receptor antagonists inhibit diabetes-induced hyperalgesia in mice. 1263 34

Atherosclerosis is the major cause of cardiovascular disease (CVD) and in addition to established risk factors as smoking, hypertension, diabetes and dyslipidemia, inflammation and autoimmune reactions have been much discussed recently. Several lines of evidence indicate that also inflammation and autoimmune reactions are highly relevant in atherosclerosis and CVD. Inflammatory cells and cytokines are present in lesions, already at an early stage; animal experiments suggest that immune reactions, though not necessary for development of atherosclerosis, can modulate disease development and systemic inflammation is associated with an enhanced risk of CVD. The enhanced risk of CVD in a major autoimmune disease, systemic lupus erythematosus (SLE), is therefore highly relevant, and in addition to being an important clinical problem, SLE-related CVD could give insights into the nature of autoimmunity in atherosclerosis and CVD in general. We recently defined traditional and non-traditional risk factors for CVD in SLE. These include increased atherosclerosis (as determined by intima-media thickness of carotid artery); raised oxidized low density lipoprotein (OxLDL) and autoantibodies to OxLDL; dyslipidemia with raised triglycerides and Lp(a) and decreased HDL-cholesterol concentrations; raised systemic inflammation; presence of anti-phospholipid antibodies including lupus anticoagulant, homocysteine-levels and more frequent osteoporosis. Disease duration, smoking, blood pressure or diabetes mellitus did not differ significantly between the groups. Taken together, immune reactions are highly relevant in atherosclerosis, and patients with autoimmune disease like SLE are at high-risk of CVD. If confirmed prospectively, non-traditional risk factors like OxLDL in the circulation, autoantibodies against OxLDL and phospholipids and inflammation could lead to new therapeutic strategies and insight into disease mechanisms.
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PMID:Autoimmunity, oxidized LDL and cardiovascular disease. 1284 1

The May 2003 COM. A 57-year-old woman presented with slurring of her speech and right arm weakness. Her past medical history included idiopathic hypertrophic subendocardial stenosis (IHSS), arthritis, asthma, congestive heart failure, hypertension and NIDDM. Neurological examination showed persistent word finding difficulty but her motor and sensory function had essentially returned to normal. Extensive laboratory studies were unrevealing. Imaging studies showed a meningeal lesion over the left posterior parietal lobe and the findings suggested an infectious or inflammatory process. A biopsy of the involved dura and meninges was performed and revealed leptomeningeal Rosai-Dorfman disease. Emperipolesis was noted. The finding of emperipolesis is characteristic of Rosai-Dorfman disease of the leptomeninges, but in 30% of cases, this feature will not be identified. Large pale histiocytes of Rosai-Dorfman disease are immunoreactive for S-100 protein and KP1, but negative for CD1a. The differential diagnosis of a chronic inflammatory infiltrate containing numerous, large histiocytes includes granulomatous diseases such as Wegener graulomatosis and sarcoid, Hodgkin disease, and Langerhans histiocytosis. CNS Rosai-Dorfman most commonly involves patients between 20- and 40-years-old, with a slight male predominance. Approximately 75% of cases are intracranial, whereas 20% involve the spine. Over 90% of CNS Rosai-Dorfman cases involve the leptomeninges and are seen by neuroimaging as a dural-based, contrast-enhancing masses that often elicit vasogenic edema in the underlying brain. Thus, clinically and radiologically, the disease is thought to represent meningioma. Leptomeningeal Rosai-Dorfman disease is considered a benign condition and in most cases surgical resection is the treatment of choice. Although the number of cases in the literature is small, disease progression following surgical resection is uncommon. Little is known regarding the pathogenesis of Rosai-Dorfman disease. Most have suggested that it represents either an autoimmune disease or a reaction to an infectious agent that has yet to be discovered. Currently it is best considered a benign, idiopathic histiocytosis.
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PMID:May 2003: 57-year-old-woman with acute loss of strength in her right upper extremity and slurred speech. 1465 68

Atherosclerosis may be considered an inflammatory disease characterised by the development of atherosclerotic plaques and ischaemic cardiovascular events. Increased prevalence of cardiovascular morbidity and mortality due to (premature) atherosclerosis has been observed in patients with autoimmune diseases like rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and Wegener's granolumatosis. This increased prevalence cannot be explained by the presence of the traditional cardiovascular risk factors such as hypertension, hyperlipidaemia, diabetes mellitus and smoking. Therefore, other risk factors must be present in patients with systemic autoimmune disease. Although the mechanisms have not been fully unravelled, endothelial cell (EC) activation through autoantibodies seems to be one of the factors involved. EC activation results in EC dysfunction. It is supposed that chronic EC dysfunction, as present in patients with systemic autoimmune disorders, contributes to the development of premature atherosclerosis and results in an increased prevalence of cardiovascular disease.
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PMID:Endothelial activation, endothelial dysfunction and premature atherosclerosis in systemic autoimmune diseases. 1469 39

Systemic lupus erythematosus (SLE) is a multifactorial polysystemic autoimmune disorder. Although life expectance in SLE has been improved by adequate immune suppressive therapy, the importance of chronic renal failure has not been reduced. Among late complications of the disease accelerated atherosclerosis attempts increasing attention. Dyslipoproteinemia and increased concentration of lipoproteins are important risk factors of atherosclerotic cardiovascular complication in SLE. Serum lipid parameters of 50 patients with lupus were examined in the present work. Thirty patients had histologically proven lupus nephritis (LN+), while the other group did not have renal involvement (LN-). Serum triglyceride, total cholesterol, LDL-C and apolipoprotein B (apoB) concentrations were significantly higher in the lupus nephritis (LN+) group. On the other hand, HDL-C and apoAI levels were also elevated in patients with LN. As a consequence of that, LDL-C/HDL-C and the apoB/apoAI ratios did not differ between patients with or without kidney involvement. This concluded the authors to measure the concentration of lipoprotein (a) in SLE patients, as Lp(a) is known to be an independent risk factor of atherosclerosis. Results indicated a significantly increased Lp(a) concentration in patients with lupus nephritis as compared to the LN- group. All but 2 patients without kidney involvement had lower than 100 mg/L Lp(a) concentration, while 27% of patients with lupus nephritis has an Lp(a) level between 100-300 mg/L. Further more, Lp(a) concentration was higher than 300 mg/L in 13% of the LN+ group. In a good correlation of these observations patients with nephritis suffered more frequently from deep venous thrombosis and ischaemic heart disease. The frequencies of hypertension and non-insulin dependent diabetes mellitus were slightly elevated in patients with nephritis. Present results suggest the importance of elevated lipoprotein (a) concentration in patients with lupus nephritis, further increasing the risk of athero-thrombotic cardiovascular complications.
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PMID:[Lipid profile in patients with systemic lupus erythematosus, with special focus on lipoprotein(a) in lupus nephritis]. 1502 32

Psychiatric manifestations are frequently associated with pernicious anemia including depression, mania, psychosis, dementia. We report a case of a patient with vitamin B12 deficiency, who has presented severe depression with delusion and Capgras' syndrome, delusion with lability of mood and hypomania successively, during a period of two Months. Case report - Mme V., a 64-Year-old woman, was admitted to the hospital because of confusion. She had no history of psychiatric problems. She had history of diabetes, hypertension and femoral prosthesis. The red blood count revealed a normocytosis with anemia (hemoglobin=11,4 g/dl). At admission she was uncooperative, disoriented in time and presented memory and attention impairment and sleep disorders. She seemed sad and older than her real age. Facial expression and spontaneous movements were reduced, her speech and movements were very slow. She had depressed mood, guilt complex, incurability and devaluation impressions. She had a Capgras' syndrome and delusion of persecution. Her neurologic examination, cerebral scanner and EEG were postponed because of uncooperation. Further investigations confirmed anemia (hemoglobin=11,4 g/dl) and revealed vitamin B12 deficiency (52 pmol/l) and normal folate level. Antibodies to parietal cells were positive in the serum and antibodies to intrinsic factor were negative. An iron deficiency was associated (serum iron=7 micromol/l; serum ferritin concentration=24 mg/l; serum transferrin concentration=3,16 g/l). This association explained normocytocis anemia. Thyroid function, hepatic and renal tests, glycemia, TP, TCA, VS, VDRL-TPHA were normal. Vitamin B12 replacement therapy was started with hydroxycobalamin 1 000 ng/day im for 10 days and iron replacement therapy. Her mental state improved dramatically within a few days. After one week of treatment the only remaining symptoms were lability of mood, delusion of persecution, Capgras' syndrome but disappeared totally 9 days after the beginning of the treatment. A neurologic examination was possible because of cooperation. All the tendon reflexes of inferior members were absent. The plantars were in flexion and there was a left inferior member hypoesthesia. The cerebral scan and EEG were normal. Fundic biopsy, realized by fibroscopy, revealed fundic atrophia and intestinal metaplasia compatible with Biermers' disease. The iron deficiency exploration concluded diet deficiency. Mme V. appeared euphoric, her speech was very rapid with play on words and overactivity. This hypomania state totally disappeared 3 days after. Six Months after her hospitalisation, she presented an hypothyroidism (TSH=3,780; T3=1,35; T4=1,08). A thyroid hormones replacement was started and she continued to receive Monthly B12 replacement. Discussion - This case report illustrates psychiatric manifestations of Biermers' disease. The clinical arguments in favour are: white woman, more than 60 Years old, no history of psychiatric problems, atypical symptoms (confusional state with psychiatric symptoms), fluctuation of symptoms (severe depression with confusional state, delusion of persecution and Capgras' syndrome; delusion with lability of mood and hypomania), dramatic improvement after 9 days of vitamin B12 replacement therapy. The biological arguments are: anemia, vitamin B12 deficiency, normal folate level, atrophia and fundic metaplasia, positive antibodies to parietal cells in the serum, association between Biermers' disease and autoimmune disease (Haschimoto thyroidite). Psychiatric manifestations can occur in the presence of low serum B12 levels but in the absence of the other well recognized neurological and haematological abnormalities of pernicious anemia. Mental or psychological changes may precede haematological signs by Months or Years. They can be the initial symptoms or the only ones. Verbank et al. described the case of a patient with vitamin B12 deficiency in whom hypomania, paranoia and depression had been successively presented during a period of 5 Years before anemia have been developed. The case of Mme V. is similar in the succession of severe depression with delusion of persecution and Capgras' syndrome, delusion with lability of mood and hypomania, during a period of two Months. This report seems to be the first one of a sequence of several psychiatric states with pernicious anemia during a period of two Months with normocytosis anemia. To illustrate this illness we reviewed the literature regarding psychopathology associated with B12 deficiency. The most common psychiatric symptoms were depression, mania, psychotic symptoms, cognitive impairment and obsessive compulsive disorder. The neuropsychiatric severity by vitamin B12 deficiency and the therapeutic efficacy depends on the duration of signs and symptoms. Conclusion - We recommend consideration of B12 deficiency and serum B12 determinations in all the patients with organic mental disorders, atypical psychiatric symptoms and fluctuation of symptomatology. B12 levels should be evaluated with treatment resistant depressive disorders, dementia, psychosis or risk factors for malnutrition such as alcoholism or advancing age associated with neurological symptoms, anemia, malabsorption, gastrointestinal surgery, parasite infestation or strict vegetarian diet. In first intention, B12 deficiency should be researched by serum B12 determination (normal 200-950 pg/ml). Studies of methylmalonic acid and homocysteine showed that they are very sensitive functional indicators of cobalamin status especially when other evidence of cobalamin (B12) deficiency was equivocal. Measurement of methylmalonic acid (normal 73-271 nmol/l) and homocysteine (normal 5,4-13,9 micromol/l) should not replace the measurement of serum cobalamin.
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PMID:[Psychiatric manifestations of vitamin B12 deficiency: a case report]. 1502 91


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