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

The white adipose tissue, especially of humans, is now recognized as the central player in the mild inflammatory state that is characteristic of obesity. The question is how the increased accumulation of lipid seen in obesity causes an inflammatory state and how this is linked to the hypertension and type 2 diabetes that accompanies obesity. Once it was thought that adipose tissue was primarily a reservoir for excess calories that were stored in the adipocytes as triacylglycerols. In times of caloric deprivation these stored lipids were mobilized as free fatty acids and the insulin resistance of obesity was attributed to free fatty acids. It is now clear that in humans the expansion of adipose tissue seen in obesity results in more blood vessels, more connective tissue fibroblasts, and especially more macrophages. There is an enhanced secretion of some interleukins and inflammatory cytokines in adipose tissue of the obese as well as increased circulating levels of many cytokines. The central theme of this chapter is that human adipose tissue is a potent source of inflammatory interleukins plus other cytokines and that the majority of this release is due to the nonfat cells in the adipose tissue except for leptin and adiponectin that are primarily secreted by adipocytes. Human adipocytes secrete at least as much plasminogen activator inhibitor-1 (PAI-1), MCP-1, interleukin-8 (IL-8), and IL-6 in vitro as they do leptin but the nonfat cells of adipose tissue secrete even more of these proteins. The secretion of leptin, on the other hand, by the nonfat cells is negligible. The amount of serum amyloid A proteins 1 & 2 (SAA 1 & 2), haptoglobin, nerve growth factor (NGF), macrophage migration inhibitory factor (MIF), and PAI-1 secreted by the adipocytes derived from a gram of adipose tissue is 144%, 75%, 72%, 37%, and 23%, respectively, of that by the nonfat cells derived from the same amount of human adipose tissue. However, the release of IL-8, MCP-1, vascular endothelial growth factor (VEGF), TGF-beta1, IL-6, PGE(2), TNF-alpha, cathepsin S, hepatocyte growth factor (HGF), IL-1beta, IL-10, resistin, C-reactive protein (CRP), and interleukin-1 receptor antagonist (IL-1Ra) by adipocytes is less than 12% of that by the nonfat cells present in human adipose tissue. Obesity markedly elevates the total release of TNF-alpha, IL-6, and IL-8 by adipose tissue but only that of TNF-alpha is enhanced in adipocytes. However, on a quantitative basis the vast majority of the TNF-alpha comes from the nonfat cells. Visceral adipose tissue also releases more VEGF, resistin, IL-6, PAI-1, TGF-beta1, IL-8, and IL-10 per gram of tissue than does abdominal subcutaneous adipose tissue. In conclusion, there is an increasing recognition that adipose tissue is an endocrine organ that secretes leptin and adiponectin along with a host of other paracrine and endocrine factors in addition to free fatty acids.
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PMID:Release of interleukins and other inflammatory cytokines by human adipose tissue is enhanced in obesity and primarily due to the nonfat cells. 1702 26

The present study was performed to assess the prophylactic effect of baicalin, a flavonoid compound, in an animal model of heatstroke. Anesthetized rats, immediately before the start of heat stress, were divided into two major groups and given the following: vehicle solution (1mL per kg body weight) or baicalin (10-40mg per kg body weight) intravenously. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats was exposed to room temperature (24 degrees C) and used as normothermic controls. Their physiologic and biochemical parameters were continuously monitored. When the vehicle-pretreated rats underwent heat stress, their survival time values were found to be 20-28min. Pretreatment with intravenous doses of baicalin significantly improved survival during heatstroke (65-248min). As compared to those of normothermic controls, all vehicle-pretreated heatstroke animals displayed higher levels of core temperature, intracranial pressure, and nitric oxide metabolite (NO(2)(-)), glutamate, glycerol, lactate/pyruvate ratio, and dihydroxybenzoic acid (DHBA) in hypothalamus. In addition, both serum and hypothalamic levels of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) as well as plasma levels of creatinine, serum urea nitrogen, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and alkaline phosphatase were elevated after heatstroke onset. In contrast, all vehicle-pretreated heatstroke animals had lower levels of mean arterial pressure, cerebral perfusion pressure, cerebral blood flow, and brain PO(2). Administration of baicalin before the start of heat exposure significantly reduced the hyperthermia, intracranial hypertension, and the increased levels of NO(2)(-), glutamate, glycerol, lactate/pyruvate ratio, and DHBA in the hypothalamus that occurred during heatstroke. The heatstroke-induced increased levels of IL-1beta and TNF-alpha in both the serum and hypothalamus, and renal and hepatic dysfunction were suppressed by baicalin pretreatment. In contrast, both the serum and hypothalamic levels of IL-10 were significantly elevated by baicalin during heatstroke. We successfully demonstrated that baicalin can be used as a prophylactic agent for heatstroke. In particular, baicalin may protect against cerebrovascular dysfunction and brain inflammation in heatstroke.
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PMID:The flavonoid baicalin protects against cerebrovascular dysfunction and brain inflammation in experimental heatstroke. 1720 94

Atherosclerosis is a chronic inflammatory disease in the intima of the arterial wall, where cytokines play a crucial role in the pathogenesis of this disease. However, the question of whether or not genetic variations in the cytokine genes could influence the development of atherosclerosis has been poorly investigated. We investigated the relationship of nine common single-nucleotide polymorphisms (SNPs) in tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-10, IL-4 and transforming growth factor (TGF)-beta1 with the atherosclerotic severity in 10 different arteries based on 1503 consecutive autopsies of elderly Japanese subjects registered in the Japanese SNPs for geriatric research (JG-SNP) study. The -1031C allele of TNF-alpha was a significant protective factor for atherogenesis in the carotid, femoral and intracranial arteries [odds ratio (OR): 0.72, 0.73 and 0.70, respectively]. The -511T of IL-1beta and the +29T of TGF-beta1 were significant risk factors for atherogenesis in the subclavian and intracranial arteries (OR: 1.35 and 1.48, respectively). In contrast, conventional risk factors for atherogenesis, such as hypertension and diabetes mellitus, conferred independent risks for almost all arteries. Functional SNPs in TNF-alpha, IL-1beta and TGF-beta1 genes play a role in atherogenesis, although their influences are less pronounced than those of conventional risk factors and appear to be limited to specific arteries in the Japanese elderly.
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PMID:Polymorphisms in pro- and anti-inflammatory cytokine genes and susceptibility to atherosclerosis: a pathological study of 1503 consecutive autopsy cases. 1721 32

Headache and/or migraine, a common problem in pediatrics and internal medicine, affect about 5% to 10% children and adolescents, and nearly 30% of middle-aged women. Headache is also one of the most common clinical manifestations of acquired Toxoplasma gondii infection of the central nervous system (CNS) in immunosuppressed subjects. We present 11 apparently nonhuman immunodeficiency virus-infected children aged 7 to 17 years (8 girls, 3 boys) and 1 adult woman with recurrent severe headaches in whom latent chronic CNS T. gondii infection not manifested by enlarged peripheral lymph nodes typical for toxoplasmosis, was found. In 7 patients, the mean serum IgG Toxoplasma antibodies concentration was 189 +/- 85 (SD) IU/mL (range 89 to 300 IU/mL), and in 5 other subjects, the indirect fluorescent antibody test titer ranged from 1:40 to 1:5120 IU/mL (n= <1:10 IU/mL). Some of the patients suffered also from atopic dermatitis (AD) and were exposed to cat and/or other pet allergens, associated with an increased IL-4 and decreased IFN-gamma production. These cytokine irregularities caused limited control of cerebral toxoplasmosis probably because IL-4 down-regulated both the production of IFN-gamma and its activity, and stimulated production of a low NO-producing population of monocytes, which allowed cysts rupture, increased parasite multiplication and finally reactivation of T. gondii infection. The immune studies performed in 4 subjects showed a decreased percentage of T lymphocytes, increased total number of lymphocytes B and serum IgM concentration, and impaired phagocytosis. In addition, few of them had also urinary tract diseases known to produce IL-6 that can mediate immunosuppressive functions, involving induction of the anti-inflammatory cytokine IL-10. These disturbances probably resulted from the host protective immune reactions associated with the chronic latent CNS T. gondii infection/inflammation. This is consistent with significantly lower enzyme indoleamine 2,3-dioxygenase (IDO) activity reported in atopic than in nonatopic individuals, and an important role that IDO and tryptophan degradation pathways plays in both, the host resistance to T. gondii infection and its reactivation. Analysis of literature information on the subjects with different types of headaches caused by foods, medications, and other substances, may suggest that their clinical symptoms and changes in laboratory data result at least in part from interference of these factors with dietary tryptophan biotransformation pathways. Several of these agents caused headache attacks through enhancing NO production via the conversion of arginine to citrulline and NO by the inducible nitric oxide synthase enzyme, which results in the high-output pathway of NO synthesis. This increased production of NO is, however, quickly down-regulated by NO itself because this biomolecule can directly inactivate NOS, may inhibit Ia expression on IFN-gamma-activated macrophages, which would limit antigen-presenting capability, and block T-cell proliferation, thus decreasing the antitoxoplasmatic activity. Moreover, NO inhibits IDO activity, thereby suppressing kynurenine formation, and at least one member of the kynurenine pathway, 3-hydroxyanthranilic acid, has been shown to inhibit NOS enzyme activity, the expression of NOS mRNA, and activation of the inflammatory transcription factor, nuclear factor-kB. In addition, the anti-inflammatory cytokines IL-4 and IL-10, TGF-beta, and a cytokine known as macrophage deactivating factor, have been shown to directly modulate NO production, sometimes expressing synergistic activity. On the other hand, IL-4 and TGF-beta can suppress IDO activity in some cells, for example human monocytes and fibroblasts, which is consistent with metabolic pathways controlled by IDO being a significant contributor to the proinflammatory system. Also, it seems that idiopathic intracranial hypertension, pseudotumor cerebri, and aseptic meningitis, induced by various factors, may result from their interference with IDO and inducible nitric oxide synthase activities, endogenous NO level, and cytokine irregularities which finally affect former T. gondii status 2mo in the brain. All these biochemical disturbances caused by the CNS T. gondii infection/inflammation may also be responsible for the relationship found between neurologic symptoms, such as headache, vertigo, and syncope observed in apparently immunocompetent children and adolescents, and physical and psychiatric symptoms in adulthood. We therefore believe that tests for T. gondii should be performed obligatorily in apparently immunocompetent patients with different types of headaches, even if they have no enlarged peripheral lymph nodes. This may help to avoid overlooking this treatable cause of the CNS disease, markedly reduce costs of hospitalization, diagnosis and treatment, and eventually prevent developing serious neurologic and psychiatric disorders.
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PMID:Recurrent headache as the main symptom of acquired cerebral toxoplasmosis in nonhuman immunodeficiency virus-infected subjects with no lymphadenopathy: the parasite may be responsible for the neurogenic inflammation postulated as a cause of different types of headaches. 1730 77

Multiorgan dysfunction ensuing from severe heatstroke includes hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. We attempted to assess whether human umbilical cord blood-derived CD34+ cell therapy improves survival during experimental heatstroke by attenuating multiorgan dysfunction. Anesthetized rats, immediately after the onset of heatstroke, were divided into 2 major groups and given CD34- or CD34+ cells (1 x 10(5)-5 x 10(5)/mL/kg body weight) i.v. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats were exposed to room temperature (26 degrees C) and used as normothermic controls. Hypotension, hepatic and renal failure (evidenced by increased serum urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels in plasma), hypercoagulable state (evidenced by increased prothrombin time, activated partial thromboplastin time, and D-dimer, and decreased platelet count and protein C in plasma), activated inflammation (evidence by increased TNF-alpha levels in serum), and cerebral dysfunction (evidenced by intracranial hypertension, cerebral hypoperfusion and hypoxia, and cerebral ischemia and injury) were monitored. When the CD34- cell-treated or untreated rats underwent heat stress, their survival time values were found to be 19 to 23 min. Resuscitation with CD34+ cells significantly improved survival time (duration, 63-291 min). As compared with normothermic controls, all CD34- cell-treated heatstroke animals displayed hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. However, CD34+ cell therapy significantly caused attenuation of all the above-mentioned heatstroke reactions. In addition, the levels of IL-10 in plasma and glial cell line-derived neurotrophic factors in brain were all significantly increased after CD34+ cell therapy during heatstroke. Our data indicate that CD34+ cell therapy may resuscitate persons who had a heatstroke by reducing multiorgan dysfunction or failure.
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PMID:Human umbilical cord blood-derived CD34+ cells cause attenuation of multiorgan dysfunction during experimental heatstroke. 1750 7

Obesity is a major risk factor for hypertension, coronary artery disease and type 2 diabetes. Weight loss is associated with significant metabolic benefits. Our objective was to examine changes in adipocytokines and interleukin (IL) 10 in obese subjects before and after weight loss. We measured anthropometric parameters, adipocytokine and IL-10 in 78 obese people who had visited obesity clinics at five university hospitals (Ajou, Ulsan, Catholic, Hanyang and Yonsei) in Korea. They restricted their caloric intake to less than their usual intake (by 500 kcal), were administered sibutramine and were given a program of exercise for 12 weeks. After 12 weeks, weight, body mass index, waist circumference, hip circumference, waist-to-hip ratio, total body fat, total cholesterol, triglyceride, tumor necrosis factor alpha (TNF-alpha), IL-6, resistin and leptin had significantly decreased, while adiponectin and IL-10 had significantly increased. A bivariate correlation analysis found that increment in IL-10 and baseline IL-10 levels significantly correlated with decrement in TNF-alpha (P<.01) and baseline adiponectin (r=.52, P<.001), respectively. These results were confirmed in a multiple regression analysis. The results suggest that weight loss after caloric restriction and medical treatment in obesity can improve metabolic risk factors through changes in some cytokines.
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PMID:Effect of weight loss on some serum cytokines in human obesity: increase in IL-10 after weight loss. 1761 71

The role of pregnancy in the progression of systemic lupus erythematosus (SLE) is still poorly understood. We analysed the effect of repeated pregnancies in MRL/lpr mice, a murine model of SLE. Seven-week old female mice were used: multiparous mice underwent three consecutive pregnancies (M); age-matched virgin mice served as controls (V). Animals were harvested at 20 weeks of age. Skin lesions were characterized by hair loss and scabs in the dorsum of the neck. Virgin skins showed thickened dermis, fibrosis and mononuclear cell infiltrates, which were practically absent in M. This was accompanied by higher IFN-gamma and lower IL-10 mRNA expression levels in V compared to M skin. Plasma IFN-gamma protein levels were also upregulated in V versus M. However, survival and kidney function were dramatically reduced and accompanied by hypertension after multiple pregnancies. Kidney histology also showed markedly increased renal lesions in M. In contrast to plasma and skin levels, both IL-10 and IFN-gamma mRNA were lower in the kidneys of V versus M mice. Concluding our findings, the pathomechanisms of lupus kidney and skin disease may be regulated differently at the organ level during pregnancy. Both IFN-gamma and IL-10 may be important regulatory cytokines at the local level.
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PMID:Skin disease is prevented but nephritis is accelerated by multiple pregnancies in autoimmune MRL/LPR mice. 1767 Aug 44

Cerebrovascular dysfunction ensuing from severe heatstroke includes intracranial hypertension, cerebral hypoperfusion, and brain inflammation. We attempted to assess whether L-arginine improves survival during experimental heatstroke by attenuating these reactions. Anesthetized rats, 70 min after the start of heat stress (43 degrees C), were divided into two major groups and given the following: vehicle solution (1 mL/kg body weight) or L-arginine (50-250 mg/kg body weight) intravenously. Another group of rats was exposed to room temperature (24 degrees C) and used as normothermic controls. Their physiological and biochemical parameters were continuously monitored. When the vehicle-treated rats underwent heat stress, their survival time values were found to be 20 to 26 min. Treatment with i.v. doses of L-arginine significantly improved the survival rate during heatstroke (54-245 min). As compared with those of normothermic controls, all vehicle-treated heatstroke animals displayed higher levels of core temperature, intracranial pressure, and NO metabolite, glutamate, glycerol, lactate-pyruvate ratio, and dihydroxybenzoic acid in hypothalamus. In addition, hypothalamic levels of IL-1beta and TNF-alpha were elevated after heatstroke onset. In contrast, all vehicle-treated heatstroke animals had lower levels of MAP, cerebral perfusion pressure, cerebral blood flow, and brain partial pressure of oxygen. Administration of L-arginine immediately after the onset of heatstroke significantly reduced the intracranial hypertension and the increased levels of NO metabolite, glutamate, glycerol, lactate-pyruvate ratio, and dihydroxybenzoic acid in the hypothalamus that occurred during heatstroke. The heatstroke-induced increased levels of IL-1beta and TNF-alpha in the hypothalamus were suppressed by L-arginine treatment. In contrast, the hypothalamic levels of IL-10 were significantly elevated by L-arginine during heatstroke. The results suggest that L-arginine may cause attenuation of heatstroke by reducing cerebrovascular dysfunction and brain inflammation.
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PMID:L-arginine causes amelioration of cerebrovascular dysfunction and brain inflammation during experimental heatstroke. 1769 25

The long search of an animal model for leprosy were carried out as many researchers since the Mycobacterium leprae discovery by Dr. Hansen in 1874. The remarkable results were left after the development of the foot-pad method by Dr. Shepard in 1960. The introduction of the T-R mouse and athymic (nude) mouse for leprosy research, alsospontaneity examples of Hansen's disease was reported to armadillo, chimpanzee and mangabay monkey, and it was confirmed that Hansen's disease was the zoonosis. Although, We have established a congenic hypertensive nude rat, SHR/NCrj-rnu (SHR.F344-Foxn(rnu)), carrying nude (rnu) and hypertension genes. SHR/NCrj-rnu rats obtained showed high susceptibility to M. leprae and showed a characteristic disease with a progressive pattern of leproma formation. Also this hypertensive nude rat strain produce high level of IL-10. Therefore, congenic hypertensive nude rat may be useful for an animal model to leprosy.
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PMID:[History for animal model of Hansen's disease and characteristics of leprosy in hypertensive nude rat]. 1880 Jun 40

The aim of the present study was to determine the rates of stroke in patients with chronic NVAF (non-valvular atrial fibrillation), evaluating the relationship between plasma levels of inflammatory variables at admission and the occurrence of stroke during a 3-year follow-up. A total of 373 consecutive patients with chronic NVAF were enrolled. Blood samples were drawn within 72 h of admission, and we evaluated plasma levels of IL (interleukin)-1beta, TNF-alpha (tumour necrosis factor-alpha), IL-6, IL-10, E-selectin, P-selectin, ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1) and vWF (von Willebrand Factor). Subsequent patient events (stroke at follow-up) were monitored over a 3 year period. By multivariate analysis, only age, hypertension and high levels of IL-6, TNF-alpha and vWF remained significant predictors of a higher risk of experiencing ischaemic stroke at follow-up. Moreover, plasma values of TNF-alpha, IL-6 and vWF had a significant area under the ROC (receiver operating characteristic) curve. In conclusion, baseline plasma levels of TNF-alpha, IL-6 and vWF are predictors of new-onset ischaemic stroke at follow-up in patients with chronic NVAF.
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PMID:Immuno-inflammatory predictors of stroke at follow-up in patients with chronic non-valvular atrial fibrillation (NVAF). 1898 May 76


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