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1.
Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease which is characterized by dysregulation of various cytokines propagating the inflammatory processes that is responsible for tissue damage. Tumor necrosis factor alpha (TNF-α) is one of the most important immunoregulatory cytokines that has been implicated in the different autoimmune diseases including SLE. Two hundred and two patients with SLE and 318 controls were included in the study. The TNF-α gene promoter region (from − 250 to − 1000 base pairs) was analyzed by direct Sanger’s DNA sequencing method to find promoter variants associated with South Indian SLE patients. We have analyzed six TNF-α genetic polymorphisms including, − 863C/A (rs1800630), − 857C/T (rs1799724), − 806C/T (rs4248158), − 646G/A (rs4248160), − 572A/C (rs4248161) and − 308G/A (rs1800629) in both SLE patients and controls. We did not find association of TNF-α gene promoter SNPs with SLE patients. However, the − 863A (rs1800630) allele showed association with lupus nephritis phenotype in patients with SLE (OR: 1.62, 95%CI 1.04–2.53, P = 0.034). We found serum TNF-α level was significantly elevated in SLE cases as compared to control and found no association with any of the polymorphisms. The haplotype analysis revealed a significant protective association between the wild TNF-α alleles at positions − 863C, − 857C, − 806C, − 646G, − 572A and − 308G (CCCGAG) haplotype with lupus nephritis phenotype (OR 0.53, 95% CI 0.35–0.82, P = 0.004). Additionally, the TNF-α − 863 C/A (rs1800630) polymorphism and HLA-DRB1*07 haplotype showed significant differences between SLE patients and controls (OR 4.79, 95% CI 1.73–13.29, P = 0.0009). In conclusion, TNF-α − 863A allele (rs1800630) polymorphism is associated with increased risk of nephritis in South Indian SLE patients. We also found an interaction between HLA-DRB1*07 allele with TNF-α − 863 C/A promoter polymorphism giving supportive evidence for the tight linkage disequilibrium between TNF-α promoter SNPs and MHC class II DRB1 alleles.  相似文献   

2.

Introduction:

The aim of this study was to investigate whether serum levels of interleukin-1β (IL–1β) has any possible correlation on inflammatory parameters such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and fibrinogen concentration in patients with familial Mediterranean fever (FMF) patients during attack-free period.

Materials and methods:

The serum levels of IL-1β, as an indicator of cytokines status, and the acute phase response proteins, CRP, ESR and fibrinogen levels were evaluated in 35 attack-free patients with FMF and 25 healthy volunteers.

Results:

Serum IL-1β levels were significantly higher in patients with FMF than control subjects (P = 0.018). There was no statistically significant difference in the serum levels of ESR, CRP and fibrinogen between two groups (P = 0.181, P = 0.816, P = 0.686, respectively). There was a significant correlation between IL-1β and CRP (r = 0.513, P = 0.002) values of FMF group.

Conclusions:

In conclusion, our results confirm the presence of increased IL-1β levels in FMF patients during attack-free period. Serum IL-1β values seems to correlate with CRP levels. The elevation of IL-1β levels may be important in monitoring subclinical inflammation of attack free period in FMF patients.  相似文献   

3.
Metabolic syndrome (MetS) results from the derangement of adipocyte physiology and carbohydrate metabolism. Obesity and insulin resistance (IR) are integral features of MetS. The adipokine alterations in MetS often correlate with IR and body fat content. High adipose tissue content is associated with a decreased production of adiponectin and excessive production of tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6), all of which induce IR. The present study evaluated the adipokine alterations in MetS and their association with IR. The findings of the current study indicate that MetS is associated with significant decrease in adiponectin and increase in TNF-α and IL-6. The present study also found that the adipocyte derived inflammatory adipokines, TNF-α and IL-6 correlate with IR while the anti-inflammatory adipokines, adiponectin does not correlate with the degree and severity of IR.  相似文献   

4.
In recent years, an important objective of cardiovascular research has been to find new markers that would improve the risk stratification and diagnosis of patients presenting with symptoms of acute coronary syndrome (ACS). Established biomarkers for diagnosis of ACS includes troponins and creatine kinase MB (CK-MB). Pregnancy associated plasma protein A (PAPP-A) is an emerging marker which has been described as a marker of plaque instability. PAPP-A is a large metalloproteinase involved in insulin-like growth factor signaling and has been shown to be involved in pathological processes like atherosclerosis. Many studies have been published regarding release of PAPP-A in circulation during ACS. The objective of this study was to evaluate the role of PAPP-A as an early marker of ACS by comparing levels of PAPP-A in patients with acute myocardial infarction (AMI) and unstable angina (UA) with asymptomatic controls. The association of PAPP-A with markers of myocardial necrosis and the association of PAPP-A levels to the presence of risk factors for coronary artery disease was also studied. We measured PAPP-A levels in patients with AMI (30), UA (23) and asymptomatic controls (45). PAPP-A was estimated using PAPP-A US (ultra sensitive) ELISA manufactured by DRG (Germany). PAPP-A levels were significantly elevated in patients with AMI and in patients with UA (mean levels 64.26 ± 1.05 and 36.23 ± 1.05 ng/ml respectively; p < 0.001). Mean PAPP-A levels in controls were 10.68 ± 1.04 ng/ml. In UA cases PAPP-A levels were elevated when the troponin I and CK-MB levels were within the normal range. No correlation was observed between PAPP-A with markers of myocardial necrosis. PAPP-A can serve as a useful biomarker in the diagnosis of ACS, especially UA, where cardiac troponin levels and CK-MB levels are not elevated and ECG changes are inconclusive.  相似文献   

5.
Thrombotic risk factors may contribute to premature coronary artery disease (CAD), in addition to the conventional risk factors. There is paucity of data on studies evaluating the role of thrombotic factors in premature CAD in Indian patients. Thus a case–control study was performed to evaluate the role of thrombotic and atherogenic factors in young patients with angiographically proven CAD who are on treatment with statins and anti-platelet drugs. 152 patients (≤55 years) with angiographically proven CAD and 102 asymptomatic controls were recruited. Clinical and biochemical data were obtained in both groups. Blood levels of thrombotic factors-fibrinogen, antithrombin-III, tissue-plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), von-Willebrand factor (v-WF), lipoprotein(a) [Lp(a)] and homocysteine were analyzed. Patients had high levels of conventional CAD risk factors (diabetes mellitus, smoking, hypertension, dyslipidemia and positive family history) compared to controls. Logistic regression analysis revealed that low antithrombin-III (odds ratio/OR 11.2; 95 % confidence interval/CI 2.29–54.01), high fibrinogen (OR 6.04; 95 % CI 1.09–33.21) and high Lp(a) (OR 4.54; 95 % CI 0.92–22.56), as important, independent risk factors in patients. PAI-1(OR 0.15; 95 % CI 0.03–0.69) levels were significantly lower in patients. But other thrombotic risk factors studied (t-PA, v-WF and homocysteine) were comparable among patients and controls. The treatment using statins and anti-platelet drugs might be contributing to the control of some of the thrombotic risk factors. The strategies aiming at lowering the levels of thrombotic risk factors along with conventional risk factors may be useful in primary and secondary prevention of CAD.  相似文献   

6.
Premature coronary artery disease (CAD) is common in India. We, therefore, studied oxidative stress, dyslipidemia, and high sensitivity-C reactive protein (hs-CRP) levels in young CAD patients. Present study consisted of male CAD patients below 40 years and age and sex matched healthy controls (n=30 each). Fasting blood samples were analyzed for serum lipid profile, malondialdehyde, antioxidant enzymes and hs-CRP levels. Dyslipidemia was observed in 90% of the young CAD patients, of which 72.2% showed increased serum triglycerides and decreased HDL-cholesterol. LDL-cholesterol levels were high in 77.8%. Serum malondialdehyde and hs-CRP levels were increased significantly (p<0.0001) as compared to controls. hs-CRP levels were in high risk range in all the young patients. However, glutathione peroxidase activity was reduced significantly (p<0.05). Our data suggests that elevated hs-CRP levels along with dyslipidemia and oxidative stress adds to the predictive value of premature CAD in young Indians.  相似文献   

7.
Nicotine, responsible for the addictive properties of tobacco, is widely used in nicotine replacement therapy for tobacco use cessation. We investigated the time-dependent effect of treatment with nicotine on the tumor suppressor, DNA repair and immune responses. Swiss Albino mice (laca strain) of both sexes received nicotine dissolved at a dose of 100 µg/ml in 2% sucrose for 24 weeks, by oral gavage, while age- and gender-matched controls received only 2% sucrose for the same period. Nicotine-treated and control mice were sacrificed 6, 16 and 24 weeks post-treatment, and their tissues evaluated for alterations in histology, oxidative stress, TNF-α levels, nitric oxide (NO) and myeloperoxidase (MPO) release, tumor suppressor response and DNA repair response. Statistical significance of results was determined using Students’ t test. The tissues of nicotine treated mice exhibited a large number of multinucleated and binucleated cells, enlarged nuclei and non-uniform distribution of cells, significant increase in expression of TNF-α gene and serum TNF-α, and time-dependent significant increase in lipid peroxidation, protein carbonylation, NO and MPO release when compared to age-and gender-matched controls. The mRNA expression of the tumor suppressor gene p53, its primary regulator Mdm2, and the DNA repair genes Brca2 and Ape1 were significantly elevated, but the corresponding protein levels remained largely unaltered. In conclusion, treatment with nicotine caused oxidative stress and inflammation which can cause widespread cellular damage from the very onset of treatment, without subverting the tumor suppressor and DNA repair responses.Electronic supplementary materialThe online version of this article (10.1007/s12291-020-00903-8) contains supplementary material, which is available to authorized users.  相似文献   

8.
Diabetes and tuberculosis are world’s most deadly epidemics. People suffering from diabetes are susceptible to tuberculosis. Molecular link between the two is largely unknown. It is known that Vitamin A receptor (RXR) heterodimerizes with Vitamin D receptor (VDR) and Peroxisome proliferator-activator receptor-γ (PPARγ) to regulate Tryptophan-aspartate containing coat protein (TACO) expression and fatty acid metabolism respectively, so it would be interesting to check the expression of these genes in diabetes mellitus (DM) patients which might explain the susceptibility of diabetics to tuberculosis. In this study, we checked the expression of RXR, VDR, TACO and Interferon-γ (IFNγ) genes in type-2 DM patients for understanding the link between the two diseases. We observed down regulation of RXR gene and corresponding up regulation of TACO gene expression. We have not observed significant change in expression of VDR and IFNγ genes in type-2 DM patients. Repression of RXR gene could hamper VDR-RXR heterodimer formation and thus would up regulate TACO gene expression which may predispose the type-2 DM patients to tuberculosis. Also, decrease in RXR-PPARγ heterodimer could be involved in DM.  相似文献   

9.
Methods for assaying lysosomal diseases in dried blood samples are very useful today due to its several advantages related to the stability of samples, its transportation, handled and analysis, and its potential use for newborn screening compared to traditional methods in leucocytes samples. For this reason, it is important to validate these assays before being used in routine laboratory. Because of different in biological markers based on ethnicity, we aimed this study to validation a DBS-based fluorometric assay for measurement of α-l-Iduronidase activity for diagnosis of MPS I patients in Iran. DBS samples were collected from 15 MPS I patients and 60 healthy age matched subjects. Diagnostic value, biological variance and α-l-Iduronidase activity were determined. DBS α-l-Iduronidase activity was significantly higher in male subjects than in female group. Using a cut-off level of 1.08 µmol/spot 20 h, sensitivity and specificity were 100 and 98 %. The linearity of test was proved and we showed that within-run and between run precision were 5.6 and 14.66 %. Measurement of α-l-Iduronidase activity in DBS samples is an accurate test for diagnosis of MPS I and because of its rapid shipping and simplicity to keeping, DBS-based enzyme activity could be considered as a useful diagnostic tool in this disease.  相似文献   

10.
Severe hemolytic anemia in β-thalassemia major and β-thalassemias/HbE (β-TM) patients requires giving blood transfusions. Chronic blood transfusions lead to iron overload consequence with organs damage and risk of alloantibody-formation. This study evaluates the prevalence of red cell alloimmunization and estimates the risk of alloantibody-formation in chronic transfusion-dependent β-TM patients. This cross sectional study was conducted on 143 β-TM patients receiving regular transfusions. We tried to determine the frequency, types and factors influencing red cell alloimmunization in these transfusion-dependent β-TM patients. Median age of 25 (17.5 %) alloantibody-formation β-TM patients was 19.0 years (inter quartile 15.5–24.0 years). The alloantibodies were Anti-Rh (E) (13.1 %), Anti-Rh (D) (0.7 %). Thirty-four patients (23.8 %) of the sample had splenectomies of which 10 (29.4 %) had alloantibody-formation. The interval from first transfusion to antibody development varied from 1.5 to 14 years. Alloantibody-formation correlated with splenectomy and splenectomy correlated with number of transfusion (p < 0.005). In multiple logistic regression used to estimate the risk of alloantibodies formation with splenectomy; OR and 95 % CI were 2.88 (1.07–7.80), p = 0.037 after adjusting for other co-variates. The rate of red cell alloimmunization was 17.5 % and splenectomy associated with increased alloantibody-formation in these transfusion-dependent β-TM patients.  相似文献   

11.
The main objective of this study is to evaluate the anti-hypertrophic potential of the aqueous extract of Enicostemma littorale (E. littorale) against isoproterenol induced cardiac hypertrophic rat models (male albino Wistar rats) through biochemical investigations. Aqueous extract of E. littorale known for various beneficial properties was administered (100 mg/kg, 12 days, oral) to isoproterenol (ISO) induced cardiac hypertrophic rats (low ISO—60 mg/kg, 12 days and high ISO—100 mg/kg, 12 days, subcutaneous) and were compared with group that was treated with the reference drug, Losartan (10 mg kg, administered for 12 days, oral). The anti-hypertrophic effect of E. littorale was evaluated by analysing the morphometric indices of the heart, ECG tracings, changes in blood biochemical parameters viz., serum glucose, serum total protein, serum albumin, lipid profile, cardiac specific enzymes (SGOT, SGPT and LDH) and histopathological examination of the heart tissue. The results fundamentally revealed that the plant extract efficiently ameliorated cardiac hypertrophy induced by ISO injected in experimental rats. The outcomes of biochemical investigations of this study highlighted the association between the hypertrophic β-adrenergic receptor signalling (β-AR) and the 5′ AMP-activated protein kinase (AMPK)—peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) axis in the metabolism of cardiac fibrosis and hypertrophy. This β-AR/AMPK-PGC1α signalling stem can serve as a key target in ameliorating cardiac hypertrophy through focus on its principal regulators. To add, we also propose that the glycoside, swertiamarin present in this plant with the reported anti-fibrotic potential in liver can be further isolated and evaluated for its anti-hypertrophic potential to treat cardiac hypertrophy.  相似文献   

12.
13.
Sustained high levels of circulating catecholamines are reported to induce cardiotoxicity. Isoproterenol (ISP), a synthetic catecholamine has been widely employed to induce myocardial injury, though the role of inflammation and apoptosis is not well established. This study was designed to investigate the underlying mechanism of oxidative damage, inflammatory signaling, cell death in ISP induced myocardial infarction in rats. Wistar albino rats were divided in two groups: group I (sham control) and group II (ischemic control). ISP (85 mg/kg, s.c.) was administered at an interval of 24 h to group II for two consecutive days. On day third, after 48 h of the first injection of ISP, blood was collected from retro orbital plexus of rat eyes to estimate the biochemical parameters. Glutathione (GSH) and superoxide dismutase (SOD) were measured for antioxidant status. Similarly, malondialdehyde (MDA) was measured as an index of lipid peroxidation. Cardiac markers (SGOT, CK-MB, TropI and LDH) and pro-inflammatory cytokines (IL-6, CRP and TNF-α) were also estimated in ISP-induced rats. At the end of experiments animals were sacrificed for histopathological studies. GSH and SOD showed significant decrease after ISP challenge as compared to sham (control) group (p < 0.01) while MDA level, increased significantly (p < 0.01). ISP, also increased the level of cardiac markers and markers of inflammation significantly (p < 0.01), which was further verified by histopathological studies of the heart tissues. The study confirmed that ISP causes detrimental changes in the myocardium by altering cardiac and inflammatory markers, which leads to severe necrosis. The deleterious effects produced by ISP substantiate its suitability as a novel animal model for evaluation of cardioprotective agents/drugs.  相似文献   

14.
Homocysteine(Hcy) has been implicated as a novel risk factor of Coronary Artery Disease (CAD) among Asian Indians, but many studies done in India failed to reveal any direct correlation. It has also been reported that Folic acid and Vitamin B12 levels inversely affect serum levels of homocysteine. In this study, we looked at the levels of homocysteine among patients with CAD. The effect of Vitamin B12, Folate and other risk factors on homocysteine levels were also evaluated. Mean homocysteine levels in cases (22.81±13.9, n=70) were significantly higher (p=<0.001) than the controls (7.77±7.3, n=70). However no statistically significant correlation could be deduced between homocysteine Vitamin B12, and Folate. Cumulative analysis have indicated an increase in homocysteine levels among patients with CAD with every additional risk factor.  相似文献   

15.
Chronic pancreatitis (CP) presenting clinically with upper abdominal pain, as well as exocrine and endocrine insufficiencies, is characterized by irreversible morphological and functional alterations in the pancreas. The objective of the present study is to investigate the plasma levels of transforming growth factor-β 1 (TGF-β1), matrix metalloproteinases MMP-1 (collagenase) and MMP-3 (stromelysin) in CP. A total of 71 CP patients and 100 control subjects were considered for the study. Plasma levels of TGF-β1, MMP-1 and MMP-3 were determined by enzyme-linked immunosorbent assay in patients and control subjects. The plasma levels of TGF-β1 and MMP-1 were significantly elevated in patients compared to control group (*P = 0.0301, **P < 0.0001). However, there was no significant difference in the plasma levels of MMP-3 between patients and controls (P = 0.3756). The elevated levels of TGF-β1 and MMP-1 may influence the inflammatory reactions by enhancing the pancreatic stellate cell activation and deposition of extracellular matrix resulting in pancreatic fibrosis. Thus, the present study highlights the role of fibrogenic cytokine marker TGF-β1 and matrix metalloproteinases in the pathogenesis of CP.  相似文献   

16.
Free radicals play an important role in the pathogenesis of tissue damage in many clinical disorders, including atherosclerosis. Antioxidants protect the body from damage caused by free radicals. In this study we investigated oxidative stress, antioxidants and inflammatory molecules in patients with acute myocardial infarction. This study has been carried out on 106 patients with acute myocardial infarction, (89 men and 17 females). The control group consisted of 50 healthy, age-matched subjects (40 men and 10 females). Levels of Glucose, lipid profile, glutathione reduced, glutathione peroxidase, Superoxide dismutase, Glycosylated hemoglobin, fibrinogen, vitamin C, vitamin E, malondialdehyde, ceruloplasmin, adenosine deaminase, lysozyme and sialic acid were measured. Malondialdehyde and ceruloplasmin levels were significantly high and antioxidants such as vitamin C, vitamin E, glutathione reduced, glutathione peroxidase and superoxide dismutase were significantly decreased in diabetic and non-diabetic AMI patients as compared with control (p<0.001). Inflammatory markers showed significant rise in diabetic patients as compared with controls. Our results clearly show increased inflammation and oxidative stress in patients with acute myocardial infarction. Depression of antioxidant system in these patients confirms this conclusion.  相似文献   

17.
Coronary artery disease (CAD) has become the most common cause of mortality in the entire world. Homocysteine is implicated as an early atherosclerotic promoter. We studied the relationship between levels of serum homocysteine with severity of coronary artery disease. Total of 70 subjects who scheduled for coronary angiogram consented to participate in this study. In all the patients Gensini scoring system was used to assess the severity of CAD. Venous samples were taken from the patients in fasting state before angiography. Homocysteine levels in patients were measured by enzyme linked immunosorbant method and were compared with respective Genseni scores of participants. Fasting serum homocysteine levels in CAD patients were significantly higher than patients without coronary artery disease (p < 0.001). Also Homocyseine levels correlated significantly with increasing severity of CAD (p < 0.001). Serum homocysteine levels correlated well with the severity of CAD.  相似文献   

18.
The present study was undertaken to explore the relationship of plasma homocysteine with other biochemical parameters in ischemic heart disease. Plasma levels of total homocysteine was measured by HPLC—fluorescence detection with internal standard in 60 ischemic heart disease patients and were compared with 30 age matched normal healthy controls. The significant increase of plasma homocysteine was observed in both myocardial infarction and chronic stable ischemic heart disease patients when compared with the controls. The hyperhomocysteinemia appears be to due to increased body demand of vitamins such as folic acid, vitamin B12, B6, B2 either alone or in combination to regulate normal homocysteine metabolism.  相似文献   

19.
Human serum paraoxonase-1 (PON1), an enzyme on HDL prevents oxidation of LDL thereby preventing the development of atherosclerosis. Studies done so far have lead to conflicting results. As studies are lacking in North-West Indian Punjabi’s, a distinct ethnic group with high incidence of coronary artery disease, we determined PONase activity in this population. It has been postulated that sudden lowering of serum PONase may lead to precipitation of acute myocardial infarction. We determined serum PONase activity and lipids in 100 patients each of AMI (within 24 h of onset), stable CAD and 100 age and sex matched healthy controls. These were again determined after 6 weeks in AMI patients. The mean serum PONase activity was lowest in AMI patients (23.26 U/ml) followed by stable CAD patients (102.0 U/ml) where as in controls was highest (179.8 U/ml). In patients with AMI, activity was significantly higher at 6 weeks as compared to that after acute event (49.39 %; p < 0.05). Sudden lowering of serum PONase activity in a population which already has lower activity may be one of the risk factors for development of AMI.  相似文献   

20.
Hemoglobin (Hb) Grey Lynn is a Hb variant caused by a substitution of Phe for Leu at position 91 of α1-globin chain, originally described in individual of unknown ethnic background. This article addresses the interaction of Hb Grey Lynn with a non-deletional α+-thalassemia found in Thailand, a hitherto un-described condition. The proband was adult Thai woman referred for investigation of mild anemia with Hb 90 g/L. Hb analyses using low pressure liquid chromatography raised a suspicion of abnormal Hb presence, which was failed to demonstrate by cellulose acetate electrophoresis and capillary electrophoresis. DNA sequencing identified a CTT (Leu) to TTT (Phe) mutation at codon 91 corresponding to the Hb Grey Lynn (Vientiane) [α91(FG3)Leu>Phe (α1) on α1-globin gene and a C deletion between codons 36 and 37 on α2-globin gene causing α+-thalassemia. As compared to those observed in a compound heterozygote for Hb Grey Lynn / α0-thalassemia reported previously, higher MCV (81.7 fL) and MCH (26.3 pg) values with a lower level of Hb Grey Lynn (19.7%) were observed in the proband. The normochromic normocytic anemia observed could be due to the interaction of Hb Grey Lynn with α+-thalassemia. The two mutations could be identified using PCR-RFLP and allele-specific PCR assays developed.  相似文献   

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