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  1. Association of serum calcium concentrations with fibrinogen and homocysteine in nondiabetic Korean subjects

    PubMed Central

    Cho, Hyun Sun; Lee, Sung Won; Shin, Juyoung; Moon, Sung Dae; Han, Je Ho; Cha, Bong Yun; Kim, Eun Sook

    2016-01-01

    Abstract Considerable evidence shows that increased serum calcium levels are associated with metabolic disorders, cardiovascular disease, and increased mortality. This study investigated whether serum calcium, within a normal range, is significantly associated with serum fibrinogen and homocysteine, markers of increased cardiovascular disease risk in nondiabetic Korean subjects. A cross-sectional analysis was performed on 1096 subjects (mean age, 55.1 ± 11.1 years; 36.1% women) undergoing a general health checkup. Serum biochemistry was analyzed including serum albumin-corrected calcium (Cac), insulin resistance (IR, using homeostasis model assessment [HOMA]), fibrinogen, and homocysteine. Compared with patients within the lowest Cac quartile, those with higher Cac levels had increased fibrinogen and homocysteine levels as well as an increased proportion of smoking, dyslipidemia, and HOMA-IR. Correlation analyses revealed linear relationships for Cac with fibrinogen and homocysteine in both genders. After adjustment for confounding factors, serum Cac was significantly associated with high fibrinogen (odds ratio [OR] for the highest vs the lowest quartile = 1.76, 95% confidence interval [CI] = 1.09–2.83, P = 0.02) and homocysteine (OR = 1.83, 95% CI = 1.07–3.11, P = 0.027). Multivariate regression models showed that Cac was linearly associated with fibrinogen (standardized β = 0.14, P < 0.001) and homocysteine (standardized β = 0.07, P = 0.009). High normal calcium concentrations were independently associated with increased levels of fibrinogen and homocysteine. Further investigation is needed to validate whether slightly increased calcium levels within the normal range indicate a higher risk of cardiovascular disease. PMID:27310988

  2. Homocysteine levels in acromegaly patients.

    PubMed

    Hekimsoy, Zeliha; Ozmen, Bilgin; Ulusoy, Sadik

    2005-12-01

    Acromegaly is associated with a two to three-fold increase in mortality related predominantly to cardiovascular disease. The excess mortality is associated most closely with higher levels of growth hormone (GH). Survival in acromegaly may be normalized to a control age-matched rate by controlling GH levels; in particular, GH levels less than 2.5 ng/mL are associated with survival rates equal to those of the general population. Hyperhomocysteinemia has also been recognized as a risk factor for cardiovascular disease, yet there are limited data on the prevalence of hyperhomocysteinemia in patients with acromegaly. Eighteen acromegaly patients (7 male, 11 female, mean age 42.8 +/- 11.0 years) in our endocrine clinic consented to having the following tests performed: complete blood count (CBC), thyroid hormones, folic acid, vitamin B12, plasma homocysteine levels, uric acid, fibrinogen, CRP, fasting glucose, insulin, C-peptide, total serum cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, GH, insulin-like growth factor-1 (IGF-1) and GH levels after an oral glucose tolerance test (OGTT). By history, fourteen had macroadenomas and four had microadenomas; eight had hypertension; two had glucose intolerance, and four had diabetes. Fifteen had had transsphenoidal or transfrontal surgery: two had been cured, but 13 others were taking long-acting octreotide. Five patients had undergone radiotherapy and the acromegaly in two was treated primarily with long-acting octreotide. CBC, thyroid hormone, folic acid, and vit B12 levels were normal in all patients. We divided the patients into two groups according to mean GH levels after an OGTT: Group 1 (GH<2.5 ng/mL, n=10), and Group 2 (GH<2.5 ng/mL, n=8). Comparison of the two groups using Mann-Whitney U testing revealed statistically significant lower levels in Group 1 of the following parameters: GH (1.91 +/- 0.90 vs. 8.58 +/- 5.55 ng/mL, p=0.002), IGF-1 (338.30 +/- 217.90 vs. 509.60 +/- 293.58 ng/dL, p=0.06), GH after

  3. Homocysteine influences blood clot properties alone and in combination with total fibrinogen but not with fibrinogen γ' in Africans.

    PubMed

    Nienaber-Rousseau, Cornelie; de Lange, Zelda; Pieters, Marlien

    2015-06-01

    Simultaneously increased fibrinogen and homocysteine (Hcy) in blood are believed to elevate the risk of cardiovascular disease mortality. However, the pathophysiological mechanisms involved are unknown. We sought to determine whether Hcy or its genetic determinants influence blood clot properties alone or in combination with fibrinogen. In addition, we investigated, for the first time, the gamma prime (γ') isoform of fibrinogen with Hcy in relation to clot architecture and lysis. Single-nucleotide polymorphisms, Hcy and hemostatic variables, including clot lysis, determined with a global fibrinolytic assay [giving lag time, slope, maximum absorbance and clot lysis time (CLT)], were measured in 1867 healthy black South Africans and cross-sectionally analyzed. Increasing Hcy did not affect fiber cross-sectional area (maximum absorbance). However, it decreased the time needed to initiate the coagulation cascade and for fibrin fibers to grow (lag time), it increased the tempo of lateral aggregation (slope) and reduced CLT. None of the single-nucleotide polymorphisms measured had effects on clot properties. Combined effects were observed between Hcy and total fibrinogen in predicting CLT. Fibrinogen γ', which affected markers of the fibrinolytic assay, did not have conjoint effects with Hcy. We believe that there is value in recognizing the combined effects of Hcy and fibrinogen, but not its γ' isoform in relation to clot structure and lysis. The enhanced fibrinolysis rate observed in patients with low fibrinogen and high Hcy may have adverse consequences for health if it disturbs hemostasis and results in a bleeding tendency. PMID:25688462

  4. Plasma homocysteine levels in acute coronary syndromes.

    PubMed

    Turgan, N; Boydak, B; Habif, S; Apakkan, S; Ozmen, D; Mutaf, I; Bayindir, O

    1999-11-01

    Hyperhomocysteinemia is currently regarded as an independent and modifiable risk factor for ischemic vascular diseases and thrombosis. We measured fasting plasma total homocysteine levels by HPLC with fluorescence detection in 30 patients presenting with acute coronary syndromes and 30 age and sex-matched control subjects. Demographic data, classical risk factors (systolic blood pressure, diabetes mellitus, smoking, ethanol intake, family history of ischaemic heart disease) and life-style habits were recorded. Lipid fractions including total cholesterol, triglycerides, HDL-cholesterol, total cholesterol/HDL-cholesterol ratio, serum creatinine, LDL-cholesterol and vitamins involved in the metabolism of homocysteine, folic acid and vitamin B12 were also assessed. Total fasting homocysteine concentrations were significantly higher in the patient group (12.2 +/- 1.01 micromol/l) than in the control subjects (7.05 +/- 0.36 micromol/l; p < 0.0001). Homocysteine correlated positively with age (r = 0.617; p < 0.01) and serum creatinine (r = 0.457; p < 0.01) in the patient group. Hyperhomocysteinemia was not associated with vitamin B12 or folate deficiency states. Vitamin B12 concentration was 273 +/- 16.4 ng/l in the control group and 284.3 +/- 32.2 ng/l in the patient group (p = NS). Serum folate concentration also was not significantly different between controls and patients; 7.57 +/- 0.58 microg/l and 8.05 +/- 0.72 microg/l, respectively. Since no significant difference was observed in the lipid parameters between patients and controls, the hyperhomocysteinemia in the patient group supports the view that homocysteine is an independent risk factor for cardiovascular diseases. Our results strongly suggest that elevated homocysteine levels are among the interacting factors in the complex, multifactorial pathophysiology of ischemic heart disease. PMID:10737556

  5. Association Between γ′ Fibrinogen Levels and Inflammation

    PubMed Central

    Alexander, Kristine S.; Madden, Theresa E.; Farrell, David H.

    2014-01-01

    Summary The γ′ fibrinogen isoform produces clots that are stiffer and more resistant to breakdown than the more common fibrinogen isoform, γA. Increased levels of γ′ fibrinogen are associated with several forms of cardiovascular disease. The purpose of this cross-sectional study is to investigate the relationship between γ′ fibrinogen, an emerging risk factor for cardiovascular disease, and inflammatory markers in subjects with a chronic inflammatory state. The 284 subjects for this study came from the Periodontitis and Vascular Events study, and γ′ fibrinogen and total fibrinogen in plasma were measured by ELISA. Information on patient demographics and health status, as well as levels of C-reactive protein, an inflammatory marker, have previously been collected for this study. The mean (SE) γ′ fibrinogen level in the subjects was 0.622 (0.017) mg/ml. Levels of γ′ fibrinogen were correlated with C-reactive protein (p = 0.006), with a one unit increase in C-reactive protein associated with a 1.9% increase in γ′ fibrinogen, after adjustment for potential confounders. Total fibrinogen was not correlated with γ′ fibrinogen in these subjects. The number of dental sites with evidence of tissue inflammation was also significantly associated with γ′ fibrinogen levels. These results provide an important step in the evolution of γ′ fibrinogen not only as a general risk factor for cardiovascular disease, but as a potentially useful biomarker for assessing a patient's inflammatory state and associated cardiovascular disease risk. PMID:21174007

  6. [Gastrointestinal disease with elevated plasma homocysteine level].

    PubMed

    Coll, P; Guttormsen, A B; Berstad, A

    1999-10-10

    Elevated plasma homocystein (tHcy) is a marker for functional deficiency of folate and/or cobalamin. Malabsorption of these vitamins occurs in various gastroenterologic diseases. A frequent mutation (C677T) in the gene coding for the enzyme methyltetrahydrofolate reductase (MTHFR) is often associated with elevated values of tHcy. We have investigated 24 patients with tHcy > 40 mumol/l for gastrointestinal disease that can contribute to such elevation. Of these, 19 were homozygous for mutated MTHFR, four were heterozygous and one was normal. We found two cases of probable celiac disease, one case of Crohn's disease and one case of ulcerative colitis. These four were homozygous for the C667T mutation. Furthermore, we found eight persons who were anacidic; four homozygous, three heterozygous and one normal. All had gastritis histologically, six had serum gastrin > 50 pmol/l, and four were already on treatment with cobalamin injections. Helicobacter pylori-infection was found in nine out of 22 persons. Gastrointestinal disease occurs frequently in patients with tHcy > 40 mumol/l, but with the exception of conditions resulting in serious deficiency of cobalamin, these diseases alone do not seem sufficient to cause such high levels. We suggest that a reasonable approach to patients with homocystein values above 40 mumol/l is to exclude cobalamin deficiency, and that further investigations should be based upon thorough anamnesis and symptoms. PMID:10563175

  7. Influence of matrix metalloproteinase-12 on fibrinogen level.

    PubMed

    Motterle, Anna; Xiao, Qingzhong; Kiechl, Stefan; Pender, Sylvia L F; Morris, Gareth E; Willeit, Johann; Caulfield, Mark J; Ye, Shu

    2012-02-01

    In vitro studies have shown that matrix metalloproteinase-12 (MMP12) can degrade fibrinogen, a clotting factor whose level predicts risk of advanced atherosclerosis and myocardial infarction. In this study, we found that mean plasma fibrinogen level was approximately 10-fold higher in MMP12 knockout mice than wildtype mice (p=0.0006). Differential allelic expression analysis of human MMP12 gene polymorphism rs17368582 in human vascular tissues showed an allele-specific effect on MMP12 expression, with one allele (T) having 1.6 fold higher expression level than the other allele (C) (p=0.0006). In a population cohort, we found that individuals homozygous for the MMP12 low expression allele had higher plasma fibrinogen levels (2.95 mg/mL compared with 2.61 mg/mL in other individuals, p=0.029) and increased risk of advanced atherosclerosis [odds ratio 6.3 (95% CI 1.9-20.8), p=0.003] and myocardial infarction [hazard ratio 5.6 (95% CI 1.7-18.3), p=0.005]. In summary, our study in mouse and humans provides in vivo evidence of an effect of MMP12 on fibrinogen level. PMID:22119538

  8. The – 148 C/T fibrinogen gene polymorphism and fibrinogen levels in ischaemic stroke: a case–control study

    PubMed Central

    van Goor, M P J; Gomez-Garcia, E; Leebeek, F; Brouwers, G; Koudstaal, P; Dippel, D

    2005-01-01

    Design: A case–control study of patients with first ever ischaemic stroke, confirmed by computed tomography. Methods: Venous blood samples were collected for fibrinogen and routine coagulation tests one week after the stroke, and after three months in about half the patients. Population controls were age and sex matched. –148 C/T fibrinogen polymorphism was determined by polymerase chain reaction followed by digestion with restriction enzymes HindIII/AluI. Results: There were 124 patients and 125 controls, mean age 56 years (range 18 to 75); 34 patients (27%) and 41 controls (33%) were heterozygous for –148 C/T fibrinogen polymorphism; six patients (5%) and five controls (4%) had the T/T genotype. The odds ratio of ischaemic stroke associated with CC homozygotes v T carriers was 0.8 (95% confidence interval, 0.5 to 1.4). Relative risk for ischaemic stroke associated with fibrinogen levels in the highest quartile was 3.9 (1.9 to 8.4) at one week, decreasing to 1.4 (0.6 to 3.3) at three months. Conclusions: –148 C/T fibrinogen gene polymorphism was not a strong risk factor for ischaemic stroke. High fibrinogen levels early after acute stroke probably represent an acute phase response. PMID:15608011

  9. Serum homocysteine level in vegetarians in District Tharparker, Sindh

    PubMed Central

    Kapoor, Aneel; Zuberi, Nudrat Anwar; Rathore, M. Imran; Baig, Mukhtiar

    2015-01-01

    Objectives: The aim of present study was to investigate serum homocysteine levels in apparently healthy vegetarians and ominvores in Mithi, district Tharparker, Sindh, Pakistan. Methods: This study was conducted in the Department of Biochemistry, Basic Medical Sciences Institute (BMSI), Jinnah Postgraduate Medical Center (JPMC), Karachi and blood samples were collected from Mithi, district Tharparker, Sindh, Pakistan, in 2012. One hundred vegetarian and one hundred omnivores (age ranging from 20-40 years) were enrolled for this study. Serum homocysteine levels were measured by the chemiluminescence enzyme immunoassay method. Results: Serum homocysteine (Hcy) level was considerably higher (p<0.001) in vegetarian group compared to omnivores. We further grouped and analyzed our study subjects according to their gender and according to Hcy level (greater than or lower than 15µmol/L). A considerable number of vegetarian subjects 30% were having Hcy >15µmol/L compared to omnivores 6%, (p<0.001). Gender-wise comparison showed that 27.02% male and 38.46% females had >15µmol/L serum Hcy level in vegetarian group and 6.9% male and 3.5% females had >15µmol/L serum Hcy level in omnivores group, but the difference was not significant in any group. Conclusion: Vegetarians are more prone to develop hyperhomocysteinemia, so they are at high risk to develop cardiovascular disease. PMID:25878628

  10. Linkage study of fibrinogen levels: the Strong Heart Family Study

    PubMed Central

    Best, Lyle G; North, Kari E; Li, Xia; Palmieri, Vittorio; Umans, Jason G; MacCluer, Jean; Laston, Sandy; Haack, Karin; Goring, Harald; Diego, Vincent P; Almasy, Laura; Lee, Elisa T; Tracy, Russell P; Cole, Shelley

    2008-01-01

    Background The pathogenesis of atherosclerosis involves both hemostatic and inflammatory mechanisms. Fibrinogen is associated with both risk of thrombosis and inflammation. A recent meta-analysis showed that risk of coronary heart disease may increase 1.8 fold for 1 g/L of increased fibrinogen, independent of traditional risk factors. It is known that fibrinogen levels may be influenced by demographic, environmental and genetic factors. Epidemiologic and candidate gene studies are available; but few genome-wide linkage studies have been conducted, particularly in minority populations. The Strong Heart Study has demonstrated an increased incidence of cardiovascular disease in the American Indian population, and therefore represents an important source for genetic-epidemiological investigations. Methods The Strong Heart Family Study enrolled over 3,600 American Indian participants in large, multi-generational families, ascertained from an ongoing population-based study in the same communities. Fibrinogen was determined using standard technique in a central laboratory and extensive additional phenotypic measures were obtained. Participants were genotyped for 382 short tandem repeat markers distributed throughout the genome; and results were analyzed using a variance decomposition method, as implemented in the SOLAR 2.0 program. Results Data from 3535 participants were included and after step-wise, linear regression analysis, two models were selected for investigation. Basic demographic adjustments constituted model 1, while model 2 considered waist circumference, diabetes mellitus and postmenopausal status as additional covariates. Five LOD scores between 1.82 and 3.02 were identified, with the maximally adjusted model showing the highest score on chromosome 7 at 28 cM. Genes for two key components of the inflammatory response, i.e. interleukin-6 and "signal transducer and activator of transcription 3" (STAT3), were identified within 2 and 8 Mb of this 1 LOD drop

  11. Tigecycline Treatment Causes a Decrease in Fibrinogen Levels

    PubMed Central

    Zhang, Qian; Zhou, Suming

    2014-01-01

    The objective of this study was to assess the impact of tigecycline treatment on coagulation parameters, specifically fibrinogen, in patients with severe infections. We examined 20 cases of tigecycline-treated patients with severe infections, including hospital-acquired pneumonia, complicated intra-abdominal infections, complicated skin and soft tissue infections, and bloodstream infections. We monitored the relative markers of coagulation and renal and liver function before, during, and after treatment. Fibrinogen (FIB) levels decreased significantly after the use of tigecycline and normalized after the cessation of treatment. FIB levels significantly decreased in the patients treated with the recommended dose or a higher treatment dose. The FIB levels decreased more in the higher-treatment-dose group. There was no difference in the decrease in FIB levels or the FIB level recovery by age. Prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) were prolonged after tigecycline use. The TT decreased after the cessation of treatment, and the PT and APTT also decreased but not to a significant level. There was no change in platelet, alanine aminotransferase (ALT), or creatinine (Cr) levels associated with treatment. The use of tigecycline was associated with decreased FIB levels, which returned to normal after the cessation of treatment. A high-dose treatment group showed greater decreases in FIB levels than did patients treated with the recommended dose. The decline in FIB was not related to patient age. The use of tigecycline was associated with prolonged PT, APTT, and TT. PMID:25547356

  12. Plasma homocysteine levels in patients with coronary heart disease.

    PubMed

    Chacko, K A

    1998-01-01

    Hyperhomocysteinemia is being identified as a risk factor for coronary heart disease but its role among Asian Indians has not been studied. This has practical importance because (1) the data generated in the West may not represent Indian population, and (2) the condition is remediable. To assess the magnitude of this problem, we studied 56 patients with coronary heart disease, and 53 control subjects. Details of diet, smoking, medication, hypertension and diabetes were recorded; lipids and sugar levels were estimated in all. Patients with renal and liver diseases were excluded. Serum homocysteine was estimated using liquid chromatography. Both the groups were comparable by age and sex. Higher, but statistically insignificant homocysteine levels were seen in patients with coronary heart disease: 10.98 +/- 9.04 nmol/ml vs 9.41 +/- 3.60 nmol/ml in control subjects. Among males, higher, but statistically insignificant levels were seen in coronary heart disease patients: 11.96 +/- 9.41 nmol/ml vs 9.87 +/- 3.50 nmol/ ml in control subjects; among females, the levels were lower though not significant: 5.10 +/- 1.64 nmol/ml vs 6.39 +/- 2.99 nmol/ml. Sub-group analysis with age 40 as dividing point did not show significant difference. Six (10.7%) patients with coronary heart disease and three (5.7%) control subjects had homocysteine levels above 95th percentile of control subjects (p = NS). Twenty-three (41.1%) coronary heart disease patients and 19 (35.9%) control subjects had levels above 10 nmol/ml (p = NS). We conclude that homocysteine is not a major risk factor for coronary heart disease in the study population. The lack of statistical significance could be due to inadequate sample size although some past studies reporting statistically significant association between coronary heart disease and homocysteine involved similar or smaller number of subjects. Larger studies are warranted to see if ethnic differences also have any role. PMID:9753851

  13. Effect of lipid-lowering and anti-hypertensive drugs on plasma homocysteine levels

    PubMed Central

    Dierkes, Jutta; Luley, Claus; Westphal, Sabine

    2007-01-01

    Elevated plasma concentrations of homocysteine, a sulfur-containing amino acid, are a risk factor for coronary, cerebral and peripheral artery disease. Next to other factors, drugs used for the prevention or treatment of cardiovascular disease may modulate plasma homocysteine levels. Thus, a drug induced homocysteine increase may counteract the desired cardioprotective effect. The aim is to summarize the current knowledge on the effect of two important classes of drugs, lipid-lowering drugs and anti-hypertensive drugs, on homocysteine metabolism. Among the lipid-lowering drugs, especially the fibric acid derivatives, which are used for treatment of hypertriglyceridemia and low HDL-cholesterol, are associated with an increase of homocysteine by 20%–50%. This increase can be reduced, but not totally avoided by the addition of folic acid, vitamin B12 and B6 to fibrates. HMG-CoA reductase inhibitors (statins) do not influence homocysteine concentrations substantially. The effects of nicotinic acid and n3-fatty acids on the homocysteine concentrations are less clear, more studies are necessary to clarify their influence on homocysteine. Antihypertensive drugs have also been studied with respect to homocysteine metabolism. A homocysteine increase has been shown after treatment with hydrochlorothiazide, a lowering was observed after treatment with ß-blockers, but no effect with ACE-inhibitors. The clinical significance of the homocysteine elevation by fibrates and thiazides is not clear. However, individual patients use these drugs for long time, indicating that even moderate increases may be important. PMID:17583180

  14. Association between Plasma Fibrinogen Levels and Mortality in Acute-on-Chronic Hepatitis B Liver Failure

    PubMed Central

    Shao, Zhexin; Zhao, Ying; Feng, Limin; Feng, Guofang; Zhang, Juanwen; Zhang, Jie

    2015-01-01

    Acute-on-chronic liver failure (AoCLF) is the most common type of liver failure and is associated with high mortality. Fibrinogen is critical in maintaining primary and secondary hemostasis. Therefore, we prospectively analyzed the association between fibrinogen and outcomes in AoCLF patients. Plasma fibrinogen was measured in 169 AoCLF, 173 chronic hepatitis B (CHB), and 171 healthy patients using a coagulation method. The predictive ability of fibrinogen for 3-month mortality in AoCLF patients was assessed using receiver operating characteristic (ROC) curve and multivariable logistic regression analyses. Plasma fibrinogen was significantly lower in nonsurvivor AoCLF patients compared with survivor AoCLF, CHB, and control patients. The sensitivity, specificity, and area under the ROC curve of 1/fibrinogen predicting mortality in AoCLF patients were 66.7%, 72.5%, and 0.746 (95% confidence interval (CI): 0.672–0.820, P < 0.001), and the fibrinogen cutoff value was 0.90 g/L. On multivariate logistic regression analysis, low fibrinogen was an independent factor predicting mortality (odds ratio: 0.304; 95% CI: 0.094–0.983; P = 0.047). Nonsurvivor AoCLF patients had significantly decreased fibrinogen levels, suggesting that low plasma fibrinogen may be a useful predictor of poor prognosis in AoCLF patients. PMID:25960593

  15. Homocysteine Serum Levels in Diabetic Patients with Non Proliferative, Proliferative and without Retinopathy

    PubMed Central

    Gagliano, Caterina; Giordano, Maria; Vacante, Marco; Caraci, Filippo; Drago, Filippo; Avitabile, Teresio; Motta, Massimo

    2014-01-01

    Homocysteine has been associated with extracellular matrix changes. The diabetic retinopathy is a neurovascular complication of diabetes mellitus and it is the leading cause of vision loss among working adults worldwide. In this study, we evaluate the role of homocysteine in diabetic retinopathy analyzing the plasma levels of homocysteine in 63 diabetic type 2 patients with nonproliferative retinopathy (NPDR), 62 patients with proliferative diabetic retinopathy (PDR), 50 healthy subjects used as control group, and 75 randomly selected patients. PMID:24877066

  16. Serum homocysteine level in patients with ankylosing spondylitis.

    PubMed

    Başkan, Bedriye Mermerci; Sivas, Filiz; Aktekin, Lale Akbulut; Doğan, Yasemin Pekin; Ozoran, Kürşat; Bodur, Hatice

    2009-10-01

    In this study serum homocystein (Hcy) level was measured and its relationship with disease activity criteria and treatment protocols was investigated in ankylosing spondylitis (AS) patients. Ninety-two AS patients and 58 healthy individuals were recruited. Erythrocyte sedimentation rate and serum C-reactive protein were determined. Bath AS disease activity index and Bath AS functional index were calculated. Serum Hcy levels >15 micromol/l were considered as hyperhomocysteinemia. The mean serum homocysteine levels were 14.40 and 12.60 micromol/l in patients with AS and the control group, respectively, and the difference between two groups was significant. While there was no significant difference between the sulfasalazine (SSZ) group with 14.25 micromol/l mean Hcy level and the methotrexate (MTX)/SSZ group with 16.05 micromol/l, there was a statistically significant difference between the Hcy levels of these two groups and Hcy level of 12.15 micromol/l of the non-steroidal anti-inflammatory drugs group, and 12.60 micromol/l Hcy level of the control group. Mean serum Hcy level was 13.65 micromol/l in patients with active AS and 14.60 micromol/l in patients with inactive AS, and there was no significant difference between the groups. In our study serum Hcy level was found to be significantly higher in patients with AS than in healthy control subjects. Especially for the AS patients receiving MTX and SSZ treatment without folic acid supplementation, addition of folic acid to their therapy may decrease the risk of cardiovascular disease which in turn decreases the mortality in these patients, but further prospective studies are needed for supporting these results. PMID:19288264

  17. Serum homocysteine, folate level and methylenetetrahydrofolate reductase 677, 1298 gene polymorphism in Korean schizophrenic patients.

    PubMed

    Lee, Young Sik; Han, Doug Hyun; Jeon, Chang Moo; Lyoo, In Kyoon; Na, Chul; Chae, Seok Lae; Cho, Soo Churl

    2006-05-15

    High homocysteine serum level has been regarded as one of the important factors that influence the development of schizophrenia. Genetic variations of methylenetetrahydrofolate reductase, which is a main enzyme reducing homocysteine level, are reported in schizophrenic patients. We measured the serum level of homocysteine/folate and methylenetetrahydrofolate reductase C677T/A1298C gene polymorphism in 235 patients with schizophrenia. Plasma homocysteine levels were higher and folate levels were lower in patients than in comparison subjects. Variations of C677T were more frequent in patients than in comparison subjects. Patients with the 677TT genotype showed higher homocysteine levels than patients with the CC and CT genotypes. These findings suggest that folate supplement may be beneficial to some schizophrenic patients with homocysteinemia due to the genetic defect of methylenetetrahydrofolate reductase. PMID:16641680

  18. Correlation of serum homocysteine levels with the severity of coronary artery disease.

    PubMed

    Shenoy, Vijetha; Mehendale, Veena; Prabhu, Krishnananda; Shetty, Ranjan; Rao, Pragna

    2014-07-01

    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. PMID:24966483

  19. Beta blocker effects on plasma homocysteine levels in patients with hypertension.

    PubMed

    Atar, Ilyas; Korkmaz, Mehmet Emin; Demircan, Senol; Atar, Inci Asli; Bozbaş, Hüseyin; Aydinalp, Alp; Ozin, Bülent; Yildirir, Aylin; Müderrisoğlu, Haldun

    2005-08-01

    Recent studies have shown that hyperhomocysteinemia might play a role in the pathogenesis of hypertension. The effects of antihypertensive agents on plasma homocysteine levels have not been tested extensively. We investigated the effects of beta-blocker therapy on homocysteine levels in patients with hypertension. In the study, 120 patients with newly diagnosed hypertension were enrolled. All patients received metoprolol succinate 100 mg/day initially. If blood pressure was above normal on the 15th day of follow-up, the metoprolol dosage was doubled. Before initiation of the antihypertensive medication and after the fourth month of treatment, homocysteine levels were measured. Of the 120 patients enrolled, 39 could not complete the study. Homocysteine levels decreased significantly by the end of the fourth month when compared with basal values (13.5+/-4.5 micromol/l versus 12.4+/-4.9 micromol/l; P = 0.001). There was no relation between homocysteine level and blood pressure control. There was a significant decrease in homocysteine levels in the women treated in this study (P = 0.001); however, this effect was absent in men (P = 0.185). We demonstrate that metoprolol succinate treatment significantly decreases plasma homocysteine levels in patients with hypertension, especially in women. PMID:16039296

  20. Increased levels of homocysteine in patients with ulcerative colitis

    PubMed Central

    Akbulut, Sabiye; Altiparmak, Emin; Topal, Firdevs; Ozaslan, Ersan; Kucukazman, Metin; Yonem, Ozlem

    2010-01-01

    AIM: To investigate serum levels of homocysteine (Hcys) and the risk that altered levels carry for thrombosis development in ulcerative colitis (UC) patients. METHODS: 55 UC patients and 45 healthy adults were included. Hcys, vitamin B12 and folic acid levels were measured in both groups. Clinical history and thromboembolic events were investigated. RESULTS: The average Hcys level in the UC patients was 13.3 ± 1.93 μmmol/L (range 4.60-87) and was higher than the average Hcys level of the control group which was 11.2 ± 3.58 μmmol/L (range 4.00-20.8) (P < 0.001). Vitamin B12 and folic acid average values were also lower in the UC group (P < 0.001). When multivariate regression analysis was performed, it was seen that folic acid deficiency was the only risk factor for hyperhomocysteinemia. Frequencies of thromboembolic complications were not statistically significantly different in UC and control groups. When those with and without a thrombosis history in the UC group were compared according to Hcys levels, it was seen that there were no statistically significant differences. A negative linear relationship was found between folic acid levels and Hcys. CONCLUSION: We could not find any correlations between Hcys levels and history of prior thromboembolic events. PMID:20480528

  1. Homocysteine Levels in Parkinson's Disease: Is Entacapone Effective?

    PubMed Central

    Guven, Hayat; Comoglu, Selim Selcuk

    2016-01-01

    Plasma homocysteine (Hcy) levels may increase in levodopa-treated patients with Parkinson's disease (PD) as a consequence of levodopa methylation via catechol-O-methyltransferase (COMT). Results from previous studies that assessed the effect of COMT inhibitors on levodopa-induced hyperhomocysteinemia are conflicting. We aimed to evaluate the effects of levodopa and entacapone on plasma Hcy levels. A hundred PD patients were enrolled to the study and divided into three treatment groups (group I: levodopa and/or dopamine agonists; group II: levodopa, entacapone, and/or a dopamine agonist; and group III: dopamine agonist alone). We measured the serum B12, folic acid, and Hcy levels in all patients. There were no statistically significant differences between groups in terms of modified Hoehn and Yahr stages, Unified Parkinson's Disease Rating Scale II/III, Standardized Mini-Mental Test scores, and serum vitamin B12 and folic acid levels. Plasma median Hcy levels were found above the normal laboratory values in groups I and II, but they were normal in group III. However, there was no statistically significant difference in plasma Hcy levels between groups. Our results showed that levodopa treatment may cause a slight increase in the Hcy levels in PD compared with dopamine agonists and that COMT inhibitors may not have a significant effect on preventing hyperhomocysteinemia. PMID:27493964

  2. Identification of gene-gene and gene-environment interactions within the fibrinogen gene cluster for fibrinogen levels in three ethnically diverse populations.

    PubMed

    Jeff, Janina M; Brown-Gentry, Kristin; Crawford, Dana C

    2015-01-01

    Elevated levels of plasma fibrinogen are associated with clot formation in the absence of inflammation or injury and is a biomarker for arterial clotting, the leading cause of cardiovascular disease. Fibrinogen levels are heritable with >50% attributed to genetic factors, however little is known about possible genetic modifiers that might explain the missing heritability. The fibrinogen gene cluster is comprised of three genes (FGA, FGB, and FGG) that make up the fibrinogen polypeptide essential for fibrinogen production in the blood. Given the known interaction with these genes, we tested 25 variants in the fibrinogen gene cluster for gene x gene and gene x environment interactions in 620 non-Hispanic blacks, 1,385 non-Hispanic whites, and 664 Mexican Americans from a cross-sectional dataset enriched with environmental data, the Third National Health and Nutrition Examination Survey (NHANES III). Using a multiplicative approach, we added cross product terms (gene x gene or gene x environment) to a linear regression model and declared significance at p < 0.05. We identified 19 unique gene x gene and 13 unique gene x environment interactions that impact fibrinogen levels in at least one population at p < 0.05. Over 90% of the gene x gene interactions identified include a variant in the rate-limiting gene, FGB that is essential for the formation of the fibrinogen polypeptide. We also detected gene x environment interactions with fibrinogen variants and sex, smoking, and body mass index. These findings highlight the potential for the discovery of genetic modifiers for complex phenotypes in multiple populations and give a better understanding of the interaction between genes and/or the environment for fibrinogen levels. The need for more powerful and robust methods to identify genetic modifiers is still warranted. PMID:25592583

  3. IDENTIFICATION OF GENE-GENE AND GENE-ENVIRONMENT INTERACTIONS WITHIN THE FIBRINOGEN GENE CLUSTER FOR FIBRINOGEN LEVELS IN THREE ETHNICALLY DIVERSE POPULATIONS

    PubMed Central

    Jeff, Janina M.; Brown-Gentry, Kristin; Crawford, Dana C.

    2014-01-01

    Elevated levels of plasma fibrinogen are associated with clot formation in the absence of inflammation or injury and is a biomarker for arterial clotting, the leading cause of cardiovascular disease. Fibrinogen levels are heritable with >50% attributed to genetic factors, however little is known about possible genetic modifiers that might explain the missing heritability. The fibrinogen gene cluster is comprised of three genes (FGA, FGB, and FGG) that make up the fibrinogen polypeptide essential for fibrinogen production in the blood. Given the known interaction with these genes, we tested 25 variants in the fibrinogen gene cluster for gene × gene and gene × environment interactions in 620 non-Hispanic blacks, 1,385 non-Hispanic whites, and 664 Mexican Americans from a cross-sectional dataset enriched with environmental data, the Third National Health and Nutrition Examination Survey (NHANES III). Using a multiplicative approach, we added cross product terms (gene × gene or gene × environment) to a linear regression model and declared significance at p < 0.05. We identified 19 unique gene × gene and 13 unique gene × environment interactions that impact fibrinogen levels in at least one population at p <0.05. Over 90% of the gene × gene interactions identified include a variant in the rate-limiting gene, FGB that is essential for the formation of the fibrinogen polypeptide. We also detected gene × environment interactions with fibrinogen variants and sex, smoking, and body mass index. These findings highlight the potential for the discovery of genetic modifiers for complex phenotypes in multiple populations and give a better understanding of the interaction between genes and/or the environment for fibrinogen levels. The need for more powerful and robust methods to identify genetic modifiers is still warranted. PMID:25592583

  4. Effect of lipopenic and hypotensive treatment on homocysteine levels in type 2 diabetics

    PubMed Central

    Oudi, Mabrouka El; Aouni, Zied; Ouertani, Haroun; Mazigh, Chakib; Machghoul, Salem

    2010-01-01

    Aim: Evaluate the effect of lipopenic and hypotensive treatment on homocysteine levels. Methods: We recruited 145 type 2 diabetics and 130 control subjects. Thirty-seven diabetics had no complications, 54 had microvascular complications and 54 had macrovascular complications. We determined the parameters homocysteine of lipid, vitamin B12, triglycerides, and folates for all subjects. Associated treatments used one or more of the following drugs, statin, fibrate, angiotensin-converting enzyme inhibitor and beta-blockers. Results: Hyperhomocysteinemia was present in 35.6% of patients. Diabetics had elevated serum levels of triglycerides (P < 0.001), homocysteine (P < 0.01), folates (P < 0.01) and vitamin B12 (P < 0.001). A strong association was found between type 2 diabetes and hyperhomocysteinemia (P < 0.001). Diabetics with associated treatment had elevated homocysteine, vitamin B12 and folate levels when compared to diabetes-free controls. For diabetics with macrovascular complications, we found significant differences in homocysteine (P = 0.010) and folate (P = 0.014) between those taking associated drugs and those who did not. For diabetics with microvascular complications, a significant difference was found in folate only (P = 0.012). Conclusion: Drugs used for hypertension and hyperlipidemia may have an effect on homocysteine levels, for this reason the interaction between drug action and homocysteine levels should be taken into consideration. PMID:20531951

  5. Age dependent levels of plasma homocysteine and cognitive performance.

    PubMed

    Agrawal, Aruna; Ilango, K; Singh, Praveen K; Karmakar, Dipankar; Singh, G P I; Kumari, Rinki; Dubey, G P

    2015-04-15

    Elevated plasma homocysteine (hcy) levels, also known as hyperhomocysteinemia (hhcy), have been associated with cognitive impairment and neurodegenerative disorders. Hhcy has been attributed to deficiency of B vitamins which can adversely affect the brain and result in memory loss and poor attention power. Monitoring hcy levels and the use of vitamin supplementation to treat hhcy may therefore prove advantageous for the prevention and management of cognitive impairment. With this in consideration, we measured plasma hcy, folate and vitamin B12 levels in 639 subjects from different age groups in two sub-regions of India. Cognitive function was also measured using attention span and immediate and delayed memory recall tests. Depression scores were obtained using the Beck Depression Inventory-II and functional impairment was assessed using the functional activities questionnaire (FAQ) score. As hhcy has also been linked to inflammation, plasma levels of high sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) were also measured. The results demonstrated significant negative correlations between hcy levels and folic acid levels, vitamin B12 levels and cognitive performance (attention span and delayed but not immediate memory recall) along with significant positive correlations between hcy levels and depression scores and hsCRP (but not IL-6) levels. A positive correlation was also observed between hcy levels and FAQ scores, however this was not found to be significant. Based on these results, folic acid and vitamin B12 intervention in people with elevated hcy levels in India could prove to be effective in lowering hcy levels and help maintain or improve cognitive function. PMID:25601573

  6. Higher Fibrinogen Levels Predict Progression of Coronary Artery Calcification in Adults with Type 1 Diabetes

    PubMed Central

    Rodrigues, T.C.; Snell-Bergeon, J.K.; Maahs, D.M; Kinney, G.L.; Rewers, M.

    2010-01-01

    Aim To determine whether fibrinogen levels predict independently progression of coronary artery calcification (CAC) in adults with type 1 diabetes. Methods Data from a prospective cohort - the Coronary Artery Calcification in Type 1 Diabetes Study - were evaluated. Fibrinogen levels at baseline were separated into quartiles. CAC was measured twice and averaged at baseline and at follow-up 2.4 ± 0.4 years later. CAC progressors were defined as participants whose square-root transformed CAC volume increased by ≥ 2.53 or development mm of clinical coronary artery disease during the follow-up period. Results Fibrinogen levels were higher in progressors than in non-progressors (276 ± 61 mg/dl versus 259 ± 61 mg/dl, p = 0.0003). CAC progression, adjusted for known cardiovascular risk factors, increased in the highest quartile. Conclusions Higher fibrinogen levels predict CAC progression in type 1 diabetes subjects, independent of standard cardiovascular risk factors. PMID:20079495

  7. Sex Difference in the Association between Serum Homocysteine Level and Non-Alcoholic Fatty Liver Disease

    PubMed Central

    Won, Bo-Youn; Lee, Soo-Hyun; Yun, Sung-Hwan; Kim, Moon-Jong; Park, Kye-Seon; Kim, Young-Sang; Haam, Ji-Hee; Kim, Hyung-Yuk; Kim, Hye-Jung; Park, Ki-Hyun

    2016-01-01

    Background The relationship between serum homocysteine levels and non-alcoholic fatty liver disease is poorly understood. This study aims to investigate the sex-specific relationship between serum homocysteine level and non-alcoholic fatty liver disease in the Korean population. Methods This cross-sectional study included 150 men and 132 women who participated in medical examination programs in Korea from January 2014 to December 2014. Patients were screened for fatty liver by abdominal ultrasound and patient blood samples were collected to measure homocysteine levels. Patients that consumed more than 20 grams of alcohol per day were excluded from this study. Results The homocysteine level (11.56 vs. 8.05 nmol/L) and the proportion of non-alcoholic fatty liver disease (60.7% vs. 19.7%) were significantly higher in men than in women. In men, elevated serum homocysteine levels were associated with a greater prevalence of non-alcoholic fatty liver disease (quartile 1, 43.6%; quartile 4, 80.6%; P=0.01); however, in females, there was no significant association between serum homocysteine levels and the prevalence of non-alcoholic fatty liver disease. In the logistic regression model adjusted for age and potential confounding parameters, the odds ratio for men was significantly higher in the uppermost quartile (model 3, quartile 4: odds ratio, 6.78; 95% confidential interval, 1.67 to 27.56); however, serum homocysteine levels in women were not associated with non-alcoholic fatty liver disease in the crude model or in models adjusted for confounders. Conclusion Serum homocysteine levels were associated with the prevalence of non-alcoholic fatty liver disease in men. PMID:27468343

  8. Comparing the Effects of Lovastatin and Cornus Mas Fruit on Fibrinogen Level in Hypercholesterolemic Rabbits

    PubMed Central

    Asgary, Sedigheh; Rafieian-Kopaei, Mahmoud; Adelnia, Azadeh; Kazemi, Somayeh; Shamsi, Fatemeh

    2010-01-01

    BACKGROUND Atherosclerosis, which is a result of gradual deposition of lipids in the lower part of blood vessel endothelium, is the leading cause of mortality and morbidity around the world. It has been proved that some inflammatory blood markers such as fibrinogen can predict the risk for cardiovascular disease conditions, not only in cardiovascular patients, but also in those who do not have any manifestations of the atherosclerotic development. In this study, the effect of cornus mas l. was evaluated on fibrinogen of hypercholesterolemic rabbits and it was also compared with lovastatin drug. METHODS In this study, 25 New Zealand adult male rabbits were randomly divided into five groups of five. They were treated for 60 days by 5 different diets, namely basic, high cholesterol, regular plus 1 g/kgBW cornus mas L. powder, high cholesterol plus 1 g/kgBW cornus mas L. powder, and high cholesterol plus 10 mg/kgBW lovastatin. At the beginning and at the end of this period, blood samples were collected from the rabbits and their serum fibrinogen levels were measured. RESULTS Cornus mas L. powder and lovastatin significantly decreased fibrinogen levels in comparison with high cholesterol group (P < 0.05). Furthermore cornus mas L. powder could reduce the fibrinogen level more than lovastatin (P < 0.05). CONCLUSION The results indicated that consumption of cornus mas L. might be beneficial in atherosclerotic patients due to its reducing effects on fibrinogen. PMID:22577405

  9. How to Assess Fibrinogen Levels and Fibrin Clot Properties in Clinical Practice?

    PubMed

    Undas, Anetta

    2016-06-01

    Fibrin formed from fibrinogen is the main component of thrombi. Clot structure is characterized by fiber thickness and pore size, which differs within a given clot and between individuals. Plasma clot architecture is largely determined by the quantity and quality of fibrinogen. Plasma fibrinogen concentrations are most commonly measured in citrated plasma using the Clauss method. However, several factors, including instrument type and reagent, may affect results. Other approaches to express the ability of fibrinogen to clot involve prothrombin time-derived or clottable protein assays, while fibrinogen antigen levels in clinical settings are measured using immunological or precipitation assays. Fibrin clot permeability (reflected by the Darcy constant, K s) being proportional to a buffer volume percolating through a clot under a given hydrostatic pressure is now the most commonly used measure of clot structure. Low K s values indicating tightly packed fibrin structure have been shown to be associated with venous and arterial thrombotic complications, while high K s might contribute to bleeding disorders. The measurement of K s, however, is not standardized and validated. This review summarizes the current knowledge on practical aspects of the measurement of fibrinogen levels and K s in patients. PMID:27071050

  10. Association between Plasma Homocysteine Levels and Neuronal Injury in HIV Infection

    PubMed Central

    Ahlgren, Erika; Hagberg, Lars; Fuchs, Dietmar; Andersson, Lars-Magnus; Nilsson, Staffan; Zetterberg, Henrik; Gisslén, Magnus

    2016-01-01

    Objective To investigate the role of homocysteine in neuronal injury in HIV infection. Methods Using a cross-sectional design and archived samples, we compared concentrations of plasma homocysteine and cerebrospinal fluid (CSF) neurofilament light protein (NFL), a sensitive marker of neuronal injury, in 83 HIV-1-infected subjects without antiretroviral treatment. We also analyzed plasma vitamin B12, serum folate, CSF, and plasma HIV RNA, the immune activation marker neopterin in CSF and serum, and albumin ratio as a marker of blood-brain barrier integrity. Twenty-two subjects provided a second sample median of 12.5 months after antiretroviral treatment initiation. Results A significant correlation was found between plasma homocysteine and CSF NFL concentrations in untreated individuals (r = 0.52, p < 0.0001). As expected, there was a significant inverse correlation between homocysteine and B12 (r = –0.41, p < 0.001) and folate (r = –0.40, p = < 0.001) levels. In a multiple linear regression analysis homocysteine stood out as an independent predictor of CSF NFL in HIV-1-infected individuals. The correlation of plasma homocysteine and CSF NFL was also present in the group receiving antiretroviral therapy (r = 0.51, p = 0.016). Conclusion A correlation between plasma homocysteine and axonal injury, as measured by CSF NFL, was found in both untreated and treated HIV. While this study is not able to prove a causal link, homocysteine and functional B12/folate deficiency appear to play a role in neural injury in HIV-infected individuals. PMID:27441551

  11. Serum homocysteine levels are correlated with behavioral and psychological symptoms of Alzheimer’s disease

    PubMed Central

    Kim, Hyun; Lee, Kang Joon

    2014-01-01

    Purpose Homocysteine has been associated with cognitive impairment and various psychiatric symptoms. This study was designed to clarify whether a relationship exists between the serum levels of homocysteine and the behavioral and psychological symptoms of dementia. Methods Patients with Alzheimer’s disease (n=77) and control subjects (n=37) were included in this study. History taking, physical examination, and cognitive assessment were carried out as part of the investigation for the diagnosis of Alzheimer’s disease based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The Mini-Mental State Examination, Global Deterioration Scale, Clinical Dementia Rating, and the Korean version of the Neuropsychiatric Inventory were applied to all patients. The patients’ serum homocysteine, folate, and vitamin B12 levels were measured. Results Patients with Alzheimer’s disease had statistically significantly lower Mini-Mental State Examination scores and higher serum homocysteine levels compared to the control subjects. Mean serum folate and vitamin B12 concentration were significantly lower in patients with Alzheimer’s disease compared to control subjects. A statistically significant positive correlation was found between the serum homocysteine levels and the Neuropsychiatric Inventory subdomains, including delusion, agitation/aggression, depression/dysphoria, elation/euphoria, apathy/indifference, and disinhibition. No statistically significant correlation was found between the serum homocysteine concentration and the Mini-Mental State Examination, Global Deterioration Scale, or Clinical Dementia Rating. Conclusion Associations between the serum homocysteine levels and behavioral and psychological symptoms of dementia were observed, raising the possibility of an etiological role. However, the correlations between the folate or vitamin B12 levels and the Neuropsychiatric Inventory scores were not significant. The pathophysiological

  12. Association of blood lead and homocysteine levels among lead exposed subjects in Vietnam and Singapore

    PubMed Central

    Chia, Sin Eng; Ali, Safiyya Mohamed; Lee, Bee Lan; Lim, Gek Hsiang; Jin, Su; Dong, Nguyen‐Viet; Tu, Nguyen Thi Hong; Ong, Choon Nam; Chia, Kee Seng

    2007-01-01

    Objectives Lead and homocysteine are both linked to cardiovascular disease. With this in mind, the authors evaluated the relation between blood lead and homocysteine in people aged 19–66 years in two Asian populations. Methods This cross‐sectional study comprised 183 workers from a lead stabiliser factory in Singapore and 323 workers from a battery factory in Vietnam. Workers were occupationally exposed to lead. Blood lead was analysed using atomic absorption spectrophotometry while plasma homocysteine was measured using high performance liquid chromatography. Results Chinese subjects had the lowest blood lead levels while the Indians had the highest. Controlling for age, sex and race, an increase of 1 μg/dl in blood lead was associated with an increase of 0.04 μmol/l of homocysteine on the log scale. Gender and ethnicity seemed to be strongly associated with the relation between lead and homocysteine. The positive relation between lead and homocysteine among the Vietnamese subjects was significant (Pearson's r = 0.254, p<0.01). When blood lead levels were divided by quartiles, the correlation coefficient between blood lead levels in the 4th quartile and homocysteine among the Vietnamese was higher (r = 0.405, p<0.01). Overall, an increase of 1 μg/dl in blood lead in all the Vietnamese subjects was associated with an increase of 0.05 μmol/l increase in homocysteine on the log scale. However, in the 4th quartile, the same increase was associated with an increase of 0.41 μmol/l of homocysteine on the log scale. Conclusions Blood lead was found to be associated with homocysteine levels in this Asian sample. Although we cannot determine causality from cross‐sectional data, it is sensible to consider the probability that this relation could explain one of the mechanisms of the impact of lead on the cardiovascular system. More studies would be needed to confirm this inference. PMID:17449564

  13. What is the influence of hormone therapy on homocysteine and crp levels in postmenopausal women?

    PubMed Central

    Lakryc, Eli Marcelo; Machado, Rogério Bonassi; Soares, José Maria; Fernandes, César Eduardo; Baracat, Edmund Chada

    2015-01-01

    OBJECTIVE: To evaluate the influence of estrogen therapy and estrogen-progestin therapy on homocysteine and C-reactive protein levels in postmenopausal women. METHODS: In total, 99 postmenopausal women were included in this double-blind, randomized clinical trial and divided into three groups: Group A used estrogen therapy alone (2.0 mg of 17β-estradiol), Group B received estrogen-progestin therapy (2.0 mg of 17 β-estradiol +1.0 mg of norethisterone acetate) and Group C received a placebo (control). The length of treatment was six months. Serum measurements of homocysteine and C-reactive protein were carried out prior to the onset of treatment and following six months of therapy. RESULTS: After six months of treatment, there was a 20.7% reduction in homocysteine levels and a 100.5% increase in C-reactive protein levels in the group of women who used estrogen therapy. With respect to the estrogen-progestin group, there was a 12.2% decrease in homocysteine levels and a 93.5% increase in C-reactive protein levels. CONCLUSION: Our data suggested that hormone therapy (unopposed estrogen or estrogen associated with progestin) may have a positive influence on decreasing cardiovascular risk due to a significant reduction in homocysteine levels. PMID:25789519

  14. Homocysteine levels in morbidly obese patients: its association with waist circumference and insulin resistance.

    PubMed

    Vayá, Amparo; Rivera, Leonor; Hernández-Mijares, Antonio; de la Fuente, Miguel; Solá, Eva; Romagnoli, Marco; Alis, R; Laiz, Begoña

    2012-01-01

    The association between morbid obesity and hyperhomocysteinemia (HH) remains controversial and the nature of this relationship needs to be clarified as several metabolic, lipidic, inflammatory and anthropometric alterations that accompany morbid obesity may be involved. In 66 morbidly obese patients, 47 women and 19 men aged 41 ± 12 years and 66 normo-weight subjects, 43 women and 23 men, aged 45 ± 11 years, we determined homocysteine (Hcy) levels along with lipidic, anthropometric, inflammatory and insulin resistance markers. In addition, we investigated the effect of Metabolic Syndrome (MS) and its components on Hcy levels. Obese patients had statistically higher Hcy levels than controls: 12.76 ± 5.30 μM vs. 10.67 ± 2.50 μM; p = 0.006. Moreover, morbidly obese subjects showed higher waist circumference, glucose, insulin, HOMA, leptin, triglycerides, fibrinogen, C reactive protein (CRP) (p < 0.001, respectively), and lower vitamin B12 (p = 0.002), folic acid and HDL-cholesterol (p < 0.001, respectively). In the multivariate regression analysis, waist circumference, glucose, leptin and folic acid levels were independent predictors for Hcy values (p < 0.050). When obese patients were classified as having MS or not, no differences in Hcy levels were found between the two groups (p = 0.752). Yet when we analysed separately each MS component, only abdominal obesity was associated with Hcy levels (p = 0.031). Moreover when considering glucose >110 mg/dL (NCEP-ATPIII criteria) instead of glucose intolerance >100 mg/dl (updated ATPIII criteria), it also was associated with HH (p = 0.042). These results were confirmed in the logistic regression analysis where abdominal obesity and glucose >115 mg/dL constitute independent predictors for HH (OR = 3.2; CI: 1.23-13.2; p = 0.032, OR: 4.6; CI: 1.7-22.2; p = 0.016, respectively). The results of our study indicate that increased Hcy levels are related mostly with abdominal obesity and with insulin resistance. Thus, HH may

  15. Plasma homocysteine and B vitamins levels in Nigerian children with nephrotic syndrome

    PubMed Central

    Orimadegun, Bose Etaniamhe; Orimadegun, Adebola Emmanuel; Ademola, Adebowale Dele; Agbedana, Emmanuel Oluyemi

    2014-01-01

    Introduction Available data on plasma homocysteine level in patients with nephrotic syndrome (NS) are controversial with increased, decreased and unchanged values reported. Therefore, plasma homocysteine and serum B vitamins in Nigerian children with NS were assessed in this study Methods Fasting blood samples were analysed for plasma homocysteine, serum folate and B vitamins in 42 children with NS and 42 age and sex-matched healthy controls in this case control study. Data were compared between NS and control using t test and Chi square. Relationships were tested with regression analysis with p set at 0.05. Results Prevalence of hyperhomocysteinaemia, low folate and cyanocobalamin in NS was 57.1%, 14.3% and 9.5% respectively. The mean homocysteine level was significantly higher in NS than control (11.3±2.6µmol/L versus 5.5±2.3µmol/L). Also, NS had lower folate and cyanocobalamin than control: 9.1±3.9ng/mL versus 11.2±3.1ng/dL and 268.5±95.7pg/mL versus 316±117.2pg/mL respectively. Weak but significant correlation between homocysteine and serum albumin (r = 0.347), folate (r = -0.607) and vitamin B12 (r = -0.185) were found in the NS group. Significant relationship was also found between homocysteine and vitamin B12 (ß = -0.64, 95% CI = -1.20, -0.08) after controlling for folate and vitamin B6 levels. Conclusion Clinically important hyperhomocysteinaemia and low B vitamins occur in Nigerian children with nephrotic syndrome. This data suggest that potential usefulness of folate and vitamin B supplementation for reducing high homocysteine levels in nephrotic syndrome need to be further investigated PMID:25404967

  16. Effects of Metformin Treatment on Homocysteine Levels and Metabolic Parameters of Women With Polycystic Ovary Syndrome

    PubMed Central

    Riahinejad, Soheila; Mirdamadi, Ahmad; Alizadeh, Elham

    2015-01-01

    Objective: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. Metformin is a biguanide commonly used to improve PCOS symptoms. Effect of metformin on the levels of serum homocysteine (Hcy) in PCOS women is unclear. The aim of this study is evaluating the effect of metformin administration on serum Hcy levels and metabolic parameters of PCOS patients. Materials and methods: Thirty three patients with PCOS were enrolled in this study who were selected randomly. All patients received metformin from the fifth day of menstrual cycle at a dose of 850 mg (one tablet daily) for 3 months. Body mass index, Triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting blood sugar and homocysteine levels were recorded at entry into the study and after 3 months treatment. Results: BMI, plasma Homocysteine concentrations and fasting blood sugar levels were significantly (p < 0.05) decreased after the treatment period. No significant changes were observed in the lipid profiles of patients. There was a weak negative correlation between homocysteine and LDL cholesterol serum levels (p = 0.04, r = -0.27). Conclusion: Treatment with metformin in PCOS women may lead to beneficial effects in terms of BMI, plasma homocysteine concentrations and fasting blood sugar with no remarkable effect on lipid profile. PMID:27047563

  17. Prospective Study of Plasma Homocysteine Level and Risk of Age-related Macular Degeneration in Women

    PubMed Central

    Christen, William G.; Cook, Nancy R.; Ridker, Paul M.; Buring, Julie E.

    2014-01-01

    Purpose Prospective data to examine the association of homocysteine and age-related macular degeneration (AMD) are limited. We examined the prospective relation of plasma homocysteine level and AMD in a large cohort of apparently healthy women. Methods We evaluated the relationship between baseline levels of plasma homocysteine and incident AMD among 27,479 female health professionals aged 40 years or older. Main outcome measures were total AMD, defined as a self-report documented by medical record evidence of an initial diagnosis after randomization, and visually significant AMD, defined as confirmed incident AMD with visual acuity of 20/30 or worse attributable to this condition. Results During an average of 10 years of follow-up, a total of 452 cases of AMD, including 182 cases of visually-significant AMD, were documented. Women in the highest versus lowest quartile of plasma homocysteine had modestly, but statistically non-significant, increased risks of total (hazard ratio [HR], 1.24; 95% confidence interval [CI], 0.95–1.63; p for trend, 0.07) and visually-significant AMD (HR, 1.41; 95% CI, 0.92–2.17; p for trend, 0.052) in age- and treatment-adjusted analyses. Conclusions These prospective data from a large cohort of apparently-healthy women do not support a strong role for homocysteine in AMD occurrence. PMID:25777307

  18. Homocysteine levels are associated with MTHFR A1298C polymorphism in Indian population.

    PubMed

    Kumar, Jitender; Das, Swapan K; Sharma, Priyanka; Karthikeyan, Ganesan; Ramakrishnan, Lakshmy; Sengupta, Shantanu

    2005-01-01

    An elevated level of homocysteine is an independent risk factor for cardiovascular diseases and is associated with other complex disorders. Homocysteine levels can be elevated due to dietary and/or genetic factors. A majority of Indian population have a low level of vitamin B12 (presumably due to vegetarian diet)--a critical nutritional factor, deficiency of which results in hyperhomocysteinemia. Hence, polymorphisms in the genes responsible for homocysteine metabolism can be perceived to have a greater impact in relation to hyperhomocysteinemia in Indian population. For this reason, the effects of diet and/or methylenetetrahydrofolate reductase (MTHFR) polymorphism were assessed in 200 individuals having varying homocysteine levels. Homocysteine levels were significantly elevated in individuals adhering to a vegetarian diet (P = 0.019) or having MTHFR A1298C polymorphism (P = 0.006). The minor allele frequency (MAF) of MTHFR C677T and A1298C was 0.15 and 0.44 respectively in this cohort. Since the MAF of these polymorphisms differed considerably from Caucasian and other Asian populations, frequencies of these polymorphisms were also determined in more than 400 individuals from different ethnic populations, selected from the entire country based on their geographical location and linguistic lineage, and was found to be similar to that of our cohort. The fact that MTHFR A1298C polymorphism is significantly associated with homocysteine levels, and that the CC genotype is present at a higher frequency in the Indian population, makes it extremely relevant in terms of its potential impact on hyperhomocysteinemia. PMID:16244782

  19. Clinical and Prognostic Significance of Preoperative Plasma Fibrinogen Levels in Patients with Operable Breast Cancer

    PubMed Central

    Lu, Xiaofei; Liu, Haixia; Li, Xiangyi; Ma, Rong

    2016-01-01

    Purpose Elevated plasma fibrinogen levels are associated with tumor progression and poor outcomes in different cancer patients. The objective of this study was to investigate the clinical and prognostic value of preoperative plasma fibrinogen levels in patients with operable breast cancer. Methods Two hundred and twenty-three patients diagnosed with breast cancer were retrospectively evaluated in this study. Plasma fibrinogen levels were examined before treatment and analyzed along with patient clinicopathological parameters, disease-free survival (DFS) and overall survival(OS). Both univariate and multivariate analyses were performed to identify the clinicopathological parameters associated with DFS and OS. Results Elevated preoperative plasma fibrinogen levels were directly associated with age of diagnose (≤47 vs. >47, p<0.001), menopause (yes vs. no, p<0.001), tumor size (T1&T2 vs.T3&T4, p = 0.033), tumor stage (Ⅰvs.Ⅱvs.Ⅲ, p = 0.034) and lymph node involvement (N = 0 vs. 1≤N≤3 vs. N≥4, p<0.001), but not with histological grade, molecular type and other Immunohistochemical parameters(ER, PR, HER2 and Ki-67). In a univariate survival analysis, tumor stage, tumor size, lymph node involvement (p<0.001/ p<0.001)and plasma fibrinogen (p<0.001/ p<0.001) levels were associated with disease-free and overall survival, but just lymph nodes involvement (p<0.001, hazard ratio [HR] = 2.9, 95% confidence interval [CI] = 1.6–5.3/ p = 0.006, HR = 3.2, 95% CI = 1.4–7.3) and plasma fibrinogen levels (p = 0.006, HR = 3.4, 95% CI = 1.4–8.3/ p = 0.002, HR = 10.1, 95% CI = 2.3–44.6) were associated with disease-free and overall survival in a multivariate survival analysis, respectively. Conclusions This study demonstrates that elevated preoperative plasma fibrinogen levels are associated with breast cancer progression and are independently associated with a poor prognosis in patients with operable breast cancer. PMID:26799214

  20. Trials That Matter: Should We Routinely Measure Homocysteine Levels and “Treat” Mild Hyperhomocysteinemia?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Several observational studies involving healthy populations in the 1990s showed positive associations between elevated homocysteine level and increased risk for ischemic heart disease and stroke. Several small trials conducted in western populations in the early and mid-1990s suggested that “daily s...

  1. Can Plasma Fibrinogen Levels Predict Bleeding After Coronary Artery Bypass Grafting?

    PubMed Central

    Jalali, Alireza; Ghiasi, Mohammadsaeid; Aghaei, Aghdas; Khaleghparast, Shiva; Ghanbari, Behrooz; Bakhshandeh, Hooman

    2014-01-01

    Background: Fibrinogen is the main biomarker for bleeding. To prevent excessive postoperative bleeding, it would be useful to identify high-risk patients before coronary artery bypass grafting (CABG). Objectives: In order to predicating bleeding after CABG, we sought to determine whether preoperative fibrinogen concentration was associated with the amount of bleeding following CABG. Patients and Methods: A total of 144 patients (mean age = 61.50 ± 9.42 years; 65.7% men), undergoing elective and isolated CABG, were included in this case-series study. The same anesthesia technique and medicines were selected for all the patients. In the ICU, the patients were assessed in terms of bleeding at 12 and 24 hours post-operation, amount of contingent blood products received, and relevant tests. Statistical tests were subsequently conducted to analyze the correlation between preoperative fibrinogen concentration and the amount of post-CABG bleeding. Results: The mean ± standard deviation of bleeding at 12 and 24 hours post-operation was 285.37 ± 280.27 and 499.31 ± 355.57 mL, respectively. The results showed that postoperative bleeding was associated with different factors whereas pre-anesthesia fibrinogen was not correlated with bleeding at 12 (P = 0.856) and 24 hours (P = 0.936) post-operation. There were correlations between the extra-corporal circulation time and bleeding at 12 hours post-operation (ρ = 0.231, P = 0.007) and bleeding at 24 hours post-operation (ρ = 0.218, P = 0.013). Conclusions: Preoperative assessment of plasma fibrinogen levels failed to predict post-CABG bleeding. PMID:25478546

  2. Signal transduction pathways in erythrocyte nitric oxide metabolism under high fibrinogen levels

    NASA Astrophysics Data System (ADS)

    Saldanha, Carlota; Freitas, T.; Lopez de Almeida, J. P.; Silva-Herdade, A.

    2014-05-01

    Previous studies show that the fibrinogen molecule modulates the metabolism of nitric oxide (NO) in erythrocyte. The in vitro induced hiperfibrinogenemia interferes in the metabolism of the NO in the erythrocyte in dependence of the phosphorylation degree of the band 3. The soluble form of fibrinogen binds into CD47 protein present in the erythrocyte membrane. The soluble thrombomodulin is an inflammatory marker that binds to the erythrocyte CD47 in a site with a sequence peptide known as 4N1K. A study done in vitro shows that when hiperfibrinogenemia was induced in the presence of the peptide 4N1K agonist of CD47 it were observed variations in the efflux of NO from erythrocyte and an increase in the concentrations of GSNO, peroxinitrite, nitrite and nitrate of the erythrocytes. The aim of this work was to study the influence of the peptide 4N1K, on the metabolism of NO in the erythrocyte under high fibrinogen concentration and in the presence of inhibitors of the status of phosphorylation of protein band 3. In this in vitro study, whole blood samples were harvested from healthy subjects and NO, peroxynitrite, nitrite, nitrate and S-nitro-glutathione (GSNO) were determined in presence of 4N1K, calpeptine, Syk inhibitor and under high fibrinogen concentrations. The results obtained in erythrocytes under high fibrinogen levels when 4N1K is present with the Syk inhibitor or with calpeptine, showed in relation to the control samples increased significant concentrations of efflux of NO and of peroxynitrite, nitrite, nitrate and GSNO. In conclusion it was verified that in the in vitro model of hiperfibrinogenemia the peptide 4N1K, agonist of CD47, induces mobilization of NO in the erythrocyte in dependence of the status of phosphorylation of protein band 3.

  3. Elevated homocysteine levels in suction-induced blister fluid of active vitiligo lesions.

    PubMed

    Anbar, Tag; Zuel-Fakkar, Nehal Mohamed; Matta, Mary Fikry; Arbab, Mai Mohammed Ibrahim

    2016-02-01

    Vitiligo is the most prevalent acquired pigmentary disorder as a result of destruction of melanocytes. Several studies have reported increased serum levels of homocysteine (Hcy) in vitiligo patients which may be the result of decreased Vitamin B12 and folic acid levels. In addition, homocystinuria is associated with pigmentary dilution. On the other hand, other studies reported normal serum homocysteine levels. Our aim was to study the Hcy level in active vitiligo patients both in serum and in suction blister fluid obtained from the lesional skin. A total of 30 patients with active vitiligo of both sexes and 30 healthy volunteers were enrolled in this study. Sera from the blood and from lesional induced bullae were obtained from the patients and controls and were assayed for Hcy by enzyme-linked immunosorbent assay (ELISA). The collected data were analyzed by SPSS version 17. There were no significant differences in the serum levels of Hcy between patients and healthy controls, however, the increase in Hcy level was highly statistically significant in the patients' lesional induced bulla compared to the healthy controls. There was no significant difference in Hcy levels between males and females and between patients with negative or positive family histories of vitiligo. The presence of a high homocysteine level in active vitiligo lesions points to a local event occurring in this lesion, which is not reflected as an increase in the patient's serum level. PMID:26678812

  4. Serum homocysteine, vitamin B12, folic acid levels and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism in vitiligo.

    PubMed

    Yasar, Ali; Gunduz, Kamer; Onur, Ece; Calkan, Mehmet

    2012-01-01

    The aim of this study was to determine serum vitamin B12, folic acid and homocysteine (Hcy) levels as well as MTHFR (C677, A1298C) gene polymorphisms in patients with vitiligo, and to compare the results with healthy controls. Forty patients with vitiligo and 40 age and sex matched healthy subjects were studied. Serum vitamin B12 and folate levels were determined by enzyme-linked immunosorbent assay. Plasma Hcy levels and MTHFR polymorphisms were determined by chemiluminescence and real time PCR methods, respectively. Mean serum vitamin B12 and Hcy levels were not significantly different while folic acid levels were significantly lower in the control group. There was no significant relationship between disease activity and vitamin B12, folic acid and homocystein levels. No significant difference in C677T gene polymorphism was detected. Heterozygote A1298C gene polymorphism in the patient group was statistically higher than the control group. There was no significant relationship between MTHFR gene polymorphisms and vitamin B12, folic acid and homocysteine levels. In conclusion, vitamin B12, folate and Hcy levels are not altered in vitiligo and MTHFR gene mutations (C677T and A1298C) do not seem to create susceptibility for vitiligo. PMID:22846211

  5. Fibrinogen gene regulation.

    PubMed

    Fish, Richard J; Neerman-Arbez, Marguerite

    2012-09-01

    The Aα, Bβ and γ polypeptide chains of fibrinogen are encoded by a three gene cluster on human chromosome four. The fibrinogen genes (FGB-FGA-FGG) are expressed almost exclusively in hepatocytes where their output is coordinated to ensure a sufficient mRNA pool for each chain and maintain an abundant plasma fibrinogen protein level. Fibrinogen gene expression is controlled by the activity of proximal promoters which contain binding sites for hepatocyte transcription factors, including proteins which influence fibrinogen transcription in response to acute-phase inflammatory stimuli. The fibrinogen gene cluster also contains cis regulatory elements; enhancer sequences with liver activities identified by sequence conservation and functional genomics. While the transcriptional control of this gene cluster is fascinating biology, the medical impetus to understand fibrinogen gene regulation stems from the association of cardiovascular disease risk with high level circulating fibrinogen. In the general population this level varies from about 1.5 to 3.5 g/l. This variation between individuals is influenced by genotype, suggesting there are genetic variants contributing to fibrinogen levels which reside in fibrinogen regulatory loci. A complete picture of how fibrinogen genes are regulated will therefore point towards novel sources of regulatory variants. In this review we discuss regulation of the fibrinogen genes from proximal promoters and enhancers, the influence of acute-phase stimulation, post-transcriptional regulation by miRNAs and functional regulatory variants identified in genetic studies. Finally, we discuss the fibrinogen locus in light of recent advances in understanding chromosomal architecture and suggest future directions for researching the mechanisms that control fibrinogen expression. PMID:22836683

  6. Polymorphisms in MTHFR, MS and CBS Genes and Homocysteine Levels in a Pakistani Population

    PubMed Central

    Yakub, Mohsin; Moti, Naushad; Parveen, Siddiqa; Chaudhry, Bushra; Azam, Iqbal; Iqbal, Mohammad Perwaiz

    2012-01-01

    Background Hyperhomocysteinemia (>15 µmol/L) is highly prevalent in South Asian populations including Pakistan. In order to investigate the genetic determinants of this condition, we studied 6 polymorphisms in genes of 3 enzymes - methylenetetrahydrofolate reductase (MTHFR; C677T; A1298C), methionine synthase (MS; A2756G), cystathionine-β-synthase (CBS; T833C/844ins68, G919A) involved in homocysteine metabolism and investigated their interactions with nutritional and environmental factors in a Pakistani population. Methodology/Principal Findings In a cross-sectional survey, 872 healthy adults (355 males and 517 females; age 18–60 years) were recruited from a low-income urban population in Karachi. Fasting venous blood was obtained and assessed for plasma/serum homocysteine; folate, vitamin B12, pyridoxal phosphate and blood lead. DNA was isolated and genotyping was performed by PCR-RFLP (restriction-fragment-length- polymorphism) based assays. The average changes in homocysteine levels for MTHFR 677CT and TT genotypes were positive [β(SE β), 2.01(0.63) and 16.19(1.8) µmol/L, respectively]. Contrary to MTHFR C677T polymorphism, the average changes in plasma homocysteine levels for MS 2756AG and GG variants were negative [β(SE β), −0.56(0.58) and −0.83(0.99) µmol/L, respectively]. The average change occurring for CBS 844ins68 heterozygous genotype (ancestral/insertion) was −1.88(0.81) µmol/L. The combined effect of MTHFR C677T, MS A2756G and CBS 844ins68 genotypes for plasma homocysteine levels was additive (p value <0.001). Odds of having hyperhomocysteinemia with MTHFR 677TT genotype was 10-fold compared to MTHFR 677CC genotype [OR (95%CI); 10.17(3.6–28.67)]. Protective effect towards hyperhomocysteinemia was observed with heterozygous (ancestral/insertion) genotype of CBS 844ins68 compared to homozygous ancestral type [OR (95% CI); 0.58 (0.34–0.99)]. Individuals with MTHFR 677CT or TT genotypes were at a greater risk of hyperhomocysteinemia in

  7. Correlation between C677T MTHFR gene polymorphism, plasma homocysteine levels and the incidence of CAD.

    PubMed

    Nakai, K; Itoh, C; Nakai, K; Habano, W; Gurwitz, D

    2001-01-01

    The lesions of coronary atherosclerosis represent the result of a complex, multicellular, inflammatory-healing response in the coronary arterial wall. In vivo and in vitro cellular and molecular studies have suggested a role for tissue homocysteine in endothelial cell injury and adverse extra-cellular matrix remodeling. Gene polymorphisms in relation with numerous risk factors might increase the incidence of coronary artery disease (CAD). In this review we have focused on the correlations between plasma homocysteine levels, the incidence of cardiovascular disease and the cytosine-to-thymidine substitution at nucleotide 677 (C677T) of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, coding for a key enzyme in methionine-homocysteine metabolism. The role of the C677T MTHFR gene polymorphism in the causation of CAD is controversial. We reviewed 12 recent case-control studies comprising 5370 genotyped patients with CAD and 4961 genotyped participants without CAD. There was no significant difference between those with and without CAD in the frequency of the C677T polymorphism (34.9 vs 33.6%). The frequency of homozygous C677T polymorphism in these groups was 10.9 versus 12.8%, respectively, although there were some ethnic differences in the C677T MTHFR polymorphism. In the analysis of the 12 studies, the odds ratio of CAD associated with the TT genotype (homozygous C677T polymorphism) was 1.18. Only slightly higher plasma homocysteine levels were observed in participants with the val/val (TT) genotype (14.4+/-2.9 micro mol/L in TT genotype vs 11.1+/-1.9 and 11.9+/-2 micro mol/L in CC and CT genotype, respectively). In addition, the relation between homocysteine increase after methionine loading and MTHFR genotypes is also controversial. However, hyperhomocysteinemia because of the C677T MTHFR allele may be corrected with oral folic acid therapy. Further investigations on the relationships between MTHFR genotypes and the incidence of CAD should be based on

  8. Effect of plasma homocysteine level and urinary monomethylarsonic acid on the risk of arsenic-associated carotid atherosclerosis

    SciTech Connect

    Wu, M.-M.; Chiou, H.-Y. . E-mail: hychiou@tmu.edu.tw; Hsueh, Y.-M.; Hong, C.-T.; Su, C.-L.; Chang, S.-F.; Huang, W.-L.; Wang, H.-T.; Wang, Y.-H.; Hsieh, Y.-C.; Chen, C.-J.

    2006-10-01

    Arsenic-contaminated well water has been shown to increase the risk of atherosclerosis. Because of involving S-adenosylmethionine, homocysteine may modify the risk by interfering with the biomethylation of ingested arsenic. In this study, we assessed the effect of plasma homocysteine level and urinary monomethylarsonic acid (MMA{sup V}) on the risk of atherosclerosis associated with arsenic. In total, 163 patients with carotid atherosclerosis and 163 controls were studied. Lifetime cumulative arsenic exposure from well water for study subjects was measured as index of arsenic exposure. Homocysteine level was determined by high-performance liquid chromatography (HPLC). Proportion of MMA{sup V} (MMA%) was calculated by dividing with total arsenic species in urine, including arsenite, arsenate, MMA{sup V}, and dimethylarsinic acid (DMA{sup V}). Results of multiple linear regression analysis show a positive correlation of plasma homocysteine levels to the cumulative arsenic exposure after controlling for atherosclerosis status and nutritional factors (P < 0.05). This correlation, however, did not change substantially the effect of arsenic exposure on the risk of atherosclerosis as analyzed in a subsequent logistic regression model. Logistic regression analyses also show that elevated plasma homocysteine levels did not confer an independent risk for developing atherosclerosis in the study population. However, the risk of having atherosclerosis was increased to 5.4-fold (95% CI, 2.0-15.0) for the study subjects with high MMA% ({>=}16.5%) and high homocysteine levels ({>=}12.7 {mu}mol/l) as compared to those with low MMA% (<9.9%) and low homocysteine levels (<12.7 {mu}mol/l). Elevated homocysteinemia may exacerbate the formation of atherosclerosis related to arsenic exposure in individuals with high levels of MMA% in urine.

  9. Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects.

    PubMed

    Hsia, Chien-Hsun; Shen, Ming-Ching; Lin, Jen-Shiou; Wen, Yao-Ke; Hwang, Kai-Lin; Cham, Thau-Ming; Yang, Nae-Cherng

    2009-03-01

    Nattokinase, a serine proteinase from Bacillus subtilis, is considered to be one of the most active functional ingredients found in natto. In this study, we hypothesized that nattokinase could reduce certain factors of blood clotting and lipids that are associated with an increase risk for cardiovascular disease (CVD). Thus, an open-label, self-controlled clinical trial was conducted on subjects of the following groups: healthy volunteers (Healthy Group), patients with cardiovascular risk factors (Cardiovascular Group), and patients undergoing dialysis (Dialysis Group). All subjects ingested 2 capsules of nattokinase (2000 fibrinolysis units per capsule) daily orally for 2 months. The laboratory measurements were performed on the screening visit and, subsequently, regularly after the initiation of the study. The intent-to-treat analysis was performed on all 45 enrolled subjects. By use of mixed model analysis, a significant time effect, but not group effect, was observed in the change from baseline of fibrinogen (P = .003), factor VII (P < .001), and factor VIII (P < .001), suggesting that the plasma levels of the 3 coagulation factors continuously declined during intake; also, the extents of decrease were similar between groups. After 2 months of administration, fibrinogen, factor VII, and factor VIII decreased 9%, 14%, and 17%, respectively, for the Healthy Group; 7%, 13%, and 19%, respectively, for the Cardiovascular Group; and 10%, 7%, and 19%, respectively, for the Dialysis Group, whereas blood lipids were unaffected by nattokinase. No significant changes of uric acid or notable adverse events were observed in any of the subjects. In summary, this study showed that oral administration of nattokinase could be considered as a CVD nutraceutical by decreasing plasma levels of fibrinogen, factor VII, and factor VIII. PMID:19358933

  10. Evaluation of an Association of Blood Homocysteine Levels With Gastric Cancer Risk From 27 Case-Control Studies.

    PubMed

    Xu, Wei; Cheng, Yuelei; Zhu, Huirong

    2016-05-01

    High blood homocysteine levels may risk gastric cancer. However, observational studies have been plagued by chance, bias, confounding, or reverse causality. In this study, we assessed the relationship between blood homocysteine levels and gastric cancer by using a Mendelian randomization method, which is independent of nongenetic confounding.We took 2 steps to perform Mendelian randomization analysis. First, we evaluated the methylenetetrahydrofolate reductase (MTHFR) C677T association with gastric cancer by a meta-analysis of case-control studies including 7566 patients with gastric cancer and 10 640 control subjects from 27 Case-Control studies. Second, MTHFR C677T polymorphism, which affects the blood homocysteine levels, was used as an instrumental variable to calculate the risk and estimate the association of gastric cancer with this single nucleotide polymorphism (SNP). We obtained an estimate to the association of blood total homocysteine levels with this SNP from a meta-analysis of Genome-Wide Association Studies (GWAS), which comprises a total of 44 147 individuals.In our Mendelian randomization analysis, we demonstrated a significant effect of the blood homocysteine levels on gastric cancer risk, representing an OR of 2.56 (95% CI = 2.41-2.72; P = 5.0×10) for gastric cancer per 1-SD increase in the natural log-transformed blood total homocysteine levels.We proved that there is a causal relationship between blood total homocysteine and risk of gastric cancer, and this study will add insight into the treatment and pathology research of gastric cancer. PMID:27196483

  11. Evaluation of an Association of Blood Homocysteine Levels With Gastric Cancer Risk From 27 Case–Control Studies

    PubMed Central

    Xu, Wei; Cheng, Yuelei; Zhu, Huirong

    2016-01-01

    Abstract High blood homocysteine levels may risk gastric cancer. However, observational studies have been plagued by chance, bias, confounding, or reverse causality. In this study, we assessed the relationship between blood homocysteine levels and gastric cancer by using a Mendelian randomization method, which is independent of nongenetic confounding. We took 2 steps to perform Mendelian randomization analysis. First, we evaluated the methylenetetrahydrofolate reductase (MTHFR) C677T association with gastric cancer by a meta-analysis of case-control studies including 7566 patients with gastric cancer and 10 640 control subjects from 27 Case–Control studies. Second, MTHFR C677T polymorphism, which affects the blood homocysteine levels, was used as an instrumental variable to calculate the risk and estimate the association of gastric cancer with this single nucleotide polymorphism (SNP). We obtained an estimate to the association of blood total homocysteine levels with this SNP from a meta-analysis of Genome-Wide Association Studies (GWAS), which comprises a total of 44 147 individuals. In our Mendelian randomization analysis, we demonstrated a significant effect of the blood homocysteine levels on gastric cancer risk, representing an OR of 2.56 (95% CI = 2.41–2.72; P = 5.0×10−4) for gastric cancer per 1-SD increase in the natural log-transformed blood total homocysteine levels. We proved that there is a causal relationship between blood total homocysteine and risk of gastric cancer, and this study will add insight into the treatment and pathology research of gastric cancer. PMID:27196483

  12. Associations of plasma fibrinogen levels with established cardiovascular disease risk factors, inflammatory markers, and other characteristics: individual participant meta-analysis of 154,211 adults in 31 prospective studies: the fibrinogen studies collaboration.

    PubMed

    Kaptoge, S; White, I R; Thompson, S G; Wood, A M; Lewington, S; Lowe, G D O; Danesh, J

    2007-10-15

    Long-term increases in plasma fibrinogen levels of 1 g/liter are associated with an approximate doubling of risk of major cardiovascular disease outcomes, but causality remains uncertain. To quantify cross-sectional associations of fibrinogen levels with established risk factors and other characteristics, the investigators combined individual data on 154,211 apparently healthy adults from 31 prospective studies conducted between 1967 and 2003, using a linear mixed model that included random effects at the cohort level. Fibrinogen levels increased with age and showed continuous, approximately linear relations with several risk markers and slightly curvilinear associations with log triglycerides, albumin, and tobacco and alcohol consumption. Female sex, Black ethnicity, lower socioeconomic status, and alcohol abstinence were each associated with modestly higher fibrinogen levels. Approximately one third of the variation in fibrinogen levels was explained by cohort, age, and sex. An additional 7% was explained by established risk factors (notably, positive associations with smoking and body mass index and an inverse association with high density lipoprotein cholesterol), and a further 10% was explained by inflammatory markers (notably, a positive association with C-reactive protein). The association with body mass index was twice as strong in women as in men, whereas the association with smoking was much stronger in men. These findings substantially advance understanding of the correlates and possible determinants of fibrinogen levels. PMID:17785713

  13. Association of homocysteine level with biopsy-proven non-alcoholic fatty liver disease: a meta-analysis

    PubMed Central

    Dai, Yining; Zhu, Jinzhou; Meng, Di; Yu, Chaohui; Li, Youming

    2016-01-01

    Previous studies have reported inconsistent findings regarding the association between plasmatic higher of homocysteine level and non-alcoholic fatty liver disease. We aimed to investigate this association by conducting a meta-analysis. Literature was searched on PubMed from inception to January 2015. Eight studies evaluating plasma level of homocysteine in biopsy-proven non-alcoholic fatty liver disease subjects compared to healthy controls were included. Compared with the controls, non-alcoholic fatty liver disease patients witnessed a higher level of homocysteine [standard mean difference (SMD): 0.66 µmol/L, 95% CI: 0.41, 0.92 µmol/L], and were associated with a significant increased risk for hyperhomocysteinemia [odds ratio (OR) 5.09, 95% CI: 1.69, 15.32]. In addition, patients with non-alcoholic fatty liver presented 0.45 µmol/L higher levels of homocysteine compared to healthy controls (95% CI: 0.09, 0.82 µmol/L), whereas non-alcoholic steatohepatitis patients had 1.02 µmol/L higher levels of homocysteine (95% CI: 0.28, 1.76 µmol/L). There was neither difference of folate level nor vitamin B12 level between non-alcoholic fatty liver disease subjects and healthy controls. This study revealed that non-alcoholic fatty liver disease patients presented an increased serum concentration of homocysteine, and were associated with an increased risk of hyperhomocysteinemia. Further studies are needed to demonstrate a causal role of hyperhomocysteinemia in non-alcoholic fatty liver disease. PMID:26798201

  14. C677T and A1298C Polymorphisms of MTHFR Gene and Their Relation to Homocysteine Levels in Turner Syndrome

    PubMed Central

    Oliveira, Kelly C.; Verreschi, Ieda T.N.; Sugawara, Eduardo K.; Silva, Vanessa C.; Galera, Bianca B.; Galera, Marcial Francis; Bianco, Bianca

    2012-01-01

    Aims: To determine the frequency of C677T and A1298C polymorphisms of the MTHFR gene and correlate them with homocysteine serum levels in patients with Turner syndrome (TS) and controls. Methods: This case–control study included 78 women with TS and a control group of 372 healthy individuals without personal or family history of cardiovascular disease and cancer. C677T (rs1801133) and A1298C (rs1801131) polymorphisms were detected by polymerase chain reaction–restriction fragment-length polymorphism and the TaqMan system, respectively. Homocysteine serum levels were determined by high-performance liquid chromatography. The results were analyzed statistically, and p<0.05 was considered to represent a significant difference. Results: The homocysteine levels change was 13.9+3.3 nM in patients with TS and 8.8+3.2 nM in the control group. No significant difference between groups was found (p=0.348). Single-marker analysis revealed no association between MTHFR C677T polymorphism and TS when genotype (p=0.063) or allelic (p=0.277) distribution was considered. Regarding MTHFR A1298C polymorphism, a statistical difference was found between the TS group and the control group, for both genotype (p<0.0001) and allele (p<0.0001) distribution. Haplotype analysis of 2 MTHFR polymorphisms identified 2 haplotypes—CC and TC—associated with TS (p<0.001 and p=0.0165, respectively). However, homocysteine levels were not higher in patients with haplotype risk. Conclusion: The results suggest that the C677T and A1298C polymorphisms of the MTHFR gene are not related to homocysteine levels in Brazilian patients with TS, despite the differential distribution of the mutated allele C (A1298C) in these patients. Further studies are needed to investigate the possible genetic interaction with homocysteine levels in TS. PMID:22283972

  15. Effect of body weight on serum homocysteine level in patients with polycystic ovarian syndrome: A case control study

    PubMed Central

    I. Al- Gareeb, Ali; Abd Al- Amieer, Wafaa Salah; M. Alkuraishy, Hayder; J. Al- Mayahi, Thabat

    2016-01-01

    Background: Polycystic ovarian syndrome (PCOS) represent one of the common endocrine disorders which influence around 8% of reproductive women whom usually suffering from obesity and increase cardiovascular risk. Serum homocysteine levels are associated with bad impact on endothelial functions and considered as an independent risk factor for cardiovascular disease. Objective: The aim was to study the level of plasma homocysteine in obese and non-obese Iraqi patients with PCOS. Materials and Methods: This study was carried out on 207 women. Of theme, 101 women with PCOS and 106 PCOS- free women served as controls. Blood sample was taken from each participant on the 2nd day of menstruation morning after an overnight fasting. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), free testosterone and androstenedione were measured. Moreover, total lipid profile and plasma homocysteine levels were measured in both groups. Results: Sixty percent of PCOS women were overweight or obese and 56% of them had a waist circumference >88cm. Moreover plasma homocysteine concentrations were found to be higher in patients with PCOS (11.5±5.41μmol/L) as compared with control (8.10±1.89 μmol/L) (p<0.002). Furthermore the homocysteine concentrations were 13.19±5.97 μmol/L and 9.38±2.99 μmol/L in both obese and normal-weight PCOS women respectively which was significantly higher than obese (p<0.002) and normal-weight (p<0.004) control women. Conclusion: Increase in body weight is not an independent risk factor to increase plasma homocysteine levels in PCOS women. PMID:27200421

  16. Association Between Serum B12 and Serum Homocysteine Levels in Diabetic Patients on Metformin

    PubMed Central

    Kothari, Nitin; Shah, Hitesh

    2016-01-01

    Introduction Type-2 Diabetes Mellitus (T2DM) and metformin both can lower serum B12 (s.B12). Raised serum Homocysteine (s.Hcy) is considered as an early marker of B12 deficiency. Aim The study aimed to check whether homocysteine levels are more sensitive indicator of s. B12 deficiency or not among diabetics using metformin. Materials and Methods Mean s.B12 and s.Hcy levels of 30 cases (diabetics on metformin <5years) were compared with 30 diabetic controls not on metformin and 31 nondiabetic controls and statistically analysed by ANOVA and post-hoc tests. Results No significant differences in either s.B12 mean or s.Hcy mean were found between cases and diabetic controls. s.B12 mean did not differ significantly but s.Hcy mean was significantly higher among nondiabetics as compared to diabetic control. s. B12 level of Nondiabetic group was in borderline category while mean s. B12 levels of cases and diabetic control groups was in normal category but nearer to the lower cut off. Mean s.Hcy values in all the groups were high. Pearson correlation showed strong association between s.B12 and s.Hcy in all the groups. Additionally equation based on linear regression was derived to calculate either of the s.B12 or s.Hcy. On Receiver Operative Characteristic (ROC) curve, area under curve value was 0.842 for the value of s.Hcy. Conclusion In this study neither metformin nor T2DM could be identified as a cause for s.B12 lowering and raised s.Hcy in the scenario of low normal levels of s.B12 (<300pmol/L). If B12 deficiency recognized early using s. Hcy, consequences due to B12 deficiency can be prevented or delayed among nondiabetics as well as among diabetics and metformin users. PMID:27190787

  17. Critical levels of brain atrophy associated with homocysteine and cognitive decline.

    PubMed

    de Jager, Celeste A

    2014-09-01

    Few B-vitamin trials to lower homocysteine (Hcy) have reported evidence of beneficial effects on cognition in older adults with cognitive impairment or Alzheimer's disease. This article reviews the role of Hcy in cognitive decline. It also considers some reasons why meta-analyses have failed to find effects of B-vitamin treatment. Findings from the successful VITACOG trial are examined from a new perspective of critical levels of Hcy and brain atrophy that may impact on the efficacy of B-vitamin treatment. It appears that there is a critical level of brain shrinkage, possibly mediated by elevated Hcy, which when reached, results in cognitive decline, especially in episodic memory performance. Supplements, food sources, and effects of folic acid fortification are discussed in relation to B12 deficiency. PMID:24927906

  18. Regular Exercise Training Increases the Number of Endothelial Progenitor Cells and Decreases Homocysteine Levels in Healthy Peripheral Blood

    PubMed Central

    Choi, Jeong Kyu; Moon, Ki Myung; Jung, Seok Yun; Kim, Ji Yong; Choi, Sung Hyun; Kim, Da Yeon; Kang, Songhwa; Chu, Chong Woo

    2014-01-01

    Endothelial progenitor cells (EPCs) are known to play an important role in the repair of damaged blood vessels. We used an endothelial progenitor cell colony-forming assay (EPC-CFA) to determine whether EPC numbers could be increased in healthy individuals through regular exercise training. The number of functional EPCs obtained from human peripheral blood-derived AC133 stem cells was measured after a 28-day regular exercise training program. The number of total endothelial progenitor cell colony-forming units (EPC-CFU) was significantly increased compared to that in the control group (p=0.02, n=5). In addition, we observed a significant decrease in homocysteine levels followed by an increase in the number of EPC-CFUs (p=0.04, n=5), indicating that the 28-day regular exercise training could increase the number of EPC colonies and decrease homocysteine levels. Moreover, an inverse correlation was observed between small-endothelial progenitor cell colony-forming units (small-EPC-CFUs) and plasma homocysteine levels in healthy men (r=-0.8125, p=0.047). We found that regular exercise training could increase the number of EPC-CFUs and decrease homocysteine levels, thus decreasing the cardiovascular disease risk in men. PMID:24757379

  19. Effect of genetic variants associated with plasma homocysteine levels on stroke risk

    PubMed Central

    Cotlarciuc, Ioana; Malik, Rainer; Holliday, Elizabeth G.; Ahmadi, Kourosh R; Pare, Guillaume; Psaty, Bruce M.; Fornage, Myriam; Hasan, Nazeeha; Rinne, Paul E.; Ikram, M. Arfan; Markus, Hugh S; Rosand, Jonathan; Mitchell, Braxton D.; Kittner, Steven J.; Meschia, James F.; van Meurs, Joyce BJ; Uitterlinden, Andre G; Worrall, Bradford B.; Dichgans, Martin; Sharma, Pankaj

    2014-01-01

    Background and Purpose Elevated homocysteine (tHcy) levels are known to be associated with increased risk of ischemic stroke (IS). Given that both tHcy and IS are heritable traits, we investigated a potential genetic relationship between homocysteine levels and stroke risk by assessing 18 polymorphisms previously associated with tHcy levels for their association with IS and its subtypes. Methods Previous meta-analysis results from an international stroke collaborative network, METASTROKE, were utilized to assess association of the 18 tHcy associated SNPs in 12,389 IS cases and 62,004 controls. We also investigated the associations in regions located within 50kb from the 18 tHcy related SNPs, and the association of a genetic risk score including the 18 SNPs. Results One SNP located in the RASIP1 gene and a cluster of three SNPs located at and near SLC17A3 were significantly associated with IS (P<0.0003) after correcting for multiple testing. For stroke subtypes, the sentinel SNP located upstream of MUT was significantly associated with SVD (small vessel disease) (P=0.0022), while one SNP located in MTHFR was significantly associated with LVD (large vessel disease) (P=0.00019). A genetic risk score including the 18 SNPs did not show significant association with IS or its subtypes. Conclusions This study found several potential associations with IS and its subtypes: an association of an MUT variant with SVD, an MTHFR variant with LVD, and associations of RASIP1 and SLC17A3 variants with overall IS. PMID:24846872

  20. Traditional and alternative nutrition--levels of homocysteine and lipid parameters in adults.

    PubMed

    Krajcovicová-Kudlácková, M; Blazícek, P; Babinská, K; Kopcová, J; Klvanová, J; Béderová, A; Magálová, T

    2000-12-01

    Values of homocysteine and lipid parameters were measured in groups of adults consuming alternative nutrition (vegetarians/lactoovo/, vegans) and compared with a group consuming traditional diet (omnivores, general population). Frequency of hyperhomocysteinemia was 53% in the vegans group, 28% in vegetarians vs. 5% in omnivores. In conditions of lower methionine intake (reduced content in plant proteins), the remethylation pathway of homocysteine metabolism prevails and it is vitamin B12 and folate-dependent. The intake of vitamin B12 is equal to zero in vegans; vegetarians consume 124% of the RDA vs. 383% in omnivores. Serum vitamin levels are significantly lower in subjects consuming alternative nutrition with deficiency observed in 24% of vegetarians, 78% of vegans vs. 0% in omnivores. Serum folate levels are within the reference range in all groups. Mild hyperhomocysteinemia in the groups consuming alternative diet is a consequence of vitamin B12 deficiency. Vegetarians and vegans meet the RDA for energy and fat, and have a favourable proportion of saturated, mono- and polyunsaturated fatty acids on total energy intake; the ratio of linoleic/alpha-linolenic acid in their diet corresponds with the recommendations. They have low cholesterol consumption and higher vitamin E and C intake. Optimal fat intake of correct composition is reflected in lower values of atherosclerosis risk factors (cholesterol, LDL-cholesterol, atherogenic index, saturated fatty acids, triacylglycerols), and significantly higher levels of protective substances (linoleic acid, alpha-linolenic acid, HDL-cholesterol, vitamin E, vitamin E/cholesterol, vitamin C). Low lipid risk factors but higher findings of mild hyperhomocysteinemia in vegetarians mean a diminished protective effect of alternative nutrition in cardiovascular disease prevention. PMID:11218148

  1. Reintroduction of a Homocysteine Level-Associated Allele into East Asians by Neanderthal Introgression.

    PubMed

    Hu, Ya; Ding, Qiliang; He, Yungang; Xu, Shuhua; Jin, Li

    2015-12-01

    In this study, we present an analysis of Neanderthal introgression at the dipeptidase 1 gene, DPEP1. A Neanderthal origin for the putative introgressive haplotypes was demonstrated using an established three-step approach. This introgression was under positive natural selection, reached a frequency of >50%, and introduced a homocysteine level- and pigmentation-associated allele (rs460879-T) into East Asians. However, the same allele was also found in non-East Asians, but not from Neanderthal introgression. It is likely that rs460879-T was lost in East Asians and was reintroduced subsequently through Neanderthal introgression. Our findings suggest that Neanderthal introgression could reintroduce an important previously existing allele into populations where the allele had been lost. This study sheds new light on understanding the contribution of Neanderthal introgression to the adaptation of non-Africans. PMID:26392408

  2. Relation between admission plasma fibrinogen levels and mortality in Chinese patients with coronary artery disease

    PubMed Central

    Peng, Yong; Wang, Hua; Li, Yi-ming; Huang, Bao-tao; Huang, Fang-yang; Xia, Tian-li; Chai, Hua; Wang, Peng-ju; Liu, Wei; Zhang, Chen; Chen, Mao; Huang, De-jia

    2016-01-01

    Fibrinogen (Fib) was considered to be a potential risk factor for the prognosis of patients with coronary artery disease (CAD), but there was lack of the evidence from Chinese contemporary population. 3020 consecutive patients with CAD confirmed by coronary angiography were enrolled and were grouped into 2 categories by the optimal Fib cut-off value (3.17 g/L) for all-cause mortality prediction. The end points were all-cause mortality and cardiac mortality. Cumulative survival curves showed that the risk of all-cause mortality was significantly higher in patients with Fib ≥3.17 g/L compared to those with Fib <3.17 g/L (mortality rate, 11.5% vs. 5.7%, p < 0.001); and cardiovascular mortality obtained results similar to those mentioned above (cardiac mortality rate, 5.9% vs. 3.6%, p = 0.002). Subgroup analysis showed that elevated Fib levels were predictive for the risk of all-cause mortality in the subgroups according to age, medical history, and diagnosis. COX multivariate regression analysis showed that plasma Fib levels remained independently associated with all-cause mortality after adjustment for multiple cardiovascular risk factors (all-cause mortality, HR 2.01, CI 1.51–2.68, p < 0.001). This study has found that Fib levels were independently associated with the mortality risk in Chinese CAD patients. PMID:27456064

  3. Role of Serum Fibrinogen Levels in Patients with Rotator Cuff Tears

    PubMed Central

    Longo, Umile Giuseppe; Petrillo, Stefano; Berton, Alessandra; Spiezia, Filippo; Loppini, Mattia; Maffulli, Nicola; Denaro, Vincenzo

    2014-01-01

    Although rotator cuff (RC) tendinopathy is a frequent pathology of the shoulder, the real understanding of its aetiopathogenesis is still unclear. Several studies showed that RC tendinopathy is more frequent in patients with hyperglycemia, diabetes, obesity, or metabolic syndrome. This paper aims to evaluate the serum concentration of fibrinogen in patients with RC tears. Metabolic disorders have been related to high concentration of serum fibrinogen and the activity of fibrinogen has been proven to be crucial in the development of microvascular damage. Thus, it may produce progression of RC degeneration by reducing the vascular supply of tendons. We report the results of a cross-sectional frequency-matched case-control study comparing the serum concentration of fibrinogen of patients with RC tears with that of a control group of patients without history of RC tears who underwent arthroscopic meniscectomy. We choose to enrol in the control group patients with pathology of the lower limb with a likely mechanic, not metabolic, cause, different from tendon pathology. We found no statistically significant differences in serum concentration of fibrinogen when comparing patients with RC tears and patients who underwent arthroscopic meniscectomy (P = 0.5). Further studies are necessary to clarify the role of fibrinogen in RC disease. PMID:24817887

  4. The effects of genotype and infant weight on adult plasma levels of fibrinogen, factor VII, and LDL cholesterol are additive.

    PubMed Central

    Henry, J A; Bolla, M; Osmond, C; Fall, C; Barker, D J; Humphries, S E

    1997-01-01

    High circulating levels of cholesterol, particularly low density lipoprotein (LDL) cholesterol and the clotting factors fibrinogen and factor VII, are associated with increased risk of myocardial infarction. Variations in the plasma levels of these factors are determined in part by polymorphisms in the genes concerned and also by weight at 1 year (infant weight). We have looked at the possibility of interactions between these genetic factors and infant weight in a sample of 290 men and 192 women from Hertfordshire using the beta-fibrinogen G/A-455, factor VII R353Q, and ApoE polymorphisms. The rare allele frequencies of the three polymorphisms were 0.19 for beta-fibrinogen, 0.10 for factor VII, and 0.07 and 0.13 for the 2 and 4 alleles of ApoE, and these frequencies were not different in subjects of different infant weight. In this sample, the polymorphisms showed the expected effects on plasma levels of fibrinogen, factor VII, and LDL cholesterol. The A-455 allele was associated with higher fibrinogen levels but the effect was only statistically significant in women (p = 0.003). The R353 allele was associated with higher factor VII activity in both men and women (p < 0.0001 for both). The ApoE2 allele was associated with lower levels of LDL cholesterol (p = 0.03 in men, p = 0.006 in women), while the ApoE4 allele was associated with higher levels (p < 0.001 in men, not significant in women). In this sample of men and women the effect of low infant weight was only associated with significant effects on fibrinogen and LDL cholesterol in the group of men (p = 0.005 and p = 0.008 respectively). Compared with the E3E3 subjects, the LDL lowering effect of the E2 allele and the raising effect of the E4 allele was greater in those with low infant weight compared with those with high infant weight (low v high infant weight for E2: 12.7% v 9.4%; for E4 12.7% v 8.5%). Although in this sample the interactive effect did not reach statistical significance, the additive effect

  5. Electrocardiogram Derived QRS Duration >120 ms is Associated With Elevated Plasma Homocysteine Levels in a Rural Australian Cross-Sectional Population

    PubMed Central

    Leng, Yvonne Lee Yin; Zhou, Yuling; Ke, Honghong; Jelinek, Herbert; McCabe, Joel; Assareh, Hassan; McLachlan, Craig S.

    2015-01-01

    Abstract Homocysteine levels in the low to moderate range for cardiovascular risk have been previously associated with left ventricular cardiac hypertrophy (LVH). Electrocardiogram (ECG) derived QRS duration has also been used as an epidemiological screening marker for cardiac hypertrophy risk. QRS duration cut offs have not been previously modeled to assess homocysteine levels in community populations. Our aims are to determine if QRS duration is associated with an elevated homocysteine level in a cross-sectional Australian aging rural population. A retrospective study design utilizing a rural health diabetic screening clinic database containing observational data from the period January 9, 2002 till September 25, 2012. One hundred seventy-eight individuals (>21 years of age) from the database were included in the study. Inclusion criteria included being nondiabetic and having both a QRS duration measure and a matching homocysteine level within the same subject. All participants were from the Albury-Wodonga area, with a mean age of >64 years for both sexes. Mean population homocysteine plasma levels were 10.4 μmol/L (SD = 3.6). The mean QRS duration was 101.8 ms (SD = 17.4). Groups were stratified on the basis of QRS duration (≤120 ms [n = 157] and >120 ms [n = 21]). QRS duration subgroup (≤120 ms vs >120 ms) mean differences across homocysteine levels were 10.1 μmol/L (SD = 3.3) and 12.2 μmol/L (SD = 4.7), respectively (P = 0.016). Other ECG parameters (PQ interval, QTc interval, and QT dispersion) measurements were not significantly associated with differences in plasma homocysteine (P = not significant). We conclude that in community populations homocysteine may be moderately elevated when QRS durations are >120 ms. Small additional increases in homocysteine levels may suggest a risk factor for ECG diagnosis of LVH. PMID:26166085

  6. Plasmatic higher levels of homocysteine in Non-alcoholic fatty liver disease (NAFLD)

    PubMed Central

    2013-01-01

    Background Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, which includes a spectrum of hepatic pathology such as simple steatosis, steatohepatitis, fibrosis and cirrhosis. The increased serum levels of homocysteine (Hcy) may be associated with hepatic fat accumulation. Genetic mutations in the folate route may only mildly impair Hcy metabolism. The aim of this study was to investigate the relation between liver steatosis with plasma homocysteine level and MTHFR C677T and A1298C polymorphisms in Brazilian patients with NAFLD. Methods Thirty-five patients diagnosed with NAFLD by liver biopsy and forty-five healthy controls neither age nor sex matched were genotyped for C677T and A1298C MTHFR polymorphisms using PCR-RFLP and PCR-ASA, respectively, and Hcy was determined by HPLC. All patients were negative for markers of Wilson’s, hemochromatosis and autoimmune diseases. Their daily alcohol intake was less than 100 g/week. A set of metabolic and serum lipid markers were also measured at the time of liver biopsies. Results The plasma Hcy level was higher in NAFLD patients compared to the control group (p = 0.0341). No statistical difference for genotypes 677C/T (p = 0.110) and 1298A/C (p = 0.343) in patients with NAFLD and control subjects was observed. The genotypes distribution was in Hardy-Weinberg equilibrium (677C/T p = 0.694 and 1298 A/C p = 0.188). The group of patients and controls showed a statistically significant difference (p < 0.001) for BMI and HOMA_IR, similarly to HDL cholesterol levels (p < 0,006), AST, ALT, γGT, AP and triglycerides levels (p < 0.001). A negative correlation was observed between levels of vitamin B12 and Hcy concentration (p = 0.005). Conclusion Our results indicate that plasma Hcy was higher in NAFLD than controls. The MTHFR C677T and A1298C polymorphisms did not differ significantly between groups, despite the 677TT homozygous frequency was higher in patients (17

  7. Associations of Toenail Selenium Levels With Inflammatory Biomarkers of Fibrinogen, High-Sensitivity C-Reactive Protein, and Interleukin-6

    PubMed Central

    Xun, Pengcheng; Liu, Kiang; Steven Morris, J.; Daviglus, Martha L.; Stevens, June; Jacobs, David R.; He, Ka

    2010-01-01

    The authors examined the associations of toenail selenium levels with blood concentrations of fibrinogen, high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6) in an 18-year follow-up study comprising 4,032 Americans aged 20–32 years at baseline (1987) from the Coronary Artery Risk Development in Young Adults (CARDIA) Trace Element Study. Toenail samples were collected in 1987, and selenium concentrations were measured by means of instrumental neutron-activation analysis. Fibrinogen level was analyzed in 1990, 1992, and 2005; hs-CRP was assessed in 1992, 2000, and 2005; and IL-6 was measured in 2005. After adjustment for potential confounders, no statistically significant associations between toenail selenium levels and any of the 3 inflammatory biomarkers were documented. Comparing the highest quintile of toenail selenium level with the lowest, odds ratios for elevated levels of fibrinogen (>460 mg/mL), hs-CRP (>3 μg/mL), and IL-6 (>3.395 pg/mL, 80th percentile) were 1.03 (95% confidence interval (CI): 0.77, 1.38; P for trend = 0.76), 1.02 (95% CI: 0.83, 1.27; P for trend = 0.92), and 0.98 (95% CI: 0.71, 1.36; P for trend = 0.82), respectively. Gender, race/ethnicity, smoking status, and selenium supplementation did not appreciably modify these results. This study found no associations between toenail selenium and inflammation as measured by fibrinogen, hs-CRP, and IL-6. PMID:20219762

  8. Elevated Plasma Homocysteine Level in Vascular Dementia Reflects the Vascular Disease Process

    PubMed Central

    Nilsson, Karin; Gustafson, Lars; Hultberg, Björn

    2013-01-01

    Background Patients with vascular dementia (VaD) exhibit particularly elevated levels of plasma total homocysteine (tHcy) compared to patients with other psychogeriatric diseases. Methods We investigated the main determinants (age, renal impairment, cobalamin/folate status and presence of extracerebral vascular disease) of plasma tHcy in 525 patients with VaD. Furthermore, 270 patients with depression were used as a reference group to reveal the potential specificity of elevated plasma tHcy in patients with VaD. Results Elevated plasma tHcy levels in patients with VaD could only partly be attributed to cobalamin/folate deficiency or renal impairment. Plasma tHcy might also be related to the vascular disease process since patients with depression and vascular disease exhibited similar plasma tHcy levels to patients with VaD. Conclusion Our findings suggest that elevated plasma tHcy might be a sensitive marker for the vascular disease process in patients with VaD and that the level also is a reflection of changes in the other main determinants of plasma tHcy. PMID:23569455

  9. Social connectedness is associated with fibrinogen level in a human social network.

    PubMed

    Kim, David A; Benjamin, Emelia J; Fowler, James H; Christakis, Nicholas A

    2016-08-31

    Socially isolated individuals face elevated rates of illness and death. Conventional measures of social connectedness reflect an individual's perceived network and can be subject to bias and variation in reporting. In this study of a large human social network, we find that greater indegree, a sociocentric measure of friendship and familial ties identified by a subject's social connections rather than by the subject, predicts significantly lower concentrations of fibrinogen (a biomarker of inflammation and cardiac risk), after adjusting for demographics, education, medical history and known predictors of cardiac risk. The association between fibrinogen and social isolation, as measured by low indegree, is comparable to the effect of smoking, and greater than that of low education, a conventional measure of socioeconomic disadvantage. By contrast, outdegree, which reflects an individual's perceived connectedness, displays a significantly weaker association with fibrinogen concentrations. PMID:27559060

  10. Association between High Serum Homocysteine Levels and Biochemical Characteristics in Women with Polycystic Ovarian Syndrome: A Systematic Review and Meta-Analysis

    PubMed Central

    Peng, Zheng; Liu, Xuexiang; Sun, Yifan; Dai, Shengming

    2016-01-01

    Background Elevated homocysteine levels have been observed in previous studies of PCOS; however, the nature of the associations between high homocysteine levels and the biochemical characteristics of polycystic ovarian syndrome (PCOS)—such as obesity, insulin resistance (IR), and androgen levels—is still uncertain. Methods A systematic search was conducted electronically up to December 28, 2015 using specific eligibility criteria. Standardized mean difference (SMD) and the corresponding 95% confidence intervals (95% CIs) were used as a measure of effect size. Results A total of 34 studies (with 1,718 cases and 1,399 controls) of homocysteine levels in PCOS were pooled in this meta-analysis. Significantly lower homocysteine levels were found in controls than in PCOS patients (SMD = 0.895, 95% CI = 0.643–1.146, P<0.001; I2 = 90.4% and P<0.001 for heterogeneity), regardless of the degree of obesity, IR, or androgen levels. Homocysteine levels in non-IR PCOS patients were significantly lower than those of PCOS patients with IR (SMD = 0.69, 95% CI = 0.37–1.01, P<0.01; I2 = 0% and P = 0.50 for heterogeneity). However, metformin treatment did not appear to cause any significant change in the homocysteine levels of PCOS patients (SMD = –0.17, 95% CI = –1.10–0.75, P = 0.71; I2 = 92% and P<0.01 for heterogeneity). Conclusions High homocysteine levels in women with PCOS are not related to degree of obesity, IR, or androgen levels. Metformin treatment cannot decrease the homocysteine levels in PCOS patients. PMID:27281026

  11. Homocysteine levels in schizophrenia and affective disorders—focus on cognition

    PubMed Central

    Moustafa, Ahmed A.; Hewedi, Doaa H.; Eissa, Abeer M.; Frydecka, Dorota; Misiak, Błażej

    2014-01-01

    Although homocysteine (Hcy) has been widely implicated in the etiology of various physical health impairments, especially cardiovascular diseases, overwhelming evidence indicates that Hcy is also involved in the pathophysiology of schizophrenia and affective disorders. There are several mechanisms linking Hcy to biological underpinnings of psychiatric disorders. It has been found that Hcy interacts with NMDA receptors, initiates oxidative stress, induces apoptosis, triggers mitochondrial dysfunction and leads to vascular damage. Elevated Hcy levels might also contribute to cognitive impairment that is widely observed among patients with affective disorders and schizophrenia. Supplementation of vitamins B and folic acid has been proved to be effective in lowering Hcy levels. There are also studies showing that this supplementation strategy might be beneficial for schizophrenia patients with respect to alleviating negative symptoms. However, there are no studies addressing the influence of add-on therapies with folate and vitamins B on cognitive performance of patients with schizophrenia and affective disorders. In this article, we provide an overview of Hcy metabolism in psychiatric disorders focusing on cognitive correlates and indicating future directions and perspectives. PMID:25339876

  12. Four-Group Classification Based on Fibrinogen Level and Fibrin Polymerization Associated With Postoperative Bleeding in Cardiac Surgery.

    PubMed

    Kawashima, Shingo; Suzuki, Yuji; Sato, Tsunehisa; Kikura, Mutsuhito; Katoh, Takasumi; Sato, Shigehito

    2016-10-01

    Fibrinogen and fibrin formation have a key role in perioperative hemostasis. The aim of this study is to examine the association of postoperative hemostasis with a combined evaluation of the fibrinogen level and fibrin polymerization in cardiac surgery. We retrospectively classified 215 consecutive cardiac surgery patients into 4 groups (Fuji-san classification) that were divided by fibrinogen level <150 mg/dL (ie, hypofibrinogenemia) and fibrinogen thromboelastometry value at 10 minutes with rotational thromboelastometry <6 mm (ie, low fibrin polymerization) at the warming of cardiopulmonary bypass. Four groups resulted; group I, the acceptable range (n = 85); group II, only hypofibrinogenemia (<150 mg/dL, ≥6 mm, n = 63); group III, hypofibrinogenemia and low fibrin polymerization (<150 mg/dL, <6 mm, n = 60); and group IV, only low fibrin polymerization (≥150 mg/dL, <6 mm, n = 7). The risk of chest tube drainage volume greater than 500 mL within the first 24 hours after surgery (with group I as the reference) was increased in group II (odds ratio [OR], 3.3; 95% confidence interval [CI], 1.5-7.4; P < .01) and group III (OR, 8.5; 95% CI, 3.5-21.7; P < .01), and the risk greater than 1000 mL (with group I as the reference) was increased in group III (OR, 4.0; 95% CI, 1.1-17.3; P = .03) and group IV (OR, 23.1; 95% CI, 3.2-201.0; P < .01). Intraoperative blood transfusions were decreased by 24.5%, after stratifying the starting amount of fresh frozen plasma by the 4-group classification in the recent consecutive 65 (30.2%) patients (P < .01). The 4-group classification is associated with postoperative bleeding and may improve the quality of perioperative blood transfusion in cardiac surgery. PMID:26207020

  13. Preoperative neutrophil–lymphocyte ratio and fibrinogen level in patients distinguish between muscle-invasive bladder cancer and non-muscle-invasive bladder cancer

    PubMed Central

    Ma, Chengquan; Lu, Bingxin; Diao, Chengwen; Zhao, Kun; Wang, Xinpeng; Ma, Baojing; Lu, Baojian; Sun, Erlin

    2016-01-01

    Introduction The aim of this study was to explore if the preoperative neutrophil–lymphocyte ratio (NLR) and fibrinogen level can help in distinguishing between muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Methods We identified 669 patients who underwent surgery at our institution, and evaluated their preoperative NLRs and fibrinogen levels. Patients were divided into two groups, NMIBC (group-I) and MIBC (group-II), according to the postoperative pathology. For the intergroup comparison, data obtained from the two groups were evaluated using independent samples t-test. The cutoff value of the NLR, fibrinogen level, and integrated NLR and fibrinogen level was determined with receiver operating characteristic (ROC) curve. Results The mean NLRs of group-I and group-II were found as 2.71±2.46 and 4.66±8.00, respectively (P<0.001). The fibrinogen levels of the two groups were ~3.13±0.70 g/L and 3.41±0.84 g/L, respectively (P=0.001). Whether the NLR, fibrinogen level, and integrated NLR and fibrinogen level can help in distinguishing between MIBC and NMIBC was evaluated with ROC curve. The cutoff value of NLR was estimated as 2.01 according to the Youden index. With this value, sensitivity was found as 67.1%, specificity was 52.7%, and area under receiver operating characteristic (ROC) curve (AUC) was 0.601 (P=0.031). The cutoff value of fibrinogen level was estimated as 3.17 g/L according to the Youden index. Accordingly, sensitivity was found as 58%, specificity was 58%, and AUC was 0.60 (P=0.001). The cutoff value of integrated NLR and fibrinogen level was found as 0.166; the sensitivity was found as 86%, specificity was 42%, and AUC was 0.801 (P=0.01). Conclusion The data obtained in this study suggested that 67.1% of Ta-T1 tumors were likely to be invasive if the NLR was >2.01 and 58% were likely to be invasive if the fibrinogen level was >3.17 g/L. When we used both the NLR and fibrinogen level to distinguish between

  14. Effect of Folic Acid, Betaine, Vitamin B6, and Vitamin B12 on Homocysteine and Dimethylglycine Levels in Middle-Aged Men Drinking White Wine

    PubMed Central

    Rajdl, Daniel; Racek, Jaroslav; Trefil, Ladislav; Stehlik, Pavel; Dobra, Jana; Babuska, Vaclav

    2016-01-01

    Moderate regular consumption of alcoholic beverages is believed to protect against atherosclerosis but can also increase homocysteine or dimethylglycine, which are putative risk factors for atherosclerosis. We aimed (1) to investigate the effect of alcohol consumption on vitamins and several metabolites involved in one-carbon metabolism; and (2) to find the most effective way of decreasing homocysteine during moderate alcohol consumption. Methods: Male volunteers (n = 117) were randomly divided into five groups: the wine-only group (control, 375 mL of white wine daily for one month) and four groups combining wine consumption with one of the supplemented substances (folic acid, betaine, and vitamins B12 or B6). Significant lowering of homocysteine concentration after the drinking period was found in subjects with concurrent folate and betaine supplementation. Vitamin B12 and vitamin B6 supplementation did not lead to a statistically significant change in homocysteine. According to a multiple linear regression model, the homocysteine change in the wine-only group was mainly determined by the interaction between the higher baseline homocysteine concentration and the change in dimethylglycine levels. Folate and betaine can attenuate possible adverse effects of moderate alcohol consumption. Dimethylglycine should be interpreted together with data on alcohol consumption and homocysteine concentration. PMID:26771632

  15. Distribution and determinants of plasma homocysteine levels in rural Chinese twins across the lifespan.

    PubMed

    Ji, Yuelong; Kong, Xiangyi; Wang, Guoying; Hong, Xiumei; Xu, Xin; Chen, Zhu; Bartell, Tami; Xu, Xiping; Tang, Genfu; Hou, Fanfan; Huo, Yong; Wang, Xiaobin; Wang, Binyan

    2014-12-01

    Plasma homocysteine (Hcy) is a modifiable, independent risk factor for cardiovascular disease (CVD) and is affected by both environmental and genetic factors. This study aimed to describe the gender- and age-specific distribution of Hcy concentration for 1117 subjects aged 10-66 years, a subset of a community-based rural Chinese twin cohort. In addition, we examined environmental and genetic contributions to variances in Hcy concentration by gender and age groups. We found that the distribution pattern for Hcy varied by both age and gender. Males had higher Hcy than females across all ages. Elevated Hcy was found in 43% of male adults and 13% of female adults. Moreover, nearly one fifth of children had elevated Hcy. Genetic factors could explain 52%, 36% and 69% of the variation in Hcy concentration among children, male adults and female adults, respectively. The MTHFR C677T variant was significantly associated with Hcy concentrations. Smokers with the TT genotype had the highest Hcy levels. Overall, our results indicate that elevated Hcy is prevalent in the children and adults in this rural Chinese population. The early identification of elevated Hcy will offer a window of opportunity for the primary prevention of CVD and metabolic syndrome. PMID:25529062

  16. Homocysteine Level Is Associated with White Matter Hyperintensity Locations in Patients with Acute Ischemic Stroke

    PubMed Central

    Song, Bo; Qin, Jie; Fang, Hui; Ji, Yan; Zhang, Rui; Sun, Shilei; Xu, Yuming

    2015-01-01

    Background and Purpose The relationship between plasma level of total homocysteine (tHcy) and white matter hyperintensities (WMHs), especially in patients with acute ischemic stroke (AIS), is controversial. The present study investigated the association between these two as well as WMH locations in a large cohort of patients with AIS. Methods Consecutive patients were reviewed from a prospective ischemic stroke database. Clinical data, including tHcy level and WMHs, were assessed. WMHs were assessed using the Fazekas scale and Age-Related White Matter Changes (ARWMC) visual grading scale. The association between tHcy and WMH locations was investigated by using multivariate logistic regression analyses. Results A total of 923 out of 1,205 patients were examined. The average age was 58.9 ± 11.9 years; 31.6% were female. Elevated tHcy level was significantly associated with WMHs. For the highest tHcy quartile, the odds ratio (OR) (95% confidence interval; CI) was 1.891 (1.257; 2.843) according to the Fazekas scale and 1.781 (1.185; 2.767) according to the ARWMC scale when compared to the lowest quartile. However, in a subgroup analysis, only WMHs in the periventricular area and left or right frontal areas were found to be independently associated with tHcy level. For the highest tHcy quartile, the OR (95% CI) was 1.761 (1.172; 2.648) for the periventricular WMHs, 1.768 (1.134; 2.756)for the left frontal WMHs, and 1.890 (1.206; 2.960)for the right frontal WMHs. Conclusions In patients with AIS, plasma tHcy level is related to WMHs, especially WMHs distributed within the periventricular and frontal areas. PMID:26641086

  17. Effects of folic acid supplementation on serum homocysteine and lipoprotein (a) levels during pregnancy

    PubMed Central

    Hekmati Azar Mehrabani, Zohreh; Ghorbanihaghjo, Amir; Sayyah Melli, Manizheh; Hamzeh-Mivehroud, Maryam; Fathi Maroufi, Nazila; Bargahi, Nasrin; Bannazadeh Amirkhiz, Maryam; Rashtchizadeh, Nadereh

    2015-01-01

    Introduction:There are many ideas concerning the etiology and pathogenesis of preeclampsia including endothelial dysfunction, inflammation and angiogenesis. Elevated levels of total homocysteine (Hcy) and lipoprotein (a) [Lp(a)] are risk factors for endothelial dysfunction. This study aimed to evaluate the effect of high dose folic acid (FA) on serum Hcy and Lp(a) concentrations with respect to methylenetetrahydrofolate reductase (MTHFR) polymorphisms 677C→T during pregnancy. Methods: In a prospective uncontrolled intervention, 90 pregnant women received 5 mg FA supplementation before pregnancy till 36th week of pregnancy. The MTHFR polymorphisms 677C→T, serum lactate dehydrogenase activity, urine protein and creatinine concentrations were measured before starting folic acid administration. Serum levels of Hcy and Lp(a) were determined before and after completion of folic acid supplementation period. Results: Supplementation of the patients with FA for 36 week decreased the median (minimum– maximum) levels of serum Hcy from 11.40 μmol/L (4.40-28.70) to 9.70 (1.60-20.80) μmol/L (p=0.001). There was no significant change in serum Lp(a) after FA supplementation (p=0.17). The overall prevalence of genotypes in pregnant women that were under study for MTHFR C677T polymorphism was 53.3% CC, 26.7% CT and 20.0% TT. There was no correlation between decreasing level of serum Hcy in the patients receiving FA and MTHFR polymorphisms. Conclusion:Although FA supplementation decreased serum levels of Hcy in different MTHFR genotypes, serum Lp(a) was not changed by FA supplements. Our data suggests that FA supplementation effects on serum Hcy is MTHFR genotype independent in pregnant women. PMID:26929921

  18. Fatty Acid Status and Its Relationship to Cognitive Decline and Homocysteine Levels in the Elderly

    PubMed Central

    Baierle, Marília; Vencato, Patrícia H.; Oldenburg, Luiza; Bordignon, Suelen; Zibetti, Murilo; Trentini, Clarissa M.; Duarte, Marta M. M. F.; Veit, Juliana C.; Somacal, Sabrina; Emanuelli, Tatiana; Grune, Tilman; Breusing, Nicolle; Garcia, Solange C.

    2014-01-01

    Polyunsaturated fatty acids (PUFAs), especially the n-3 series, are known for their protective effects. Considering that cardiovascular diseases are risk factors for dementia, which is common at aging, the aim of this study was to evaluate whether fatty acid status in the elderly was associated with cognitive function and cardiovascular risk. Forty-five elderly persons (age ≥60 years) were included and divided into two groups based on their Mini-Mental Status Examination score adjusted for educational level: the case group (n = 12) and the control group (n = 33). Serum fatty acid composition, homocysteine (Hcy), hs-CRP, lipid profile and different cognitive domains were evaluated. The case group, characterized by reduced cognitive performance, showed higher levels of 14:0, 16:0, 16:1n-7 fatty acids and lower levels of 22:0, 24:1n-9, 22:6n-3 (DHA) and total PUFAs compared to the control group (p < 0.05). The n-6/n-3 ratio was elevated in both study groups, whereas alterations in Hcy, hs-CRP and lipid profile were observed in the case group. Cognitive function was positively associated with the 24:1n-9, DHA and total n-3 PUFAs, while 14:0, 16:0 and 16:1n-7 fatty acids, the n-6/n-3 ratio and Hcy were inversely associated. In addition, n-3 PUFAs, particularly DHA, were inversely associated with cardiovascular risk, assessed by Hcy levels in the elderly. PMID:25221976

  19. Higher Fibrinogen Level is Independently Linked with the Presence and Severity of New-Onset Coronary Atherosclerosis among Han Chinese Population

    PubMed Central

    Zhang, Yan; Zhu, Cheng-Gang; Guo, Yuan-Lin; Xu, Rui-Xia; Li, Sha; Dong, Qian; Li, Jian-Jun

    2014-01-01

    Background Fibrinogen is a coagulation/inflammatory biomarker strongly associated with atherogenesis. However, no data is currently available regarding the association of fibrinogen level with the presence and severity of new-onset coronary atherosclerosis assessed by Gensini score (GS), particularly in Han Chinese with a large sample size. Methods and Results We studied 2288 consecutive, new-onset subjects undergoing coronary angiography with angina-like chest pain. Clinical and laboratory data were collected. Coronary stenotic lesions were considered to be the incidence of coronary atherosclerosis. The severity of coronary stenosis was determined by the GS system. Data indicated that patients with high GS had significantly elevated fibrinogen level (p<0.001). The prevalence and severity of coronary atherosclerosis were dramatically increased according to fibrinogen tertiles. Spearman correlation analysis revealed a positive association between fibrinogen level and GS (r = 0.138, p<0.001). Multivariate logistic regression analysis demonstrated that plasma fibrinogen level was independently associated with high GS (OR = 1.275, 95% CI 1.082–1.502, p = 0.004) after adjusting for potential confounders. Moreover, fibrinogen level was also independently related to the presence of coronary atherosclerosis (fibrinogen tertile 2: OR = 1.192, 95% CI 0.889–1.598, p = 0.241; tertile 3: OR = 2.003, 95% CI 1.383–2.903, p <0.001) and high GS (fibrinogen tertile 2: OR = 1.079, 95% CI 0.833–1.397, p = 0.565; tertile 3: OR = 1.524, 95% CI 1.155–2.011, p = 0.003) in a dose-dependent manner. Receiver-operating characteristic curve analysis showed that the best fibrinogen cut-off value for predicting the severity of coronary stenosis was 3.21 g/L. Conclusions Higher fibrinogen level is independently linked with the presence and severity of new-onset coronary atherosclerosis in Han Chinese population. PMID:25426943

  20. Plasma homocysteine levels related to interactions between folate status and methylenetetrahydrofolate reductase: a study in 52 healthy subjects.

    PubMed

    Zittoun, J; Tonetti, C; Bories, D; Pignon, J M; Tulliez, M

    1998-11-01

    Hyperhomocysteinemia, a risk factor for vascular disease, is related to vitamin B12, vitamin B6, and especially folate deficiency, or to genetic factors such as mutations in methylenetetrahydrofolate reductase (MTHFR), an enzyme involved in the remethylation pathway of homocysteine to methionine. Recently, a C677 --> T mutation identified in the MTHFR gene was found to be frequently associated with decreased MTHFR activity and an elevated plasma homocysteine concentration. Since hyperhomocysteinemia seems to be determined by both genetic and environmental factors, we studied the interactions between MTHFR (phenotype and genotype) and folate status, including methyltetrahydrofolate (methylTHF), the product of MTHFR, on the homocysteine concentration in 52 healthy subjects, (28 women and 24 men; mean age, 32.7 years). MTHFR activity seems to be dependent on folate status, as shown by a lower activity in folate-deficient subjects and a return to normal values after supplementation with folic acid, and also by a decreased enzymatic activity on phytohemagglutinin (PHA)-stimulated lymphocytes grown in a folic acid-deficient medium. Conversely, the C677 --> T mutation seems to influence folate metabolism. Subjects who were homozygous for this mutation (+/+) had significantly higher plasma homocysteine and lower plasma folate and total and methylfolate levels in red blood cells (RBCs) than heterozygous (+/-) and normal (-/-) subjects. The ratio of RBC methylfolate to RBC total folate was, respectively, 0.27 in +/+, 0.66 in +/-, and 0.71 in -/-. This mutation seems to have an impact on methylTHF generation. These data illustrate the interactions between nutritional and genetic factors. PMID:9826223

  1. C677T methylenetetrahydrofolate reductase and plasma homocysteine levels among Thai vegans and omnivores.

    PubMed

    Kajanachumpol, Saowanee; Atamasirikul, Kalayanee; Tantibhedhyangkul, Phieuvit

    2013-01-01

    Hyperhomocysteinemia among vegetarians and vegans is caused mostly by vitamin B12 deficiency. A C-to-T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene results in a thermolabile MTHFR, which may affect homocysteine (Hcy) levels. The importance of this gene mutation among populations depends on the T allele frequency. Blood Hcy, vitamin B12, folate, vitamin B6, and MTHFR C677T mutation status were determined in 109 vegans and 86 omnivores aged 30 - 50 years. The vegans had significantly higher Hcy levels than the omnivores, geometric means (95 % CI) 19.2 (17.0 - 21.7) µmol/L vs. 8.53 (8.12 - 8.95) µmol/L, p < 0.001. A C-to-T mutation in the vegans increased plasma Hcy, albeit insignificantly; geometric means 18.2 µmol/L, 20.4 µmol/L, and 30.0 µmol/L respectively in CC, CT, and TT MTHFR genotypes. There was also a significant decrease in serum folate; geometric means 12.1 ng/mL, 9.33 ng/mL, and 7.20 ng/mL respectively, in the CC, CT, and TT mutants, p = 0.006, and particularly, in the TT mutant compared with the CC wild type, 7.20 ng/mL vs. 12.1 ng/mL, p = 0.023. These findings were not seen in the omnivores. It was concluded that hyperhomocysteinemia is prevalent among Thai vegans due to vitamin B12 deficiency. C-to-T MTHFR mutation contributes only modestly to the hyperhomocysteinemia. PMID:24491881

  2. Fibrinogen Brescia

    PubMed Central

    Brennan, Stephen O.; Wyatt, Jane; Medicina, Daniela; Callea, Francesco; George, Peter M.

    2000-01-01

    The proposita suffered from liver cirrhosis and biopsy showed type 1 membrane-bound fiberglass inclusions. The hepatic inclusion bodies were weakly periodic acid-Schiff diastase-positive, and on immunoperoxidase staining reacted specifically with anti-fibrinogen antisera. Coagulation investigations revealed low functional and antigenic fibrinogen together with a prolonged thrombin time of 37 seconds (normal, 17 to 22 seconds) suggestive of a hypodysfibrinogenemia. DNA sequencing of all three fibrinogen genes showed a single heterozygous mutation of GGG (Gly)→CGG (Arg) at codon 284 of the γ-chain gene. However, examination of purified fibrinogen chains by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, reverse-phase high-performance liquid chromatography, ion-exchange high-performance liquid chromatography, and isoelectric focusing, failed to show any evidence of the mutant γBr chain in plasma fibrinogen. This finding was substantiated by electrospray ionization mass spectrometry, which showed only a normal γ (and Bβ) chain mass, but a large increase in the portion of their disialo isoforms. We speculate that misfolding of the variant protein causes hepatic retention and the subsequent hypofibrinogenemia, and that the functional defect (dysfibrinogenemia) results from hypersialylation of otherwise normal Bβ and γ chains consequent to the liver cirrhosis. These conclusions were supported by studies on six other family members with hypofibrinogenemia, and essentially normal clotting times, who were heterozygous for the γ284 Gly→Arg mutation. PMID:10880389

  3. Elevated Total Homocysteine Levels in Acute Ischemic Stroke Are Associated With Long-Term Mortality

    PubMed Central

    Shi, Zhihong; Guan, Yalin; Huo, Ya Ruth; Liu, Shuling; Zhang, Meilin; Lu, Hui; Yue, Wei; Wang, Jinhuan

    2015-01-01

    Background and Purpose— Total homocysteine (tHcy) levels are associated with secondary vascular events and mortality after stroke. The aim of this study was to investigate whether tHcy levels in the acute phase of a stroke contribute to the recurrence of cerebro-cardiovascular events and mortality. Methods— A total of 3799 patients were recruited after hospital admission for acute ischemic stroke. Levels of tHcy were measured within 24 hours after primary admission. Patients were followed for a median of 48 months. Results— During the follow-up period, 233 (6.1%) patients died. After adjustment for age, smoking status, diabetes mellitus, and other cardiovascular risk factors, patients in the highest tHcy quartile (>18.6 μmol/L) had a 1.61-fold increased risk of death (adjusted hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.03–2.53) compared with patients in the lowest quartile (≤10 μmol/L). Further subgroup analysis showed that this correlation was only significant in the large-artery atherosclerosis stroke subtype (adjusted HR, 1.80; 95% CI, 1.05–3.07); this correlation was not significant in the small-vessel occlusion subtype (adjusted HR, 0.80; 95% CI, 0.30–2.12). The risk of stroke-related mortality was 2.27-fold higher for patients in the third tHcy quartile (adjusted HR, 2.27; 95% CI, 1.06–4.86) and 2.15-fold more likely for patients in the fourth quartile (adjusted HR, 2.15; 95% CI, 1.01–4.63) than for patients in the lowest tHcy quartile. The risk of cardiovascular-related mortality and the risk of recurrent ischemic stroke were not associated with tHcy levels. Conclusions— Our findings suggest that elevated tHcy levels in the acute phase of an ischemic stroke can predict mortality, especially in stroke patients with the large-vessel atherosclerosis subtype. PMID:26199315

  4. Blood homocysteine and vitamin B levels are not associated with cognitive skills in healthy normally ageing subjects.

    PubMed

    Ravaglia, G; Forti, P; Maioli, F; Zanardi, V; Dalmonte, E; Grossi, G; Cucinotta, D; Macini, P; Caldarera, M

    2000-01-01

    Increased plasma total homocysteine (tHcy) levels are a known risk factor for vascular disease and have been reported in association with cognitive impairment of old age. Alternatively, however, increased tHcy levels may simply be an indicator of B vitamin deficiency. We evaluated the relationship between plasma tHcy levels, serum vitamin B12 and folate levels, and the scores at a battery of neuropsychological tests in 54 healthy cognitively normal subjects aged 65 years and over. Hyperhomocysteinemia prevalence (plasma tHcy>15 micromol/L) was about 24%. In univariate analysis, vitamin B12 levels were associated with both verbal memory and visuo-spatial skills, whereas no association was found between psychometric test scores and folate levels or tHcy levels. However, none of the univariate associations of neuropsychological test scores and serum B12 vitamin levels was confirmed when adjusting for age, education and other confounding variables. In conclusion, although a relationship between homocysteine, B vitamins and poor cognitive skills in the elderly is plausible, this study does not suggests that such relationship is biologically important. PMID:11115804

  5. Influence of heparin on fibrinogen and D-dimer plasma levels in acute myocardial infarction treated with streptokinase.

    PubMed

    Salvioni, A; Marenzi, G C; Agostoni, P; Grazi, S; Guazzi, M D

    1994-05-01

    The purpose of this study was to investigate whether, to what extent, and through which mechanisms intravenous heparin, administered before and after streptokinase, affects the plasma levels of D-dimer and fibrinogen in myocardial infarction. Data concerning mortality and incidence of coronary recanalization in patients receiving heparin and thrombolytic therapy after acute myocardial infarction are controversial; furthermore, the mechanisms through which heparin acts in combination with thrombolytic therapy are unclear. Thirty-eight patients with acute myocardial infarction treated with streptokinase were considered. Nineteen of them received, immediately before the beginning of thrombolytic treatment, a bolus of heparin (100 U.kg-1 intravenously) and, 2 h later, intravenous heparin in doses raising the partial thromboplastin time to 2-2.5 times the normal value (Group 1); the remaining 19 did not receive anticoagulant treatment (Group 2). Multiple determinations of plasma D-dimer and fibrinogen levels were obtained in all patients before, and in the seven days following thrombolytic treatment. Six hours after streptokinase, fibrinogen decreased from 304 +/- 34 to 61 +/- 34 mg.dl-1 in Group 1 and from 312 +/- 29 to 38 +/- 21 mg.dl-1 in Group 2 (P < 0.02 versus Group 1). The same difference between groups persisted at the 12th and at the 18th hour. D-dimer values, from 0.5 +/- 0.1 microgram.dl-1 in Group 1 and 0.4 +/- 0.1 microgram.dl-1 in Group 2, increased at the 1st hour to 37.2 +/- 36.5 micrograms.dl-1 and 52.2 +/- 39.8 micrograms.dl-1, respectively. A peak value was reached in both groups at the 6th hour, which was followed by a slow decrease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8056006

  6. Plasma homocysteine level is a risk factor for osteoporotic fractures in elderly patients

    PubMed Central

    Zhu, Yuefeng; Shen, Jie; Cheng, Qun; Fan, Yongqian; Lin, Weilong

    2016-01-01

    Objective To study the relationship of plasma homocysteine (Hcy), bone turnover biomarkers (BTB), and bone mineral density (BMD) with osteoporotic fracture (OPF) in elderly people. Methods Eighty-two patients (aged 65 years or older) admitted to our orthopedics department between October 2014 and May 2015 were randomly divided into three groups: 1) OPF group: 39 cases with the mean age 81.82±5.49 years, which included 24 females and 15 males; 2) high-energy fracture (HEF) group: 22 cases with the mean age 78.88±5.75 years, which included 16 females and six males; 3) non-bone-fracture group: 21 cases with mean age 79.75±5.47 years without bone fracture, which included 14 females and seven males. Plasma Hcy, BTB, and BMD were measured. Analysis of variance and multiple regression analysis were used in the statistical analysis. Results There was no significant difference in either age or sex among the three groups. There were significant differences in plasma Hcy and hip BMD between the OPF and HEF groups; there was also significant difference in plasma Hcy, 25-(OH) Vit D, and hip BMD between the OPF and non-fracture groups. There was no difference in lumbar spine BMD between the OPF group and the other two groups. There was no significant difference in plasma Hcy, 25-(OH) Vit D, hip or lumbar spine BMD between the HEF and non-fracture group. There was no significant difference in procollagen type I N-propeptide of type I collagen, serum C-terminal cross-linking telopeptide of type I collagen, and parathyroid hormone among the three groups. Plasma Hcy was linearly correlated with age and serum C-terminal cross-linking telopeptide of type I collagen, but not correlated with either hip or lumbar spine BMD or any other BTBs. Conclusion In this study, we found that the plasma Hcy level in elderly patients with OPF is higher than that of nonosteoporotic patients. It is not correlated with BMD, but positively correlated with bone resorption markers. An increased Hcy

  7. Levels of circulating homocysteine, vitamin B6, vitamin B12, and folate in different types of open-angle glaucoma

    PubMed Central

    Turgut, Burak; Kaya, Murat; Arslan, Sermal; Demir, Tamer; Güler, Mete; Kaya, Mehmet Kaan

    2010-01-01

    Objective: To compare the levels of plasma homocysteine (Hcy), vitamin B6 (vit-B6), serum vitamin B12 (vit-B12), and folate in healthy individuals and in patients with normal tension glaucoma (NTG), pseudoexfoliative glaucoma (PXG), or primary open-angle glaucoma (POAG). Study design: A prospective controlled trial. Participants and methods: Forty healthy subjects, 48 patients with NTG, 38 patients with PXG, and 34 patients with POAG were included in the study. Those who used vitamin supplements or medications affecting Hcy and vitamin levels were excluded from the study. The levels of Hcy and vit-B6 were measured by High Performance Liquid Chromatography (HPLC). The levels of serum vit-B12 and folic acid were measured by competitive chemiluminescent enzyme immunoassay (CEI). One-way analysis if variance (ANOVA), analysis of covariance (ANCOVA), and the Tukey honestly significant difference test were used for statistical analysis. Results: The mean Hcy level of the PXG group was 15.46 ± 9.27 μmol/L which was significantly higher (P = 0.03) than that of the control group. There were no statistical differences in serum vit-B12 and folate levels among control subjects and NTG, PXG and POAG groups (P > 0.05). It was found that the mean plasma vit-B6 level was significantly higher in subjects with NTG (P = 0.03) and POAG (P = 0.025) versus controls. Mean vit-B6 levels in NTG and POAG were 30.50 ± 11.29 μg/L and 30 ± 12.15 μg/L, respectively. Conclusions: The plasma level of Hcy was found to be increased only in PXG patients and the plasma levels of vit-B6 were found to increase in the NTG and POAG sample groups. Using homocysteine and vit-B6 levels as the determinants of hyperhomocysteinemia still needs further research. PMID:20458351

  8. High levels of homocysteine downregulate apolipoprotein E expression via nuclear factor kappa B

    PubMed Central

    Trusca, Violeta G; Mihai, Adina D; Fuior, Elena V; Fenyo, Ioana M; Gafencu, Anca V

    2016-01-01

    AIM: To investigate the effect of high homocysteine (Hcy) levels on apolipoprotein E (apoE) expression and the signaling pathways involved in this gene regulation. METHODS: Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot were used to assess apoE expression in cells treated with various concentrations (50-500 μmol/L) of Hcy. Calcium phosphate-transient transfections were performed in HEK-293 and RAW 264.7 cells to evaluate the effect of Hcy on apoE regulatory elements [promoter and distal multienhancer 2 (ME2)]. To this aim, plasmids containing the proximal apoE promoter [(-500/+73)apoE construct] alone or in the presence of ME2 [ME2/(-500/+73)apoE construct] to drive the expression of the reporter luciferase gene were used. Co-transfection experiments were carried out to investigate the downstream effectors of Hcy-mediated regulation of apoE promoter by using specific inhibitors or a dominant negative form of IKβ. In other co-transfections, the luciferase reporter was under the control of synthetic promoters containing multiple specific binding sites for nuclear factor kappa B (NF-κB), activator protein-1 (AP-1) or nuclear factor of activated T cells (NFAT). Chromatin immunoprecipitation (ChIP) assay was accomplished to detect the binding of NF-κB p65 subunit to the apoE promoter in HEK-293 treated with 500 μmol/L Hcy. As control, cells were incubated with similar concentration of cysteine. NF-κB p65 proteins bound to DNA were immunoprecipitated with anti-p65 antibodies and DNA was identified by PCR using primers amplifying the region -100/+4 of the apoE gene. RESULTS: RT-PCR revealed that high levels of Hcy (250-750 μmol/L) induced a 2-3 fold decrease in apoE mRNA levels in HEK-293 cells, while apoE gene expression was not significantly affected by treatment with lower concentrations of Hcy (100 μmol/L). Immunoblotting data provided additional evidence for the negative role of Hcy in apoE expression. Hcy decreased apoE promoter

  9. Plasma folate, but not homocysteine, is associated with Apolipoprotein A1 levels in a non-fortified population

    PubMed Central

    2013-01-01

    Background Elevated total plasma homocysteine (tHcy) in humans is associated with cardiovascular disease but prevention trials have failed to confirm causality. Reported reasons for this association have been that homocysteine and its major genetic determinant methylenetetrahydrofolate reductase (MTHFR) may have an effect on HDL and Apolipoprotein (Apo) A1 levels. We wanted to study if tHcy and its major determinants were correlated with Apo A1 levels in a large population without folate fortification. Methods This study was a prospective incident nested case-referent study within the Northern Sweden Health and Disease Study Cohort (NSHDSC), including 545 cases with first myocardial infarction and 1054 matched referents, median age at inclusion was 59 years. Univariate and multiple regression analyzes was used to study the associations between apolipoproteins Apo A1 and B, tHcy, folate and vitamin B12 in plasma as well as MTHFR polymorphisms 677C>T and 1298A>C. Results Apo A1 and Apo B were strongly associated with the risk of a first myocardial infarction. tHcy was not associated with Apo A1 levels. Instead, folate had an independent positive association with Apo A1 levels in univariate and multiple regression models. The associations were seen in all men and women, among referents but not among cases. MTHFR polymorphisms had no clear effect on Apo A1 levels. Conclusions Analyzing over 1500 subjects we found an independent positive association between plasma folate (major dietary determinant of tHcy) and Apo A1 levels among those who later did not develop a first myocardial infarction. No association was seen between tHcy and Apo A1. PMID:23697869

  10. A Quantile Regression Approach Can Reveal the Effect of Fruit and Vegetable Consumption on Plasma Homocysteine Levels

    PubMed Central

    Verly-Jr, Eliseu; Steluti, Josiane; Fisberg, Regina Mara; Marchioni, Dirce Maria Lobo

    2014-01-01

    Introduction A reduction in homocysteine concentration due to the use of supplemental folic acid is well recognized, although evidence of the same effect for natural folate sources, such as fruits and vegetables (FV), is lacking. The traditional statistical analysis approaches do not provide further information. As an alternative, quantile regression allows for the exploration of the effects of covariates through percentiles of the conditional distribution of the dependent variable. Objective To investigate how the associations of FV intake with plasma total homocysteine (tHcy) differ through percentiles in the distribution using quantile regression. Materials and Methods A cross-sectional population-based survey was conducted among 499 residents of Sao Paulo City, Brazil. The participants provided food intake and fasting blood samples. Fruit and vegetable intake was predicted by adjusting for day-to-day variation using a proper measurement error model. We performed a quantile regression to verify the association between tHcy and the predicted FV intake. The predicted values of tHcy for each percentile model were calculated considering an increase of 200 g in the FV intake for each percentile. Results The results showed that tHcy was inversely associated with FV intake when assessed by linear regression whereas, the association was different when using quantile regression. The relationship with FV consumption was inverse and significant for almost all percentiles of tHcy. The coefficients increased as the percentile of tHcy increased. A simulated increase of 200 g in the FV intake could decrease the tHcy levels in the overall percentiles, but the higher percentiles of tHcy benefited more. Conclusions This study confirms that the effect of FV intake on lowering the tHcy levels is dependent on the level of tHcy using an innovative statistical approach. From a public health point of view, encouraging people to increase FV intake would benefit people with high levels

  11. A Phospholipid-Protein Complex from Antarctic Krill Reduced Plasma Homocysteine Levels and Increased Plasma Trimethylamine-N-Oxide (TMAO) and Carnitine Levels in Male Wistar Rats

    PubMed Central

    Bjørndal, Bodil; Ramsvik, Marie S.; Lindquist, Carine; Nordrehaug, Jan E.; Bruheim, Inge; Svardal, Asbjørn; Nygård, Ottar; Berge, Rolf K.

    2015-01-01

    Seafood is assumed to be beneficial for cardiovascular health, mainly based on plasma lipid lowering and anti-inflammatory effects of n-3 polyunsaturated fatty acids. However, other plasma risk factors linked to cardiovascular disease are less studied. This study aimed to penetrate the effect of a phospholipid-protein complex (PPC) from Antarctic krill on one-carbon metabolism and production of trimethylamine-N-oxide (TMAO) in rats. Male Wistar rats were fed isoenergetic control, 6%, or 11% PPC diets for four weeks. Rats fed PPC had reduced total homocysteine plasma level and increased levels of choline, dimethylglycine and cysteine, whereas the plasma level of methionine was unchanged compared to control. PPC feeding increased the plasma level of TMAO, carnitine, its precursors trimethyllysine and γ-butyrobetaine. There was a close correlation between plasma TMAO and carnitine, trimethyllysine, and γ-butyrobetaine, but not between TMAO and choline. The present data suggest that PPC has a homocysteine lowering effect and is associated with altered plasma concentrations of metabolites related to one-carbon metabolism and B-vitamin status in rats. Moreover, the present study reveals a non-obligatory role of gut microbiota in the increased plasma TMAO level as it can be explained by the PPC’s content of TMAO. The increased level of carnitine and carnitine precursors is interpreted to reflect increased carnitine biosynthesis. PMID:26371012

  12. Increased glutamate and homocysteine and decreased glutamine levels in autism: a review and strategies for future studies of amino acids in autism.

    PubMed

    Ghanizadeh, Ahmad

    2013-01-01

    There are many reports about the significant roles of some amino acids in neurobiology and treatment of autism. This is a critical review of amino acids levels in autism. No published review article about the level of amino acids in autism was found. The levels of glutamate and homocystein are increased in autism while the levels of glutamine and tryptophan are decreased. Findings regarding the plasma levels of taurine and lysine are controversial. The urinary levels of homocysteine and essential amino acids in both the untreated and treated autistic children are significantly less than those in the controls. The current literature suffers from many methodological shortcomings which needed to be considered in future studies. Some of them are age, gender, developmental level, autism symptoms severity, type of autism spectrum disorders, medical comorbidities, intelligent quotient, diet, concomitant medications, body mass index, and technical method of assessment of amino acids. PMID:24167375

  13. Preoperative Plasma Fibrinogen Level Represents an Independent Prognostic Factor in a Chinese Cohort of Patients with Upper Tract Urothelial Carcinoma

    PubMed Central

    Jin, Jie; Zhou, Li-Qun; He, Zhi-Song; Shen, Cheng; He, Qun; Li, Jun; Liu, Li-Bo; Wang, Cong; Chen, Xiao-Yu; Fan, Yu; Hu, Shuai; Zhang, Lei; Yu, Wei; Han, Wen-Ke

    2016-01-01

    Background Increased plasma fibrinogen is thought to contribute to tumor progression and metastasis. The association of plasma fibrinogen with clinicopathological characteristics, and the optimal cutoff with an ideal predictive value has not been fully determined in patients with upper tract urothelial carcinoma (UTUC). We aimed to investigate the clinical significance of this parameter in a Chinese cohort of patients with UTUC. Methods A retrospective study was conducted to analyze the clinical data of 184 operable UTUC patients in a Chinese cohort with a high incidence of chronic kidney disease (CKD). An optimal cutoff was set for further analysis according to validated web-based software. The associations of plasma fibrinogen with clinicopathological characteristics and survival were assessed. Multivariate analyses were performed to determine the independent prognostic factors. Results Elevated plasma fibrinogen was significantly associated with tumor necrosis, lymph node involvement, and a higher preoperative CKD stage, pathological tumor stage and grade (all P < 0.05). Kaplan-Meier analysis showed that plasma fibrinogen ≥ 3.54 g/L predicted a poorer overall and cancer-specific survival than < 3.54 g/L (P < 0.001 for both). Multivariate analyses revealed that elevated preoperative plasma fibrinogen was an independent negative prognostic factor for overall survival (HR = 2.026; 95% CI: 1.226–3.349; P = 0.006) and cancer-specific survival (HR = 1.886; 95% CI: 1.019–3.490; P = 0.043). Conclusions Increased plasma fibrinogen was an independent prognostic risk factor for poor outcomes in UTUC. This parameter may serve as an effective biomarker with easy accessibility for evaluating prognosis for patients with UTUC. PMID:26930207

  14. The changing of serum vitamin B12 and homocysteine levels after gastrectomy in patients with gastric cancer: do they associate with clinicopathological factors?

    PubMed

    Bilici, Ahmet; Sonkaya, Alper; Ercan, Serif; Ustaalioglu, Bala Basak Oven; Seker, Mesut; Aliustaoglu, Mehmet; Orcun, Asuman; Gumus, Mahmut

    2015-02-01

    After total (TG) or distal subtotal gastrectomy (DG), patients are at high risk of vitamin B12 (vit-B12) deficiency, which results in elevation of homocysteine levels. The changing of serum vit-B12 and homocysteine levels in patients with gastric cancer is not well known. Seventy-two patients with gastric cancer who had undergone currative gastrectomy and 50 healthy controls were included. Serum vit-B12 and homocysteine levels were analyzed in gastric cancer patients. In addition, these parameters were compared with those of healthy control subjects. While serum vit-B12 levels in gastrectomized patients were significantly lower than that of healthy controls (221.8 ± 125.6 pg/mL vs. 309.9 ± 174.3 pg/mL, p = 0.002), homocysteine levels were significantly higher in patients with gastric cancer (14.2 ± 6.7 μmol/L vs. 12.5 ± 6.1 μmol/L, p = 0.016). Mean serum folate level was found to be high in healthy controls (7.3 ng/mL) compared to patients (9.2 ng/mL, p = 0.027). Out of 72 patients, 40 patients (55.6 %) with gastric cancer developed vit-B12 deficiency after gastrectomy. Vit-B12 deficiency was found to be related with gastrectomy type (p = 0.02) and homocysteine levels (p = 0.014). In patients who underwent TG, the incidence of vit-B12 deficiency was significantly higher compared with those with DG (67.5 vs. 32.5 %). In addition, serum vit-B12 level in patients with DG was significantly higher than that of patients with TG (248.3 ± 122.0 pg/mL vs. 200.8 ± 126.7 pg/mL, p = 0.041), whereas homocysteine levels were significantly lower in DG group compared with TG group (12.1 ± 6.1 μmol/L vs. 15.8 ± 6.9 μmol/L, p = 0.014). A logistic regression analysis showed that the extent of gastrectomy was found to be an independent factor for predicting the occurrence of vit-B12 deficiency (p < 0.001, odds ratio 1.38). Our results showed that cumulative vit-B12 deficiency rate was significantly higher

  15. Serum levels of homocysteine, folate and vitamin B12 in patients with vitiligo before and after treatment with narrow band ultraviolet B phototherapy and in a group of controls.

    PubMed

    Ataş, Hatice; Cemil, Bengü Çevirgen; Gönül, Müzeyyen; Baştürk, Eda; Çiçek, Emel

    2015-07-01

    The association between vitamin B12, folate, homocysteine and vitiligo were studied in several studies, but the results are contradictory. Narrow-band ultraviolet B (NBUVB) phototherapy is now considered as a gold standard for the treatment of diffuse vitiligo. The effects of NBUVB phototherapy on both vitamin B12, folate and homocysteine levels have not been studied in vitiligo patients yet. Serum levels of vitamin B12, folate and homocysteine were measured in vitiligo patients and control group and also both before and after NBUVB phototherapy in vitiligo patients. While levels of homocysteine in patients with vitiligo were significantly higher than controls (16.9±8.4 vs. 10. 9±3.4 μmol/L; p<0,001) vitamin B12 and folate levels were not different (p>0.05). NBUVB phototherapy led to a 33.7±21.9% (0-75%) response in patients with vitiligo after 80 seccions. Treatment with NBUVB improved vitiligo and decreased serum levels of vitamin B12 (375±151 vs. 346±119 pg/ml, p=0.024), while serum levels of folate and homocysteine did not change significantly after treatment (p=0.914, p=0.127). Further studies are needed to clarify the influence of NBUVB phototherapy on folate, vitamin B12 and homocysteine levels in patients with vitiligo. Furthermore, studies with the analysis of skin levels of homocysteine rather than circulating levels may be useful to elucidate the effects of phototherapy on homocysteine levels. PMID:25941975

  16. The determination of homocysteine-thiolactone in biological samples.

    PubMed

    Jakubowski, Hieronim

    2002-09-01

    Homocysteine-thiolactone, a cyclic thioester of homocysteine, is synthesized by methionyl-tRNA synthetase in all cell types. A new assay for the determination of homocysteine-thiolactone in biological samples is described. The assay involves separation of homocysteine-thiolactone from macromolecules by ultrafiltration. Homocysteine-thiolactone is further purified and quantified by high-pressure liquid chromatography either on a reverse phase or a cation exchange micro-bore column. The detection and quantitation are obtained by monitoring the absorbance at 240 nm, a maximum in a UV spectrum of homocysteine-thiolactone. The sensitivity of detection is 5 pmol. This assay has been applied to bacteria (Escherichia coli and Mycobacterium smegmatis), the yeast Saccharomyces cerevisiae, cultured human vascular endothelial cells, and human plasma. The data support the conclusion that homocysteine-thiolactone is a ubiquitous metabolite whose levels are directly related to homocysteine levels. PMID:12234471

  17. Assessment of Folic Acid Supplementation in Pregnant Women by Estimation of Serum Levels of Tetrahydrofolic Acid, Dihydrofolate Reductase, and Homocysteine

    PubMed Central

    Saxena, Vartika; Mirza, Anissa Atif; Kumari, Ranjeeta; Sharma, Kapil; Bharadwaj, Jyoti

    2016-01-01

    Background. Status of folic acid use in pregnant women of the hilly regions in North India was little known. This study was carried out to assess the folic acid use and estimate folate metabolites in pregnant women of this region. Materials and Methods. This cross-sectional study is comprised of 76 pregnant women, whose folic acid supplementation was assessed by a questionnaire and serum levels of homocysteine, tetrahydrofolic acid (THFA), and dihydrofolate reductase (DHFR) were estimated using Enzyme Linked Immunoassays. Results. The study data revealed awareness of folic acid use during pregnancy was present in 46.1% and 23.7% were taking folic acid supplements. The study depicted that there was no statistically significant difference between serum levels of THFA and DHFR in pregnant women with and without folic acid supplements (p = 0.790). Hyperhomocysteinemia was present in 15.78% of the participants. Conclusion. Less awareness about folic acid supplementation and low use of folic acid by pregnant women were observed in this region. Sufficient dietary ingestion may suffice for the escalated requirements in pregnancy, but since this cannot be ensured, hence folic acid supplementation should be made as an integral part of education and reproductive health programs for its better metabolic use, growth, and development of fetus. PMID:27064332

  18. Elevated Serum Levels of Homocysteine as an Early Prognostic Factor of Psychiatric Disorders in Children and Adolescents

    PubMed Central

    Kevere, Laura; Purvina, Santa; Bauze, Daiga; Zeibarts, Marcis; Andrezina, Raisa; Rizevs, Arnis; Jelisejevs, Sergejs; Piekuse, Linda; Kreile, Madara; Purvins, Indulis

    2012-01-01

    Background and Goal. The aim was to examine the serum levels of homocysteine (Hcy) and their associations with the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism in patients with schizophrenia and mood disorders as well as controls. Materials and Methods. There were 198 patients: 82 with schizophrenia spectrum disorders, 22 with mood disorders, and 94 controls. The level of Hcy was determined by an isocratic high-performance liquid chromatography system. MTHFR C677T polymorphism was analysed using the restriction fragment length polymorphism-polymerase chain reaction method. Results. The average level of Hcy was 11.94 ± 5.6 μmol/L for patients with schizophrenia, 11.65 ± 3.3 μmol/L for patients with affective disorders, versus 6.80 ± 2.93 μmol/L in a control. The highest level of Hcy has been observed in patients with episodic-recurrent course of schizophrenia (11.30 ± 7.74 μmol/L), paranoid schizophrenia continuous (12.76 ± 5.25 μmol/L), and in patients with affective disorders (11.65 ± 3.26 μmol/L). An association between the MTHFR gene C677T polymorphism and Hcy level was found by linear regression analysis (r = 1.41, P = 0.029). Conclusions. The data indicate a link between Hcy levels and schizophrenia and mood disorders. No associations between the level of Hcy in patients with schizophrenia and mood disorders and the MTHFR C677T polymorphism were found. PMID:23091720

  19. Prognostic Value of Elevated Homocysteine Levels in Korean Patients with Coronary Artery Disease: A Propensity Score Matched Analysis

    PubMed Central

    Kwon, Sung Woo; Kim, Jong-Youn; Suh, Young Ju; Lee, Dae Hyung; Yoon, Young Won; Lee, Byoung Kwon; Jung, Young-Hak; Choi, Eui-Young; Hong, Bum-Kee; Rim, Se-Joong

    2016-01-01

    Background and Objectives We sought to determine whether an elevated homocysteine (Hcy) level is associated with a worse prognosis in Korean patients with coronary artery disease (CAD). Subjects and Methods A total of 5839 patients (60.4% male, mean age 61.3±11.2 years) with CAD were enrolled from 2000 to 2010 at Gangnam Severance Hospital. CAD was diagnosed by invasive coronary angiography. Laboratory values including Hcy level were obtained on the day of coronary angiography and analyses were performed shortly after sampling. Patients were divided into two groups according to their Hcy levels. Baseline risk factors, coronary angiographic findings, length of follow-up, and composite endpoints including cardiac death (CD) and non-fatal myocardial infarction (NFMI) were recorded. 1:1 propensity score matched analysis was also performed. Results Over a mean follow-up period of 4.4±2.5 years, there were 132 composite endpoints (75 CD and 57 NFMI) with an event rate of 2.3%. Mean Hcy level was 9.9±4.3 µmol/L (normal Hcy 7.9±1.5 µmol/L and elevated Hcy 13.9±5.1 µmol/L). Kaplan-Meier survival analysis showed an association of elevated Hcy level with worse prognosis (p<0.0001). In addition, a multivariate Cox regression analysis showed an association of elevated Hcy level with worse prognosis for both the entire cohort (hazard ratio [HR] 2.077, 95% confidence interval [CI] 1.467-2.941, p<0.0001) and the propensity score matched cohort (HR 1.982, 95% CI 1.305-3.009, p=0.001). Conclusion Elevated Hcy level is associated with worse outcomes in Korean patients with CAD. PMID:27014345

  20. Homocysteine and essential hypertension.

    PubMed

    Rodrigo, Ramón; Passalacqua, Walter; Araya, Julia; Orellana, Myriam; Rivera, Gonzalo

    2003-12-01

    The authors examine the available clinical and experimental data supporting the view that homocysteine, an alternative risk factor of cardiovascular disease, may play a role in the pathogenesis of essential hypertension. The mechanism of this disease has not been elucidated, but it may be related to impairment of vascular endothelial and smooth muscle cell function. Therefore, the occurrence of endothelial dysfunction could contribute to alterations of the endothelium-dependent vasomotor regulation. Elevated homocysteinemia diminishes the vasodilation by nitric oxide, increases oxidative stress, stimulates the proliferation of vascular smooth muscle cells, and alters the elastic properties of the vascular wall. Thus, homocysteine contributes to elevate the blood pressure. Also it is known that elevated plasma levels of homocysteine could lead to oxidant injury to the endothelium. The correction of elevated homocysteinemia by administration of vitamins B12 and B6 plus folic acid, could be a useful adjuvant therapy of hypertension. However, further controlled randomized trials are necessary to establish the efficacy and tolerability of these potentially therapeutic agents. PMID:14615465

  1. Evolution of procalcitonin, C-reactive protein and fibrinogen levels in neutropenic leukaemia patients with invasive pulmonary aspergillosis or mucormycosis.

    PubMed

    Roques, Marjorie; Chretien, Marie Lorraine; Favennec, Camille; Lafon, Ingrid; Ferrant, Emmanuelle; Legouge, Caroline; Plocque, Alexia; Golfier, Camille; Duvillard, Laurence; Amoureux, Lucie; Bastie, Jean Noel; Maurin-Bernier, Lory; Dalle, Frederic; Caillot, Denis

    2016-06-01

    Unlike bacterial infections, the value of procalcitonin (PCT) in detecting fungal infections in leukaemia patients is not clear. To determine whether the monitoring of PCT coupled with C-reactive protein (CRP) and fibrinogen (Fib) could be helpful in the management of pulmonary aspergillosis (IPA) or mucormycosis (PM), we retrospectively analysed the evolution of PCT, CRP and Fib levels in 94 leukaemia patients with proven/probable IPA (n = 77) or PM (n = 17) from D-12 to D12 relative to IFI onset defined as D0. Overall, 2140 assays were performed. From D-12 to D0, 12%, 5% and 1.4% of patients had PCT >0.5, 1 and 1.5 μg l(-1) , respectively, while CRP was >50, 75 and 100 mg l(-1) in 84%, 70% and 57% and Fib was >4, 5 and 6 g l(-1) in 96%, 80% and 61% of cases respectively (P < 10(-7) ). The same trends were observed from D1 to D12. Overall, between D-12 and D12, only 6.4% of patients had PCT >1.5 μg l(-1) , while CRP >100 mg l(-1) and Fib >6 g l(-1) were observed in 80% and 75% of cases respectively (P < 10(-7) ). In leukaemia patients, IPA or PM was accompanied by a significant increase in CRP and Fib while PCT remained low. PMID:26931315

  2. Circulating levels of fibrin/fibrinogen degradation fragment E in normal pregnancy, and in association with intrauterine growth retardation and perinatal asphyxia.

    PubMed

    Gordon, Y B; Ratky, S M; Sola, C M; Lewis, J; Baker, L R; Chard, T

    1975-12-01

    Levels of fibrin/fibrinogen degradation products have been measured by aspecific and sensitive radioimmunoassay for degradation fragment E (FgE) in pregnant patients. Maternal FgE levels rose from the 16th week reaching a plateau at the 36th week in normal pregnancy. There was no correlation between maternal FgE levels and maternal age, parity or the occurrence of perinatal asphyxia. A minority of patients (5 per cent) with evidence of intrauterine growth retardation showed prolonged elevation of FgE levels. PMID:1203212

  3. High homocysteine levels prevent via H2 S the CoCl2 -induced alteration of lymphocyte viability.

    PubMed

    Bruzzese, Laurie; Fenouillet, Emmanuel; Fromonot, Julien; Durand-Gorde, Josée-Martine; Condo, Jocelyne; Kipson, Nathalie; Mottola, Giovanna; Deharo, Pierre; Guieu, Régis; Ruf, Jean

    2016-08-01

    High homocysteine (HCy) levels are associated with lymphocyte-mediated inflammatory responses that are sometimes in turn related to hypoxia. Because adenosine is a potent lymphocyte suppressor produced in hypoxic conditions and shares metabolic pathways with HCy, we addressed the influence of high HCy levels on the hypoxia-induced, adenosine-mediated, alteration of lymphocyte viability. We treated mitogen-stimulated human lymphocytes isolated from healthy individuals and the human lymphoma T-cell line CEM with cobalt chloride (CoCl2 )to reproduce hypoxia. We found that CoCl2 -altered cell viability was dose-dependently reversed using HCy. In turn, the HCy effect was inhibited using DL-propargylglycine, a specific inhibitor of the hydrogen sulphide (H2 S)-synthesizing enzyme cystathionine-γ-lyase involved in HCy catabolism. We then addressed the intracellular metabolic pathway of adenosine and HCy, and the role of the adenosine A2A receptor (A2 A R). We observed that: (i) hypoxic conditions lowered the intracellular concentration of HCy by increasing adenosine production, which resulted in high A2 A R expression and 3', 5'-cyclic adenosine monophosphate production; (ii) increasing intracellular HCy concentration reversed the hypoxia-induced adenosinergic signalling despite high adenosine concentration by promoting both S-adenosylhomocysteine and H2 S production; (iii) DL-propargylglycine that inhibits H2 S production abolished the HCy effect. Together, these data suggest that high HCy levels prevent, via H2 S production and the resulting down-regulation of A2 A R expression, the hypoxia-induced adenosinergic alteration of lymphocyte viability. We point out the relevance of these mechanisms in the pathophysiology of cardiovascular diseases. PMID:27061011

  4. Plasma total homocysteine level in association with folate, pyridoxine, and cobalamin status among Iranian primary breast cancer patients.

    PubMed

    Pirouzpanah, Saeed; Taleban, Forough-Azam; Mehdipour, Parvin; Atri, Morteza; Foroutan-Ghaznavi, Mitra

    2014-01-01

    Recently the elevated plasma total homocysteine (tHcy) concentration has been concerned as the secondary feature of tumoral proliferation and enhances the likelihood of thrombogenesis in cancer patients. The objective of this study was to determine the associations between folate, cobalamin, and pyridoxine with fasting plasma tHcy concentration in breast cancer (BC) patients. The intake levels of nutrients were assessed using a validated food frequency questionnaire in 141 newly diagnosed BC patients. The plasma tHcy and pyridoxal-5-phosphate were measured using high performance liquid chromatography with fluorescence detector. Plasma tHcy levels were observed to be significantly higher among BC participants with Stage III where the plasma concentrations of folate was also comparatively less (P < 0.05) than other stages. Dietary pyridoxine was even being consumed less at this stage (P < 0.05). The plasma, dietary, and residual variables of folate were inversely correlated with plasma tHcy concentration (P < 0.05). Dietary cobalamin was also associated negatively with tHcy (P < 0.05). The odds ratio of comparing the highest tertile of plasma cobalamin (>394 pmol/l) and folate (>11.4 ng/ml) vs. the lowest categories were associated with reduced odds of high tHcy occurrence with 0.20 (95% confidence interval: 0.04-0.98) and 0.14 (95% confidence interval: 0.03-0.64), respectively. In conclusion, nutrition-related methyl-group insufficiency could lead to imbalance in tHcy metabolism, as a possible cancer marker. PMID:25157842

  5. Homocysteine and cognitive function in elderly people.

    PubMed

    Garcia, Angeles; Zanibbi, Katherine

    2004-10-12

    Dementia is highly prevalent among elderly people, and projections show that the number of people affected might triple over the next 50 years, mainly because of a large increase in the oldest-old segment of the population. Because of this and the disease's devastating effects, measures for the prevention and early detection of dementia are crucial. Age and years of education are among the most relevant risk factors for dementia, but in recent years the role of homocysteine has also been investigated. Homocysteine is an amino acid produced in the metabolism of methionine, a process dependent on the B vitamins cobalamin, vitamin B6 and folic acid. There is evidence that increased serum homocysteine levels are associated with declining cognitive function and dementia. We review this evidence in addition to the potential mechanisms through which homocysteine acts on the brain to cause cognitive dysfunction, the metabolism of homocysteine and factors associated with alteration of the normal metabolism. PMID:15477631

  6. Molecular mechanisms of homocysteine toxicity.

    PubMed

    Boldyrev, A A

    2009-06-01

    Hyperhomocysteinemia is a risk factor for a number of cardiovascular and neurodegenerative processes as well as a complicating factor in normal pregnancy. Toxic effects of homocysteine and the product of its spontaneous oxidation, homocysteic acid, are based on their ability to activate NMDA receptors, increasing intracellular levels of ionized calcium and reactive oxygen species. Even a short-term exposure of cells to homocysteic acid at concentrations characteristic of hyperhomocysteinemia induces their apoptotic transformation. The discovery of NMDA receptors both in neuronal tissue and in several other tissues and organs (including immunocompetent cells) makes them a target for toxic action of homocysteine. The neuropeptide carnosine was found to protect the organism from homocysteine toxicity. Treatment of pregnant rats with carnosine under conditions of alimentary hyperhomocysteinemia increases viability and functional activity of their progeny. PMID:19645662

  7. Elevated homocysteine levels in human immunodeficiency virus-infected patients under antiretroviral therapy: A meta-analysis

    PubMed Central

    Deminice, Rafael; Silva, Talita Capoani Vieira; de Oliveira, Vitor Hugo Fernando

    2015-01-01

    AIM: To evaluate the association between the levels of homocysteine (Hcy), folate, vitamin B12 in human immunodeficiency virus (HIV)-infected patients who were treated with antiretroviral therapy (ART) or not treated with ART. METHODS: The PubMed and Scielo databases were searched. Eligible studies regarding plasma Hcy level in HIV-infected patients were firstly identified. After careful analysis by two independent researches, the identified articles were included in the review according to two outcomes (1) Hcy, folate and vitamin B12 blood concentration in HIV-infected subjects vs health controls and; (2) Hcy blood concentration in HIV-infected subjects under ART vs not treated with ART. RevMan (version 5.2) was employed for data synthesis. RESULTS: A total of 12 studies were included in outcome 1 (1649 participants, 932 cases and 717 controls). Outcome 1 meta-analysis demonstrated higher plasma Hcy (2.05 µmol/L; 95%CI: 0.10 to 4.00, P < 0.01) and decreased plasma folate concentrations (-2.74 ng/mL; 95%CI: -5.18 to -0.29, P < 0.01) in HIV-infected patients compared to healthy controls. No changes in vitamin B12 plasma concentration were observed between groups. All studies included in the outcome 2 meta-analysis (1167 participants; 404 HIV-infected exposed to ART and 757 HIV-infected non-ART patients) demonstrated higher mean Hcy concentration in subjects HIV-infected under ART compared to non-ART HIV subjects (4.13 µmol/L; 95%CI: 1.34 to 6.92, P < 0.01). CONCLUSION: This meta-analysis demonstrated that the levels of Hcy and folate, but not vitamin B12, were associated with HIV infection. In addition, Hcy levels were higher in HIV-infected patients who were under ART compared to HIV-infected patients who were not exposed to ART. Our results suggest that hyperhomocysteinemia should be included among the several important metabolic disturbances that are associated with ART in patients with HIV infection. PMID:25964880

  8. Plasma homocysteine levels, methylene tetrahydrofolate reductase A1298C gene polymorphism and risk of retinal vein thrombosis.

    PubMed

    Ghaznavi, Habib; Soheili, Zahra; Samiei, Shahram; Soltanpour, Mohammad Soleiman

    2016-09-01

    There are limited data regarding the role of methylene tetrahydrofolate reductase (MTHFR) A1298C polymorphism and hyperhomocysteinemia as risk factors for retinal vein thrombosis (RVT) in Iranians. This study aimed to examine a possible association between fasting plasma total homocysteine (tHcy) levels, MTHFR A1298C polymorphism and RVT development in Iranian patients. Our study population consisted of 73 patients with a diagnosis of RVT (52.7 ± 16.2 years) and 73 age and sex-matched healthy controls (49.1 ± 14.6 years). Genotyping for the MTHFR A1298Cpolymorphism was conducted by PCR-RFLP technique and plasma tHcy levels were measured by an enzyme immunoassay method. Fasting plasma tHcy levels were 20.29 ± 8.5 μmol/l in RVT patients and 10.9 ± 3.1 μmol/l in control subjects. The number of cases with abnormal tHcy values (hyperhomocysteinemia) was significantly higher in the RVT patients than control subjects (P = 0.0001). The prevalence of MTHFR 1298CC homozygote genotype was similar in RVT patients and controls (17.8 vs.15.1%, P = 0.45). There were no significant differences in genotype distribution of MTHFR A1298C polymorphism between males and females in both RVT patients and controls (P > 0.05). The frequency of the 1298C allele was 39.1 and 35.6% in patients and controls, respectively, and did not differ significantly between them (P = 0.23). Moreover, heterozygote and homozygote genotypes in the RVT patients had significantly higher abnormal tHcy values than corresponding genotypes in control subjects (P < 0.001). Our study demonstrated that hyperhomocysteinemia but not homozygosity for MTHFR A1298C polymorphism is a significant risk factor for RVT in the Iranian population. PMID:26650461

  9. Homocysteine in ocular diseases.

    PubMed

    Ajith, Thekkuttuparambil Ananthanarayanan; Ranimenon

    2015-10-23

    Homocysteine (Hcy) is a derived sulfur-containing and non-proteinogenic amino acid. The metabolism of Hcy occurs either through the remethylation to methionine or transsulfuration to cysteine. Studies have identified hyperhomocysteinemia (HHcy) as one of the possible risk factors for a multitude of diseases including vascular, neurodegenerative and ocular diseases. Association of HHcy with eye diseases such as retinopathy, pseudoexfoliative glaucoma maculopathy, cataract, optic atrophy and retinal vessel atherosclerosis is established. The molecular mechanism underlying these ocular diseases has been reported as impaired vascular endothelial function, apoptosis of retinal ganglion cells, extracellular matrix alterations, decreased lysyl oxidase activity and oxidative stress. The formed homocysteine-thiolactone in HHcy has stronger cytotoxicity and pro-inflammatory properties which can induce lens opacification and optic nerve damage. The metabolism of Hcy requires enzymes with vitamins such as folic acid, vitamins B12 and B6. Despite the mixed conclusion of various studies regarding the level of these vitamins in elder people, studies recommended the treatment with folate and B12 to reduce Hcy levels in subjects with or without any defect in the enzymes involved in its metabolism. The levels of Hcy, folate, B6 as well as B12 should be measured early in patients with visual impairment that would aid to screen patients for life-threatening disorders related with HHcy. Elder patients may supplement with these vitamins in order to attenuate the ocular damages. This article discusses the association of Hcy in ocular diseases and the possible mechanism in the pathogenesis. PMID:26343924

  10. Effect of N-acetylcysteine administration on homocysteine level, oxidative damage to proteins, and levels of iron (Fe) and Fe-related proteins in lead-exposed workers.

    PubMed

    Kasperczyk, Sławomir; Dobrakowski, Michał; Kasperczyk, Aleksandra; Romuk, Ewa; Rykaczewska-Czerwińska, Monika; Pawlas, Natalia; Birkner, Ewa

    2016-09-01

    N-Acetylcysteine (NAC) could be included in protocols designed for the treatment of lead toxicity. Therefore, in this study, we decided to investigate the influence of NAC administration on homocysteine (Hcy) levels, oxidative damage to proteins, and the levels of iron (Fe), transferrin (TRF), and haptoglobin (HPG) in lead (Pb)-exposed workers. The examined population (n = 171) was composed of male employees who worked with Pb. They were randomized into four groups. Workers who were not administered any antioxidants, drugs, vitamins, or dietary supplements were classified as the reference group (n = 49). The remaining three groups consisted of workers who were treated orally with NAC at three different doses (1 × 200, 2 × 200, or 2 × 400 mg) for 12 weeks. After the treatment, blood Pb levels significantly decreased in the groups receiving NAC compared with the reference group. The protein concentration was not affected by NAC administration. In contrast, Hcy levels significantly decreased or showed a strong tendency toward lower values depending on the NAC dose. Levels of the protein carbonyl groups were significantly decreased in all of the groups receiving NAC. Conversely, glutamate dehydrogenase activity was significantly elevated in all of the groups receiving NAC, while the level of protein thiol groups was significantly elevated only in the group receiving 200 mg of NAC. Treatment with NAC did not significantly affect Fe and TRF levels, whereas HPG levels showed a tendency toward lower values. Treatment with NAC normalized the level of Hcy and decreased oxidative stress as measured by the protein carbonyl content; this effect occurred in a dose-dependent manner. Moreover, small doses of NAC elevated the levels of protein thiol groups. Therefore, NAC could be introduced as an alternative therapy for chronic Pb toxicity in humans. PMID:25731901

  11. The effects of long-term resistance exercise on the relationship between neurocognitive performance and GH, IGF-1, and homocysteine levels in the elderly

    PubMed Central

    Tsai, Chia-Liang; Wang, Chun-Hao; Pan, Chien-Yu; Chen, Fu-Chen

    2015-01-01

    This study aimed to investigate the effects of a long-term resistance exercise intervention on executive functions in healthy elderly males, and to further understand the potential neurophysiological mechanisms mediating the changes. The study assessed forty-eight healthy elderly males randomly assigned to exercise (n = 24) or control (n = 24) groups. The assessment included neuropsychological and neuroelectric measures during a variant of the oddball task paradigm, as well as growth hormone (GH), insulin-like growth factor-1 (IGF-1), and homocysteine levels at baseline and after either a 12 month intervention of resistance exercise training or control period. The results showed that the control group had a significantly lower accuracy rate and smaller P3a and P3b amplitudes in the oddball condition after 12 months. The exercise group exhibited improved reaction times (RTs), sustained P3a and P3b amplitudes, increased levels of serum IGF-1, and decreased levels of serum homocysteine. The changes in IGF-1 levels were significantly correlated with the changes in RT and P3b amplitude of the oddball condition in the exercise group. In conclusion, significantly enhanced serum IGF-1 levels after 12 months of resistance exercise were inversely correlated with neurocognitive decline in the elderly. These findings suggest that regular resistance exercise might be a promising strategy to attenuate the trajectory of cognitive aging in healthy elderly individuals, possibly mediated by IGF-1. PMID:25713518

  12. Rare and low-frequency variants and their association with plasma levels of fibrinogen, FVII, FVIII, and vWF

    PubMed Central

    Huffman, Jennifer E.; de Vries, Paul S.; Morrison, Alanna C.; Sabater-Lleal, Maria; Kacprowski, Tim; Auer, Paul L.; Brody, Jennifer A.; Chasman, Daniel I.; Chen, Ming-Huei; Guo, Xiuqing; Lin, Li-An; Marioni, Riccardo E.; Müller-Nurasyid, Martina; Yanek, Lisa R.; Pankratz, Nathan; Grove, Megan L.; de Maat, Moniek P. M.; Cushman, Mary; Wiggins, Kerri L.; Qi, Lihong; Sennblad, Bengt; Harris, Sarah E.; Polasek, Ozren; Riess, Helene; Rivadeneira, Fernando; Rose, Lynda M.; Goel, Anuj; Taylor, Kent D.; Teumer, Alexander; Uitterlinden, André G.; Vaidya, Dhananjay; Yao, Jie; Tang, Weihong; Levy, Daniel; Waldenberger, Melanie; Becker, Diane M.; Folsom, Aaron R.; Giulianini, Franco; Greinacher, Andreas; Hofman, Albert; Huang, Chiang-Ching; Kooperberg, Charles; Silveira, Angela; Starr, John M.; Strauch, Konstantin; Strawbridge, Rona J.; Wright, Alan F.; McKnight, Barbara; Franco, Oscar H.; Zakai, Neil; Mathias, Rasika A.; Psaty, Bruce M.; Ridker, Paul M.; Tofler, Geoffrey H.; Völker, Uwe; Watkins, Hugh; Fornage, Myriam; Hamsten, Anders; Deary, Ian J.; Boerwinkle, Eric; Koenig, Wolfgang; Rotter, Jerome I.; Hayward, Caroline; Dehghan, Abbas; Reiner, Alex P.; O’Donnell, Christopher J.

    2015-01-01

    Fibrinogen, coagulation factor VII (FVII), and factor VIII (FVIII) and its carrier von Willebrand factor (vWF) play key roles in hemostasis. Previously identified common variants explain only a small fraction of the trait heritabilities, and additional variations may be explained by associations with rarer variants with larger effects. The aim of this study was to identify low-frequency (minor allele frequency [MAF] ≥0.01 and <0.05) and rare (MAF <0.01) variants that influence plasma concentrations of these 4 hemostatic factors by meta-analyzing exome chip data from up to 76 000 participants of 4 ancestries. We identified 12 novel associations of low-frequency (n = 2) and rare (n = 10) variants across the fibrinogen, FVII, FVIII, and vWF traits that were independent of previously identified associations. Novel loci were found within previously reported genes and had effect sizes much larger than and independent of previously identified common variants. In addition, associations at KCNT1, HID1, and KATNB1 identified new candidate genes related to hemostasis for follow-up replication and functional genomic analysis. Newly identified low-frequency and rare-variant associations accounted for modest amounts of trait variance and therefore are unlikely to increase predicted trait heritability but provide new information for understanding individual variation in hemostasis pathways. PMID:26105150

  13. Rare and low-frequency variants and their association with plasma levels of fibrinogen, FVII, FVIII, and vWF.

    PubMed

    Huffman, Jennifer E; de Vries, Paul S; Morrison, Alanna C; Sabater-Lleal, Maria; Kacprowski, Tim; Auer, Paul L; Brody, Jennifer A; Chasman, Daniel I; Chen, Ming-Huei; Guo, Xiuqing; Lin, Li-An; Marioni, Riccardo E; Müller-Nurasyid, Martina; Yanek, Lisa R; Pankratz, Nathan; Grove, Megan L; de Maat, Moniek P M; Cushman, Mary; Wiggins, Kerri L; Qi, Lihong; Sennblad, Bengt; Harris, Sarah E; Polasek, Ozren; Riess, Helene; Rivadeneira, Fernando; Rose, Lynda M; Goel, Anuj; Taylor, Kent D; Teumer, Alexander; Uitterlinden, André G; Vaidya, Dhananjay; Yao, Jie; Tang, Weihong; Levy, Daniel; Waldenberger, Melanie; Becker, Diane M; Folsom, Aaron R; Giulianini, Franco; Greinacher, Andreas; Hofman, Albert; Huang, Chiang-Ching; Kooperberg, Charles; Silveira, Angela; Starr, John M; Strauch, Konstantin; Strawbridge, Rona J; Wright, Alan F; McKnight, Barbara; Franco, Oscar H; Zakai, Neil; Mathias, Rasika A; Psaty, Bruce M; Ridker, Paul M; Tofler, Geoffrey H; Völker, Uwe; Watkins, Hugh; Fornage, Myriam; Hamsten, Anders; Deary, Ian J; Boerwinkle, Eric; Koenig, Wolfgang; Rotter, Jerome I; Hayward, Caroline; Dehghan, Abbas; Reiner, Alex P; O'Donnell, Christopher J; Smith, Nicholas L

    2015-09-10

    Fibrinogen, coagulation factor VII (FVII), and factor VIII (FVIII) and its carrier von Willebrand factor (vWF) play key roles in hemostasis. Previously identified common variants explain only a small fraction of the trait heritabilities, and additional variations may be explained by associations with rarer variants with larger effects. The aim of this study was to identify low-frequency (minor allele frequency [MAF] ≥0.01 and <0.05) and rare (MAF <0.01) variants that influence plasma concentrations of these 4 hemostatic factors by meta-analyzing exome chip data from up to 76,000 participants of 4 ancestries. We identified 12 novel associations of low-frequency (n = 2) and rare (n = 10) variants across the fibrinogen, FVII, FVIII, and vWF traits that were independent of previously identified associations. Novel loci were found within previously reported genes and had effect sizes much larger than and independent of previously identified common variants. In addition, associations at KCNT1, HID1, and KATNB1 identified new candidate genes related to hemostasis for follow-up replication and functional genomic analysis. Newly identified low-frequency and rare-variant associations accounted for modest amounts of trait variance and therefore are unlikely to increase predicted trait heritability but provide new information for understanding individual variation in hemostasis pathways. PMID:26105150

  14. Homocysteine Level and Mechanisms of Injury in Parkinson's Disease as Related to MTHFR, MTR, and MTHFD1 Genes Polymorphisms and L-Dopa Treatment

    PubMed Central

    Rozycka, Agata; Jagodzinski, Pawel P.; Kozubski, Wojciech; Lianeri, Margarita; Dorszewska, Jolanta

    2013-01-01

    An elevated concentration of total homocysteine (tHcy) in plasma and cerebrospinal fluid is considered to be a risk factor for Alzheimer's disease (AD) and Parkinson's disease (PD). Homocysteine (Hcy) levels are influenced by folate concentrations and numerous genetic factors through the folate cycle, however, their role in the pathogenesis of PD remains controversial. Hcy exerts a neurotoxic action and may participate in the mechanisms of neurodegeneration, such as excitotoxicity, oxidative stress, calcium accumulation, and apoptosis. Elevated Hcy levels can lead to prooxidative activity, most probably through direct interaction with N-methyl-D-aspartate (NMDA) receptors and sensitization of dopaminergic neurons to age-related dysfunction and death. Several studies have shown that higher concentration of Hcy in PD is related to long-term administration of levodopa (L-dopa). An elevation of plasma tHcy levels can also reflect deficiencies of cofactors in remethylation of Hcy to methionine (Met) (folates and vitamin B12) and in its transsulfuration to cysteine (Cys) (vitamin B6). It is believed that the increase in the concentration of Hcy in PD can affect genetic polymorphisms of the folate metabolic pathway genes, such as MTHFR (C677T, A1298C and G1793A), MTR (A2756G), and MTHFD1 (G1958A), whose frequencies tend to increase in PD patients, as well as the reduced concentration of B vitamins. In PD, increased levels of Hcy may lead to dementia, depression and progression of the disease. PMID:24532985

  15. Amniotic fluid levels of fibrin(ogen) degradation fragment E and alpha-fetoprotein in normal pregnancy and with fetal neural tube defect.

    PubMed

    Gordon, Y B; Ratky, S M; Leighton, P C; Kitau, M J; Chard, T

    1976-10-01

    Amniotic fluid levels of alpha-fetoprotein (AFP) and fibrin(ogen) degradation fragment E (FgE) were measured in 214 normal subjects and 27 pregnancies associated with an abnormal fetus (open neural tube defect or exomphalos). AFP levels showed no overlap between the normal and abnormal groups, thus confirming the reliability of the AFP assay in the detection of these abnormalities. FgE levels however showed considerable overlap and could not be used as a diagnostic parameter. Agarose gel chromatography of the amniotic fluid revealed the presence of large molecular weight FgE related antigen in open neural tube defect suggesting that leakage of proteins from exposed capillaries is responsible for the elevation of amniotic fluid protein levels. PMID:62585

  16. Folic acid mitigated cardiac dysfunction by normalizing the levels of tissue inhibitor of metalloproteinase and homocysteine-metabolizing enzymes postmyocardial infarction in mice

    PubMed Central

    Qipshidze, Natia; Tyagi, Neetu; Sen, Utpal; Givvimani, Srikanth; Metreveli, Naira; Lominadze, David

    2010-01-01

    Myocardial infarction (MI) results in significant metabolic derangement, causing accumulation of metabolic by product, such as homocysteine (Hcy). Hcy is a nonprotein amino acid generated during nucleic acid methylation and demethylation of methionine. Folic acid (FA) decreases Hcy levels by remethylating the Hcy to methionine, by 5-methylene tetrahydrofolate reductase (5-MTHFR). Although clinical trials were inconclusive regarding the role of Hcy in MI, in animal models, the levels of 5-MTHFR were decreased, and FA mitigated the MI injury. We hypothesized that FA mitigated MI-induced injury, in part, by mitigating cardiac remodeling during chronic heart failure. Thus, MI was induced in 12-wk-old male C57BL/J mice by ligating the left anterior descending artery, and FA (0.03 g/l in drinking water) was administered for 4 wk after the surgery. Cardiac function was assessed by echocardiography and by a Millar pressure-volume catheter. The levels of Hcy-metabolizing enzymes, cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 5-MTHFR, were estimated by Western blot analyses. The results suggest that FA administered post-MI significantly improved cardiac ejection fraction and induced tissue inhibitor of metalloproteinase, CBS, CSE, and 5-MTHFR. We showed that FA supplementation resulted in significant improvement of myocardial function after MI. The study eluted the importance of homocysteine (Hcy) metabolism and FA supplementation in cardiovascular disease. PMID:20802128

  17. Fibrinogen reduction and coagulation in cardiac surgery: an investigational study.

    PubMed

    Gielen, Chantal L I; Grimbergen, Jos; Klautz, Robert J M; Koopman, Jaap; Quax, Paul H A

    2015-09-01

    Fibrinogen as precursor of fibrin plays an essential role in clot formation. There are three main mechanisms associated with a reduction in fibrinogen concentration during cardiac surgery: hemodilution, consumption, and degradation. Moreover, early fibrinogen degradation products (FgDPs) can interfere with normal fibrin formation of intact fibrinogen. The aim of this study was to determine the relative contributions of hemodilution, consumption, and degradation to fibrinogen loss in cardiac surgery and to evaluate the effects fibrinogen degradation products on blood clot formation in vitro. First, fibrin and fibrinogen concentrations, their degradation products, hematocrit, and albumin concentrations were compared in 10 patients before and after isolated coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass. Second, ex-vivo fibrinogen supplementation experiments were performed. Finally, the effects of purified FgDPs on clotting time and clot firmness were established in vitro in whole blood by ROTEM. Fibrinogen plasma concentration decreased 30% during surgery. This drop appears to be mainly caused by hemodilution, as both hematocrit and albumin levels decreased and no relevant increase in D-dimer levels and FgDPs was observed. Furthermore, the coagulation profile normalized after addition of purified fibrinogen. Early FgDPs demonstrated a significant impact on in-vitro whole blood clotting. Although early FgDPs have a pronounced effect on blood clot formation in vitro and therefore may induce or enhance in vivo coagulopathy, the drop of fibrinogen concentration seen after CABG surgery (using tranexamic acid) is primarily caused by hemodilution. PMID:26083991

  18. The determination of homocysteine-thiolactone in human plasma.

    PubMed

    Chwatko, Grazyna; Jakubowski, Hieronim

    2005-02-15

    The thioester homocysteine-thiolactone, a reactive metabolite of homocysteine, has been implicated in human cardiovascular disease. However, data on the levels of homocysteine-thiolactone in humans are limited, mostly due to a lack of facile and reliable assays. Here we describe a sensitive assay for the determination of plasma homocysteine-thiolactone and demonstrate its utility with a cohort of 60 healthy human subjects. Plasma homocysteine-thiolactone is first separated from macromolecules by ultrafiltration and then selectively extracted with chloroform/methanol. Further purification of plasma homocysteine-thiolactone is achieved by high-performance liquid chromatography on a cation exchange microbore column. The detection and quantification is by monitoring fluorescence after postcolumn derivatization with o-phthaldialdehyde. The limit of detection is 0.36 nM. Using this assay, homocysteine-thiolactone concentrations in plasma from normal healthy human subjects (n=60) were found to vary from zero to 34.8 nM, with an average of 2.82+/-6.13 nM. In 29 of the 60 human plasma samples analyzed, homocysteine-thiolactone levels were below the detection limit. Homocysteine-thiolactone represented from 0 to 0.28%, on average 0.023+/-0.05%, of plasma total homocysteine. PMID:15691507

  19. [PROGNOSTIC VALUE OF SOME HEMOSTASIS-RELATED, HOMOCYSTEINE, HIGH SENSITIVE C R P AND MULTIDETECTOR COMPUTED TOMOGRAPHY PARAMETERS IN PULMONARY EMBOLISM].

    PubMed

    Todua, F; Akhvlediani, M; Vorobiova, E; Baramidze, A; Tsivtsivadze, G; Gachechiladze, D

    2016-05-01

    Nowadays, an arsenal of diagnostic methods is used in diagnosis of pulmonary embolism, which includes x-ray, angiography, perfusion-ventilation scintigraphy, CT and magnetic resonance imaging, Doppler and laboratory studies. Purpose of our study was to evaluate the diagnostic significance of determination of some parameters of hemostasis (D-dimer, Soluble fibrinmonomer complexes, fibrinogen), homocysteine, hs-CRP and multidetector computed tomography in suspected pulmonary embolism. We have examined 54 patients -31 men and 23 women, aged 18 to 76 years, with characteristics of pulmonary embolism. According to our data, Multidetector computed tomography angiopulmonography , measuring D-dimer, fibrinogen and related hyperhomocysteinemia with increased level of hs-CRP may serve as binding, diagnostically significant laboratory markers in the diagnosis and treatment efficacy of pulmonary thromboembolism. PMID:27348165

  20. Inhibition of homocysteine-induced endoplasmic reticulum stress and endothelial cell damage by l-serine and glycine.

    PubMed

    Sim, Woo-Cheol; Han, Inhoi; Lee, Wonseok; Choi, You-Jin; Lee, Kang-Yo; Kim, Dong Gwang; Jung, Seung-Hwan; Oh, Seon-Hee; Lee, Byung-Hoon

    2016-08-01

    Hyperhomocysteinemia is an independent risk factor for several cardiovascular diseases. The use of vitamins to modulate homocysteine metabolism substantially lowers the risk by reducing plasma homocysteine levels. In this study, we evaluated the effects of l-serine and related amino acids on homocysteine-induced endoplasmic reticulum (ER) stress and endothelial cell damage using EA.hy926 human endothelial cells. Homocysteine treatment decreased cell viability and increased apoptosis, which were reversed by cotreatment with l-serine. l-Serine inhibited homocysteine-induced ER stress as verified by decreased glucose-regulated protein 78kDa (GRP78) and C/EBP homologous protein (CHOP) expression as well as X-box binding protein 1 (xbp1) mRNA splicing. The effects of l-serine on homocysteine-induced ER stress are not attributed to intracellular homocysteine metabolism, but instead to decreased homocysteine uptake. Glycine exerted effects on homocysteine-induced ER stress, apoptosis, and cell viability that were comparable to those of l-serine. Although glycine did not affect homocysteine uptake or export, coincubation of homocysteine with glycine for 24h reduced the intracellular concentration of homocysteine. Taken together, l-serine and glycine cause homocysteine-induced endothelial cell damage by reducing the level of intracellular homocysteine. l-Serine acts by competitively inhibiting homocysteine uptake in the cells. However, the mechanism(s) by which glycine lowers homocysteine levels are unclear. PMID:27064126

  1. Atherosclerosis in male patients with ankylosing spondylitis: the relation with methylenetetrahydrofolate reductase (C677T) gene polymorphism and plasma homocysteine levels.

    PubMed

    Geçene, Muharrem; Tuncay, Figen; Borman, Pınar; Yücel, Dogan; Senes, Mehmet; Yılmaz, Behice Kaniye

    2013-06-01

    The aim of this study was to determine the intima-media thickness (IMT) in carotid arteries and to assess the relation of these values with plasma homocysteine (pHcy) levels and methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism in patients with Ankylosing spondylitis (AS). Serum lipids, vitamin B12, folic acid, pHcy and acute phase protein levels were measured in all cases. MTHFR C677T gene polymorphisms were determined, and IMT of main carotid artery were evaluated ultrasonographically in all subjects. Bath Ankylosing Spondylitis Disease Activity Index, Ankylosing Spondylitis Disease Activity score and Bath Ankylosing Spondylitis Metrology Index were used to assess disease activity and spinal mobility. Fifty AS patients (mean age of 36.6 ± 4.79 years) and 50 control subjects (36.34 ± 4.72 years) were included in the study. Plasma homocysteine levels of AS patients and control group were also similar (14.26 ± 9.96 vs. 11.81 ± 5.53 μmol/L). Hyperhomocysteinemia was present in 11 subjects in patient group (22.0 %), while it was seen in 5 subjects in the control group (10.0 %). The MTHFR C677T genotype distribution was as follows: CC 31 (62 %), CT 14 (28 %), TT 5 (10 %) in AS patients. The mean carotid IMT values were also found to be similar between the groups. The most important factor influencing pHcy level was found as MTHFR 677TT genotype. We indicated no difference of atherosclerosis indices revealed by IMT values and pHcy levels AS patients and control subjects. But an association between MTHFR 677 gene polymorphism and pHcy levels was concluded, which may suggest that MTHFR 677 TT polymorphism may be a potential prognostic factor for cardiovascular disease in patients with AS. PMID:23247802

  2. Homocysteine and Familial Longevity: The Leiden Longevity Study

    PubMed Central

    Wijsman, Carolien A.; van Heemst, Diana; Rozing, Maarten P.; Slagboom, P. Eline; Beekman, Marian; de Craen, Anton J. M.; Maier, Andrea B.; Westendorp, Rudi G. J.; Blom, Henk J.; Mooijaart, Simon P.

    2011-01-01

    Homocysteine concentrations are a read-out of methionine metabolism and have been related to changes in lifespan in animal models. In humans, high homocysteine concentrations are an important predictor of age related disease. We aimed to explore the association of homocysteine with familial longevity by testing whether homocysteine is lower in individuals that are genetically enriched for longevity. We measured concentrations of total homocysteine in 1907 subjects from the Leiden Longevity Study consisting of 1309 offspring of nonagenarian siblings, who are enriched with familial factors promoting longevity, and 598 partners thereof as population controls. We found that homocysteine was related to age, creatinine, folate, vitamin B levels and medical history of hypertension and stroke in both groups (all p<0.001). However, levels of homocysteine did not differ between offspring enriched for longevity and their partners, and no differences in the age-related rise in homocysteine levels were found between groups (p for interaction 0.63). The results suggest that homocysteine metabolism is not likely to predict familial longevity. PMID:21408159

  3. Serum Levels of High-sensitivity C-Reactive Protein at Admission Are More Strongly Associated with Poststroke Depression in Acute Ischemic Stroke than Homocysteine Levels.

    PubMed

    Tang, Chao-Zhi; Zhang, Yu-Ling; Wang, Wen-Sheng; Li, Wei-Guo; Shi, Ji-Peng

    2016-05-01

    Inflammatory processes have fundamental roles in depression. The primary purpose of this study was to assess the serum levels of high-sensitivity C-reactive protein (Hs-CRP) and homocysteine (HCY) at admission to the presence of poststroke depression (PSD). From December 2012 to December 2013, first-ever acute ischemic stroke patients who were admitted to the hospital within the first 24 h after stroke onset were consecutively recruited and followed up for 6 months. Serum levels of Hs-CRP and HCY were tested at admission. Based on the symptoms, diagnoses of depression were made in accordance with DSM-IV criteria for depression at 6 months after stroke. Ninety-five patients (42.0 %) showed depression (major + minor) at 6 months after admission, and in 69 patients (30.5 %), this depression was classified as major. In the 69 patients with major depression, our results showed significantly higher Hs-CRP and HCY levels at admission than patients without major depression. After adjusting all other possible covariates, Hs-CRP and HCY still were independent predicators of PSD with adjusted OR of 1.332 (95 % CI, 1.230-1.452; P < 0.001) and 1.138 (95 % CI, 1.072-1.274; P < 0.001), respectively. The area under the receiver operating characteristic curve values of Hs-CRP and HCY were 0.765 (95 % CI, 0.701-0.9825) and 0.684 (95 % CI, 0.610-0.757) for PSD, respectively. The prognostic accuracy of combined model (HCY and Hs-CRP) was higher compared to those biomarkers alone and other markers. Elevated serum levels of Hs-CRP and HCY at admission were found to be associated with depression 6 months after stroke, suggesting that these alterations might participate in the pathophysiology of depression symptoms in stroke patients. PMID:25941076

  4. Elevated Levels of Serum Fibrin and Fibrinogen Degradation Products Are Independent Predictors of Larger Coronary Plaques and Greater Plaque Necrotic Core

    PubMed Central

    Corban, Michel T; Hung, Olivia Y; Mekonnen, Girum; Eshtehardi, Parham; Eapen, Danny J; Rasoul-Arzrumly, Emad; Kassem, Hatem Al; Manocha, Pankaj; Ko, Yi-An; Sperling, Laurence S; Quyyumi, Arshed A; Samady, Habib

    2016-01-01

    Background Co-existence of vulnerable plaque and pro-thrombotic state may provoke acute coronary events. It was hypothesized that elevated serum levels of fibrin and fibrinogen degradation products (FDP) are associated with larger total plaque and necrotic core (NC) areas. Methods and Results Seventy-five patients presenting with stable anginal symptoms (69%) or stabilized acute coronary syndrome (ACS; 31%), and found to have non-obstructive coronary artery disease (CAD) with a fractional flow reserve >0.8, were studied. Invasive virtual histology intravascular ultrasound (VH-IVUS) was performed in 68 LAD arteries, 6 circumflex arteries, and 1 right coronary artery. Serum FDP levels were measured using ELISA technique. Plaque volumetrics and composition were assessed in each VH-IVUS frame and averaged. The median age of patients was 56 (47–63) years; 52% were men and 23% had diabetes. The average length of coronary artery studied was 62 mm. After adjustment for systemic risk factors, medications, CRP levels and ACS, male gender (P<0.001) and serum FDP levels (P=0.02) were independent predictors of a larger NC area. Older age (P<0.001), male gender (P<0.0001) and increased serum FDP level (P=0.03) were associated with a larger plaque area. Conclusions In patients with CAD, a higher serum level of FDP is independently associated with larger plaques and greater plaque NC. PMID:26911453

  5. Characterization of homocysteine metabolism in the rat kidney.

    PubMed Central

    House, J D; Brosnan, M E; Brosnan, J T

    1997-01-01

    Epidemiological studies have provided strong evidence that an elevated plasma homocysteine concentration is an important independent risk factor for cardiovascular disease. We have shown, in the rat, that the kidney is a major site for the removal and subsequent metabolism of plasma homocysteine [Bostom, Brosnan, Hall, Nadeau and Selhub (1995) Atherosclerosis 116, 59-62]. To characterize the role of the kidney in homocysteine metabolism further, we measured the disappearance of homocysteine in isolated renal cortical tubules of the rat. Renal tubules metabolized homocysteine primarily through the transulphuration pathway, producing cystathionine and cysteine (78% of homocysteine disappearance). Methionine production accounted for less than 2% of the disappearance of homocysteine. Cystathionine, and subsequently cysteine, production rates, as well as the rate of disappearance of homocysteine, were sensitive to the level of serine in the incubation medium, as increased serine concentrations permitted higher rates of cystathionine and cysteine production. On the basis of enrichment profiles of cystathionine beta-synthase and cystathionine gamma-lyase, in comparison with marker enzymes of known location, we concluded that cystathionine beta-synthase was enriched in the outer cortex, specifically in cells of the proximal convoluted tubule. Cystathionine gamma-lyase exhibited higher enrichment patterns in the inner cortex and outer medulla, with strong evidence of an enrichment in cells of the proximal straight tubule. These studies indicate that factors that influence the transulphuration of homocysteine may influence the renal clearance of this amino acid. PMID:9359866

  6. Increased CSF Homocysteine in Pathological Gamblers Compared with Healthy Controls

    ERIC Educational Resources Information Center

    Nordin, Conny; Sjodin, Ingemar

    2009-01-01

    Neurocognitive disturbances suggesting a frontal lobe dysfunction have been observed in pathological gamblers and alcohol dependents. Given that a high homocysteine level has been suggested to be a mediating factor in alcohol-related cognitive decline, we have determined homocysteine and cobalamine in cerebrospinal fluid (CSF) obtained from 11…

  7. Correlation between the 677C>T polymorphism in the methylene tetrahydrofolate reductase gene and serum homocysteine levels in coronary heart disease.

    PubMed

    Chen, Y Y; Wang, B N; Yu, X P

    2016-01-01

    The aim of the current study was to explore the correlation between serum homocysteine (HCY) levels and the methylene tetrahydrofolate reductase (MTHFR) gene 677C/T polymorphism and coronary heart disease (CHD). We consecutively enrolled 208 patients with CHD confirmed by CTA or coronary angiography from our hospital. An additional 200 healthy volunteers were enrolled as the control group. Serum HCY levels, MTHFR C677T genotype, and other related indicators were evaluated for the two groups. Compared to those in the control group, the serum HCY levels in the CHD patients were significantly higher (P < 0.05). The proportion of individuals with the heterozygous MTHFR CT genotype and homozygous mutant TT genotype among CHD patients was significantly higher than that in the control group (P < 0.05). In the acute coronary syndrome (ACS) subgroup, the proportion of those with the CT and TT genotypes was significantly higher than that of the stable CHD subgroup (P < 0.05). In summary, serum HCY levels were elevated in CHD patients, and the frequency of the CT and TT genotypes were also significantly increased, especially among the ACS subgroup. Taken together, this suggests that serum HCY levels and MTHFR C677T genotypes are correlated with CHD. PMID:27051002

  8. Elevated Homocysteine Level and Folate Deficiency Associated with Increased Overall Risk of Carcinogenesis: Meta-Analysis of 83 Case-Control Studies Involving 35,758 Individuals

    PubMed Central

    Wu, Wei; Guo, Ye; Cui, Wei

    2015-01-01

    Background Results of the association of folate metabolism and carcinogenesis are conflicting. We performed a meta-analysis to examine the effect of the interaction of serum concentration of homocysteine (Hcy), folate, and vitamin B12 and 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphism on risk of cancer overall. Method Two reviewers independently searched for all published studies of Hcy and cancer in PubMed, EMBASE-MEDLINE and Chinese databases. Pooled results were reported as odds ratios (ORs) and mean differences and presented with 95% confidence intervals (95% CIs) and 2-sided probability values. Results We identified 83 eligible studies of 15,046 cases and 20,712 controls. High level of Hcy but low level of folate was associated with risk of cancer overall, with little effect by type of cancer or ethnicity. Vitamin B12 level was inversely associated with only urinary-system and gastrointestinal carcinomas and for Asian and Middle Eastern patients. As well, MTHFR C677T, A1298C and G1793A polymorphisms were related to elevated serum level of Hcy, and folate and vitamin B12 deficiency. However, only MTHFR C677T homogeneity/wild-type (TT/CC) polymorphism was positively associated with overall risk of cancer. Conclusion Elevated serum Hcy level and folate deficiency are associated with increased overall risk of cancer. PMID:25985325

  9. Homocysteine and arterial thrombosis: Challenge and opportunity.

    PubMed

    Di Minno, Matteo N D; Tremoli, Elena; Coppola, Antonio; Lupoli, Roberta; Di Minno, Giovanni

    2010-05-01

    The correlation between homocysteine and vascular disease has been assessed in several clinical studies that demonstrated that elevation of plasma total homocysteine (tHcy) was an independent risk factor for atheriosclerotic disease. Major advances of homocysteine metabolism disorders have been made during the last few years, encompassing the rare homozygous enzyme deficiencies, as well as more common milder abnormalities. In experimental and clinical studies, a homocysteine-mediated oxidant stress has been shown to trigger platelet activation, in turn leading to a tendency to thrombosis, in patients with severe hyperhomocysteinaemia. Likewise, the hypomethylation hypothesis on acquired hyperhomocysteinaemia (chronic renal disease) and the interrelationship between hyperhomocysteinaemia and impaired fibrinolysis, have added further biological plausibility to the role for hyperhomocysteinaemia in vascular medicine. However, whether hyperhomocysteinaemia is causal or a marker of vascular disease, and whether plasma tHcy is only an indicator of the metabolic status remains to be clarified. The role of the intake of some vitamins (folic acid, vit.B12, vit.B6) on cardiovascular disease (CVD) is poorly understood: in spite of the lowering of homocysteine (Hcy) levels, vitamin supplementation failed to exert significant effects on cardiovascular risk. On the other hand, although some lipid-modifying treatments increase Hcy levels in diabetics, there is no evidence that this attenuates the beneficial effects of such treatments on the cardiovascular risk. Because of these uncertainties in the area, the data available do not provide support for routine screening and treatment for elevated Hcy to prevent CVD. PMID:20352150

  10. Indications and Risks of Fibrinogen in Surgery and Trauma.

    PubMed

    Spahn, Donat R; Spahn, Gabriela H; Stein, Philipp

    2016-03-01

    Fibrinogen has a central role in coagulation. Following trauma and perioperatively, low fibrinogen levels have been found to be risk factors for exaggerated bleeding, transfusion needs, and adverse outcome. Conversely, treatment with exogenous fibrinogen in critically bleeding patients with low fibrinogen levels has been shown to decrease transfusion needs. Because following trauma and in many perioperative situations fibrinogen is the first coagulation "element" to become critically low, it appears reasonable to target fibrinogen in clinical coagulation algorithms aiming at early specific and goal-directed treatment. A low fibrinogen can be a low plasma concentration or a low functional fibrinogen as assessed by point-of-care techniques such as thromboelastography (TEG) or thromboelastometry (ROTEM). This review summarizes the evidence base for perioperative algorithm-based fibrinogen administration, including the exact thresholds for fibrinogen administration used in the different algorithms. Algorithm-based individualized goal-directed use of fibrinogen resulted in highly significant reduction in transfusion needs, adverse outcomes, in certain studies even mortality, and where investigated reduced costs, with high safety levels at the same time. Best evidence exists in cardiac surgery, followed by trauma, postpartum hemorrhage, and liver transplantation. The introduction of these concepts is highly demanding and requires a tremendous educational effort to familiarize all health care workers with the necessary knowledge and the skills of how to run TEG/ROTEM tests. Future research is needed to compare the efficacy, safety, and costs of different algorithms. This, however, should not prevent us from introducing these expedient point-of-care-based algorithms clinically today. PMID:26716503

  11. Cobalamin and homocysteine in older adults: do we need to test for serum levels in the work-up of dementia?

    PubMed

    Garcia, Angeles

    2007-10-01

    This article reviews available information on the relationship between cobalamin (Cbl), homocysteine (tHcy) and cognitive decline and dementia in older adults with the aim to propose recommendations as to the need to perform such determinations in the work-up for dementia. The article includes brief reviews of the magnitude of the problem, effects of the Canadian folic acid fortification program on the Cbl and tHcy status in older adults, relation between Cbl and tHcy and cognition and cognitive changes, and available data on treatment trials up to March 2007. Recommendations and levels of evidence were assigned and approved by consensus following the directives of the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia. The review concludes that determination of Cbl (vit B12) levels are recommended in the work-up for dementia and cognitive decline because of the high prevalence of Cbl deficits in this population, independently of the possible effects of normalization of Cbl levels on cognitive function. Even though elevated tHcy is a risk factor for dementia, there is no proo of that normalization of tHcy levels changes the course of the disease. Clinical trials on that regard are on going. PMID:19595952

  12. Leukocyte Telomere Length is Associated With Serum Vitamin B12 and Homocysteine Levels in Older Adults With the Presence of Systemic Inflammation

    PubMed Central

    2016-01-01

    Folate, vitamin B12, and homocysteine (HCY) are involved in the metabolism of nucleic acid precursors and it has been hypothesized that they also influence telomere length, a biomarker of aging. However, previous studies have reported inconsistent findings, and data for older adults are limited. Our study aimed to evaluate associations between leukocyte telomere length (LTL) and serum folate, vitamin B12, and HCY levels among adults aged 55 years and over. In a cross-sectional study in 798 men and women aged 55-79 years, serum folate, vitamin B12, and HCY levels were measured using chemiluminescent immunometric assays, and relative LTL was assessed using quantitative real-time polymerase chain reaction. To evaluate associations between LTL and serum folate, vitamin B12, and HCY levels, multiple linear regression models were used. In multiple models adjusted for age, sex, serum high sensitive C-reactive protein (hs-CRP) levels, and other potential confounding factors, we found no association between LTL and serum folate, vitamin B12, and HCY levels. However, we did find a significant inverse association between HCY levels and LTL in participants with serum hs-CRP levels of ≥ 2 mg/L (p < 0.05). Moreover, there was a trend toward an association between HCY and vitamin B12 levels in these individuals (p = 0.08). In those with serum hs-CRP levels of < 2 mg/L, HCY was inversely associated with vitamin B12 levels (p < 0.001) and had no association with LTL. Our findings suggest that increased serum HCY levels, when combined with the presence of systemic inflammation, may play a role in accelerating biological aging. PMID:26839872

  13. Elevated homocysteine level in first-episode schizophrenia patients--the relevance of family history of schizophrenia and lifetime diagnosis of cannabis abuse.

    PubMed

    Misiak, Blazej; Frydecka, Dorota; Slezak, Ryszard; Piotrowski, Patryk; Kiejna, Andrzej

    2014-09-01

    Accumulating evidence indicates that elevated homocysteine (Hcy) level occurs in first-episode schizophrenia (FES) patients. We included 56 FES patients and 53 healthy controls (HC). Plasma level of Hcy was significantly higher in FES patients than HC (p = 0.044). In addition, plasma levels of high-density lipoproteins (HDL) and folate were significantly lower in FES than in HC (p < 0.001). Positive family history of schizophrenia was associated with lower plasma HDL (p = 0.041) and vitamin B12 (p = 0.017), as well as higher level of Hcy (p = 0.017). Patients with FES, who abused cannabis, had higher levels of Hcy (p = 0.017), as well as lower levels of vitamin B12 (p = 0.017) and HDL (p = 0.041). Plasma Hcy negatively correlated with duration of untreated psychosis (r = -0.272, p = 0.042). There was a positive correlation between Hcy level and the severity of negative symptoms (r = 0.363, p = 0.006) and general psychopathology (r = 0.349, p = 0.008) assessed using Positive and Negative Syndrome Scale (PANSS). Vitamin B12 level was negatively associated with the severity of negative symptoms (r = -0.406, p = 0.002), while folate level negatively correlated with general psychopathology score (r = -0.365, p = 0.006) in PANSS. These results indicate that the severity of one-carbon metabolism alterations and HDL deficiency might be associated with family history of schizophrenia and cannabis abuse. Lower vitamin B12 and folate along with elevated Hcy may influence the severity of FES psychopathology. PMID:24682777

  14. Comparison of C-reactive protein and fibrinogen levels in patients having anterior wall ST-Segment elevation myocardial infarction with versus without left ventricular thrombus (from a primary percutaneous coronary intervention cohort).

    PubMed

    Shacham, Yacov; Leshem-Rubinow, Eran; Ben Assa, Eyal; Rogowski, Ori; Topilsky, Yan; Roth, Arie; Steinvil, Arie

    2013-07-01

    We tested the hypothesis that admission serum inflammatory biomarkers may predict risk of early left ventricular (LV) thrombus formation in patients with first-ever anterior wall ST-segment elevation myocardial infarction (STEMI). Medical records of 207 patients admitted to our department between January 2006 and April 2012 for first-ever diagnosed anterior wall STEMI and treated with primary percutaneous coronary intervention (PPCI) were reviewed. Serum C-reactive protein (CRP) and fibrinogen levels were determined from blood samples taken before PPCI. Patients underwent an initial cardiac echocardiography on days 1 or 2 of admission and a second echocardiography on days 5 to 7 of hospitalization. An early LV thrombus was detected on the second echocardiogram in 11 patients (11 of 207, 5%), 6 of whom had also displayed an LV thrombus already during their first echocardiogram. Patients with an LV thrombus had significantly higher mean serum CRP levels than those without an LV thrombus (48 mg/L vs 8.4 mg/L, p = 0.001), and a trend for higher fibrinogen levels was also observed (398 ± 135 mg/dl vs 312 ± 82 mg/dl, p = 0.063). Following adjustment to other variables and the performance of multiple logistic regression, the CRP (relative risk 4.63, p = 0.004) and fibrinogen (relative risk 1.006, p = 0.033) levels were independent predictors of LV thrombus formation. We conclude that admission serum CRP and fibrinogen levels are independent predictors for early LV thrombus formation complicating a first-ever anterior wall STEMI. PMID:23562384

  15. Converging Evidence of Mitochondrial Dysfunction in a Yeast Model of Homocysteine Metabolism Imbalance*

    PubMed Central

    Kumar, Arun; John, Lijo; Maity, Shuvadeep; Manchanda, Mini; Sharma, Abhay; Saini, Neeru; Chakraborty, Kausik; Sengupta, Shantanu

    2011-01-01

    An elevated level of homocysteine, a thiol amino acid, is associated with various complex disorders. The cellular effects of homocysteine and its precursors S-adenosylhomocysteine (AdoHcy) and S-adenosylmethionine (AdoMet) are, however, poorly understood. We used Saccharomyces cerevisiae as a model to understand the basis of pathogenicity induced by homocysteine and its precursors. Both homocysteine and AdoHcy but not AdoMet inhibited the growth of the str4Δ strain (which lacks the enzyme that converts homocysteine to cystathionine-mimicking vascular cells). Addition of AdoMet abrogated the inhibitory effect of AdoHcy but not that of homocysteine indicating that an increase in the AdoMet/AdoHcy ratio is sufficient to overcome the AdoHcy-mediated growth defect but not that of homocysteine. Also, the transcriptomic profile of AdoHcy and homocysteine showed gross dissimilarity based on gene enrichment analysis. Furthermore, compared with homocysteine, AdoHcy treatment caused a higher level of oxidative stress in the cells. However, unlike a previously reported response in wild type (Kumar, A., John, L., Alam, M. M., Gupta, A., Sharma, G., Pillai, B., and Sengupta, S. (2006) Biochem. J. 396, 61–69), the str4Δ strain did not exhibit an endoplasmic reticulum stress response. This suggests that homocysteine induces varied response depending on the flux of homocysteine metabolism. We also observed altered expression of mitochondrial genes, defective membrane potential, and fragmentation of the mitochondrial network together with the increased expression of fission genes indicating that the imbalance in homocysteine metabolism has a major effect on mitochondrial functions. Furthermore, treatment of cells with homocysteine or AdoHcy resulted in apoptosis as revealed by annexin V staining and TUNEL assay. Cumulatively, our results suggest that elevated levels of homocysteine lead to mitochondrial dysfunction, which could potentially initiate pro-apoptotic pathways, and

  16. [Homocysteine--a routine biochemical parameter in cardiovascular diseases?].

    PubMed

    Gábor, D; Hrnciar, J; Hricová, I; Zacharová, M

    1999-01-01

    An elevated level of total homocysteine (tHcy) in blood-hyperhomocysteinemia, is prevalent and strong risk factor for atherosclerotic vascular disease in the coronary, cerebral and peripheral vessels and for thromboembolism (arterial and venous). Elevated total homocysteine confers a graded risk with no threshold, is independent of but may enhance the effect of conventional risk factors. Hyperhomocysteinemia seems to be a particularly strong predictor of cardiovaskular mortality. Supplementation with B-vitamins, in particular with folic acid, is an efficient, safe and inexpensive means to reduce an elevated total homocysteine level. PMID:10422525

  17. Adverse vascular effects of homocysteine are modulated by endothelium-derived relaxing factor and related oxides of nitrogen.

    PubMed Central

    Stamler, J S; Osborne, J A; Jaraki, O; Rabbani, L E; Mullins, M; Singel, D; Loscalzo, J

    1993-01-01

    Elevated levels of homocysteine are associated with an increased risk of atherosclerosis and thrombosis. The reactivity of the sulfhydryl group of homocysteine has been implicated in molecular mechanisms underlying this increased risk. There is also increasingly compelling evidence that thiols react in the presence of nitric oxide (NO) and endothelium-derived relaxing factor (EDRF) to form S-nitrosothiols, compounds with potent vasodilatory and antiplatelet effects. We, therefore, hypothesized that S-nitrosation of homocysteine would confer these beneficial bioactivities to the thiol, and at the same time attenuate its pathogenicity. We found that prolonged (> 3 h) exposure of endothelial cells to homocysteine results in impaired EDRF responses. By contrast, brief (15 min) exposure of endothelial cells, stimulated to secrete EDRF, to homocysteine results in the formation of S-NO-homocysteine, a potent antiplatelet agent and vasodilator. In contrast to homocysteine, S-NO-homocysteine does not support H2O2 generation and does not undergo conversion to homocysteine thiolactone, reaction products believed to contribute to endothelial toxicity. These results suggest that the normal endothelium modulates the potential, adverse effects of homocysteine by releasing EDRF and forming the adduct S-NO-homocysteine. The adverse vascular properties of homocysteine may result from an inability to sustain S-NO formation owing to a progressive imbalance between the production of NO by progressively dysfunctional endothelial cells and the levels of homocysteine. PMID:8380812

  18. The levels of vitamın B12, folate and homocysteine in mothers and their babies with neural tube defects.

    PubMed

    Peker, Erdal; Demir, Nihat; Tuncer, Oğuz; Üstyol, Lokman; Balahoroğlu, Ragıp; Kaba, Sultan; Karaman, Kamuran

    2016-09-01

    The aim of the present study was to determine the serum levels of vitamin B12, folate, and homocysteine (Hcy) in mothers and their babies, and to assess the association between these levels and neural tube defect (NTD). The study group included 92 baby-mother pairs, where the babies had NTD, and the control group included 102 pairs, where the babies had no NTD, from May 2012 to May 2015. Plasma vitamin B12, folate, and Hcy levels of the babies and mothers were measured, and compared with each other. NTD was diagnosed in 2.6% of our babies. The vitamin B12 levels in the mothers and the babies in the study group were determined as 166.2 ± 63.7 pg/mL and 240.3 ± 120.3 pg/mL, and in the control group as 1 9 0 ± 80.2 pg/mL and 299.5 ± 151.4 pg/mL, respectively. There was a significant difference between the two groups in terms of both the mothers' and the babies' vitamin B12 levels (p = 0.024 and p = 0.003, respectively). The plasma folate levels of the mothers in the study group (5.2 ± 3 ng/mL) were significantly lower than control group (6.4 ± 4.3 ng/mL, p = 0.032).The plasma Hcy level of the mothers in the study group (9.3 ± 3.8 μmol/L) was significantly higher than the control group (7 ± 3.8 μmol/L, p < 0.001). High plasma Hcy levels and low plasma folate and vitamin B12 levels are risk factors for NTD. Our results show that the risk for NTD can be decreased by fortification of mothers-to-be, particularly in rural areas with folate and vitamin B12 deficiency, which would lower the plasma Hcy level. PMID:26479326

  19. Methylenetetrahydrofolate reductase (MTHFR-677 and MTHFR-1298) genotypes and haplotypes and plasma homocysteine levels in patients with occlusive artery disease and deep venous thrombosis.

    PubMed

    Spiroski, Igor; Kedev, Sashko; Antov, Slobodan; Arsov, Todor; Krstevska, Marija; Dzhekova-Stojkova, Sloboda; Bosilkova, Gordana; Kostovska, Stojanka; Trajkov, Dejan; Petlichkovski, Aleksandar; Strezova, Ana; Efinska-Mladenovska, Olivija; Spiroski, Mirko

    2008-01-01

    The aim was to investigate different genotypes and haplotypes of methylenetetrahydrofolate reductase (MTHFR-677, -1298) and plasma concentration of total homocysteine (tHcy) in Macedonian patients with occlusive artery disease (OAD) and deep venous thrombosis (DVT). Investigated groups consists of 80 healthy, 74 patients with OAD, and 63 patients with DVT. Plasma tHcy was measured with Microplate Enzyme Immunoassay. Identification of MTHFR genotypes and haplotypes was done with CVD StripAssay. The probability level (P-value) was evaluated by the Student's t-test. Plasma concentration of tHcy in CC and CT genotypes of MTHFR C677T was significantly increased in patients with OAD and in patients with DVT. Plasma concentration of tHcy in AC genotype of MTHFR A1298C was increased in patients with OAD and in patients with DVT. Plasma concentration of tHcy was significantly increased in AA genotype of patients with OAD, but not in patients with DVT. We found a significant increase of plasma tHcy in patients with OAD in comparison with healthy respondents for normal:heterozygote (CC:AC), heterozygote:normal (CT:AA), and heterozygote:heterozygote (CT:AC) haplotypes. Plasma concentration of tHcy in patients with DVT in comparison with healthy respondents was significantly increased for normal:normal (CC:AA), normal heterozygote (CC:AC), and heterozygote:heterozygote (CT:AC) haplotypes. We conclude that MTHFR C677T and MTHFR A1289C genotypes and haplotypes are connected with tHcy plasma levels in Macedonian patients with OAD and DVT. PMID:18800176

  20. Associations of plasma natriuretic peptide, adrenomedullin, and homocysteine levels with alterations in arterial stiffness: The Framingham Heart Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Experimental studies suggest that the natriuretic peptides influence lipid and fatty acid metabolism. Although it has been shown that obese individuals have reduced natriuretic peptide levels, conflicting data exist on the relation of natriuretic peptide levels to other metabolic risk factors. We ex...

  1. Fibrinogen induces endothelial cell permeability

    PubMed Central

    Tyagi, Neetu; Roberts, Andrew M.; Dean, William L.; Tyagi, Suresh C.

    2010-01-01

    Many cardiovascular and cerebrovascular disorders are accompanied by an increased blood content of fibrinogen (Fg), a high molecular weight plasma adhesion protein. Fg is a biomarker of inflammation and its degradation products have been associated with microvascular leakage. We tested the hypothesis that at pathologically high levels, Fg increases endothelial cell (EC) permeability through extracellular signal regulated kinase (ERK) signaling and by inducing F-actin formation. In cultured ECs, Fg binding to intercellular adhesion molecule-1 and to α5β1 integrin, caused phosphorylation of ERK. Subsequently, F-actin formation increased and coincided with formation of gaps between ECs, which corresponded with increased permeability of ECs to albumin. Our data suggest that formation of F-actin and gaps may be the mechanism for increased albumin leakage through the EC monolayer. The present study indicates that elevated un-degraded Fg may be a factor causing microvascular permeability that typically accompanies cardiovascular and cerebrovascular disorders. PMID:17849175

  2. Effects of bromocriptine mesylate on homocysteine and high-sensitivity C-reactive protein levels in patients with type-2 diabetes mellitus

    PubMed Central

    Niafar, Mitra; Pourafkari, Leili; Shahsavarinia, Kavus; Milanchian, Nushin; Niafar, Farhad; Nader, Nader D.

    2016-01-01

    Introduction: Quick release bromocriptine (BROM-QR), currently approved for glycemic control, reduces the risk of cardiovascular events in adults with type-2 diabetes mellitus (T2DM). This study evaluates the effect of BROM-QR on homocysteine (HOMC) and high sensitive C-reactive protein (hs-CRP), the biochemical markers of coronary atherosclerosis/inflammation, in patients with uncontrolled T2DM. Methods: In this non-randomized, before-and-after clinical trial, patients with uncontrolled T2DM on stable doses of two oral hypoglycemic agents received BROM-QR for 6 months. The change in serum concentrations of HOMC was the primary endpoint. Anthropometric measurements such as body mass index (BMI) and waist circumference were measured at the baseline and at the completion of treatment along with fasting plasma glucose (FPG), HbA1c, total cholesterol, triglyceride, creatinine and hs-CRP. Multivariate regression analysis was performed to identify factors associated with changes in the levels of HOMC. Results: In 64 patients (46 completed 6 months of treatment), age was 55±7 years and the duration of T2DM was 8.0 ± 4.4 years. On enrollment, mean HbA1c, FPG, hs-CRP and HOMC levels were 9.0± 1.3 percent, 184 ± 42 mg/dL, 3.8± 3.4 mg/dl and 10.8 ± 6.2 micromole/L; respectively. Mean decrease of 0.7 ± 1.1 percent for HbA1c (P = 0.001) and 22 ± 44 mg/dL for FPG was observed (P = 0.002). HOMC levels decreased to 8.5 ± 5.2 micromole/L (P = 0.011) while hs-CRP levels remained unchanged at 3.7 ± 2.9 mg/dL (P = 0.835). Conclusion: While HOMC and HbA1c levels decreased significantly after 6 months of treatment with BROM-QR in patients with T2DM, serum levels of hs-CRP, total cholesterol and triglyceride did not significantly change. PMID:27069561

  3. Thromboembolic events in patients with severe inherited fibrinogen deficiency.

    PubMed

    Rottenstreich, Amihai; Lask, Avigal; Schliamser, Lilliana; Zivelin, Ariella; Seligsohn, Uri; Kalish, Yosef

    2016-08-01

    Inherited afibrinogenemia and hypofibrinogenemia are rare bleeding disorders characterized by markedly reduced levels of fibrinogen in blood. Thrombotic complications in these disorders have been rarely described. We performed a multicenter retrospective study and reviewed the occurrence of thrombotic complications among patients with inherited fibrinogen deficiency. Cases were identified during a review of medical records of all patients with inherited fibrinogen deficiency followed at three different university hospitals in Israel. Nine patients were included in this study: five were afibrinogenemic and four hypofibrinogenemic. There were seven thrombotic events, mostly venous, that occurred in four out of nine patients (44 %). All thrombotic events occurred in afibrinogenemic patients. Mean age at the time of thrombosis was 45 (range 28-61) years. Thrombophilic evaluation performed was negative in all cases. At the time of thrombosis in five out of seven (71.4 %) events, fibrinogen replacement therapy was concurrently given. Therapeutic approach was different among patients ranging from supportive therapy alone, antiplatelet agents and anticoagulant therapy with the concurrent administration of fibrinogen replacement therapy. This study discloses a high rate of thrombosis in patients with afibrinogenemia. Events were both venous and arterial and may be recurrent. Management is highly problematic due to the precarious balance between bleeding and thrombotic risk in these patients. Fibrinogen replacement therapy should be cautiously used in these patients as most thrombotic events followed the administration of fibrinogen replacement therapy. Larger cohorts are warranted to better characterize the best management strategy in these paradoxical events. PMID:26712130

  4. Detection of Homocysteine and Cysteine

    PubMed Central

    Wang, Weihua; Xu, Xiangyang; Kim, Kyu Kwang; Escobedo, Jorge O.; Fakayode, Sayo O.; Fletcher, Kristin A.; Lowry, Mark; Schowalter, Corin M.; Lawrence, Candace M.; Fronczek, Frank R.; Warner, Isiah M.

    2012-01-01

    At elevated levels, homocysteine (Hcy, 1) is a risk factor for cardiovascular diseases, Alzheimer’s disease, neural tube defects, and osteoporosis. Both 1 and cysteine (Cys, 3) are linked to neurotoxicity. The biochemical mechanisms by which 1 and 3 are involved in disease states are relatively unclear. Herein, we describe simple methods for detecting either Hcy or Cys in the visible spectral region with the highest selectivity reported to date without using biochemical techniques or preparative separations. Simple methods and readily available reagents allow for the detection of Cys and Hcy in the range of their physiologically relevant levels. New HPLC postcolumn detection methods for biological thiols are reported. The potential biomedical relevance of the chemical mechanisms involved in the detection of 1 is described. PMID:16277539

  5. A Protein Extract from Chicken Reduces Plasma Homocysteine in Rats

    PubMed Central

    Lysne, Vegard; Bjørndal, Bodil; Vik, Rita; Nordrehaug, Jan Erik; Skorve, Jon; Nygård, Ottar; Berge, Rolf K.

    2015-01-01

    The present study aimed to evaluate effects of a water-soluble protein fraction of chicken (CP), with a low methionine/glycine ratio, on plasma homocysteine and metabolites related to homocysteine metabolism. Male Wistar rats were fed either a control diet with 20% w/w casein as the protein source, or an experimental diet where 6, 14 or 20% w/w of the casein was replaced with the same amount of CP for four weeks. Rats fed CP had reduced plasma total homocysteine level and markedly increased levels of the choline pathway metabolites betaine, dimethylglycine, sarcosine, glycine and serine, as well as the transsulfuration pathway metabolites cystathionine and cysteine. Hepatic mRNA level of enzymes involved in homocysteine remethylation, methionine synthase and betaine-homocysteine S-methyltransferase, were unchanged, whereas cystathionine gamma-lyase of the transsulfuration pathway was increased in the CP treated rats. Plasma concentrations of vitamin B2, folate, cobalamin, and the B-6 catabolite pyridoxic acid were increased in the 20% CP-treated rats. In conclusion, the CP diet was associated with lower plasma homocysteine concentration and higher levels of serine, choline oxidation and transsulfuration metabolites compared to a casein diet. The status of related B-vitamins was also affected by CP. PMID:26053618

  6. A Protein Extract from Chicken Reduces Plasma Homocysteine in Rats.

    PubMed

    Lysne, Vegard; Bjørndal, Bodil; Vik, Rita; Nordrehaug, Jan Erik; Skorve, Jon; Nygård, Ottar; Berge, Rolf K

    2015-06-01

    The present study aimed to evaluate effects of a water-soluble protein fraction of chicken (CP), with a low methionine/glycine ratio, on plasma homocysteine and metabolites related to homocysteine metabolism. Male Wistar rats were fed either a control diet with 20% w/w casein as the protein source, or an experimental diet where 6, 14 or 20% w/w of the casein was replaced with the same amount of CP for four weeks. Rats fed CP had reduced plasma total homocysteine level and markedly increased levels of the choline pathway metabolites betaine, dimethylglycine, sarcosine, glycine and serine, as well as the transsulfuration pathway metabolites cystathionine and cysteine. Hepatic mRNA level of enzymes involved in homocysteine remethylation, methionine synthase and betaine-homocysteine S-methyltransferase, were unchanged, whereas cystathionine gamma-lyase of the transsulfuration pathway was increased in the CP treated rats. Plasma concentrations of vitamin B2, folate, cobalamin, and the B-6 catabolite pyridoxic acid were increased in the 20% CP-treated rats. In conclusion, the CP diet was associated with lower plasma homocysteine concentration and higher levels of serine, choline oxidation and transsulfuration metabolites compared to a casein diet. The status of related B-vitamins was also affected by CP. PMID:26053618

  7. Homocystein as a Risk Factor for Developing Complications in Chronic Renal Failure

    PubMed Central

    Jakovljevic, Biljana; Gasic, Branislav; Kovacevic, Pedja; Rajkovaca, Zvezdana; Kovacevic, Tijana

    2015-01-01

    Aim: Cardiovascular diseases are leading cause of death in patients with chronic renal failure. The aim of our study was to establish connection between levels of homocysteine and traditional and nontraditional risk factors for developing cardiovascular diseases in dialysis and pre dialysis patients. Methods: We included 33 pre dialysis (23 in stage three and 10 in stage four of chronic kidney disease) and 43 patients receiving hemodialysis longer than six months. Besides standard laboratory parameters, levels of homocysteine and blood pressure were measured in all patients. Glomerular filtration rate was measured in pre dialysis patients and dialysis quality parameters in dialysis patients. Results: Homocysteine levels were elevated in all patients (19±5.42mmol/l). The connection between homocysteine levels and other cardiovascular diseases risk factors was not established in pre dialysis patients. In patients treated with hemodialysis we found negative correlation between homocysteine levels and patients’ age (p<0.05) and positive correlation between homocysteine levels and length of dialysis (p<0.01) as well as between homocysteine and anemia parameters (erythrocytes, hemoglobin), (p<0.01). Homocysteine and LDL (and total cholesterol) were in negative correlation (p<0.01). Conclusion: Homocysteine, as one of nontraditional cardiovascular diseases risk factors, is elevated in all patients with chronic renal failure and it’s positive correlation with some other risk factors was found. PMID:26005384

  8. Fibrinogen stability under surfactant interaction.

    PubMed

    Hassan, Natalia; Barbosa, Leandro R S; Itri, Rosangela; Ruso, Juan M

    2011-10-01

    Differential scanning calorimetry (DSC), circular dichroism (CD), difference spectroscopy (UV-vis), Raman spectroscopy, and small-angle X-ray scattering (SAXS) measurements have been performed in the present work to provide a quantitatively comprehensive physicochemical description of the complexation between bovine fibrinogen and the sodium perfluorooctanoate, sodium octanoate, and sodium dodecanoate in glycine buffer (pH 8.5). It has been found that sodium octanoate and dodecanoate act as fibrinogen destabilizer. Meanwhile, sodium perfluorooctanoate acts as a structure stabilizer at low molar concentration and as a destabilizer at high molar concentration. Fibrinogen's secondary structure is affected by all three studied surfactants (decrease in α-helix and an increase in β-sheet content) to a different extent. DSC and UV-vis revealed the existence of intermediate states in the thermal unfolding process of fibrinogen. In addition, SAXS data analysis showed that pure fibrinogen adopts a paired-dimer structure in solution. Such a structure is unaltered by sodium octanoate and perfluoroctanoate. However, interaction of sodium dodecanoate with the fibrinogen affects the protein conformation leading to a complex formation. Taken together, all results evidence that both surfactant hydrophobicity and tail length mediate the fibrinogen stability upon interaction. PMID:21722913

  9. Homocysteine and Cognitive Performance in Elders with Self-Neglect

    NASA Technical Reports Server (NTRS)

    Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

    2009-01-01

    Elevated plasma homocysteine has been associated with altered cognitive performance in older adults. Elders referred to Adult Protective Services (APS) for self-neglect have been reported to have elevated plasma homocysteine levels and to suffer from cognitive impairment. This study assesses the association, if any, between plasma homocysteine and cognitive performance among elders with self-neglect. Methods: Sixty-five community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 matched controls (matched for age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS), the Wolf-Klein Clock Drawing Tests (CDT) and a comprehensive nutritional biochemistry panel, which included plasma homocysteine. Student s t tests and Pearson correlations were conducted to assess for bivariate associations. Results: Elders with self-neglect had significantly higher plasma homocysteine levels (M=12.68umol/L, sd=4.4) compared to the controls (M=10.40umol/L, sd=3.61;t=3.21, df=127, p=.002). There were no statistically significant associations between cognitive performance and plasma homocysteine in the self-neglect group, however there was a significant correlation between plasma homocysteine and the CDT among the controls (r=-.296, p=.022). Conclusion: Mean plasma homocysteine levels were significantly higher in elders with self-neglect, however, they do not appear to be related to cognitive performance, indicating that cognitive impairment in elder self-neglect involve mechanisms other than hyperhomocysteinemia. These findings warrant further investigation

  10. Why is homocysteine toxic for the nervous and immune systems?

    PubMed

    Boldyrev, Alexander; Bryushkova, Ekaterina; Mashkina, Anna; Vladychenskaya, Elizaveta

    2013-02-01

    Hyperhomocysteinemia is a risk factor for a number of neurodegenerative and cardiovascular diseases. We have shown that homocysteine induces excitotoxic effects in cells expressing glutamate receptors of the NMDA class. These receptors were found not only in neurons but also in immune-competent cells, neutrophils, red blood cells, cardiomyocytes, and osteoblasts. Activation of these cells by homocysteine results in an increase in cytoplasmic calcium ions, accumulation of reactive oxygen species, and activation of MAP kinase. An overload of immune-competent cells activates both necrotic and apoptotic cell death, whereas the neuropeptide carnosine (an antioxidant and immune modulator) protects cells against both processes. In a model of prenatal hyperhomocysteinemia in rats, we have found that carnosine protects animals against homocysteine toxicity with no change of the blood homocysteine levels. The efficiency of carnosine has also been demonstrated in clinical trials of chronic brain ischemia and Parkinson's disease. PMID:23237596

  11. Role of plasma homocysteine levels and MTHFR polymorphisms on IQ scores in children and young adults with epilepsy treated with antiepileptic drugs.

    PubMed

    Di Rosa, Gabriella; Lenzo, Patrizia; Parisi, Eleonora; Neri, Milena; Guerrera, Silvia; Nicotera, Antonio; Alibrandi, Angela; Germanò, Eva; Caccamo, Daniela; Spanò, Maria; Tortorella, Gaetano

    2013-12-01

    Homocysteine (Hcy) is a sulfur-containing amino acid involved in methionine metabolism. High plasma total Hcy (tHcy) has been quite frequently reported in patients with epilepsy treated with antiepileptic drugs (AEDs) mainly related to plasma folate reduction induced by AEDs themselves. The role of C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase gene (MTHFR) on the increase of plasma tHcy in patients with epilepsy taking AEDs is still controversial. Cognitive impairment may be associated with epilepsy either as the result of the epileptic syndrome per se or as a side effect induced by the AEDs. High plasma tHcy levels were associated with lower cognitive performances in patients affected by Alzheimer's disease and mild cognitive impairment and in healthy elderly. We searched for a correlation between plasma tHcy levels with the intelligence quotient (IQ) scores in a population of children and young adults with epilepsy treated with old and/or newer AEDs. The study group encompassed 179 patients (92 M, 51.5%) followed at our Unit of Child Neuropsychiatry and aged between 4 and 25years (mean+SD: 14.03±4.25). The inclusion criteria included the following: 1) diagnosis of epilepsy of "unknown cause" (cryptogenic) according to the ILAE classification, 2) age older than 3years, 3) stabilized antiepileptic treatment for at least 6months, and 4) clinical records of cognitive tests, plasma tHcy value, and results of MTHFR polymorphisms. Patients' mean tHcy value was 9.71±3.13μM/L (tHcy<9μM/L as our laboratory cutoff in nonepileptic controls). The mean TIQ score was 85.22 (SD±24.12); the mean VIQ score was 86.32 (SD±20.86); and the mean PIQ score was 86.94 (SD±21.51). C677T and A1298C MTHFR polymorphisms were detected in 74/92 (80%) examined patients and distributed into the following: CT (22.3%), TT (14.9%), CC (10.3%) for C677T, AC (16%), CC (1.1%), and AA (30.3%) for A1298C. Plasma tHcy levels were not significantly related to the IQ scores

  12. Analysis of the safety and pharmacodynamics of human fibrinogen concentrate in animals

    SciTech Connect

    Beyerle, Andrea; Nolte, Marc W.; Solomon, Cristina; Herzog, Eva; Dickneite, Gerhard

    2014-10-01

    Fibrinogen, a soluble 340 kDa plasma glycoprotein, is critical in achieving and maintaining hemostasis. Reduced fibrinogen levels are associated with an increased risk of bleeding and recent research has investigated the efficacy of fibrinogen concentrate for controlling perioperative bleeding. European guidelines on the management of perioperative bleeding recommend the use of fibrinogen concentrate if significant bleeding is accompanied by plasma fibrinogen levels less than 1.5–2.0 g/l. Plasma-derived human fibrinogen concentrate has been available for therapeutic use since 1956. The overall aim of the comprehensive series of non-clinical investigations presented was to evaluate i) the pharmacodynamic and pharmacokinetic characteristics and ii) the safety and tolerability profile of human fibrinogen concentrate Haemocomplettan P® (RiaSTAP®). Pharmacodynamic characteristics were assessed in rabbits, pharmacokinetic parameters were determined in rabbits and rats and a safety pharmacology study was performed in beagle dogs. Additional toxicology tests included: single-dose toxicity tests in mice and rats; local tolerance tests in rabbits; and neoantigenicity tests in rabbits and guinea pigs following the introduction of pasteurization in the manufacturing process. Human fibrinogen concentrate was shown to be pharmacodynamically active in rabbits and dogs and well tolerated, with no adverse events and no influence on circulation, respiration or hematological parameters in rabbits, mice, rats and dogs. In these non-clinical investigations, human fibrinogen concentrate showed a good safety profile. This data adds to the safety information available to date, strengthening the current body of knowledge regarding this hemostatic agent. - Highlights: • A comprehensive series of pre-clinical investigations of human fibrinogen concentrate. • Human fibrinogen concentrate was shown to be pharmacodynamically active. • Human fibrinogen concentrate was well tolerated

  13. Homocysteine and inflammation: predictors of cognitive decline in older persons?

    PubMed

    van den Kommer, T N; Dik, M G; Comijs, H C; Jonker, C; Deeg, D J H

    2010-10-01

    The aim of the current study was to examine the association between homocysteine and 6-year cognitive decline, and the modifying role of the inflammatory markers Interleukin-6 (IL-6), C-reactive protein (CRP) and alpha-1-antichymotrypsin (ACT). Data were collected within the Longitudinal Aging Study Amsterdam (ages >or=65 years) and analyzed using multiple longitudinal regression models (N=1257 of whom N=1076 had longitudinal data). Cognition was measured with the Mini-Mental State Examination (general cognition), Auditory Verbal Learning Test (memory), Coding Task (information processing speed) and Raven Coloured Progressive Matrices (fluid intelligence). Higher homocysteine at baseline was negatively associated with prolonged lower cognitive functioning and a faster rate of decline in information processing speed and fluid intelligence. The negative association between higher homocysteine and immediate recall was strongest in persons with a high level of IL-6. Only in the highest tertile of CRP, higher homocysteine was negatively associated with retention. In the middle tertile of ACT, higher homocysteine was associated with lower information processing speed and faster decline. Both in the lower and middle tertile of CRP, higher homocysteine was associated with a faster rate of decline in information processing speed. The results implicate that a combination of both risk factors may be used as a marker for cognitive impairment. PMID:19004529

  14. B Vitamins, Homocysteine and Bone Health

    PubMed Central

    Fratoni, Valentina; Brandi, Maria Luisa

    2015-01-01

    Nutrition is one of the most important modifiable factors involved in the development and maintenance of good bone health. Calcium and Vitamin D have confirmed and established roles in the maintenance of proper bone health. However, other nutritional factors could also be implicated. This review will explore the emerging evidence of the supporting role of certain B Vitamins as modifiable factors associated with bone health. Individuals with high levels of homocysteine (hcy) exhibit reduced bone mineral density (BMD), alteration in microarchitecture and increased bone fragility. The pathophysiology caused by high serum homocysteine is not completely clear regarding fractures, but it may involve factors, such as bone mineral density, bone turnover, bone blood flow and collagen cross-linking. It is uncertain whether supplementation with B Vitamins, such as folate, Vitamin B1, and Vitamin B6, could decrease hip fracture incidence, but the results of further clinical trials should be awaited before a conclusion is drawn. PMID:25830943

  15. Vegetarians and cardiovascular risk factors: hemostasis, inflammatory markers and plasma homocysteine.

    PubMed

    Mezzano, D; Muñoz, X; Martínez, C; Cuevas, A; Panes, O; Aranda, E; Guasch, V; Strobel, P; Muñoz, B; Rodríguez, S; Pereira, J; Leighton, F

    1999-06-01

    We studied hemostatic and inflammatory cardiovascular risk factors (CVRF), and total plasma homocysteine (tHcy) in 26 vegetarians (23 lacto- or ovolactovegetarians and 3 vegans), matched by age, sex and socioeconomic status with omnivorous controls. Vegetarians had significantly lower proportion of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids in plasma lipids, significantly shortened bleeding time, and increased blood platelet count and in vitro platelet function (aggregation and secretion). Plasma levels of all coagulation or fibrinolytic factors and natural inhibitors synthesized in the liver were lower in vegetarians than in controls. Whereas for some factors this decrease was statistically significant (fibrinogen, factor VIIc, antithrombin III, protein S, plasminogen) for the remaining (factors VIIIc, Vc, prothrombin, protein C) a trend in the same direction was found. For hemostatic proteins of predominantly extrahepatic origin (von Willebrand factor. tPA, PAI-1) this tendency was not present. No significant differences in inflammatory proteins (C-reactive protein and alpha1-protease inhibitor) were detected in both groups. tHcy was significantly increased in vegetarians, and correlated only with cobalamin levels. The increased platelet function and tHcy found in vegetarians may counteract the known cardiovascular health benefits of vegetarian diet (VD). PMID:10404767

  16. Combined effect of folate and adiposity on homocysteine in children at three years of age

    PubMed Central

    Lee, Hye Ah; Park, Bo Hyun; Ha, Eun Hee; Kim, Young Ju; Park, Eun Ae; Park, Hyesook

    2016-01-01

    BACKGROUND/OBJECTIVES Cardiovascular diseases is a major cause of death and is responsible for 23.8% of deaths in Korea. Clinical symptoms manifest in adulthood, but susceptibility begins in utero. Elevated homocysteine levels and adiposity might be linked to a greater risk in children as well as adults. We hypothesized that those who have simultaneous risk for folate and adiposity would be affected with elevated homocysteine levels at 3 years of age. SUBJECTS/METHODS From the ongoing birth cohort at Ewha Womans University Mok-Dong Hospital, we compared adiposity parameters, serum homocysteine, and folate levels in 238 children (118 boys and 120 girls) at three years of age. The relationship between birth outcome, current weight and body mass index (BMI), postnatal growth, and homocysteine level were assessed using correlation and general linear model. Additionally, we assessed the combined effect between blood folate status and adiposity on current homocysteine levels. RESULTS Birth characteristics were not correlated with homocysteine. Current weight, BMI, upper-arm circumference, skinfold thickness, waist circumference, and hip circumference were positively correlated with homocysteine at three years of age (P < 0.05). Folate level was negatively correlated with homocysteine at three years of age (P < 0.0001). A relative high anthropometric measure which is compatible with adiposity and low folate level was associated with high homocysteine levels. CONCLUSION We found a combined effect of adiposity and folate levels with homocysteine levels at three years of age. This implicates the beneficial role of folate supplementation in the high-risk population at an early age. PMID:26865919

  17. Prognostic significance of preoperative fibrinogen in patients with colon cancer

    PubMed Central

    Sun, Zhen-Qiang; Han, Xiao-Na; Wang, Hai-Jiang; Tang, Yong; Zhao, Ze-Liang; Qu, Yan-Li; Xu, Rui-Wei; Liu, Yan-Yan; Yu, Xian-Bo

    2014-01-01

    AIM: To investigate the prognostic significance of preoperative fibrinogen levels in colon cancer patients. METHODS: A total of 255 colon cancer patients treated at the Affiliated Tumor Hospital of Xinjiang Medical University from June 1st 2005 to June 1st 2008 were enrolled in the study. All patients received radical surgery as their primary treatment method. Preoperative fibrinogen was detected by the Clauss method, and all patients were followed up after surgery. Preoperative fibrinogen measurements were correlated with a number of clinicopathological parameters using the Student t test and analysis of variance. Survival analyses were performed by the Kaplan-Meier method and Cox regression modeling to measure 5-year disease-free survival (DFS) and overall survival (OS). RESULTS: The mean preoperative fibrinogen concentration of all colon cancer patients was 3.17 ± 0.88 g/L. Statistically significant differences were found between preoperative fibrinogen levels and the clinicopathological parameters of age, smoking status, tumor size, tumor location, tumor-node-metastasis (TNM) stage, modified Glasgow prognostic scores (mGPS), white blood cell (WBC) count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and carcinoembryonic antigen (CEA) levels. Univariate survival analysis showed that TNM stage, tumor cell differentiation grade, vascular invasion, mGPS score, preoperative fibrinogen, WBC, NLR, PLR and CEA all correlated with both OS and DFS. Alpha-fetoprotein (AFP) and body mass index correlated only with OS. Kaplan-Meier analysis revealed that both OS and DFS of the total cohort, as well as of the stage II and III patients, were higher in the hypofibrinogen group compared to the hyperfibrinogen group (all P < 0.05). In contrast, there was no significant difference between OS and DFS in stage I patients with low or high fibrinogen levels. Cox regression analysis indicated preoperative fibrinogen levels, TNM stage, mGPS score, CEA, and

  18. Nutritional status influences plasma fibrinogen concentration: evidence from the THUSA survey.

    PubMed

    James, S; Vorster, H H; Venter, C S; Kruger, H S; Nell, T A; Veldman, F J; Ubbink, J B

    2000-06-01

    Nutritional status and risk factors for chronic diseases, including plasma fibrinogen and its determinants, of Africans in the Northwest Province of South Africa, have been studied in a cross-sectional survey. A representative sample of 1854 "apparently healthy" African men and women volunteers aged 15 years and older was recruited from 37 randomly selected sites throughout the Province and stratified for level of urbanisation. Information was collected using validated and culture-sensitive questionnaires. Fasting blood samples were drawn, and all measurements were done with standardised methodology using appropriate equipment, procedures, and controls. Fibrinogen concentration was measured in citrated plasma with the method of Clauss, using the ACL200 automated system and the international fibrinogen standard. The results revealed a population with a high mean plasma fibrinogen (3.17+/-1.10 g/L for HIV-negative men and 3. 64+/-1.12 g/L for HIV-negative women). Factors known to influence plasma fibrinogen, such as age, gender, smoking habit, and physical activity, were also observed in this population. Young rural men and women had the lowest fibrinogen level. Nasal snuff taking and HIV infection did not influence fibrinogen concentration. Multivariate analyses revealed that lower plasma fibrinogen was associated with low to normal body mass index in women, and with dietary intakes compatible with prudent dietary guidelines in men and women (low intakes of animal protein; trans fatty acids and higher intakes of plant protein; dietary fibre, vitamin E, and iron, and a high dietary P/S ratio). Subjects in the higher quartiles of plasma fibrinogen had significantly lower iron, vitamin E, and vitamin B6 (women) status. Increases in fibrinogen were associated with significant increases in serum lipids. Both under- and overnutrition seem to be associated with high plasma fibrinogen. It is concluded that overall nutritional status, possibly in addition to specific

  19. Risk of neural tube defect-affected pregnancy is associated with a block in maternal one-carbon metabolism at the level of N-5-methyltetrahydrofolate:homocysteine methyltransferase.

    PubMed

    Lucock, M D; Wild, J; Lumb, C H; Oliver, M; Kendall, R; Daskalakis, I; Schorah, C J; Levene, M I

    1997-06-01

    The disposition of whole blood mono-to hexaglutamyl methylfolate and plasma homocysteine (HCY) was used to evaluate potential lesion sites in one-carbon metabolism which could be responsible for neural tube defect(NTD)-affected pregnancies. An isocratic high-performance liquid chromatographic system (HPLC) with photodiode array detection was used to quantify and speciate whole-blood methylfolate into mono-, di-, tri-, tetra-, penta-, and hexaglutamate forms. This technique was also used with off-line radioassay to identify nonmethyl whole-blood folates. Isocratic HPLC with fluorescence detection was used to quantify SBDF derivatized homocysteine in plasma. The study investigated blood from 11 women who had experienced a previous NTD-affected pregnancy and 11 controls of similar age and social class. No subjects were pregnant. HCY levels were significantly higher in NTD subjects (P = 0.0486, 95% CI-2.799,0.001 using the Mann-Whitney test), as was the ratio of known intracellular (tri-to hexaglutamyl) methylfolate compared to extracellular (mono- and diglutamyl) methylfolate (P = 0.0062 95% CI-0.543, 3.862 using the Mann-Whitney test). Vitamin B12, red cell folate, circulating total methylfolate, and circulating mono-to hexaglutamyl methylfolates showed no difference between population groups. The disposition between individual and cumulative glutamate chain lengths of methylfolate showed significant trends which differed between population groups: (i) total blood methylfolate (Glu1-6) appears to be utilized by N-5-methyltetrahydrofolate:homocysteine methyltransferase (MS) in control blood but not NTD blood, where it appears to accumulate following a 45-min incubation; (ii) whole-blood hexaglutamyl methylfolate (5CH3-H4PteGlus) becomes a larger proportion of the total blood methylfolate in NTD than in control populations; and (iii) the intermediate glutamate chains of methylfolate (Glu1-5) remain relatively constant as 5CH3-H4PteGlu6 accumulates in NTD but appear to

  20. Evaluation of Serum Fibrinogen, Plasminogen, α2-Anti-Plasmin, and Plasminogen Activator Inhibitor Levels (PAI) and Their Correlation with Presence of Retinopathy in Patients with Type 1 DM

    PubMed Central

    Polat, Sefika Burcak; Ugurlu, Nagihan; Yulek, Fatma; Simavli, Huseyin; Ersoy, Reyhan; Cakir, Bekir; Erel, Ozcan

    2014-01-01

    Background. Diabetic retinopathy (DR) is the leading cause of blindness in the world. Retinopathy can still progress despite optimal metabolic control. The aim of the study was to determine whether different degrees of DR (proliferative or nonproliferative) were associated with abnormally modulated hemostatic parameters in patients with T1DM. Method. 52 T1DM patients and 40 healthy controls were enrolled in the study. Patients were subdivided into three categories. Group I was defined as those without retinopathy, group II with NPRP, and group III with PRP. We compared these subgroups with each other and the control group (Group IV) according to the serum fibrinogen, plasminogen, alpha2-anti-plasmin (α2-anti-plasmin), and PAI. Results. We detected that PAI-1, serum fibrinogen, and plasminogen levels were similar between the diabetic and control groups (P = 0.209, P = 0.224, and P = 0.244, resp.), whereas α2-anti-plasmin was higher in Groups I, II, and III compared to the control group (P < 0.01, P < 0.05, and P < 0.001, resp.). There was a positive correlation between serum α2-anti-plasmin and HbA1c levels (r = 0,268, P = 0.031). Conclusion. To our knowledge there is scarce data in the literature about α2-anti-plasmin levels in type 1 diabetes. A positive correlation between α2-anti-plasmin with HbA1c suggests that fibrinolytic markers may improve with disease regulation and better glycemic control. PMID:24818165

  1. Exposure of fibrinogen receptors in human platelets by surface proteolysis with elastase.

    PubMed Central

    Kornecki, E; Ehrlich, Y H; De Mars, D D; Lenox, R H

    1986-01-01

    Human platelets that were preincubated with porcine elastase aggregated spontaneously upon the addition of fibrinogen. Maximal aggregation to fibrinogen was observed with platelets pretreated with an elastase concentration of 111 micrograms/ml, and half-maximal aggregation occurred after treatment with 11 micrograms/ml elastase. Binding of radiolabeled fibrinogen to elastase-treated platelets was specific, saturable, and showed a single class of 48,400 +/- 9,697 fibrinogen-binding sites per platelet with a dissociation constant of 6.30 +/- 1.48 X 10(-7) M. ATP, apyrase, and the stimulators of platelet adenylate cyclase forskolin, prostaglandin E1, prostacyclin, and N6, 2'-O-dibutyryl cyclic AMP did not inhibit the fibrinogen-induced aggregation of elastase-treated platelets. EDTA completely blocked the initiation of aggregation and reversed the fibrinogen-induced aggregation of elastase-treated platelets. Monoclonal and polyclonal antibodies directed against glycoproteins (GP) IIb and IIIa completely blocked the fibrinogen-induced aggregation of elastase-treated platelets. Immunoprecipitates with these antibodies obtained from detergent extracts of surface-radiolabeled, intact, and elastase-treated platelets contained the glycoproteins IIb and IIIa. We conclude that surface proteolysis by low concentrations of elastase can expose fibrinogen-binding sites associated with GPIIb and GPIIIa on the platelet surface, resulting in spontaneous aggregation upon the addition of fibrinogen. These findings may be relevant to hemostatic changes observed in patients with increased levels of circulating elastase. Images PMID:3005363

  2. Biochemical and structural analysis of the interaction between β-amyloid and fibrinogen.

    PubMed

    Zamolodchikov, Daria; Berk-Rauch, Hanna E; Oren, Deena A; Stor, Daniel S; Singh, Pradeep K; Kawasaki, Masanori; Aso, Kazuyoshi; Strickland, Sidney; Ahn, Hyung Jin

    2016-08-25

    The majority of patients with Alzheimer disease (AD) suffer from impaired cerebral circulation. Accumulating evidence suggests that fibrinogen, the main protein component of blood clots, plays an important role in this circulatory dysfunction in AD. Fibrinogen interacts with β-amyloid (Aβ), forming plasmin-resistant abnormal blood clots, and increased fibrin deposition is found in the brains of AD patients and mouse models. In this study, we investigated the biochemical and structural details of the Aβ-fibrinogen interaction. We identified the central region of Aβ42 as the most critical region for the interaction, which can be inhibited by specific antibodies against the central region of Aβ and by naturally occurring p3 peptides, Aβ17-40 and Aβ17-42. X-ray crystallographic analysis revealed that Aβ42 binding to fragment D of fibrinogen induced a structural change in the C-terminal region of the fibrinogen β-chain (β384-393). Furthermore, we identified an additional Aβ-binding site within the αC region of fibrinogen. Aβ binding to this αC region blocked plasmin-mediated fibrin cleavage at this site, resulting in the generation of increased levels of a plasmin-resistant fibrin degradation fragment. Overall, our study elucidates the Aβ-fibrinogen interaction and clarifies the mechanism by which Aβ-fibrinogen binding delays fibrinolysis by plasmin. These results may facilitate the development of effective therapeutics against the Aβ-fibrinogen interaction to treat cerebrovascular abnormalities in AD. PMID:27389717

  3. Toxic effects of mildly elevated homocysteine concentrations in neuronal-like cells.

    PubMed

    Currò, M; Gugliandolo, A; Gangemi, C; Risitano, R; Ientile, R; Caccamo, D

    2014-08-01

    Epidemiological and experimental evidence indicated that hyperhomocysteinemia is associated with neurodegeneration. However, homocysteine neurotoxic effects have been so far investigated mostly by employing homocysteine concentrations (≥100 µM) much higher than homocysteine mean plasma levels (20 µM) observed in patients with neurodegenerative disorders. While evaluating the effects of a prolonged exposure to ~20 µM homocysteine in neuronal-like differentiated SH-SY5Y cells, we observed a 35% loss of cell viability and a four-fold increase in reactive oxygen species levels in cells incubated with homocysteine for five days compared with controls. Moreover, homocysteine increased by 30% and around two-fold, respectively, the Comet-positive cell number and DNA damage indexes (tail length, T-DNA, olive tail moment) compared with controls. Cell response to homocysteine-induced DNA damage involved the up-regulation of Bax and, at a greater extent, Bcl-2, but not caspase-3, in association with a p53-independent increase of p21 levels; concomitantly, also p16 levels were increased. When looking at time-dependent changes in cyclin expression, we found that a significant up-regulation of cyclins D1, A1, E1, but not B1, concomitant with p21 down-regulation, occurred in cells incubated with homocysteine for three days. However, in line with the observed increase of p21 and p16 levels, a five days incubation with homocysteine induced cyclin down-regulation accompanied by a strong reduction of phosphorylated pRB amounts. These results suggest that, when prolonged, the exposure of neuronal-like cells to mildly elevated homocysteine concentrations triggers oxidative and genotoxic stress involving an early induction of cyclins, that is late repressed by G1-S check-point regulators. PMID:24867323

  4. Helicobacter pylori infection, vitamin B12 and homocysteine. A review.

    PubMed

    Dierkes, Jutta; Ebert, Matthias; Malfertheiner, Peter; Luley, Claus

    2003-01-01

    It has been suggested that there is an association between Helicobacter pylori infection, reduced cobalamin absorption and cobalamin status and, consequently, elevated homocysteine levels. This would offer an explanation why H. pylori infection is associated with coronary heart disease. To date, more than 25 studies have been published that either deal with H. pylori infection and homocysteine, H. pylori infection and cobalamin status, or both. The design of these studies differs widely in terms of definition of H. pylori status, measuring cobalamin status, selection of study cohorts and geographical study areas. Therefore, results are fairly inconclusive at present and do not suggest a major role of H. pylori infection in the development of cobalamin deficiency and elevated homocysteine levels. PMID:14571097

  5. Venous ulceration, fibrinogen and fibrinolysis.

    PubMed Central

    Leach, R. D.

    1984-01-01

    The effect of long and short-term venous hypertension upon lymph fibrinogen concentrations was studied in an attempt to explain the peri-capillary deposition of fibrin reported in patients with post-phlebitic syndromes. The clearance of radioactive fibrinogen/thrombin clots from the subcutaneous tissues of rats and human volunteers was also studied. Both long- and short-term venous hypertension were found to increase fibrinogen transport across the interstitial space by more than 600%. Not only was there evidence of fibrinolytic activity in the lymph but after long-term venous hypertension alpha 2 antiplasmin activity was also detectable. Skin biopsies from the venous hypertensive ankles showed deposition of interstitial fibrin. The clearance of radioactive fibrinogen/thrombin clots from the subcutaneous tissues of the rat was found to be delayed if the rats were given epsilon amino caproic acid but it could not be increased with stanozolol. In human subjects it was found that patients with lipodermatosclerosis had delayed clot clearance and retarded blood fibrinolytic activity when compared with normal volunteers and patients with uncomplicated varicose veins. The principle cause why tall men are more subject to ulcers than short men, Dr Young conceived to be then length of the column of blood in their veins; which by its pressure, renders the legs less able to recover when hurt by any violence. Images Fig. 1 Fig. 2 Fig. 5 PMID:6742738

  6. Alcohol consumption and plasma homocysteine.

    PubMed

    Sakuta, Hidenari; Suzuki, Takashi

    2005-10-01

    A few reports show that consumption of spirits and of wine correlate with elevated plasma total homocysteine (tHcy), which is associated with the risk of cardiovascular disease. We analyzed the relation between tHcy and current daily ethanol consumption cross-sectionally in middle-aged Japanese men (n = 974, age 51-59 years). Plasma tHcy was positively associated with consumption of whiskey but not with consumption of shochu (Japanese spirits), sake, beer, or wine. Odds ratios of an increase in daily intake of 30 ml ethanol (approximately 1 standard deviation) for hyperhomocysteinemia (>14.0 micromol/l) were 2.58 (95% confidence interval, 1.29-5.14) for whiskey, 1.08 (0.78-1.50) for shochu, 0.99 (0.59-1.66) for sake, 0.98 (0.58-1.63) for beer, and 1.70 (0.31-9.50) for wine in a multivariate logistic regression analysis adjusted for the daily number of cigarettes smoked, physical activity, vegetable consumption, and serum creatinine levels. After inclusion of plasma folate and vitamin B12 in the multivariate analysis model, the association between whiskey ethanol consumption and hyperhomocysteinemia remained significant with odds ratio of 2.79 (1.36-5.72). These results suggest that whiskey consumption correlates with hyperhomocysteinemia independently of plasma folate or vitamin B12 or lifestyle factors in the population studied. PMID:16584970

  7. Rapid measurement of fibrinogen concentration in whole blood using a steel ball coagulometer

    PubMed Central

    Schlimp, Christoph J.; Khadem, Anna; Klotz, Anton; Solomon, Cristina; Hochleitner, Gerald; Ponschab, Martin; Redl, Heinz; Schöchl, Herbert

    2015-01-01

    BACKGROUND Fibrinogen plays a key role in hemostasis and is the first coagulation factor to reach critical levels in bleeding patients. Current European guidelines on the management of traumatic or perioperative bleeding recommend fibrinogen supplementation at specific threshold levels. Whole blood viscoelastic tests provide fast evaluation of fibrin deficits. Fast measurement of plasma fibrinogen concentration is not yet available. We investigated a method to rapidly determine whole blood fibrinogen concentration using standard Clauss assays and a steel ball coagulometer and provide an estimate of the “plasma-equivalent” fibrinogen concentration within minutes by adjustment of the measured whole blood fibrinogen concentration with a quickly measureable hemoglobin-derived hematocrit. METHODS The feasibility of this approach was tested with a Clauss assay using multiple porcine fresh blood samples obtained during in vivo bleeding, hemodilution, and after treatment with hemostatic therapy. Two different Clauss assays were then tested using multiple human volunteers’ blood samples diluted in vitro and supplemented with fibrinogen concentrate. Comparative measurements with fibrin-based thromboelastometry tests were performed. RESULTS Regression and Bland-Altman analyses of derived “plasma-equivalent” fibrinogen and measured plasma fibrinogen concentration was excellent in porcine and human blood samples, especially in the ranges relevant to traumatic or perioperative bleeding. CONCLUSION Fast whole blood fibrinogen measurements could be considered as an alternative to plasma fibrinogen measurement for acute bleeding management in trauma and perioperative care settings. Further studies are needed to prove this concept and determine the turnaround times for its clinical application in emergency departments and operating theaters. PMID:25742256

  8. Recombinant human fibrinogen and sulfation of the. gamma. prime chain

    SciTech Connect

    Farrell, D.H.; Huang, S.; Chung, D.W.; Davie, E.W. ); Mulvihill, E.R. )

    1991-10-01

    Human fibrinogen and the homodimeric {gamma}{prime}-chain-containing variant have been expressed in BHK cells using cDNAs coding for the {alpha},{beta}, and {gamma} (or {gamma}{prime}) chains. The fibrinogens were secreted at levels greater than 4 {mu}g (mg of total cell protein){sup {minus}1}day{sup {minus}1} and were biologically active in clotting assays. Recombinant fibrinogen containing the {gamma}' chain incorporated {sup 35}SO{sub 4} into its chains during biosynthesis, while no incorporation occurred in the protein containing the {gamma} chain. The identity of the sulfated {gamma}{prime} chain was verified by its ability to form dimers during clotting. In addition, carboxypeptidase {Upsilon} digestion of the recombinant fibrinogen containing the {gamma}{prime} chain released 96% of the {sup 35}S label from the sulfated chain, and the radioactive material was identified as tyrosine O-sulfate. These results clarify previous findings of the sulfation of tyrosine in human fibrinogen.

  9. Homocysteine and Carotid Plaque Stability: A Cross-Sectional Study in Chinese Adults

    PubMed Central

    Liu, Chao; Gao, Xiang; Wang, Anxin; Guo, Yuming; Li, Wen; Zhao, Xingquan; Liang, Wannian

    2014-01-01

    Background and Purpose This study aimed to explore the possible association of plasma total homocysteine with carotid plaque stability. Methods A cross-sectional study was conducted from 2010 to 2011. A stratified random sample of 2,919 Chinese participants aged 40 years or older was enrolled. Plasma total homocysteine levels were measured and carotid plaques were evaluated by ultrasonography. Logistic regression model was used to analyze the association of homocysteine levels to the progression of carotid plaque development, while adjusting for demographics and vascular risk factors. Results The mean level of plasma homocysteine in the subjects was 14.9 µmol/l. Along with increase in homocysteine level, the risk of advanced carotid plaque elevated (odds ratio = 1.28; 95% confidence interval = 1.09–1.51) after adjusting for age, sex, and other potential confounders. Stratified by sex, higher homocysteine level was strongly associated with advanced carotid plaque in men (OR = 1.41; 95% confidence interval = 1.17–1.70), but not in women. Conclusion The findings suggest that plasma level of homocysteine may be associated with advanced carotid plaque, which constitutes high risks of stroke, in male Chinese adults. PMID:24736609

  10. Evaluation of a rapid method of determination of plasma fibrinogen.

    PubMed

    Thomson, G W; McSherry, B J; Valli, V E

    1974-07-01

    An evaluation was made of a rapid semiautomated method of determining fibrinogen levels in bovine plasma. This method, the fibrometer method of Morse, Panek and Menga (8), is based on the principle that when thrombin is added to suitably diluted plasma the time of clotting is linearly related to the fibrinogen concentration. A standard curve prepared using bovine plasma had an r value of .9987 and analysis of variance showed there was no significant deviation from regression. A comparison of the fibrometer method and the biuret method of Ware, Guest and Seegers done on 158 bovine plasma samples showed good correlation between the two methods. It was concluded that the fibrometer method does measure bovine fibrinogen and has considerable merit for use in clinical diseases of cattle. PMID:4277474

  11. A study on human serum albumin influence on glycation of fibrinogen

    SciTech Connect

    Kielmas, Martyna; Szewczuk, Zbigniew; Stefanowicz, Piotr

    2013-09-13

    Highlights: •The glycation of fibrinogen was investigated by isotopic labeling method. •The potential glycation sites in fibrinogen were identified. •Human serum albumin (HSA) inhibits the glycation of fibrinogen. •The effect of HSA on fibrinogen glycation is sequence-dependent. -- Abstract: Although in vivo glycation proceeds in complex mixture of proteins, previous studies did not take in consideration the influence of protein–protein interaction on Maillard reaction. The aim of our study was to test the influence of human serum albumin (HSA) on glycation of fibrinogen. The isotopic labeling using [{sup 13}C{sub 6}] glucose combined with LC-MS were applied as tool for identification possible glycation sites in fibrinogen and for evaluation the effect of HSA on the glycation level of selected amino acids in fibrinogen. The obtained data indicate that the addition of HSA protects the fibrinogen from glycation. The level of glycation in presence of HSA is reduced by 30–60% and depends on the location of glycated residue in sequence of protein.

  12. Alleviation of hepatic fat accumulation by betaine involves reduction of homocysteine via up-regulation of betaine-homocysteine methyltransferase (BHMT).

    PubMed

    Ahn, Chul Won; Jun, Doo Sung; Na, Jong Deok; Choi, Yeo Jin; Kim, Young Chul

    2016-08-26

    We investigated the anti-lipogenic effect of betaine in rats fed methionine and choline-deficient diet (MCD). Intake of MCD for 3 wk resulted in a significant accumulation of hepatic lipids, which was prevented by betaine supplementation in drinking water (1%). Phosphorylation of AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), sterol regulatory element-binding protein-1c (SREBP-1c), and liver kinase B1 (LKB1) was inhibited by MCD intake, and these changes were all inhibited by betaine feeding. Meanwhile, betaine supplementation reversed the reduction of methionine and S-adenosylmethionine (SAM), and the elevation of homocysteine levels in the liver, which could be attributable to the induction of betaine-homocysteine methyltransferase (BHMT) and methionine adenosyltransferase (MAT). Different cell lines were used to clarify the role of homocysteine on activation of the AMPK pathway. Homocysteine treatment decreased pAMPK, pACC, pSREBP-1c and pLKB1 in HepG2 cells. Metformin-induced activation of AMPK was also inhibited by homocysteine. Treatment with hydroxylamine, a cystathionine β-synthase inhibitor, resulted in a reduction of pAMPK, pACC and pSREBP-1c, accompanied by an elevation of intracellular homocysteine. Betaine treatment prevented the homocysteine-induced reduction of pAMPK, pACC, pSREBP-1c and pLKB1 in H4IIE cells, but not in HepG2 cells. Also the elevation of cellular homocysteine and inhibition of protein expression of BHMT were prevented by betaine only in H4IIE cells which express BHMT. The results suggest that the beneficial effect of betaine against hepatic lipid accumulation may be attributed, at least in part, to the depletion of homocysteine via up-regulation of BHMT in hepatocytes. PMID:27320863

  13. Ablation of MMP9 gene ameliorates paracellular permeability and fibrinogen-amyloid beta complex formation during hyperhomocysteinemia.

    PubMed

    Muradashvili, Nino; Tyagi, Reeta; Metreveli, Naira; Tyagi, Suresh C; Lominadze, David

    2014-09-01

    Increased blood level of homocysteine (Hcy), called hyperhomocysteinemia (HHcy) accompanies many cognitive disorders including Alzheimer's disease. We hypothesized that HHcy-enhanced cerebrovascular permeability occurs via activation of matrix metalloproteinase-9 (MMP9) and leads to an increased formation of fibrinogen-β-amyloid (Fg-Aβ) complex. Cerebrovascular permeability changes were assessed in C57BL/6J (wild type, WT), cystathionine-β-synthase heterozygote (Cbs+/-, a genetic model of HHcy), MMP9 gene knockout (Mmp9-/-), and Cbs and Mmp9 double knockout (Cbs+/-/Mmp9-/-) mice using a dual-tracer probing method. Expression of vascular endothelial cadherin (VE-cadherin) and Fg-Aβ complex formation was assessed in mouse brain cryosections by immunohistochemistry. Short-term memory of mice was assessed with a novel object recognition test. The cerebrovascular permeability in Cbs+/- mice was increased via mainly the paracellular transport pathway. VE-cadherin expression was the lowest and Fg-Aβ complex formation was the highest along with the diminished short-term memory in Cbs+/- mice. These effects of HHcy were ameliorated in Cbs+/-/Mmp9-/- mice. Thus, HHcy causes activation of MMP9 increasing cerebrovascular permeability by downregulation of VE-cadherin resulting in an enhanced formation of Fg-Aβ complex that can be associated with loss of memory. These data may lead to the identification of new targets for therapeutic intervention that can modulate HHcy-induced cerebrovascular permeability and resultant pathologies. PMID:24865997

  14. Fibrinogen synthesis in serum-free hepatocyte cultures: Stimulation by glucocorticoids

    PubMed Central

    Grieninger, Gerd; Hertzberg, Kathe M.; Pindyck, Johanna

    1978-01-01

    Fibrinogen synthesis was investigated in cultures of chicken embryo hepatocytes initiated and maintained in chemically defined, serum-free medium. 11-Hydroxy glucocorticoids caused a 3-fold stimulation of fibrinogen synthesis. Half-maximal stimulation was achieved with 1 nM corticosterone or hydrocortisone, as compared with only 0.1 nM dexamethasone. Increased fibrinogen production in the presence of these glucocorticoids was characterized by a 4-hr delay in onset, a sensitivity to actinomycin D, and a requirement for the continuous presence of the steroid. Crossed immunoelectrophoresis permitted analysis of the simultaneous effects of glucocorticoids on the synthesis of more than 20 plasma proteins secreted in culture. The absence of an effect on the synthesis of most of these proteins was in sharp contrast to the 3-fold increase in fibrinogen production. Sera from a variety of animals also stimulated an increase in fibrinogen synthesis that was similar in degree but less specific than that due to glucocorticoids and that partially masked the response of the cells to the steroid hormones. The presence of an anticoagulant in the medium was found to be necessary for detection of the fibrinogen secreted in culture. Although insulin was routinely included in the chemically defined medium, the cells synthesized fibrinogen and responded to glucocorticoids in the absence of hormonal supplementation of the medium. These findings are consistent with the thesis that variations in glucocorticoid levels contribute to the regulation of fibrinogen production in the intact animal. Images PMID:281699

  15. Fibrinogen synthesis in serum-free hepatocyte cultures: stimulation by glucocorticoids.

    PubMed

    Grieninger, G; Hertzberg, K M; Pindyck, J

    1978-11-01

    Fibrinogen synthesis was investigated in cultures of chicken embryo hepatocytes initiated and maintained in chemically defined, serum-free medium. 11-Hydroxy glucocorticoids caused a 3-fold stimulation of fibrinogen synthesis. Half-maximal stimulation was achieved with 1 nM corticosterone or hydrocortisone, as compared with only 0.1 nM dexamethasone. Increased fibrinogen production in the presence of these glucocorticoids was characterized by a 4-hr delay in onset, a sensitivity to actinomycin D, and a requirement for the continuous presence of the steroid. Crossed immunoelectrophoresis permitted analysis of the simultaneous effects of glucocorticoids on the synthesis of more than 20 plasma proteins secreted in culture. The absence of an effect on the synthesis of most of these proteins was in sharp contrast to the 3-fold increase in fibrinogen production. Sera from a variety of animals also stimulated an increase in fibrinogen synthesis that was similar in degree but less specific than that due to glucocorticoids and that partially masked the response of the cells to the steroid hormones. The presence of an anticoagulant in the medium was found to be necessary for detection of the fibrinogen secreted in culture. Although insulin was routinely included in the chemically defined medium, the cells synthesized fibrinogen and responded to glucocorticoids in the absence of hormonal supplementation of the medium. These findings are consistent with the thesis that variations in glucocorticoid levels contribute to the regulation of fibrinogen production in the intact animal. PMID:281699

  16. Biosynthesis, assembly and secretion of fibrinogen in cultured rat hepatocytes.

    PubMed Central

    Hirose, S; Oda, K; Ikehara, Y

    1988-01-01

    The biosynthesis, assembly and secretion of fibrinogen were investigated in cultured rat hepatocytes which were incubated with [35S]methionine. When initial rates of the synthesis of three fibrinogen subunits were compared, the A alpha-subunit was found to be synthesized significantly slower than the B beta- and gamma-subunits. Pulse-chase experiments revealed that the secreted fibrinogen contained different proportions of the newly synthesized subunits, depending upon the chase times. Radioactivity in the A alpha subunit, which initially had the highest level of the three, was rapidly decreased in parallel with the chase time. The gamma-subunit had an increasing amount of the radioactivity in the secreted molecule during the chase periods, whereas that in the B beta-subunit was gradually decreased at the later stages of chase. Analysis of intracellular components of fibrinogen confirmed that the nascent A alpha-subunit was most rapidly exhausted, and the gamma-subunit occupied the largest proportion among the non-assembled subunits at later stages of chase. Taken together, these results suggest that the synthesis of A alpha-subunit, which has the lowest rate, could be the rate-limiting step in the production and secretion of fibrinogen in cultured rat hepatocytes, in contrast with what has been proposed for human and rabbit fibrinogen, namely that the synthesis of B beta-subunit is the rate-limiting step. The results also indicate that there is a large intracellular pool of gamma-subunit. Images Fig. 2. Fig. 3. PMID:3401211

  17. Effect of a Klamath algae product ("AFA-B12") on blood levels of vitamin B12 and homocysteine in vegan subjects: a pilot study.

    PubMed

    Baroni, Luciana; Scoglio, Stefano; Benedetti, Serena; Bonetto, Chiara; Pagliarani, Silvia; Benedetti, Yanina; Rocchi, Marco; Canestrari, Franco

    2009-03-01

    Vitamin B12 is a critical nutrient that is often inadequate in a plant-based (vegan) diet, thus the inclusion of a reliable vitamin B12 source in a vegan diet is recommended as essential. Unfortunately, many natural sources of vitamin B12 have been proven to contain biologically inactive vitamin B12 analogues, inadequate for human supplementation. The aim of this non-randomized open trial was to determine whether supplementation with a natural Klamath algae-based product ("AFA-B12", Aphanizomenon flos-aquae algae plus a proprietary mix of enzymes) could favorably affect the vitamin B12 status of a group of 15 vegan subjects. By assessing blood concentration of vitamin B12, folate, and more importantly homocysteine (Hcy, a reliable marker in vegans of their B12 absorption), the vitamin B12 status of the participants at the end of the 3-month intervention period, while receiving the Klamath-algae supplement (T2), was compared with their vitamin B12 status at the end of the 3-month control period (T1), when they were not receiving any supplement, having stopped taking their usual vitamin B12 supplement at the beginning of the study (T0). Compared to the control period, in the intervention period participants improved their vitamin B12 status, significantly reducing Hcy blood concentration (p=0.003). In conclusion, the Klamath algae product AFA-B12 appears to be, in a preliminary study, an adequate and reliable source of vitamin B12 in humans. PMID:20108213

  18. Fibrinogen and catheter-directed thrombolysis.

    PubMed

    Ross, Reagan L; Beck, Adam W

    2014-12-01

    Fibrinogen is a complex glycoprotein that is known to play a significant role in the process of thrombus formation and evolution, and has been linked to the pathophysiology of atherosclerosis. Given the importance of fibrinogen in these processes, it has been evaluated as a biomarker for atherosclerotic disease and as a marker during treatment for venous and arterial thrombosis. Here we describe the expansive role that fibrinogen plays in human physiology. PMID:26073829

  19. Impact of Preemptive Fibrinogen Concentrate on Transfusion Requirements in Liver Transplantation: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

    PubMed

    Sabate, A; Gutierrez, R; Beltran, J; Mellado, P; Blasi, A; Acosta, F; Costa, M; Reyes, R; Torres, F

    2016-08-01

    We hypothesized that preemptive fibrinogen administration to obtain an initial plasma level of 2.9 g/L would reduce transfusion requirements in liver transplantation. A randomized, multicenter, hemoglobin-stratified, double-blind, fibrinogen-versus-saline-controlled trial was conducted. The primary end point was the percentage of patients requiring red blood cells. We evaluated 51 patients allocated to fibrinogen and 48 allocated to saline; the primary end point was assessed using data for 92 patients because the electronic record forms were offline for three patients in the fibrinogen group and four in the saline group. We injected a median of 3.54 g fibrinogen preemptively in the fibrinogen group. Nine patients in the saline group (20.9%) required fibrinogen at graft reperfusion (compared with one patient [2.1%] in the fibrinogen group; p = 0.005). Blood was transfused to 52.9% (95% confidence interval [CI] 42.5-63.3%) in the fibrinogen group and 42.74% (95% CI 28.3-57.2%) in the saline group (p = 0.217). Relative risk for blood transfusion was 0.80 (95% CI 0.57-1.13). Thrombotic events occurred in one patient (2.1%) and five patients (11.4%) in the fibrinogen and saline groups, respectively. Seven patients (14.6%) in the fibrinogen group and nine (20.3%) in the saline group required reoperation. Preemptive administration of fibrinogen concentrate did not influence transfusion requirements. PMID:26880105

  20. Homocysteine and the pathogenesis of atherosclerosis.

    PubMed

    McCully, Kilmer S

    2015-03-01

    The homocysteine theory of arteriosclerosis was discovered by study of arteriosclerotic plaques occurring in homocystinuria, a disease caused by deficiencies of cystathionine synthase, methionine synthase or methylenetetrahydrofolate reductase. According to the homocysteine theory, metabolic and nutritional abnormalities leading to elevation of plasma homocysteine cause atherosclerosis in the general population without these rare enzymatic abnormalities. Through studies of metabolism of homocysteine thiolactone, the anhydride of homocysteine, in cell cultures from homocystinuric children, the pathway for synthesis of sulfate was found to be dependent upon thioretinamide, the amide formed from retinoic acid and homocysteine thiolactone. Two molecules of thioretinamide form the complex thioretinaco with cobalamin, and oxidative phosphorylation is catalyzed by reduction of oxygen, which is bound to thioretinaco ozonide, by electrons from electron transport particles. Atherogenesis is attributed to formation of aggregates of homocysteinylated lipoproteins with microorganisms, which obstruct the vasa vasorum during formation of arterial vulnerable plaques. PMID:25653125

  1. A comparison of the fibrinogen receptor distribution on adherent platelets using both soluble fibrinogen and fibrinogen immobilized on gold beads.

    PubMed

    Estry, D W; Mattson, J C; Mahoney, G J; Oesterle, J R

    1991-04-01

    The distribution of fibrinogen receptors was determined on the surface of adherent platelets using both direct labeling with the ligand fibrinogen which was immobilized on gold particles (Fg-Au) and indirect immunogold (Ig-Au) labeling of bound soluble fibrinogen identified with a rabbit polyclonal anti-fibrinogen antibody. Two distinctly different patterns of labeling were obtained and appeared to depend on whether solid phase fibrinogen (Fg-Au) or soluble phase released fibrinogen were bound to the membrane receptor. The membrane-bound Fg-Au reorganized in patterns that closely mimicked the organization of the underlying cytoskeleton. In approximately 18% of the adherent platelets, Fg-Au was seen in channels or vesicle-like structures lying deep to the platelet surface suggesting internalization into the open canalicular system and/or endocytosis. The labeling pattern obtained when identifying the location of membrane-bound soluble released fibrinogen by Ig-Au was diffuse and lacked the organizational patterns characteristic of Fg-Au. Unlike the Fg-Au probe, early dendritic platelets were heavily labeled by the soluble phase fibrinogen using the Ig-Au technique. Although the label covered the entire exposed platelet membrane in fully spread platelets, labeling over the peripheral web was more dense than that over the intermediate or granulomere zone. The diffuse organization and heavier peripheral distributional pattern of the glycoprotein IIb-IIIa (GP IIb-IIIa) receptor in fixed, adherent platelets, was also seen with the GP IIb-IIIa receptor-specific antibody AP-2. The binding of both the Fg-Au and Ig-Au were inhibited using the tetrapeptide Arg-Gly-Asp-Ser (RGDS) (93% and 98% inhibition, respectively), AP-2 (98% and 97%, respectively) and platelets from patients with Glanzmann's thrombasthenia (GT) (99% and 98%, respectively). The data presented provides the first report that receptor reorganization, following binding of fibrinogen, appears to be related to

  2. The Effects of Acute Exercise and Exercise Training on Plasma Homocysteine: A Meta-Analysis

    PubMed Central

    Deminice, Rafael; Ribeiro, Diogo Farias; Frajacomo, Fernando Tadeu Trevisan

    2016-01-01

    Background Although studies have demonstrated that physical exercise alters homocysteine levels in the blood, meta-analyses of the effects of acute exercise and exercise training on homocysteine blood concentration have not been performed, especially regarding the duration and intensity of exercise, which could affect homocysteine levels differently. Objective The aim of this meta-analysis was to ascertain the effects of acute exercise and exercise training on homocysteine levels in the blood. Method A review was conducted according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses using the online databases PubMed, SPORTDiscus, and SciELO to identify relevant studies published through June 2015. Review Manager was used to calculate the effect size of acute exercise and exercise training using the change in Hcy plasmaserum concentration from baseline to post-acute exercise and trained vs. sedentary control groups, respectively. Weighted mean differences were calculated using random effect models. Results Given the abundance of studies, acute exercise trials were divided into two subgroups according to exercise volume and intensity, whereas the effects of exercise training were analyzed together. Overall, 22 studies with a total of 520 participants indicated increased plasma homocysteine concentration after acute exercise (1.18 μmol/L, 95% CI: 0.71 to 1.65, p < .01). Results of a subgroup analysis indicated that either long-term exercise of low-to-moderate intensity (1.39 μmol/L, 95% CI: 0.9 to 1.89, p < .01) or short-term exercise of high intensity (0.83 μmol/L, 95% CI: 0.19 to 1.40, p < .01) elevated homocysteine levels in the blood. Increased homocysteine induced by exercise was significantly associated with volume of exercise, but not intensity. By contrast, resistance training reduced plasma homocysteine concentration (-1.53 μmol/L, 95% CI: -2.77 to -0.28, p = .02), though aerobic training did not. The cumulative

  3. Over 50 Years of Fibrinogen Concentrate.

    PubMed

    Costa-Filho, Rubens; Hochleitner, Gerald; Wendt, Michael; Teruya, Alexandre; Spahn, Donat R

    2016-03-01

    March 2013 represented the 50th anniversary of the first license granted for a fibrinogen concentrate. In this review, we look at the history of bleeding management that led to the development of fibrinogen concentrate, discuss its current use, and consider future developments for this product. PMID:26294722

  4. Over 50 Years of Fibrinogen Concentrate

    PubMed Central

    Hochleitner, Gerald; Wendt, Michael; Teruya, Alexandre; Spahn, Donat R.

    2015-01-01

    March 2013 represented the 50th anniversary of the first license granted for a fibrinogen concentrate. In this review, we look at the history of bleeding management that led to the development of fibrinogen concentrate, discuss its current use, and consider future developments for this product. PMID:26294722

  5. The role of Homocysteine as a predictor for coronary heart disease

    PubMed Central

    Lühmann, Dagmar; Schramm, Susanne; Raspe, Heiner

    2007-01-01

    Background and objective There is an ongoing debate on the role of the cytotoxic aminoacid homocysteine as a causal risk factor for the development of coronary heart disease. Results from multiple case control-studies demonstrate, that there is a strong association between high plasma levels of homoysteine and prevalent coronary heart disease, independent of other classic risk factors. Furthermore, results from interventional studies point out that elevated plasma levels of homocysteine may effectively be lowered by the intake of folic acid and B vitamins. In order to use this information for the construction of a new preventive strategy against coronary heart disease, more information is needed: first, whether homocysteine actually is a causal risk factor with relevant predictive properties and, second, whether by lowering elevated homocysteine plasma concentrations cardiac morbidity can be reduced. Currently in Germany the determination of homocysteine plasma levels is reimbursed for by statutory health insurance in patients with manifest coronary heart disease and in patients at high risk for coronary heart disease but not for screening purposes in asymptomatic low risk populations. Against this background the following assessment sets out to answer four questions: Is an elevated homocysteine plasma concentration a strong, consistent and independent (of other classic risk factors) predictor for coronary heart disease? Does a therapeutic lowering of elevated homoysteine plasma levels reduce the risk of developing coronary events? What is the cost-effectiveness relationship of homocysteine testing for preventive purposes? Are there morally, socially or legally relevant aspects that should be considered when implementing a preventive strategy as outlined above? Methods In order to answer the first question, a systematic overview of prospective studies and metaanalyses of prospective studies is undertaken. Studies are included that analyse the association of

  6. Fibrinogen

    MedlinePlus

    ... or secondary Hemophilia A Hemophilia B Placenta abruption - definition Update Date 1/27/2015 Updated by: Yi- ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  7. Quantitation of platelet and fibrinogen-fibrin deposition on components of tissue valves (Ionescu-Shiley) in calves

    SciTech Connect

    Dewanjee, M.K.; Solis, E.; Lenker, J.; Tidwell, C.; Mackey, S.; Didisheim, P.; Kaye, M.P.

    1986-07-01

    With /sup 111/In-labeled platelets and /sup 125/I-labeled bovine fibrinogen, regional mapping of platelet and fibrinogen deposition on leaflets and sewing rings was obtained. Ten Holstein calves received 25-mm mitral valves (ISLM) and were killed 1, 14, and 30 days after implantation. Twenty-four hours before the calves were killed, 350 to 450 microCi of /sup 111/In-labeled platelets and 200 to 250 microCi of /sup 125/I-labeled bovine fibrinogen were administered intravenously. The components of the tissue valves, i.e., three leaflets and sewing rings, were separated. Each leaflet was cut into four sections: free edge, central zone, flexion zone, and attachment zone. From the radioactivity in blood, leaflet zones, sewing rings, area of leaflet zones, platelet count, and fibrinogen level in blood, the mean regional density of adherent platelets, fibrinogen-fibrin, and fibrinogen/platelet were calculated. The density of platelets and fibrinogen deposited on the components of the valves decreases with time postimplantation. The number of fibrinogen molecules per platelet is fivefold to 20-fold higher than that of the receptor concentration on platelets on leaflet zones, suggesting the heterogeneity of fibrinogen-fibrin in thrombus and components of the valve.

  8. Comparison of Protein N-Homocysteinylation in Rat Plasma under Elevated Homocysteine Using a Specific Chemical Labeling Method.

    PubMed

    Zang, Tianzhu; Pottenplackel, Ligi Paul; Handy, Diane E; Loscalzo, Joseph; Dai, Shujia; Deth, Richard C; Zhou, Zhaohui Sunny; Ma, Jisheng

    2016-01-01

    Elevated blood concentrations of homocysteine have been well established as a risk factor for cardiovascular diseases and neuropsychiatric diseases, yet the etiologic relationship of homocysteine to these disorders remains poorly understood. Protein N-homocysteinylation has been hypothesized as a contributing factor; however, it has not been examined globally owing to the lack of suitable detection methods. We recently developed a selective chemical method to label N-homocysteinylated proteins with a biotin-aldehyde tag followed by Western blotting analysis, which was further optimized in this study. We then investigated the variation of protein N-homocysteinylation in plasma from rats on a vitamin B12 deficient diet. Elevated "total homocysteine" concentrations were determined in rats with a vitamin B12 deficient diet. Correspondingly, overall levels of plasma protein N-homocysteinylation displayed an increased trend, and furthermore, more pronounced and statistically significant changes (e.g., 1.8-fold, p-value: 0.03) were observed for some individual protein bands. Our results suggest that, as expected, a general metabolic correlation exists between "total homocysteine" and N-homocysteinylation, although other factors are involved in homocysteine/homocysteine thiolactone metabolism, such as the transsulfuration of homocysteine by cystathionine β-synthase or the hydrolysis of homocysteine thiolactone by paraoxonase 1 (PON1), may play more significant or direct roles in determining the level of N-homocysteinylation. PMID:27617989

  9. 1,25-dihydroxyvitamin D3 influences cellular homocysteine levels in murine pre-osteoblastic MC3T3-E1 cells by direct regulation of cystathionine β-synthase

    PubMed Central

    Kriebitzsch, Carsten; Verlinden, Lieve; Eelen, Guy; van Schoor, Natasja M.; Swart, Karin; Lips, Paul; Meyer, Mark B.; Pike, J Wesley; Boonen, Steven; Carlberg, Carsten; Vitvitsky, Victor; Bouillon, Roger; Banerjee, Ruma; Verstuyf, Annemieke

    2011-01-01

    High homocysteine (HCY) levels are a risk factor for osteoporotic fracture. Furthermore, bone quality and strength are compromised by elevated HCY due to its negative impact on collagen maturation. HCY is cleared by cystathionine β-synthase (CBS), the first enzyme in the transsulfuration pathway. CBS converts HCY to cystathionine, thereby committing it to cysteine synthesis. A microarray experiment on MC3T3-E1 murine pre-osteoblasts treated with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] revealed a cluster of genes including the cbs gene, of which the transcription was rapidly and strongly induced by 1,25(OH)2D3. Quantitative real-time PCR and Western blot analysis confirmed higher levels of cbs mRNA and protein after 1,25(OH)2D3 treatment in murine and human cells. Moreover, measurement of CBS enzyme activity and quantitative measurements of HCY, cystathionine and cysteine concentrations were consistent with elevated transsulfuration activity in 1,25(OH)2D3-treated cells. The importance of a functional vitamin D receptor (VDR) for transcriptional regulation of cbs was shown in primary murine VDR knock-out osteoblasts, in which up-regulation of cbs in response to 1,25(OH)2D3 was abolished. Chromatin immunoprecipitation on chip and transfection studies revealed a functional vitamin D response element in the second intron of cbs. To further explore the potential clinical relevance of our ex vivo findings, human data from the Longitudinal Aging Study Amsterdam suggested a correlation between vitamin D status [25(OH)D3 levels] and HCY levels. In conclusion, this study demonstrated that cbs is a primary 1,25(OH)2D3 target gene which renders HCY metabolism responsive to 1,25(OH)2D3. PMID:21898591

  10. NADPH oxidase 4 regulates homocysteine metabolism and protects against acetaminophen-induced liver damage in mice

    PubMed Central

    Murray, Thomas V.A.; Dong, Xuebin; Sawyer, Greta J.; Caldwell, Anna; Halket, John; Sherwood, Roy; Quaglia, Alberto; Dew, Tracy; Anilkumar, Narayana; Burr, Simon; Mistry, Rajesh K.; Martin, Daniel; Schröder, Katrin; Brandes, Ralf P.; Hughes, Robin D.; Shah, Ajay M.; Brewer, Alison C.

    2015-01-01

    Glutathione is the major intracellular redox buffer in the liver and is critical for hepatic detoxification of xenobiotics and other environmental toxins. Hepatic glutathione is also a major systemic store for other organs and thus impacts on pathologies such as Alzheimer's disease, Sickle Cell Anaemia and chronic diseases associated with aging. Glutathione levels are determined in part by the availability of cysteine, generated from homocysteine through the transsulfuration pathway. The partitioning of homocysteine between remethylation and transsulfuration pathways is known to be subject to redox-dependent regulation, but the underlying mechanisms are not known. An association between plasma Hcy and a single nucleotide polymorphism within the NADPH oxidase 4 locus led us to investigate the involvement of this reactive oxygen species- generating enzyme in homocysteine metabolism. Here we demonstrate that NADPH oxidase 4 ablation in mice results in increased flux of homocysteine through the betaine-dependent remethylation pathway to methionine, catalysed by betaine-homocysteine-methyltransferase within the liver. As a consequence NADPH oxidase 4-null mice display significantly lowered plasma homocysteine and the flux of homocysteine through the transsulfuration pathway is reduced, resulting in lower hepatic cysteine and glutathione levels. Mice deficient in NADPH oxidase 4 had markedly increased susceptibility to acetaminophen-induced hepatic injury which could be corrected by administration of N-acetyl cysteine. We thus conclude that under physiological conditions, NADPH oxidase 4-derived reactive oxygen species is a regulator of the partitioning of the metabolic flux of homocysteine, which impacts upon hepatic cysteine and glutathione levels and thereby upon defence against environmental toxins. PMID:26472193

  11. Bacteriophage lysin mediates the binding of streptococcus mitis to human platelets through interaction with fibrinogen.

    PubMed

    Seo, Ho Seong; Xiong, Yan Q; Mitchell, Jennifer; Seepersaud, Ravin; Bayer, Arnold S; Sullam, Paul M

    2010-01-01

    The binding of bacteria to human platelets is a likely central mechanism in the pathogenesis of infective endocarditis. We have previously found that platelet binding by Streptococcus mitis SF100 is mediated by surface components encoded by a lysogenic bacteriophage, SM1. We now demonstrate that SM1-encoded lysin contributes to platelet binding via its direct interaction with fibrinogen. Far Western blotting of platelets revealed that fibrinogen was the major membrane-associated protein bound by lysin. Analysis of lysin binding with purified fibrinogen in vitro confirmed that these proteins could bind directly, and that this interaction was both saturable and inhibitable. Lysin bound both the Aalpha and Bbeta chains of fibrinogen, but not the gamma subunit. Binding of lysin to the Bbeta chain was further localized to a region within the fibrinogen D fragment. Disruption of the SF100 lysin gene resulted in an 83+/-3.1% reduction (mean +/- SD) in binding to immobilized fibrinogen by this mutant strain (PS1006). Preincubation of this isogenic mutant with purified lysin restored fibrinogen binding to wild type levels. When tested in a co-infection model of endocarditis, loss of lysin expression resulted in a significant reduction in virulence, as measured by achievable bacterial densities (CFU/g) within vegetations, kidneys, and spleens. These results indicate that bacteriophage-encoded lysin is a multifunctional protein, representing a new class of fibrinogen-binding proteins. Lysin appears to be cell wall-associated through its interaction with choline. Once on the bacterial surface, lysin can bind fibrinogen directly, which appears to be an important interaction for the pathogenesis of endocarditis. PMID:20714354

  12. Associations between Serum 25-hydroxyvitamin D and Lipids, Lipoprotein Cholesterols, and Homocysteine

    PubMed Central

    Glueck, Charles J.; Jetty, Vybhav; Rothschild, Matan; Duhon, Gregory; Shah, Parth; Prince, Marloe; Lee, Kevin; Goldenberg, Michael; Kumar, Ashwin; Goldenberg, Naila; Wang, Ping

    2016-01-01

    Background: Serum 25(OH) vitamin D levels are inversely associated with cardiovascular disease (CVD) mortality, mediated in part by independent positive relationships with high-density lipoprotein cholesterol (HDLC) and inverse relationships with low-density lipoprotein cholesterol (LDLC), triglyceride, and homocysteine. Aims: In this study, we assessed relationships between fasting serum vitamin D and lipids, lipoprotein cholesterols, and homocysteine. Materials and Methods: We studied 1534 patients sequentially referred to our center from 2007 to 2016. Fasting serum total 25(OH) vitamin D, plasma cholesterol, triglyceride, HDLC, LDLC, and homocysteine were measured. Stepwise regression models were used with total cholesterol, triglyceride, HDLC, LDLC, and homocysteine as dependent variables and explanatory variables age, race, gender, body mass index (BMI), and serum vitamin D levels. Relationships between quintiles of serum vitamin D and triglycerides, HDLC, LDLC, and homocysteine were assessed after covariance adjusting for age, race, gender, and BMI. Results: Fasting serum vitamin D was positively correlated with age, HDLC, and White race, and was inversely correlated with BMI, total and LDL cholesterol, triglyceride, and fasting serum homocysteine (P ≤ 0.0001 for all). Serum vitamin D was a significant independent inverse explanatory variable for total cholesterol, triglyceride, and LDL cholesterol, and accounted for the largest amount of variance in serum total cholesterol (partial R2 =3.6%), triglyceride (partial R2 =3.1%), and LDLC (partial R2 =2.9%) (P < 0.0001 for all). Serum vitamin D was a significant positive explanatory variable for HDLC (partial R2 = 1.4%, P < 0.0001), and a significant inverse explanatory variable for homocysteine (partial R2 = 6.0–12.6%). Conclusions: In hyperlipidemic patients, serum vitamin D was a significant independent inverse determinant of total cholesterol, LDLC, triglyceride, and homocysteine, and a significant

  13. High homocysteine induces betaine depletion

    PubMed Central

    Imbard, Apolline; Benoist, Jean-François; Esse, Ruben; Gupta, Sapna; Lebon, Sophie; de Vriese, An S; de Baulny, Helene Ogier; Kruger, Warren; Schiff, Manuel; Blom, Henk J.

    2015-01-01

    Betaine is the substrate of the liver- and kidney-specific betaine-homocysteine (Hcy) methyltransferase (BHMT), an alternate pathway for Hcy remethylation. We hypothesized that BHMT is a major pathway for homocysteine removal in cases of hyperhomocysteinaemia (HHcy). Therefore, we measured betaine in plasma and tissues from patients and animal models of HHcy of genetic and acquired cause. Plasma was collected from patients presenting HHcy without any Hcy interfering treatment. Plasma and tissues were collected from rat models of HHcy induced by diet and from a mouse model of cystathionine β-synthase (CBS) deficiency. S-adenosyl-methionine (AdoMet), S-adenosyl-homocysteine (AdoHcy), methionine, betaine and dimethylglycine (DMG) were quantified by ESI—LC–MS/MS. mRNA expression was quantified using quantitative real-time (QRT)-PCR. For all patients with diverse causes of HHcy, plasma betaine concentrations were below the normal values of our laboratory. In the diet-induced HHcy rat model, betaine was decreased in all tissues analysed (liver, brain, heart). In the mouse CBS deficiency model, betaine was decreased in plasma, liver, heart and brain, but was conserved in kidney. Surprisingly, BHMT expression and activity was decreased in liver. However, in kidney, BHMT and SLC6A12 expression was increased in CBS-deficient mice. Chronic HHcy, irrespective of its cause, induces betaine depletion in plasma and tissues (liver, brain and heart), indicating a global decrease in the body betaine pool. In kidney, betaine concentrations were not affected, possibly due to overexpression of the betaine transporter SLC6A12 where betaine may be conserved because of its crucial role as an osmolyte. PMID:26182429

  14. Effect of Vitamin B12 and Folic Acid Supplementation on Bone Mineral Density and Quantitative Ultrasound Parameters in Older People with an Elevated Plasma Homocysteine Level: B-PROOF, a Randomized Controlled Trial.

    PubMed

    Enneman, Anke W; Swart, Karin M A; van Wijngaarden, Janneke P; van Dijk, Suzanne C; Ham, Annelies C; Brouwer-Brolsma, Elske M; van der Zwaluw, Nikita L; Dhonukshe-Rutten, Rosalie A M; van der Cammen, Tischa J M; de Groot, Lisette C P G M; van Meurs, Joyce; Lips, Paul; Uitterlinden, André G; Zillikens, M Carola; van Schoor, Natasja M; van der Velde, Nathalie

    2015-05-01

    High plasma homocysteine (Hcy) levels are associated with increased osteoporotic fracture incidence. However, the mechanism remains unclear. We investigated the effect of Hcy-lowering vitamin B12 and folic acid treatment on bone mineral density (BMD) and calcaneal quantitative ultrasound (QUS) parameters. This randomized, double-blind, placebo-controlled trial included participants aged ≥65 years with plasma Hcy levels between 12 and 50 µmol/L. The intervention comprised 2-year supplementation with either a combination of 500 µg B12, 400 µg folic acid, and 600 IU vitamin D or placebo with 600 IU vitamin D only. In total, 1111 participants underwent repeated dual-energy X-ray assessment and 1165 participants underwent QUS. Femoral neck (FN) BMD, lumbar spine (LS) BMD, calcaneal broadband ultrasound attenuation (BUA), and calcaneal speed of sound (SOS) were assessed. After 2 years, FN-BMD and BUA had significantly decreased, while LS-BMD significantly increased (all p < 0.01) and SOS did not change in either treatment arm. No statistically significant differences between the intervention and placebo group were present for FN-BMD (p = 0.24), LS-BMD (p = 0.16), SOS (p = 0.67), and BUA (p = 0.96). However, exploratory subgroup analyses revealed a small positive effect of the intervention on BUA at follow-up among compliant persons >80 years (estimated marginal mean 64.4 dB/MHz for the intervention group and 61.0 dB/MHz for the placebo group, p = 0.04 for difference). In conclusion, this study showed no overall effect of treatment with vitamin B12 and folic acid on BMD or QUS parameters in elderly, mildly hyperhomocysteinemic persons, but suggests a small beneficial effect on BUA in persons >80 years who were compliant in taking the supplement. PMID:25712255

  15. Mice expressing a mutant form of fibrinogen that cannot support fibrin formation exhibit compromised antimicrobial host defense

    PubMed Central

    Prasad, Joni M.; Gorkun, Oleg V.; Raghu, Harini; Thornton, Sherry; Mullins, Eric S.; Palumbo, Joseph S.; Ko, Ya-Ping; Höök, Magnus; David, Tovo; Coughlin, Shaun R.; Degen, Jay L.

    2015-01-01

    Fibrin(ogen) is central to hemostasis and thrombosis and also contributes to multiple physiologic and pathologic processes beyond coagulation. However, the precise contribution of soluble fibrinogen vs insoluble fibrin matrices to vascular integrity, tissue repair, inflammation, and disease has been undefined and unapproachable. To establish the means to distinguish fibrinogen- and fibrin-dependent processes in vivo, FibAEK mice were generated that carry normal levels of circulating fibrinogen but lack the capacity for fibrin polymer formation due to a germ-line mutation in the Aα chain thrombin cleavage site. Homozygous FibAEK mice developed to term and exhibited postnatal survival superior to that of fibrinogen-deficient mice. Unlike fibrinogen-deficient mice, platelet-rich plasma from FibAEK mice supported normal platelet aggregation in vitro, highlighting that fibrinogenAEK retains the functional capacity to support interactions with platelets. Thrombin failed to release fibrinopeptide-A from fibrinogenAEK and failed to induce polymer formation with FibAEK plasma or purified fibrinogenAEK in 37°C mixtures regardless of incubation time. FibAEK mice displayed both an absence of fibrin polymer formation following liver injury, as assessed by electron microscopy, and a failure to generate stable occlusive thrombi following FeCl3 injury of carotid arteries. FibAEK mice exhibited a profound impediment in Staphylococcus aureus clearance following intraperitoneal infection similar to fibrinogen-deficient mice, yet FibAEK mice displayed a significant infection dose-dependent survival advantage over fibrinogen-deficient mice following peritonitis challenge. Collectively, these findings establish for the first time that fibrin polymer is the molecular form critical for antimicrobial mechanisms while simultaneously highlighting biologically meaningful contributions and functions of the soluble molecule. PMID:26228483

  16. Mice expressing a mutant form of fibrinogen that cannot support fibrin formation exhibit compromised antimicrobial host defense.

    PubMed

    Prasad, Joni M; Gorkun, Oleg V; Raghu, Harini; Thornton, Sherry; Mullins, Eric S; Palumbo, Joseph S; Ko, Ya-Ping; Höök, Magnus; David, Tovo; Coughlin, Shaun R; Degen, Jay L; Flick, Matthew J

    2015-10-22

    Fibrin(ogen) is central to hemostasis and thrombosis and also contributes to multiple physiologic and pathologic processes beyond coagulation. However, the precise contribution of soluble fibrinogen vs insoluble fibrin matrices to vascular integrity, tissue repair, inflammation, and disease has been undefined and unapproachable. To establish the means to distinguish fibrinogen- and fibrin-dependent processes in vivo, Fib(AEK) mice were generated that carry normal levels of circulating fibrinogen but lack the capacity for fibrin polymer formation due to a germ-line mutation in the Aα chain thrombin cleavage site. Homozygous Fib(AEK) mice developed to term and exhibited postnatal survival superior to that of fibrinogen-deficient mice. Unlike fibrinogen-deficient mice, platelet-rich plasma from Fib(AEK) mice supported normal platelet aggregation in vitro, highlighting that fibrinogen(AEK) retains the functional capacity to support interactions with platelets. Thrombin failed to release fibrinopeptide-A from fibrinogen(AEK) and failed to induce polymer formation with Fib(AEK) plasma or purified fibrinogen(AEK) in 37°C mixtures regardless of incubation time. Fib(AEK) mice displayed both an absence of fibrin polymer formation following liver injury, as assessed by electron microscopy, and a failure to generate stable occlusive thrombi following FeCl3 injury of carotid arteries. Fib(AEK) mice exhibited a profound impediment in Staphylococcus aureus clearance following intraperitoneal infection similar to fibrinogen-deficient mice, yet Fib(AEK) mice displayed a significant infection dose-dependent survival advantage over fibrinogen-deficient mice following peritonitis challenge. Collectively, these findings establish for the first time that fibrin polymer is the molecular form critical for antimicrobial mechanisms while simultaneously highlighting biologically meaningful contributions and functions of the soluble molecule. PMID:26228483

  17. Homocysteine, Cortisol, Diabetes Mellitus, and Psychopathology

    PubMed Central

    Kontoangelos, K.; Papageorgiou, C. C.; Raptis, A. E.; Tsiotra, P.; Lambadiari, V.; Papadimitriou, G. N.; Rabavilas, A. D.; Dimitriadis, G.; Raptis, S. A.

    2015-01-01

    Objective. This study investigates the association of homocysteine and cortisol with psychological factors in type 2 diabetic patients. Method. Homocysteine, cortisol, and psychological variables were analyzed from 131 diabetic patients. Psychological factors were assessed with the Eysenck Personality Questionnaire (EPQ), Hostility and Direction of Hostility Questionnaire (HDHQ), the Symptom Checklist 90-R (SCL 90-R), the Zung Self-Rating Depression Scale (ZDRS), and the Maudsley O-C Inventory Questionnaire (MOCI). Blood samples were taken by measuring homocysteine and cortisol in both subgroups during the initial phase of the study (T0). One year later (T1), the uncontrolled diabetic patients were reevaluated with the use of the same psychometric instruments and with an identical blood analysis. Results. The relation of psychoticism and homocysteine is positive among controlled diabetic patients (P value = 0.006 < 0.05) and negative among uncontrolled ones (P value = 0.137). Higher values of cortisol correspond to lower scores on extraversion subscale (rp = −0.223, P value = 0.010). Controlled diabetic patients showed a statistically significant negative relationship between homocysteine and the act-out hostility subscale (rsp = −0.247, P = 0.023). There is a statistically significant relationship between homocysteine and somatization (rsp = −0.220, P = 0.043). Conclusions. These findings support the notion that homocysteine and cortisol are related to trait and state psychological factors in patients with diabetes mellitus type 2. PMID:25722989

  18. Fibrinogen and rhegmatogenous retinal detachment: a pilot prospective study

    PubMed Central

    Theocharis, IP

    2010-01-01

    Purpose: To examine the correlation, if any, between fibrinogen plasma levels (FPL) and the clinical features of rhegmatogenous retinal detachment (RRD). Methods: FPL were measured preoperatively in 33 patients with primary RRD. Patient characteristics and detachment features such as the numbers of breaks and the extent of the detachment were recorded; Results: No statistically significant correlation was found between FPL and the number of breaks. A statistically significant correlation was found between FPL and the extent of the RRD, even if the influence of the number of breaks was excluded. Conclusions: FPL correlate with retinal detachment extent, which implicates an acute inflammatory response to detachment traumatic phenomenon or a role of the fibrinogen molecule in retinal adhesiveness. PMID:20186280

  19. Energetics of thrombin-fibrinogen interaction.

    PubMed

    Hopfner, K P; Di Cera, E

    1992-11-24

    The kinetic mechanism of thrombin-fibrinogen interaction has been elucidated by steady-state measurements of synthetic substrate hydrolysis by human alpha-thrombin in the presence of human fibrinogen used as a competitive inhibitor and sucrose used as a viscogenic agent. Sucrose greatly affects the FKm for thrombin-fibrinogen interaction, without altering the intrinsic properties of the system. Under conditions of pH 7.5 and 0.1 M NaCl, fibrinogen behaves like a sticky substrate for thrombin, with acylation being comparable to dissociation in the temperature range 20-37 degrees C. In the same temperature range, deacylation is much faster than acylation. The van't Hoff enthalpy of binding for thrombin-fibrinogen interaction is -24 +/- 3 kcal/mol and the entropy is -55 +/- 11 cal mol-1 deg-1. A chemical compensation effect is present in the binding of fibrinogen and synthetic amide substrates to thrombin, with the delta H and delta G values being linked through a linear relationship. PMID:1445891

  20. Effect of Fibrinogen on Platelet Reactivity Measured by the VerifyNow P2Y12 Assay.

    PubMed

    Dobrovolsky, A B; Laguta, P S; Guskova, E V; Yarovaya, E B; Titaeva, E V; Storozhilova, A N; Panchenko, E P

    2016-05-01

    The VerifyNow assay is based upon the ability of activated platelets to cross-link beads coated with fibrinogen. However, fibrinogen is an abundant protein of blood, and therefore it may affect test results by competing with fibrinogen of beads for binding to platelets. To test this assumption, we assessed the influence of artificial alteration of fibrinogen level in blood samples obtained from donors (n = 9) and patients on clopidogrel therapy (n = 8) on the results of the VerifyNow P2Y12 assay. Fibrinogen level was altered by adding to blood samples 1/10 volume of fibrinogen solution (10.56 g/liter) or corresponding buffer. Relative to baseline, addition of buffer significantly increased platelet reactivity, whereas addition of fibrinogen decreased it. Analysis of the relationship between change in platelet reactivity values (dBase and dPRU) and change in fibrinogen concentration (dFg) revealed strong negative correlations: dBase = -63.3 × dFg - 27.1 (r = -0.924, p < 0.0005) and dPRU = -54.4 × dFg - 21.8 (r = -0.764, p < 0.0005). Thus, the results of our experiments suggest that: (i) blood fibrinogen strongly influences results of the VerifyNow P2Y12 assay, and (ii) correcting for fibrinogen effect may be needed to improve the accuracy of the test in the measuring of antiplatelet effect of clopidogrel therapy. PMID:27297894

  1. Recovery of fibrinogen concentrate after intraosseous application is equivalent to the intravenous route in a porcine model of hemodilution

    PubMed Central

    Schlimp, Christoph J.; Solomon, Cristina; Keibl, Claudia; Zipperle, Johannes; Nürnberger, Sylvia; Öhlinger, Wolfgang; Redl, Heinz; Schöchl, Herbert

    2014-01-01

    BACKGROUND Fibrinogen concentrate is increasingly considered as a hemostatic agent for trauma patients experiencing bleeding. Placing a venous access is sometimes challenging during severe hemorrhage. Intraosseous access may be considered instead. Studies of intraosseous infusion of coagulation factor concentrates are limited. We investigated in vivo recovery following intraosseous administration of fibrinogen concentrate and compared the results with intravenous administration. METHODS This study was performed on 12 pigs (mean [SD] body weight, 34.1 [2.8] kg). Following controlled blood loss (35 mL/kg) and fluid replacement with balanced crystalloid solution, intraosseous (n = 6) administration of fibrinogen concentrate (80 mg per kilogram of bodyweight) in the proximal tibia was compared with intravenous (n = 6) administration of the same dose (fibrinogen infusion time approximately 5 minutes in both groups). The following laboratory parameters were assessed: blood cell count, prothrombin time index, activated partial thromboplastin time, and plasma fibrinogen concentration (Clauss assay). Coagulation status was also assessed by thromboelastometry. RESULTS All tested laboratory parameters were comparable between the intraosseous and intravenous groups at baseline, hemodilution, and 30 minutes after fibrinogen concentrate administration. In vivo recovery of fibrinogen was also similar in the two groups (89% [23%] and 91% [22%], respectively). There were no significant between-group differences in any of the thromboelastometric parameters. Histologic examination indicated no adverse effects on the tissue surrounding the intraosseous administration site. CONCLUSION This study suggests that intraosseous administration of fibrinogen concentrate results in a recovery of fibrinogen similar to that of intravenous administration. The intraosseous route of fibrinogen concentrate could be a valuable alternative in situations where intravenous access is not feasible or would

  2. Protein adsorption to polyethylene glycol modified liposomes from fibrinogen solution and from plasma.

    PubMed

    Price, M E; Cornelius, R M; Brash, J L

    2001-06-01

    Unmodified and polyethylene glycol (PEG) modified neutral and negatively charged liposomes were prepared by freeze-thaw and extrusion followed by chromatographic purification. The effects of PEG molecular weight (PEG 550, 2000, 5000), PEG loading (0-15 mol%), and liposome surface charge on fibrinogen adsorption were quantified using radiolabeling techniques. All adsorption isotherms increased monotonically over the concentration range 0-3 mg/ml and adsorption levels were low. Negatively charged liposomes adsorbed significantly more fibrinogen than neutral liposomes. PEG modification had no effect on fibrinogen adsorption to neutral liposomes. An inverse relationship was found between PEG loading of negatively charged liposomes and fibrinogen adsorption. PEGs of all three molecular weights at a loading of 5 mol% reduced fibrinogen adsorption to negatively charged liposomes. Protein adsorption from diluted plasma (10% normal strength) to four different liposome types (neutral, PEG-neutral, negatively charged, and PEG-negatively charged) was investigated using gel electrophoresis and immunoblotting. The profiles of adsorbed proteins were similar on all four liposome types, but distinctly different from the profile of plasma itself, indicating a partitioning effect of the lipid surfaces. alpha2-macroglobulin and fibronectin were significantly enriched on the liposomes whereas albumin, transferrin, and fibrinogen were depleted compared to plasma. Apolipoprotein AI was a major component of the adsorbed protein layers. The blot of complement protein C3 adsorbed on the liposomes suggested that the complement system was activated. PMID:11406096

  3. Platelet Glycoproteins and Fibrinogen in Recovery from Idiopathic Sudden Hearing Loss

    PubMed Central

    Gorzelniak, Kerstin; Bremer, Alexis; Rudack, Claudia; Walter, Michael

    2014-01-01

    Background The pathomechanism and location of idiopathic sudden sensorineural hearing loss (ISSHL) is unclear. In a previous case-control study, we found elevated fibrinogen concentrations and a higher prevalence of T allele carriers of the glycoprotein (Gp) Ia C807T polymorphism in ISSHL patients. Methodology 127 patients with ISSHL (mean age 53.3 years, 48.8% females), who underwent a standard therapy with high dose steroids, pentoxifyllin and sterofundine over 8 days were included. We examined the influence of GpIa genotype and fibrinogen (BclI-, A312-, HaeIII-) genotype and fibrinogen plasma levels on hearing recovery after 8 weeks (change from baseline: 0 dB  =  no recovery, >0 to 10 dB = moderate recovery, >10 dB = good recovery). In a subsample of 59 patients with ISSHL, we further studied the association of platelet glycoprotein GpIa, Ib and IIIa densities on hearing recovery as well as the possible effect-modification of platelet glycoproteins on hearing recovery by plasma fibrinogen. Results In univariate analysis, neither the GpIa genotype nor fibrinogen genotype (all p>0.1) but lower fibrinogen levels (p = 0.029), less vertigo (p = 0.002) and lower GpIIIa receptor density (p = 0.037, n = 59) were associated with hearing recovery. In multivariate analysis, fibrinogen significantly modified the effect of GPIa receptor density on good hearing recovery (effect-modification on multiplicative scale OR = 0.45 (95% confidence interval (0.21–0.94)), p = 0.03). GPIb receptor density below the mean was associated with a 2-fold increase in good hearing recovery both in patients with fibrinogen levels above (p = 0.04) as well as in patients with fibrinogen levels below the mean (p = 0.06). There was no indication for an effect-modification (p = 0.97). Conclusions The findings suggest a vascular/rheological origin of ISSHL with unique features of thrombosis in the inner ear artery that may include complex

  4. Neprilysin Inhibits Coagulation through Proteolytic Inactivation of Fibrinogen

    PubMed Central

    Burrell, Matthew; Henderson, Simon J.; Ravnefjord, Anna; Schweikart, Fritz; Fowler, Susan B.; Witt, Susanne; Hansson, Kenny M.; Webster, Carl I.

    2016-01-01

    Neprilysin (NEP) is an endogenous protease that degrades a wide range of peptides including amyloid beta (Aβ), the main pathological component of Alzheimer’s disease (AD). We have engineered NEP as a potential therapeutic for AD but found in pre-clinical safety testing that this variant increased prothrombin time (PT) and activated partial thromboplastin time (APTT). The objective of the current study was to investigate the effect of wild type NEP and the engineered variant on coagulation and define the mechanism by which this effect is mediated. PT and APTT were measured in cynomolgus monkeys and rats dosed with a human serum albumin fusion with an engineered variant of NEP (HSA-NEPv) as well as in control plasma spiked with wild type or variant enzyme. The coagulation factor targeted by NEP was determined using in vitro prothrombinase, calibrated automated thrombogram (CAT) and fibrin formation assays as well as N-terminal sequencing of fibrinogen treated with the enzyme. We demonstrate that HSA-NEP wild type and HSA-NEPv unexpectedly impaired coagulation, increasing PT and APTT in plasma samples and abolishing fibrin formation from fibrinogen. This effect was mediated through cleavage of the N-termini of the Aα- and Bβ-chains of fibrinogen thereby significantly impairing initiation of fibrin formation by thrombin. Fibrinogen has therefore been identified for the first time as a substrate for NEP wild type suggesting that the enzyme may have a role in regulating fibrin formation. Reductions in NEP levels observed in AD and cerebral amyloid angiopathy may contribute to neurovascular degeneration observed in these conditions. PMID:27437944

  5. Neprilysin Inhibits Coagulation through Proteolytic Inactivation of Fibrinogen.

    PubMed

    Burrell, Matthew; Henderson, Simon J; Ravnefjord, Anna; Schweikart, Fritz; Fowler, Susan B; Witt, Susanne; Hansson, Kenny M; Webster, Carl I

    2016-01-01

    Neprilysin (NEP) is an endogenous protease that degrades a wide range of peptides including amyloid beta (Aβ), the main pathological component of Alzheimer's disease (AD). We have engineered NEP as a potential therapeutic for AD but found in pre-clinical safety testing that this variant increased prothrombin time (PT) and activated partial thromboplastin time (APTT). The objective of the current study was to investigate the effect of wild type NEP and the engineered variant on coagulation and define the mechanism by which this effect is mediated. PT and APTT were measured in cynomolgus monkeys and rats dosed with a human serum albumin fusion with an engineered variant of NEP (HSA-NEPv) as well as in control plasma spiked with wild type or variant enzyme. The coagulation factor targeted by NEP was determined using in vitro prothrombinase, calibrated automated thrombogram (CAT) and fibrin formation assays as well as N-terminal sequencing of fibrinogen treated with the enzyme. We demonstrate that HSA-NEP wild type and HSA-NEPv unexpectedly impaired coagulation, increasing PT and APTT in plasma samples and abolishing fibrin formation from fibrinogen. This effect was mediated through cleavage of the N-termini of the Aα- and Bβ-chains of fibrinogen thereby significantly impairing initiation of fibrin formation by thrombin. Fibrinogen has therefore been identified for the first time as a substrate for NEP wild type suggesting that the enzyme may have a role in regulating fibrin formation. Reductions in NEP levels observed in AD and cerebral amyloid angiopathy may contribute to neurovascular degeneration observed in these conditions. PMID:27437944

  6. Lowering homocysteine levels with folic acid and B-vitamins do not reduce early atherosclerosis, but could interfere with cognitive decline and Alzheimer's disease.

    PubMed

    Cacciapuoti, Federico

    2013-10-01

    Inheired or acquired hyperhomocysteinemia (HHcy) is associated with several impairments, as certain tumors, deep venous thrombosis, tube neural defects, osteoporosis, early atherosclerosis and vascular acute events (IMA, stroke, PVD), mild cognitive impairments till Alzheimer's disease (AD). But, vascular and neuronal derangements are the most frequent HHcy-manifestations. As far as early atherosclerosis, some clinical trials demonstrated that folates and B6-12 vitamins supplementation is unable to reduce atherosclerotic lesions and cardiovascular events, even if it lowers HHcy levels. Thus, for atherosclerosis and its acute events (IMA, stroke, PVD) HHcy acts as a powerful biomarker rather than a risk factor. For that, the supplementation with folates and B vitamins to lower atherosclerotic lesions-events in hyperhomocysteinemic patients is not recommended. On the contrary, several clinical investigations demonstrated that folates and vitamins administration is able to reduce Hcy serum levels and antagonize some mechanisms favouring neurodegenerative impairments, as mild cognitive impairment, AD and dementia. Thus, contrarily to the atherosclerotic manifestations in hyperhomocysteinemic patients, preventive treatment with folates and B6-12 vitamins reduces Hcy concentration and could prevent or delay cognitive decline and AD. PMID:23224755

  7. Homocysteine excess: delineating the possible mechanism of neurotoxicity and depression.

    PubMed

    Bhatia, Pankaj; Singh, Nirmal

    2015-12-01

    Homocysteine (Hcy) is a nonproteogenic sulfur containing amino acid derived from dietary methionine through demethylation. Homocysteine can be re-methylated to methionine [precursor of S-adenosylmethionine (SAM)] via the re-methylation or 5-methyltetrahydrofolate pathway or undergoes transsulfuration to form cysteine by the action of metabolic enzymes and cofactors. Impaired metabolism due to genetic alteration in metabolic enzymes (methionine synthase, methyltetrahydrofolate reductase (MTHFR), cystathionine β-synthase (CβS), and cystathionine-γ-lyase (CγL) or deficiency in cofactors (vitamin B6 , B12 , folate) may lead to acquired metabolic anomaly known as hyperhomocysteinemia. Hcy excess decreases the S-adenosylmethionine (SAM)-dependent synthesis of catecholamines, viz. dopamine, norepinephrine, epinephrine, and noncatecholamine, viz. serotonin (5-HT), due to genetic alteration in key enzyme MTHFR in the homocysteine metabolism pathway that leads to depression. Thus, hyperhomocysteinemia (HHcy)-induced SAM level is influenced by the single nucleotide polymorphism (SNP) MTHFR C677T. Furthermore, HHcy leads to production of precarious neurotoxic product homocysteic acid (HCA) and cysteine sulfinic acid (CSA) which acts as an N-methyl-D-aspartate (NMDA) receptor agonist and has neurotoxic effects on dopaminergic neurons. In the current review, an attempt has been made to discuss the neurotoxic effects of HHcy in the pathogenesis of depression. PMID:26376956

  8. Population PK/PD model of homocysteine concentrations after high-dose methotrexate treatment in patients with acute lymphoblastic leukemia.

    PubMed

    Rühs, Hauke; Becker, Achim; Drescher, Anne; Panetta, John C; Pui, Ching-Hon; Relling, Mary V; Jaehde, Ulrich

    2012-01-01

    Elevated homocysteine concentrations have been associated with methotrexate-induced neurotoxicity. Based on methotrexate and homocysteine plasma concentrations of 494 children with acute lymphoblastic leukemia treated with high-dose methotrexate in the TOTAL XV study, a pharmacokinetic/pharmacodynamic (PK/PD) model was built with NONMEM. Several compartment and indirect response models were investigated. The pharmacokinetic disposition of methotrexate was best described by a two-compartment model. Homocysteine concentrations were included by an indirect response model where methotrexate inhibition of the homocysteine elimination rate was described by an E(max) model. The homocysteine baseline level was found to be age-dependent. Simulations revealed that folinate rescue therapy does not affect peak concentrations of homocysteine but leads to a modestly reduced homocysteine exposure. In conclusion, our PK/PD model describes the increase of methotrexate-induced HCY concentrations with satisfactory precision and can be applied to assess the effect of folinate regimens on the HCY concentration-time course. PMID:23049924

  9. Increased plasma homocysteine in liver cirrhosis.

    PubMed

    Bosy-Westphal, A; Petersen, S; Hinrichsen, H; Czech, N; J Müller, M

    2001-05-01

    Background: Homocysteine (Hcy), is an atherogenic and thrombogenic risk factor which has also been proposed to be involved in hepatic fibrinogenesis. Hcy metabolism, depends on the cofactors folate, vit. B12, and the vit. B6 vitamer pyridoxalphosphate (PLP). Metabolism of these vitamins is frequently disturbed in cirrhotics, but little is known about plasma Hcy levels in these patients. Methods: Plasma levels of Hcy, methionine, serine, cysteine, PLP, vit. B12 and folate, and standard clinical/biochemical parameters of liver disease were measured in 43 postabsorptive patients with biopsy proven cirrhosis of different origin. Results: 74% of the patients had elevated plasma Hcy levels defined as >13.4 µmol/l (mean+2SD of healthy age matched controls). Increased plasma Hcy concentrations were seen in alcoholic as well as in non-alcoholic cirrhosis. Excluding patients with impaired renal function (n=7), Hcy concentrations remained elevated in 69% of the patients. We found a high prevalence of pathological plasma vitamin concentrations of 33% for increased vit. B12 levels and 5% and 80% for decreased folate and vit. B6 levels, respectively. Mean plasma vitamin B12 concentrations increased, folate remained unchanged and PLP concentrations decreased with deteriorating liver function. Hcy concentrations were correlated with levels of creatinine (r=0.44, P<0.01), serine (r=-0.46, P<0.01), and cysteine (r=0.38, P<0.05), but showed no association with parameters of liver function and with plasma levels of folate, vit. B12 und vit. B6. This was contrary to data obtained in healthy individuals. In a stepwise multiple regression serine and cysteine best explained the variance in Hcy levels. Conclusions: Elevated basal Hcy-plasma levels are frequently seen cirrhotic patients. Variations of Hcy concentration in liver cirrhosis are not explained by plasma levels of cofactors of Hcy metabolism. PMID:11282484

  10. Nitric oxide releasing material adsorbs more fibrinogen.

    PubMed

    Lantvit, Sarah M; Barrett, Brittany J; Reynolds, Melissa M

    2013-11-01

    One mechanism of the failure of blood-contacting devices is clotting. Nitric oxide (NO) releasing materials are seen as a viable solution to the mediation of surface clotting by preventing platelet activation; however, NO's involvement in preventing clot formation extends beyond controlling platelet function. In this study, we evaluate NO's effect on factor XII (fibrinogen) adsorption and activation, which causes the initiation of the intrinsic arm of the coagulation cascade. This is done by utilizing a model plasticized poly(vinyl) chloride (PVC), N-diazeniumdiolate system and looking at the adsorption of fibrinogen, an important clotting protein, to these surfaces. The materials have been prepared in such a way to eliminate changes in surface properties between the control (plasticized PVC) and composite (NO-releasing) materials. This allows us to isolate NO release and determine the effect on the adsorption of fibrinogen, to the material surface. Surprisingly, it was found that an NO releasing material with a surface flux of 17.4 ± 0.5 × 10(-10) mol NO cm(-2) min(-1) showed a significant increase in the amount of fibrinogen adsorbed to the material surface compared to one with a flux of 13.0 ± 1.6 × 10(-10) mol NO cm(-2) min(-1) and the control (2334 ± 496, 226 ± 99, and 103 ±31% fibrinogen adsorbed of control, respectively). This study suggests that NO's role in controlling clotting is extended beyond platelet activation. PMID:23554300

  11. Methyl Vitamin B12 but not methylfolate rescues a motor neuron-like cell line from homocysteine-mediated cell death.

    PubMed

    Hemendinger, Richelle A; Armstrong, Edward J; Brooks, Benjamin Rix

    2011-03-15

    Homocysteine is an excitatory amino acid implicated in multiple diseases including amyotrophic lateral sclerosis (ALS). Information on the toxicity of homocysteine in motor neurons is limited and few studies have examined how this toxicity can be modulated. In NSC-34D cells (a hybrid cell line derived from motor neuron-neuroblastoma), homocysteine induces apoptotic cell death in the millimolar range with a TC₅₀ (toxic concentration at which 50% of maximal cell death is achieved) of 2.2 mM, confirmed by activation of caspase 3/7. Induction of apoptosis was independent of short-term reactive oxygen species (ROS) generation. Methyl Vitamin B12 (MeCbl) and methyl tetrahydrofolate (MTHF), used clinically to treat elevated homocysteine levels, were tested for their ability to reverse homocysteine-mediated motor neuron cell death. MeCbl in the micromolar range was able to provide neuroprotection (2 h pretreatment prior to homocysteine) and neurorescue (simultaneous exposure with homocysteine) against millimolar homocysteine with an IC₅₀ (concentration at which 50% of maximal cell death is inhibited) of 0.6 μM and 0.4 μM, respectively. In contrast, MTHF (up to 10 μM) had no effect on homocysteine-mediated cell death. MeCbl inhibited caspase 3/7 activation by homocysteine in a time- and dose-dependent manner, whereas MTHF had no effect. We conclude that MeCbl is effective against homocysteine-induced cell death in motor neurons in a ROS-independent manner, via a reduction in caspase activation and apoptosis. MeCbl decreases Hcy induced motor neuron death in vitro in a hybrid cell line derived from motor neuron-neuroblastoma and may play a role in the treatment of late stage ALS where HCy levels are increased in animal models of ALS. PMID:21237187

  12. Methyl Vitamin B12 but not methylfolate rescues a motor neuron-like cell line from homocysteine-mediated cell death

    SciTech Connect

    Hemendinger, Richelle A. Armstrong, Edward J.; Brooks, Benjamin Rix

    2011-03-15

    Homocysteine is an excitatory amino acid implicated in multiple diseases including amyotrophic lateral sclerosis (ALS). Information on the toxicity of homocysteine in motor neurons is limited and few studies have examined how this toxicity can be modulated. In NSC-34D cells (a hybrid cell line derived from motor neuron-neuroblastoma), homocysteine induces apoptotic cell death in the millimolar range with a TC{sub 50} (toxic concentration at which 50% of maximal cell death is achieved) of 2.2 mM, confirmed by activation of caspase 3/7. Induction of apoptosis was independent of short-term reactive oxygen species (ROS) generation. Methyl Vitamin B12 (MeCbl) and methyl tetrahydrofolate (MTHF), used clinically to treat elevated homocysteine levels, were tested for their ability to reverse homocysteine-mediated motor neuron cell death. MeCbl in the micromolar range was able to provide neuroprotection (2 h pretreatment prior to homocysteine) and neurorescue (simultaneous exposure with homocysteine) against millimolar homocysteine with an IC{sub 50} (concentration at which 50% of maximal cell death is inhibited) of 0.6 {mu}M and 0.4 {mu}M, respectively. In contrast, MTHF (up to 10 {mu}M) had no effect on homocysteine-mediated cell death. MeCbl inhibited caspase 3/7 activation by homocysteine in a time- and dose-dependent manner, whereas MTHF had no effect. We conclude that MeCbl is effective against homocysteine-induced cell death in motor neurons in a ROS-independent manner, via a reduction in caspase activation and apoptosis. MeCbl decreases Hcy induced motor neuron death in vitro in a hybrid cell line derived from motor neuron-neuroblastoma and may play a role in the treatment of late stage ALS where HCy levels are increased in animal models of ALS.

  13. Increased concentration of plasminogen activator inhibitor-1 and fibrinogen in individuals with metabolic syndrome.

    PubMed

    Palomo, Iván G; Gutiérrez, César L; Alarcón, Marcelo L; Jaramillo, Julio C; Segovia, Fabián M; Leiva, Elba M; Mujica, Verónica E; Icaza, Gloria N; Díaz, Nora S; Moore-Carrasco, Rodrigo

    2009-01-01

    Metabolic syndrome (MS) is closely linked to a generalized metabolic disorder referred to as insulin resistance. Disturbances in the hemostasis and fibrinolytic systems are a feature of MS. The aim of this study was to determine the concentration levels of fibrinogen and plasminogen activator inhibitor-1 (PAI-1) in a group of patients with MS with respect to a non-MS group, and to evaluate their possible relation with other risk factors in MS. The study was carried out in a total of 186 male and female non-smoking individuals aged 45-64 years, 93 with MS (ATP III criteria) and 93 without MS. Plasmatic levels of PAI-1 were measured by ELISA, and those of fibrinogen by the Claus method. The plasmatic levels of PAI-1 (men 49.2±19.8 vs. 35.0±12.2 ng/ml and women 42.0±19.7 vs. 31.6±14.6 ng/ml; p=0.0026) and fibrinogen (274.0±82.1 vs. 232.7±66.6 ng/ml; p=0.0002) were significantly higher in the MS group than in the non-MS group. PAI-1 was significantly associated with diastolic blood pressure, triglycerides and waist circumference. Fibrinogen was negatively associated with HDL-c. High plasmatic levels of PAI-1 and fibrinogen contribute to the cardiovascular risk that characterizes individuals with MS. PMID:21475821

  14. Homocysteine lowering interventions for preventing cardiovascular events

    PubMed Central

    Martí-Carvajal, Arturo J; Solà, Ivan; Lathyris, Dimitrios; Salanti, Georgia

    2014-01-01

    Background Cardiovascular disease such as coronary artery disease, stroke and congestive heart failure, is a leading cause of death worldwide. A postulated risk factor is elevated circulating total homocysteine (tHcy) levels which is influenced mainly by blood levels of cyanocobalamin (vitamin B12), folic acid (vitamin B9) and pyridoxine (vitamin B6). There is uncertainty regarding the strength of association between tHcy and the risk of cardiovascular disease. Objectives To assess the clinical effectiveness of homocysteine-lowering interventions (HLI) in people with or without pre-existing cardiovascular disease. Search methods We searched The Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (issue 3 2008), MEDLINE (1950 to August 2008), EMBASE (1988 to August 2008), and LILACS (1982 to September 2, 2008). We also searched in Allied and Complementary Medicine (AMED; 1985 to August 2008), ISI Web of Science (1993 to August 2008), and the Cochrane Stroke Group Specialised Register (April 2007). We hand searched pertinent journals and the reference lists of included papers. We also contacted researchers in the field. There was no language restriction in the search. Selection criteria We included randomised clinical trials (RCTs) assessing the effects of HLI for preventing cardiovascular events with a follow-up period of 1 year or longer. We considered myocardial infarction and stroke as the primary outcomes. We excluded studies in patients with end-stage renal disease. Data collection and analysis We independently performed study selection, risk of bias assessment and data extraction. We estimated relative risks (RR) for dichotomous outcomes. We measured statistical heterogeneity using I2. We used a random-effects model to synthesise the findings. Main results We included eight RCTs involving 24,210 participants with a low risk of bias in general terms. HLI did not reduce the risk of non-fatal or fatal myocardial infarction, stroke, or

  15. Stimulation of fibrinogen synthesis in cultured rat hepatocytes by fibrinogen degradation product fragment D.

    PubMed Central

    LaDuca, F M; Tinsley, L A; Dang, C V; Bell, W R

    1989-01-01

    The direct stimulation of fibrinogen biosynthesis by fibrinogen degradation produces (FDPs) was studied in rat hepatocyte cultures. Pure rat FDP fragment D (FDP-D) (Mr 90,000) and FDP fragment E (FDP-E) (Mr 40,000) and mixtures of the two (FDP-DE) were added to rat hepatocytes cultured in serum-free hormonally defined medium. Hydrocortisone (20 microM) significantly increased synthesis of fibrinogen, as determined by incorporation of [35S]methionine. FDP-D and FDP-E did not increase fibrinogen synthesis in the presence of hydrocortisone. However, hepatocytes cultured without hydrocortisone displayed increased fibrinogen synthesis (2.0- to 2.8-fold) with FDP-D (2.6-6.7 microM) but not with FDP-E (5.7 microM). At these FDP concentrations the synthesis of albumin, haptoglobin, and transferrin was not increased. FDP-D-induced fibrinogen synthesis was inhibited (greater than 90%) by actinomycin D and cycloheximide, indicating that the increase in [35S]methionine incorporation was from de novo protein synthesis. The role of FDP-D was further substantiated by showing that FDP-D, but not FDP-E, bound to the hepatocytes. These data indicate that FDP-D, but not FDP-E, directly and specifically stimulates fibrinogen synthesis in rat hepatocytes; this stimulation does not require any additional serum or protein cofactors. Images PMID:2813424

  16. Iron modulates the alpha chain of fibrinogen.

    PubMed

    Nielsen, Vance G; Jacobsen, Wayne K

    2016-04-01

    Iron-bound fibrinogen has been noted to accelerate plasmatic coagulation in patients with divergent conditions involving upregulation of heme oxygenase activity, including hemodialysis, Alzheimer's disease, sickle cell anemia, and chronic migraine. Our goal was to determine if a site of iron-fibrinogen interaction was on the alpha chain. Using thrombelastography, we compared the coagulation kinetic profiles of plasma exposed to 0-10 µM ferric chloride after activation of coagulation with thrombin generated by contact activation of plasma with the plastic sample cup or by exposure to 1 µg/ml of Calloselasma rhodostoma venom (rich in ancrod activity), which causes coagulation via polymerization of alpha chain monomers. Venom mediated coagulation always occurred before thrombin activated thrombus formation, and ferric chloride always diminished the time of onset of coagulation and increased the velocity of clot growth. Iron enhances plasmatic coagulation kinetics by modulating the alpha chain of fibrinogen. PMID:26782808

  17. THE CONVERSION OF FIBRINOGEN TO FIBRIN

    PubMed Central

    Shulman, Sidney; Katz, Sidney; Ferry, John D.

    1953-01-01

    1. Fibrin clots prepared in the absence of calcium can be dissolved in solutions of lithium chloride and bromide and sodium bromide and iodide, as well as of guanidine hydrochloride and urea. These salts do not denature fibrinogen under the same conditions of concentration, temperature, and time. Sedimentation experiments on the fibrin solutions show in each case a single sharp peak with a sedimentation constant close to that of fibrinogen. 2. At lower concentrations, these salts inhibit the clotting of fibrinogen by thrombin, but in the case of lithium bromide and sodium iodide, at least, allow an intermediate polymer to accumulate whose sedimentation constant is close to that of the polymer observed in systems inhibited by hexamethylene glycol or urea. PMID:13069679

  18. Importance of fibrinogen in dilutional coagulopathy after neurosurgical procedures: A descriptive study

    PubMed Central

    Nair, Shalini; Nair, Bijesh Ravindran; Vidyasagar, Ajay; Joseph, Mathew

    2016-01-01

    Background and Aims: The routine management of coagulopathy during surgery involves assessing haemoglobin, prothrombin time (PT), activated partial thromboplastin time (aPTT) and platelets. Correction of these parameters involves administration of blood, fresh frozen plasma and platelet concentrates. The study was aimed at identifying the most common coagulation abnormality during neurosurgical procedures and the treatment of dilutional coagulopathy with blood components. Methods: During 2 years period, all adult patients undergoing neurosurgical procedures who were transfused two or more units of red cells were prospectively evaluated for the presence of a coagulopathy. PT, aPTT, platelet count and fibrinogen levels were estimated before starting a component therapy. Results: After assessing PT, aPTT, platelet count and fibrinogen levels following two or more blood transfusions, thirty patients were found to have at least one abnormal parameter that required administration of a blood product. The most common abnormality was a low fibrinogen level, seen in 26 patients; this was the only abnormality in three patients. No patient was found to have an abnormal PT or aPTT without either the fibrinogen concentration or platelet count or both being low. Conclusion: Low fibrinogen concentration was the most common coagulation abnormality found after blood transfusions for neurosurgical procedures. PMID:27601735

  19. Tumor response and survival in patients with advanced non-small-cell lung cancer: the predictive value of chemotherapy-induced changes in fibrinogen

    PubMed Central

    2012-01-01

    Background Hyperfibrinogenemia is a common problem associated with various carcinomas, and is accompanied by hypercoagulablity. In advanced non-small-cell lung cancer (NSCLC) it remains unclear whether or not chemotherapy-induced changes in fibrinogen level relate to chemotherapeutic response and prognosis. The purposes of this study were to: 1) analyze the association between chemotherapy-induced changes in plasma fibrinogen level and the chemotherapeutic response after the first two courses of standard first-line platinum-based chemotherapy; and 2) evaluate the prognostic significance of the basal plasma fibrinogen level in patients with advanced NSCLC. Methods In this retrospective study, the data from 160 patients with advanced NSCLC were collected. The association between the changes in fibrinogen and the response to chemotherapy, or between the pre-and post-chemotherapy fibrinogen levels and patient clinical characteristics, were analyzed using SPSS software. In addition, the prognostic value of pre-chemotherapy fibrinogen levels was assessed. Results The median pre-chemotherapy plasma fibrinogen level was 4.4 g/L. Pre-chemotherapy plasma fibrinogen levels correlated significantly with gender (p = 0.041). Post-chemotherapy plasma fibrinogen levels correlated with gender (p = 0.023), age (p = 0.018), ECOG (p = 0.002) and tumor response (p = 0.049). Plasma fibrinogen levels markedly decreased after chemotherapy in 98 (61.25 %) patients with pre-chemotherapy hyperfibrinogenemia (p = 0.008); and in this population there was a significant link between the decrease in fibrinogen level, and initial partial response (PR; p = 0.017) and stable disease (SD; p = 0.031). Univariate and multivariate analysis revealed that higher levels of fibrinogen (≥4.4 g/L) and ECOG 1 were positively associated with shorter overall survival (OS). CEA and CA125 also decreased significantly (p =0.015, p =0.000) in DCR group after chemotherapy. Conclusions This study showed that the

  20. Plasma homocysteine concentration in children with chronic renal failure.

    PubMed

    Merouani, A; Lambert, M; Delvin, E E; Genest, J; Robitaille, P; Rozen, R

    2001-10-01

    Hyperhomocysteinemia, a risk factor for vascular disease, is commonly found in adult patients with end-stage renal disease. Major determinants of elevated plasma homocysteine levels in these patients include deficiencies in folate and vitamin B12, methylenetetrahydrofolate reductase (MTHFR) genotype and renal function. Little information is available for children with chronic renal failure (CRF). The prevalence and the factors that affect plasma homocysteine concentration were determined in children. Twenty-nine children with various degrees of CRF (15 were dialyzed, 14 were not dialyzed) were compared with 57 age- and sex-matched healthy children. Homocysteine concentrations were higher in patients than controls (17.3 micromol/l vs 6.8 micromol/l, P<0.0001) and hyperhomocysteinemia (>95th percentile for controls: 14.0 micromol/l) was seen in 62.0% of patients and 5.2% of controls. Folate concentrations were lower in patients (9.9 nmol/l) than controls (13.5 nmol/l), P<0.01. Vitamin B12 was similar in patients (322 pmol/l) and controls (284 pmol/l). Dialyzed patients have a higher prevalence of hyperhomocysteinemia than nondialyzed patients (87% vs 35%). Dialyzed patients with MTHFR mutation have higher plasma homocysteine (28.5 micromol/l) than nondialyzed patients with the mutation (10.7 micromol/l), P<0.002. In our study, differences between controls and patients in plasma homocysteine concentrations are observed when age is greater then 92 months, folate less than 21.6 nmol/l and vitamin B12 less than 522 pmol/l. Our study shows that hyperhomocysteinemia is common in children with CRF and is associated with low folate and normal vitamin B12 status, compared to normal children. Among the patients, the dialyzed patients with the MTHFR mutation are particularly at risk for hyperhomocysteinemia. Further studies are needed to investigate therapeutic interventions and the potential link with vascular complications in these patients. PMID:11605787

  1. Association between Homocysteine and Bone Mineral Density according to Age and Sex in Healthy Adults

    PubMed Central

    Kim, Joo Il; Moon, Ji Hyun; Chung, Hye Won; Kong, Mi Hee

    2016-01-01

    Background There are several studies about the relationship between serum homocysteine levels and bone mineral density (BMD), but the results are varied, and the studies are limited in Korea. In our study, the relationship between serum homocysteine levels and BMD by part according to age and sex is investigated. Methods From March 2012 to July 2015, the 3,337 healthy adults who took a medical examination were recruited. Subjects filled in the self-recording type questionnaire and physical examination, blood test, BMD of lumbar spine and femur were measured. After sorting by aging (≤49 year old, 50-59 year old, ≥60 year old) and sex, the results were adjusted with age and body mass index (BMI) and the relationship between serum homocysteine levels and BMD by lumbar spine and femur was analyzed by multiple regression analysis. Results As results of analysis, with the adjustment with age and BMI, all age groups of men had no significant relationship between log-converted serum homocysteine levels and BMD. In women aged under 50, there were significantly negative relationships at lumbar spine (β=-0.028, P=0.038), femur neck (β=-0.062, P=0.001), and total hip (β=-0.076, P<0.001), but there was no significant relationship in other age groups (50-59 year old and ≥60 year old). Conclusions As the serum homocysteine levels increased in women aged under 50, BMD of the lumbar spine and femur decreased, and correlations between homocysteine and BMD were different by sex and age. PMID:27622176

  2. [Homocysteine, vitamin B-12, folic acid and the cognitive decline in the elderly].

    PubMed

    Smach, M A; Naffeti, S; Charfeddine, B; Ben Abdallah, J; Othmen, L B; Letaef, A; Limem, K

    2013-10-01

    Hyperhomocysteinemia is a risk factor for neurological diseases, but the underlying pathophysiology has not been adequately explained. Mild hyperhomocysteinemia, which is sometimes associated with a low plasma level of vitamin B9, B12 and folic acid, is responsible in the toxicity in neural cell by activating NMDA receptor. Indeed, even if vitamin supplementation has clearly proven its efficiency on lowering plasma levels of homocysteine, recent studies do not show any positive effect of vitamin therapy on cognitive function. The hypothesis that this therapy is inefficient has been recently reinforced by two randomized trials on the effects of vitamin supplementation. Several hypotheses still need to be explored: Mechanisms of homocysteine toxicity and that of total uselessness of vitamin supplementation; the possible need to complete the actual data with further, more powerful studies in order to prove the role of homocysteine in the development of neurodegenerative diseases and a clinical effect of vitamin therapy. PMID:22647793

  3. Retinoids stimulate fibrinogen production both in vitro (hepatocytes) and in vivo. Induction requires activation of the retinoid X receptor.

    PubMed

    Nicodeme, E; Nicaud, M; Issandou, M

    1995-10-01

    The in vitro effects of retinoids on fibrinogen synthesis were investigated in HepG2 cells and primary human hepatocytes. In vivo effects were studied in the rat. In HepG2 cells, maximal stimulation (twofold) of fibrinogen secretion was obtained when cells were incubated in the presence of 1 mumol/L all-trans retinoic acid (T-RA) for 24 hours. A comparable increase was observed for both de novo fibrinogen synthesis and fibrinogen beta chain mRNA level. In primary cultures of human hepatocytes, treatment with 1 mumol/L T-RA for 72 hours also gave a twofold increase in fibrinogen production. Furthermore, rats treated for 6 days with 100 mg.kg-1.d-1 T-RA presented increased fibrinogen plasma levels (110%). A selective retinoic X receptor (RXR) agonist, 4-[1-3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-ethenyl]benzoi c acid (3-methyl TTNEB), as well as 9-cis retinoic acid, a natural RXR ligand, mimicked the effects of T-RA on fibrinogen synthesis in vitro at lower concentrations. In contrast, a selective retinoic A receptor alpha (RAR alpha) agonist was a poor activator. The ED50 of the different retinoids on fibrinogen secretion by HepG2 cells was 25 nmol/L for T-RA, 4 nmol/L for 9-cis retinoic acid, 11 nmol/L for the synthetic RXR agonist, and > 500 nmol/L for the RAR alpha agonist. However, incubation of HepG2 cells with RXR agonist together with RAR alpha agonist resulted in a further increase in fibrinogen production. The secretion of two other acute-phase proteins, alpha-antichymotrypsin and caeruloplasmin, was also stimulated by retinoids in HepG2 cells but by a different regulatory mechanism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7583541

  4. Molecular characterization of betaine-homocysteine methyltransferase 1 from the liver, and effects of aestivation on its expressions and homocysteine concentrations in the liver, kidney and muscle, of the African lungfish, Protopterus annectens.

    PubMed

    Ong, Jasmine L Y; Woo, Jia M; Hiong, Kum C; Ching, Biyun; Wong, Wai P; Chew, Shit F; Ip, Yuen K

    2015-05-01

    Homocysteine accumulation has numerous deleterious effects, and betaine-homocysteine S-methyltransferase (BHMT) catalyses the synthesis of methionine from homocysteine and betaine. This study aimed to determine homocysteine concentrations, and mRNA expression levels and protein abundances of bhmt1/Bhmt1 in the liver, kidney and muscle of the African lungfish, Protopterus annectens, during the induction (6 days), maintenance (6 months) or arousal (3 days after arousal) phase of aestivation. The homocysteine concentration decreased significantly in the liver of P. annectens after 6 days or 6 months of aestivation, but it returned to the control level upon arousal. By contrast, homocysteine concentrations in the kidney and muscle remained unchanged during the three phases of aestivation. The complete coding cDNA sequence of bhmt1 from P. annectens consisted of 1236 bp, coding for 412 amino acids. The Bhmt1 from P. annectens had a close phylogenetic relationship with those from tetrapods and Callorhinchus milii. The expression of bhmt1 was detected in multiple organs/tissues of P. annectens, and this is the first report on the expression of bhmt1/Bhmt1 in animal skeletal muscle. The mRNA and protein expression levels of bhmt1/Bhmt1 were up-regulated in the liver of P. annectens during the induction and maintenance phases of aestivation, possibly to regulate the hepatic homocysteine concentration. The significant increase in hepatic Bhmt1 protein abundance during the arousal phase could be a response to increased cellular methylation for the purpose of tissue reconstruction. Unlike the liver, Bhmt1 expression in the kidney and muscle of P. annectens was regulated translationally, and its up-regulation could be crucial to prevent homocysteine accumulation. PMID:25575738

  5. Utility of plasma fibrinogen in the differential diagnosis of thyrotoxicosis

    PubMed Central

    Ma, Jie; Liu, Rui; Wu, Di; Miao, Wei; Chen, Qian; Li, Yushu; Guan, Haixia

    2015-01-01

    Background: A study had reported that a low TSH level is associated with elevated plasma fibrinogen (FIB) levels. Our purpose was to investigate the role of FIB in the differential diagnosis of thyrotoxicosis. Methods: The data of 104 patients with primary thyrotoxicosis at the First Hospital of China Medical University from July 2010 to March 2011 were analyzed and divided into three groups: 45 cases of subacute thyroiditis, 50 cases of Graves’ disease, and 9 cases of toxic multinodular goiter. The patients with subacute thyroiditis were followed up before and after the treatment. FIB levels of the three groups were compared. Results: There was no significant difference in serum TSH, FT3 and FT4 between the patients with three different causes of thyrotoxicosis (P > 0.05). The proportion of hyperfibrinogenemia in patients with subacute thyroiditis was 98%. The FIB levels of patients with subacute thyroiditis were significantly higher than those with Graves’ disease and toxic multinodular goiter (P < 0.05). Levels of ESR show a similar tendency. The FIB levels returned to normal with the remission of subacute thyroiditis. Conclusions: Elevated plasma fibrinogen is a common manifestation of the active phase of subacute thyroiditis. A FIB test can be used for the differential diagnosis of thyrotoxicosis. We can anticipate the outcome of subacute thyroiditis through the dynamic changes of FIB. PMID:25785116

  6. Hydroxyl density affects the interaction of fibrinogen with silica nanoparticles at physiological concentration.

    PubMed

    Marucco, Arianna; Turci, Francesco; O'Neill, Luke; Byrne, Hugh J; Fubini, Bice; Fenoglio, Ivana

    2014-04-01

    An increasing interest in the interaction between blood serum proteins and nanoparticles has emerged over the last years. In fact, this process plays a key role in the biological response to nanoparticles. The behavior of proteins at the biofluid/material interface is driven by the physico-chemical properties of the surface. However, much research is still needed to gain insight into the process at a molecular level. In this study, the effect of silanol density on the interaction of fibrinogen at physiological concentrations with silica nanoparticle/flat surfaces has been studied. Silica nanoparticles and silica wafers were modified and characterized to obtain a set of samples with different silanols density. The interaction with fibrinogen has been studied by evaluating the extent of coverage (bicinchoninic acid assay) and the irreversibility of adsorption (shift of the ζ potential). To clarify the molecular mechanism of fibrinogen/surface interactions, confocal micro-Raman spectroscopy (nanoparticles) and atomic force microscopy (wafers) were used. Finally the effect of fibrinogen on the agglomeration of nanoparticles has been evaluated by Flow Particle Image Analysis. The data reported here show that a minimal variation in the state of the silica surface modifies the adsorption behavior of fibrinogen, which appears mediated by a competition between protein/protein and protein/surface interactions. By comparing the data obtained on nanoparticles and silicon-supported silica layers, we found that hydrophilicity increases the tendency of fibrinogen molecules to interact with the surface rather than with other molecules, thus inhibiting fibrinogen self-assembly. This study contributes to the knowledge of the processes occurring at the surface/biological fluids interface, needed for the design of new biocompatible materials. PMID:24491335

  7. Role of fibrinogen in acute ischemic kidney injury.

    PubMed

    Sörensen-Zender, I; Rong, S; Susnik, N; Lange, J; Gueler, F; Degen, J L; Melk, A; Haller, H; Schmitt, R

    2013-09-01

    Renal ischemia-reperfusion (I/R) is associated with activation of the coagulation system and accumulation of blood clotting factors in the kidney. The aim of the present study was to examine the functional impact of fibrinogen on renal inflammation, damage, and repair in the context of I/R injury. In this study, we found that I/R was associated with a significant increase in the renal deposition of circulating fibrinogen. In parallel, I/R stress induced the de novo expression of fibrinogen in tubular epithelial cells, as reflected by RT-PCR, immunofluorescence, and in situ hybridization. In vitro, fibrinogen expression was induced by oncostatin M and hyper-IL-6 in primary tubular epithelial cells, and fibrinogen-containing medium had an inhibitory effect on tubular epithelial cell adhesion and migration. Fibrinogen(+/-) mice showed similar survival as wild-type mice but better preservation in early postischemic renal function. In fibrinogen(-/-) mice, renal function and survival were significantly worse than in fibrinogen(+/-) mice. Renal transplant experiments revealed reduced expression of tubular damage markers and attenuated proinflammatory cytokine expression but increased inflammatory cell infiltrates and transforming growth factor-β expression in fibrinogen(-/-) isografts. These data point to heterogeneous effects of fibrinogen in renal I/R injury. While a complete lack of fibrinogen may be detrimental, partial reduction of fibrinogen in heterozygous mice can improve renal function and overall outcome. PMID:23804451

  8. Salidroside improves homocysteine-induced endothelial dysfunction by reducing oxidative stress.

    PubMed

    Leung, Sin Bond; Zhang, Huina; Lau, Chi Wai; Huang, Yu; Lin, Zhixiu

    2013-01-01

    Hyperhomocysteinemia is associated with an increased risk for cardiovascular diseases through increased oxidative stress. Salidroside is an active ingredient of the root of Rhodiola rosea with documented antioxidative, antihypoxia and neuroprotective properties. However, the vascular benefits of salidroside against endothelial dysfunction have yet to be explored. The present study, therefore, aimed to investigate the protective effect of salidroside on homocysteine-induced endothelial dysfunction. Functional studies on the rat aortas were performed to delineate the vascular effect of salidroside. DHE imaging was used to evaluate the reactive oxygen species (ROS) level in aortic wall and endothelial cells. Western blotting was performed to assess the protein expression associated with oxidative stress and nitric oxide (NO) bioavailability. Exposure to homocysteine attenuated endothelium-dependent relaxations in rat aortas while salidroside pretreatment rescued it. Salidroside inhibited homocystein-induced elevation in the NOX2 expression and ROS overproduction in both aortas and cultured endothelial cells and increased phosphorylation of eNOS which was diminished by homocysteine. The present study shows that salidroside is effective in preserving the NO bioavailability and thus protects against homocysteine-induced impairment of endothelium-dependent relaxations, largely through inhibiting the NOX2 expression and ROS production. Our results indicate a therapeutic potential of salidroside in the management of oxidative-stress-associated cardiovascular dysfunction. PMID:23589720

  9. Ethnic Differences in the Prevalence of High Homocysteine Levels Among Low-Income Rural Kazakh and Uyghur Adults in Far Western China and Its Implications for Preventive Public Health

    PubMed Central

    Guo, Shuxia; Pang, Hongrui; Guo, Heng; Zhang, Mei; He, Jia; Yan, Yizhong; Niu, Qiang; Muratbek; Rui, Dongsheng; Li, Shugang; Ma, Rulin; Zhang, Jingyu; Liu, Jiaming; Ding, Yusong

    2015-01-01

    Objective: Homocysteine (Hcy) is a relevant biomarker of vascular disease: serum Hcy concentrations will increase the risk of systolic hypertension, whereas hyperhomocysteinemia (HHcy) has a synergistic effect with hypertension and increases the risk of cardiovascular disease. However, information has primarily been gathered from high-income and urban settings, and little is known regarding low-income rural settings. This study focused on a low-income rural and nomadic minority residing in far western China. Hcy levels were tested, and the prevalences of HHcy and H-type hypertension were investigated in this population. Methods: This study used a stratified cluster random sampling method, selecting 2,180 individuals as subjects from Kazakh and Uyghur inhabitants (≥25 years old) of 18 villages in Xinjiang, China, which is approximately 4407 km from the capital, Beijing. Hcy levels were determined using a double reagent enzymatic cycling method. HHcy (Hcy > 10 μmol/L) was defined by the criteria of the American Heart Association. Results: The Kazakh geometrical mean of Hcy was 13.34 μmol/L, and the Uyghur mean was 13.75 μmol/L; the mean values were higher in males than in females of both ethnicities (15.99 μmol/L vs. 11.63 μmol/L; 15.71 μmol/L vs. 11.91 μmol/L, respectively, p < 0.01). The serum levels of Hcy increased with increasing age in both ethnicities, and except for Kazakh individuals >65 years old, Hcy serum levels were higher in males than in females in all age groups of both ethnicities, with a p value less than 0.01. The Kazakh prevalence of HHcy was 80.0%, and the Uyghur prevalence was 78.2%; the male prevalence was higher than that in females for both ethnicities (93.5% vs. 69.6%; 90.8% vs. 64.6%, respectively, p < 0.05). Among the Kazakh, the prevalence of hypertension was 35.1%, and the prevalence was higher in males than in females (44.3% vs. 28.1%, p < 0.001); 87.6% of the Kazakh individuals had H-type hypertension, and the prevalence was

  10. The influence of homocysteine and oxidative stress on pregnancy outcome.

    PubMed

    Micle, O; Muresan, M; Antal, L; Bodog, F; Bodog, A

    2012-02-22

    Oxidative stress in utero-placental tissues plays an important role in the development of placental-related diseases. Maternal hiperhomocysteinemia is associated with placental mediated diseases, such as preeclampsia, spontaneous abortion and placental abruption. The aim of our study is to appreciate the clinical usefulness of the dosage serum homocysteine and malondialdehyde, as an oxidative stress marker, in the pregnancies complicated with risk of abortion or preterm birth. The study was performed at the Obstetric Gynecology Clinical Hospital Oradea from December 2009 until April 2010. It included 18 patients with risk of abortion (group 1), 22 with preterm birth (group 2). The results were compared with a control group composed by 14 healthy pregnant women. Serum homocysteine level was measured by an enzymatic method, on the instrument Hitachi 912, Roche, reagent: Axis-Shield Enzymatic. For proving the oxidative stress we established the level of malondialdehyde using a method with thiobarbituric acid TBA (Kei Satoh 1978) and the level of ceruloplasmin with the Ravin method .Also AST, ALT,CRP, iron, uric acid, urea were assessed.High level of homocysteine in both groups of study in comparison with the control group was found. The concentration of MDA was significantly higher in pregnancies complicated with risk of abortion and preterm birth compared to the control group (p=0.040, p=0.031). Considerable differences of ceruloplasmin concentration between group 1 and group 2 (p=0.045), and between group 2 and control group (p=0.034), was noticed but not any important differences between group 1 and control group (p=0.683). In women with risk of abortion or with preterm birth an oxidative stress and a hyperhomocysteinemia are present. PMID:22574089

  11. Dietary intake of S-(α-carboxybutyl)-DL-homocysteine induces hyperhomocysteinemia in rats

    PubMed Central

    Strakova, Jana; Williams, Kelly T.; Gupta, Sapna; Schalinske, Kevin L.; Kruger, Warren D.; Rozen, Rima; Jiracek, Jiri; Li, Lucas; Garrow, Timothy A.

    2010-01-01

    Betaine homocysteine S-methyltransferase (BHMT) catalyzes the transfer of a methyl group from betaine to homocysteine forming dimethylglycine and methionine. We previously showed that inhibiting BHMT in mice by intraperitoneal injection of S-(α-carboxybutyl)-DL-homocysteine (CBHcy) results in hyperhomocysteinemia. In the present study, CBHcy was fed to rats to determine whether it could be absorbed and cause hyperhomocysteinemia as observed for the intraperitoneal administration of the compound in mice. We hypothesized that dietary administered CBHcy will be absorbed and will result in the inhibition of BHMT and cause hyperhomocysteinemia. Rats were meal-fed every 8 hours an L-amino acid-defined diet either containing or devoid of CBHcy (5 mg/meal) for 3 days. The treatment decreased liver BHMT activity by 90% and had no effect on methionine synthase, methylenetetrahydrofolate reductase, phosphatidylethanolamine N-methyltransferase and CTP:phosphocholine cytidylyltransferase activities. In contrast, cystathionine β-synthase activity and immunodetectable protein decreased (56 and 26%, respectively) and glycine N-methyltransferase activity increased (52%) in CBHcy-treated rats. Liver S-adenosylmethionine levels decreased by 25% in CBHcy-treated rats and S-adenosylhomocysteine levels did not change. Further, plasma choline decreased (22%) and plasma betaine increased (15-fold) in CBHcy-treated rats. The treatment had no effect on global DNA and CpG island methylation, liver histology and plasma markers of liver damage. We conclude that CBHcy mediated BHMT inhibition causes an elevation in total plasma homocysteine that is not normalized by the folate-dependent conversion of homocysteine to methionine. Further, metabolic changes caused by BHMT inhibition affect cystathionine β-synthase and glycine N-methyltransferase activities, which further deteriorate plasma homocysteine levels. PMID:20797482

  12. [Mechanisms that protect against homocysteine toxicity].

    PubMed

    Zimny, Jarosław

    2008-01-01

    Elevated concentrations of homocysteine (Hcy) in human tissues have been correlated with some diseases, such as cardio-vascular, neurodegenerative, and kidney disorders. Hcy occurs in human blood in several forms. The most reactive is homocysteine thiolactone (HcyTl). It spontaneously homocysteinylates proteins impairing their functions. As has been evidenced recently, organisms developed protective mechanisms against the HcyTl toxicity. The first mechanism discovered was the calcium-dependent enzyme occurring in mammalian sera, known till then as paraoxonase, which hydrolyzes HcyTl to Hcy. Chronologically second mechanism discovered was urinary excretion of HcyTl. The third protective mechanism is the HcyTl hydrolysis catalyzed by intracellular enzyme known as bleomycin hydrolase. This review outlines current knowledge of the Hcy toxicity and of the three aforementioned protective mechanisms, emphasizing the role of bleomycin hydrolase/ homocysteine-thiolactonase. PMID:18610586

  13. Homocysteine thiolactone affects protein ubiquitination in yeast.

    PubMed

    Bretes, Ewa; Zimny, Jarosław

    2013-01-01

    The formation of homocysteine thiolactone (HcyTl) from homocysteine occurs in all examined so far organisms including bacteria, yeast, and humans. Protein N-homocysteinylation at the ε-amino group of lysine is an adverse result of HcyTl accumulation. Since tagging of proteins by ubiquitination before their proteasomal degradation takes place at the same residue, we wondered how N-homocysteinylation may affect the ubiquitination of proteins. We used different yeast strains carrying mutations in genes involved in the homocysteine metabolism. We found positive correlation between the concentration of endogenous HcyTl and the concentration of ubiquitinated proteins. This suggests that N-homocysteinylation of proteins apparently does not preclude but rather promotes their decomposition. PMID:24051443

  14. Transcriptional regulation of methionine synthase by homocysteine and choline in Aspergillus nidulans.

    PubMed Central

    Kacprzak, Magdalena M; Lewandowska, Irmina; Matthews, Rowena G; Paszewski, Andrzej

    2003-01-01

    Roles played by homocysteine and choline in the regulation of MS (methionine synthase) have been examined in fungi. The Aspergillus nidulans metH gene encoding MS was cloned and characterized. Its transcription was not regulated by methionine, but was enhanced by homocysteine and repressed by choline and betaine. MS activity levels were regulated in a similar way. The repression by betaine was due to its metabolic conversion to choline, which was found to be very efficient in A. nidulans. Betaine and choline supplementation stimulated growth of leaky metH mutants apparently by decreasing the demand for methyl groups and thus saving methionine and S -adenosylmethionine. We have also found that homocysteine stimulates transcription of MS-encoding genes in Saccharomyces cerevisiae and Schizosaccharomyces pombe. PMID:12954077

  15. Influence of fibrinogen and haematocrit on erythrocyte sedimentation kinetics.

    PubMed

    Holley, L; Woodland, N; Hung, W T; Cordatos, K; Reuben, A

    1999-01-01

    This study investigates the influence of haematocrit, fibrinogen concentration and fibrinogen availability (amount of fibrinogen per red blood cell) on erythrocyte sedimentation. The Westergren technique was applied to blood samples from 36 subjects and to their blood manipulated to haematocrits of 10, 20, 30 and 40%. Readings were taken every 10 minutes for 300 minutes. Previous studies indicate that erythrocyte sedimentation occurs in three phases. In this study, we show that haematocrit has little influence on either the rate of fall of particles in the first phase (m1) or the duration of the first phase. This is also true for fibrinogen availability and for fibrinogen concentration at low haematocrits. At high haematocrits m1 increases with fibrinogen concentration. The rate of fall of rouleaux during phase 2 (m2) and ESR60 both decrease exponentially with haematocrit and increase linearly with fibrinogen concentration. While m2 is more closely correlated to fibrinogen availability than to fibrinogen concentration or to haematocrit, this is not the case for ESR60. Thus haematocrit, fibrinogen concentration and fibrinogen availability are more important to the velocity of sedimentation in the second phase than to the sedimenting velocity during phase 1 or to the duration of phase 1. PMID:10690265

  16. Homocysteine provokes leukocyte-endothelium interaction by downregulation of nitric oxide.

    PubMed

    Pruefer, D; Scalia, R; Lefer, A M

    1999-12-01

    Recent evidence indicates that chronic hyperhomocysteinemia, which is found in from 9 to 15% of the general population, is an independent risk factor for the development of atherosclerosis. We sought to elucidate the mechanism by which exposure of the vascular wall to high levels of homocysteine initiates this inflammatory reaction. We examined the acute effect of homocysteine on endothelial dysfunction in isolated rat arteries and on microcirculatory leukocyte-endothelium interaction in vivo. Intravital microscopy of rat mesenteric venules was performed by superfusing the mesentery with increasing concentrations of homocysteine (1-5 mmol/l). There was a significant concentration- and time-dependent increase in leukocyte rolling, adherence, and extravasation compared with control rats superfused with Krebs-Henseleit solution (p < 0.01). Moreover, immunohistochemical staining demonstrated significantly increased P-selectin and intercellular adhesion molecule-1 (ICAM-1) expression on intestinal venules after homocysteine superfusion. In contrast, mesenteric superfusion with the nitric oxide donor 4-hydroxymethyl-furazan-3-carboxylic acid oxide (CAS1609, 1 micromol/l) significantly attenuated homocysteine-induced leukocyte rolling, adherence, and transmigration to control levels (p < 0.01). CAS1609 also attenuated both P-selectin and ICAM-1 expression on mesenteric venules and decreased CD18 expression on isolated leukocytes. Superior mesenteric arteries incubated with 5 mmol/l homocysteine developed significant (p < 0.01) endothelial dysfunction (i.e., impaired relaxation to endothelium-dependent dilators). Acute hyperhomocysteinemia induces endothelial dysfunction, characterized by a loss of endothelium-derived nitric oxide, leading to an inflammatory state. This state results in increased leukocyte rolling, adherence, and transmigration by upregulation of cell adhesion molecules. Our data suggest that hyperhomocysteinemia inhibits the important homeostatic role of

  17. A Multi-Ethnic Meta-Analysis of Genome-Wide Association Studies in Over 100,000 Subjects Identifies 23 Fibrinogen-Associated Loci but no Strong Evidence of a Causal Association between Circulating Fibrinogen and Cardiovascular Disease

    PubMed Central

    Sabater-Lleal, Maria; Huang, Jie; Chasman, Daniel; Naitza, Silvia; Dehghan, Abbas; Johnson, Andrew D; Teumer, Alexander; Reiner, Alex P; Folkersen, Lasse; Basu, Saonli; Rudnicka, Alicja R; Trompet, Stella; Mälarstig, Anders; Baumert, Jens; Bis, Joshua C.; Guo, Xiuqing; Hottenga, Jouke J; Shin, So-Youn; Lopez, Lorna M; Lahti, Jari; Tanaka, Toshiko; Yanek, Lisa R; Oudot-Mellakh, Tiphaine; Wilson, James F; Navarro, Pau; Huffman, Jennifer E; Zemunik, Tatijana; Redline, Susan; Mehra, Reena; Pulanic, Drazen; Rudan, Igor; Wright, Alan F; Kolcic, Ivana; Polasek, Ozren; Wild, Sarah H; Campbell, Harry; Curb, J David; Wallace, Robert; Liu, Simin; Eaton, Charles B.; Becker, Diane M.; Becker, Lewis C.; Bandinelli, Stefania; Räikkönen, Katri; Widen, Elisabeth; Palotie, Aarno; Fornage, Myriam; Green, David; Gross, Myron; Davies, Gail; Harris, Sarah E; Liewald, David C; Starr, John M; Williams, Frances M.K.; Grant, P.J.; Spector, Timothy D.; Strawbridge, Rona J; Silveira, Angela; Sennblad, Bengt; Rivadeneira, Fernando; Uitterlinden, Andre G; Franco, Oscar H; Hofman, Albert; van Dongen, Jenny; Willemsen, G; Boomsma, Dorret I; Yao, Jie; Jenny, Nancy Swords; Haritunians, Talin; McKnight, Barbara; Lumley, Thomas; Taylor, Kent D; Rotter, Jerome I; Psaty, Bruce M; Peters, Annette; Gieger, Christian; Illig, Thomas; Grotevendt, Anne; Homuth, Georg; Völzke, Henry; Kocher, Thomas; Goel, Anuj; Franzosi, Maria Grazia; Seedorf, Udo; Clarke, Robert; Steri, Maristella; Tarasov, Kirill V; Sanna, Serena; Schlessinger, David; Stott, David J; Sattar, Naveed; Buckley, Brendan M; Rumley, Ann; Lowe, Gordon D; McArdle, Wendy L; Chen, Ming-Huei; Tofler, Geoffrey H; Song, Jaejoon; Boerwinkle, Eric; Folsom, Aaron R.; Rose, Lynda M.; Franco-Cereceda, Anders; Teichert, Martina; Ikram, M Arfan; Mosley, Thomas H; Bevan, Steve; Dichgans, Martin; Rothwell, Peter M.; Sudlow, Cathie L M; Hopewell, Jemma C.; Chambers, John C.; Saleheen, Danish; Kooner, Jaspal S.; Danesh, John; Nelson, Christopher P; Erdmann, Jeanette; Reilly, Muredach P.; Kathiresan, Sekar; Schunkert, Heribert; Morange, Pierre-Emmanuel; Ferrucci, Luigi; Eriksson, Johan G; Jacobs, David; Deary, Ian J; Soranzo, Nicole; Witteman, Jacqueline CM; de Geus, Eco JC; Tracy, Russell P.; Hayward, Caroline; Koenig, Wolfgang; Cucca, Francesco; Jukema, J Wouter; Eriksson, Per; Seshadri, Sudha; Markus, Hugh S.; Watkins, Hugh; Samani, Nilesh J; Wallaschofski, Henri; Smith, Nicholas L.; Tregouet, David; Ridker, Paul M.; Tang, Weihong; Strachan, David P.; Hamsten, Anders; O’Donnell, Christopher J.

    2013-01-01

    Background Estimates of the heritability of plasma fibrinogen concentration, an established predictor of cardiovascular disease (CVD), range from 34 to 50%. Genetic variants so far identified by genome-wide association (GWA) studies only explain a small proportion (< 2%) of its variation. Methods and Results We conducted a meta-analysis of 28 GWA studies, including more than 90,000 subjects of European ancestry, the first GWA meta-analysis of fibrinogen levels in 7 African Americans studies totaling 8,289 samples, and a GWA study in Hispanic-Americans totaling 1,366 samples. Evaluation for association of SNPs with clinical outcomes included a total of 40,695 cases and 85,582 controls for coronary artery disease (CAD), 4,752 cases and 24,030 controls for stroke, and 3,208 cases and 46,167 controls for venous thromboembolism (VTE). Overall, we identified 24 genome-wide significant (P<5×10−8) independent signals in 23 loci, including 15 novel associations, together accounting for 3.7% of plasma fibrinogen variation. Gene-set enrichment analysis highlighted key roles in fibrinogen regulation for the three structural fibrinogen genes and pathways related to inflammation, adipocytokines and thyrotrophin-releasing hormone signaling. Whereas lead SNPs in a few loci were significantly associated with CAD, the combined effect of all 24 fibrinogen-associated lead SNPs was not significant for CAD, stroke or VTE. Conclusion We identify 23 robustly associated fibrinogen loci, 15 of which are new. Clinical outcome analysis of these loci does not support a causal relationship between circulating levels of fibrinogen and CAD, stroke or VTE. PMID:23969696

  18. Plasma Fibrinogen as a Biomarker for Mortality and Hospitalized Exacerbations in People with COPD

    PubMed Central

    Mannino, David M; Tal-Singer, Ruth; Lomas, David A.; Vestbo, Jorgen; Graham Barr, R.; Tetzlaff, Kay; Lowings, Michael; Rennard, Stephen I.; Snyder, Jeffrey; Goldman, Mitchell; Martin, Ubaldo J.; Merrill, Deborah; Martin, Amber L.; Simeone, Jason C.; Fahrbach, Kyle; Murphy, Brian; Leidy, Nancy; Miller, Bruce

    2014-01-01

    Background In 2010 the COPD Foundation established the COPD Biomarkers Qualification Consortium (CBQC) as a partnership between the Foundation, the Food and Drug Administration (FDA), and the pharmaceutical industry to pool publicly-funded and industry data to develop innovative tools to facilitate the development and approval of new therapies for COPD. We present data from the initial project seeking regulatory qualification of fibrinogen as a biomarker for the stratification of COPD patients into clinical trials. Methods This analysis pooled data from 4 publicly-funded studies and 1 industry study into a common database resulting in 6376 individuals with spirometric evidence of COPD. We used a threshold of 350 mg/dL to determine high vs. low fibrinogen, and determined the subsequent risk of hospitalizations from exacerbations and death using Cox proportional hazards models. Results High fibrinogen levels at baseline were present in 2853 (44.7%) of individuals with COPD. High fibrinogen was associated with an increased risk of hospitalized COPD exacerbations within 12 months (hazard ratio [HR]: 1.64; 95% confidence interval [CI]: 1.39–1.93) among participants in the Atherosclerosis Risk in Communities Study (ARIC), the Cardiovascular Health Study (CHS), and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. High fibrinogen was associated with an increased risk of death within 36 months (HR: 1.94; 95% CI: 1.62–2.31) among all participants. Conclusions Fibrinogen levels ≥ 350 mg/dL identify COPD individuals at an increased risk of exacerbations and death and could be a useful biomarker for enriching clinical trials in the COPD population. PMID:25685850

  19. Sensitive Immunoassays of Nitrated Fibrinogen in Human Biofluids

    SciTech Connect

    Tang, Zhiwen; Wu, Hong; Du, Dan; Wang, Jun; Wang, Hua; Qian, Weijun; Bigelow, Diana J.; Pounds, Joel G.; Smith, Richard D.; Lin, Yuehe

    2010-05-05

    Three new sandwich immunoassays for detection of nitrated biomarker have been established with potential applications in biomedical studies and clinical practice. In this study, nitrated human fibrinogen, a potential oxidative stress biomarker for several pathologies, was chosen as the target. To improve the sensitivity and overcome the interference caused by the complexity of human biofluids, we developed three sandwich strategies using various combinations of primary antibody and secondary antibody. All three strategies demonstrated high sensitivity and selectivity towards nitrated forms of fibrinogen in buffer, but their performances were dramatically reduced when tested with human plasma and serum samples. Systematically optimizations were carried out to investigate the effects of numerous factors, including sampling, coating, blocking, and immunoreactions. Our final optimization results indicate that two of these strategies retain sufficient sensitivity and selectivity for use as assays in human physiological samples. Specifically, detection limits reached the pM level and the linear response ranges were up to nM level with a correlation coefficient > 0.99. To our best knowledge, this is the first example of using an electrochemical immunoassay for a nitrated biomarker in a physiological fluid. This novel approach provides a rapid, sensitive, selective, cost efficient and robust bioassay for detection of oxidative stress in pathology and for clinical applications. Moreover, the sandwich strategies developed in this paper can be readily used to establish effective methods targeting other nitration biomarkers.

  20. Dietary homocysteine promotes atherosclerosis in apoE-deficient mice by inducing scavenger receptors expression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Elevated plasma homocysteine (Hcy) levels have been recognized as an independent risk factor for cardiovascular and cerebrovascular diseases. However, the causative mechanisms have not been delineated. Scavenger receptors such as scavenger receptor-AI/II (SR-A), CD36, and lectin-like oxidized LDL ...

  1. HOMOCYSTEINE INDUCED ATHEROSCLEROSIS DOES NOT DEPEND ON PROINFLAMMATORY CYTOKINES AND CHEMOKINES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Elevated plasma homocysteine (Hcy) levels are recognized as risk factors for cardio- and cerebrovascular diseases. ApoE mice fed with Hcy have increased cholesterol and aortic lesions, but underlying mechanisms need to be delineated. Hcy forms protein adducts and triggers immune activation. In ApoE...

  2. Copper deficiency decreases plasma homocysteine in rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The purpose of this study was to determine the effects of copper deficiency on key aspects of homocysteine metabolism that involve methionine recycling and transsulfuration. Male weanling Sprague-Dawley rats were fed AIN-93-G-based diets containing <1 or approximately 6 mg Cu/kg. After 6 wk (experim...

  3. Public health significance of elevated homocysteine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Homocysteine is a sulfur amino acid whose metabolism stands at the intersection of two pathways: remethylation, which requires folic acid and vitamin B12 coenzymes; and transsulfuration, which requires pyridoxal-5'-phosphate, the vitamin B6 coenzyme. Data from a number of laboratories suggest that m...

  4. Functional evaluation of an inherited abnormal fibrinogen: fibrinogen “Baltimore”

    PubMed Central

    Beck, Eugene A.; Shainoff, John R.; Vogel, Alfred; Jackson, Dudley P.

    1971-01-01

    The rate of clotting and the rate of development and degree of turbidity after addition of thrombin to plasma or purified fibrinogen from a patient with fibrinogen Baltimore was delayed when compared with normal, especially in the presence of low concentrations of thrombin. Optimal coagulation and development of translucent, rather than opaque, clots occurred at a lower pH with the abnormal fibrinogen than with normal. Development of turbidity during clotting of the abnormal plasma or fibrinogen was less than normal at each pH tested, but was maximal in both at approximately pH 6.4. The physical quality of clots formed from fibrinogen Baltimore was abnormal, as demonstrated by a decreased amplitude on thromboelastography. The morphologic appearance of fibrin strands formed from fibrinogen Baltimore by thrombin at pH 7.4 was abnormal when examined by phase contrast or electron microscopy, but those formed by thrombin at pH 6.4 or by thrombin and calcium chloride were similar to, though less compact, than normal fibrin. The periodicity of fibrin formed from fibrinogen Baltimore was similar to normal and was 231-233 Å. A study of the release of the fibrinopeptides from the patient's fibrinogen and its chromatographic subfractions verified the existence of both a normally behaving and a defective form of fibrinogen in the patient's plasma. The defective form differed from normal in three functionally different ways: (a) the rate of release of fibrinopeptides A and AP was slower than normal; (b) no visible clot formation accompanied either partial or complete release of the fibrinopeptides from the defective form in 0.3 M NaCl at pH 7.4; and (c) the defective component possessed a high proportion of phosphorylated, relative to nonphosphorylated, fibrinopeptide A, while the coagulable component contained very little of the phosphorylated peptide (AP). The high phosphate content of the defective component did not appear to be the cause of the abnormality, but may be the

  5. Antiadhesive effect of fibrinogen: a safeguard for thrombus stability

    PubMed Central

    Lishko, Valeryi K.; Burke, Timothy; Ugarova, Tatiana

    2007-01-01

    The recruitment of phagocytic leukocytes to sites of vessel wall injury plays an important role in thrombus dissolution by proteases elaborated on their adhesion. However, leukocyte adhesion to the fibrin clot can be detrimental at the early stages of wound healing when hemostatic plug integrity is critical for preventing blood loss. Adhesion of circulating leukocytes to the insoluble fibrin(ogen) matrix is mediated by integrins and occurs in the presence of a high concentration of plasma fibrinogen. In this study, the possibility that soluble fibrinogen could protect fibrin from excessive adhesion of leukocytes was examined. Fibrinogen was a potent inhibitor of adhesion of U937 monocytoid cells and neutrophils to fibrin gel and immobilized fibrin(ogen). An investigation of the mechanism by which soluble fibrinogen exerts its influence on leukocyte adhesion indicated that it did not block integrins but rather associated with the fibrin(ogen) substrate. Consequently, leukocytes that engage fibrinogen molecules loosely bound to the surface of fibrin(ogen) matrix are not able to consolidate their grip on the substrate; subsequently, cells detach. This conclusion is based on the evidence obtained in adhesion studies using various cells and performed under static and flow conditions. These findings reveal a new role of fibrinogen in integrin-mediated leukocyte adhesion and suggest that this mechanism may protect the thrombus from premature dissolution. PMID:16849640

  6. Different effects of cabergoline and bromocriptine on metabolic and cardiovascular risk factors in patients with elevated prolactin levels.

    PubMed

    Krysiak, Robert; Okopien, Bogusław

    2015-03-01

    Hyperprolactinaemia is suggested to be associated with metabolic and hormonal complications. No previous study has compared the effect of different dopamine agonists on plasma lipids, carbohydrate metabolism markers and cardiovascular risk factors in patients with elevated prolactin levels. The study included eight bromocriptine-resistant women with prolactinoma (group 1) and twelve matched women with hyperprolactinaemia unrelated to prolactinoma (group 2). Group 1 was then treated with cabergoline, while group 2 with bromocriptine. Plasma lipids, glucose homeostasis markers and plasma levels of prolactin, insulin-like growth factor-1 (IGF-1) and cardiovascular risk factors were assessed before and after 6 months of therapy. Both treatments normalized plasma prolactin levels. Cabergoline reduced triglycerides, 2-hr post-challenge plasma glucose, the homeostatic model assessment of insulin resistance (HOMA-IR), and circulating levels of IGF-1, free fatty acids (FFA), uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine and fibrinogen, as well as increased HDL cholesterol and 25-hydroxyvitamin D. With the exception of a reduction in HOMA-IR, bromocriptine treatment produced no significant effect on the investigated biomarkers. Cabergoline was superior to bromocriptine in affecting 2-hr post-challenge plasma glucose levels, HOMA-IR, as well as circulating levels of IGF-1, FFA, uric acid, hsCRP, homocysteine, fibrinogen and 25-hydroxyvitamin D. Our results may suggest that cabergoline is superior to bromocriptine when it comes to affecting atherogenic dyslipidaemia, insulin sensitivity and circulating levels of cardiovascular risk factors in hyperprolactinaemic patients. These findings seem to support previous observations that cabergoline may be a better treatment for patients with elevated prolactin levels than bromocriptine. PMID:25123447

  7. The fibrinogen γA/γ’ isoform does not promote acute arterial thrombosis in mice

    PubMed Central

    Walton, Bethany L; Getz, Todd M; Bergmeier, Wolfgang; Lin, Feng-Chang; de Willige, Shirley Uitte; Wolberg, Alisa S

    2014-01-01

    Background Elevated plasma fibrinogen associates with arterial thrombosis in humans and promotes thrombosis in mice by increasing fibrin formation and thrombus fibrin content. Fibrinogen is composed of six polypeptide chains: (Aα, Bβ, and γ)2. Alternative splicing of the γ chain leads to a dominant form (γA/γA) and a minor species (γA/γ’). Epidemiologic studies have detected elevated γA/γ’ fibrinogen in patients with arterial thrombosis, suggesting this isoform promotes thrombosis. However, in vitro data show that γA/γ’ is anticoagulant due to its ability to sequester thrombin, and suggest its expression is upregulated in response to inflammatory processes. Objective To determine whether γA/γ’ fibrinogen is prothrombotic in vivo. Methods We separated γA/γA and γA/γ’ fibrinogen from human plasma-purified fibrinogen and determined effects on in vitro plasma clot formation, and in vivo thrombus formation and circulating thrombin-antithrombin complexes in mice. Results and Conclusions Both γA/γA and γA/γ’ fibrinogen were cleaved by murine and human thrombin and were incorporated into murine and human clots. When γA/γA or γA/γ’ was spiked into plasma, γA/γA increased the fibrin formation rate to a greater extent than γA/γ’. In mice, compared to controls, γA/γA infusion shortened the time to carotid artery occlusion, whereas γA/γ’ infusion did not. Additionally, γA/γ’ infusion led to lower levels of plasma thrombin-antithrombin complexes following arterial injury, whereas γA/γA infusion did not. These data suggest that γA/γ’ binds thrombin in vivo, and decreases prothrombotic activity. Together, these findings indicate that elevated levels of γA/γA fibrinogen promote arterial thrombosis in vivo, whereas γA/γ’ does not. PMID:24916154

  8. A Community Based Study of the Relationship Between Homocysteine and Some of the Life Style Factors

    PubMed Central

    Ghose, M.; Borah, N. C.; Choudhury, N.

    2010-01-01

    Till date no community based data on plasma homocysteine is available in North Eastern Region. Hence, the present study was conducted to analyze and correlate the plasma homocysteine level with some life style factors like diet, alcohol intake, smoking habit and body weight, in a cross-section of population. 12 h fasting samples of 970 apparently healthy, Assamese population of both genders in the age group of 35–86 years, mostly from the urban area of Assam were tested for plasma total homocysteine level over a period of 3 years. Out of 970 volunteers, hyperhomocysteinemia was detected in 533 (55%) individuals with a mean value of 18.41 μmol/l. Of that hyperhomocysteinemia, 89.1% were in the range of moderately high and rest 10.9% were intermediate high. Another finding was that males had a tendency towards greater value (mean = 20.36 μmol/l) than females (mean = 16.37 μmol/l). It was observed that the relationship of homocysteine levels to gender and some of the life style factors were also significant. PMID:21731201

  9. Plasma fibrinogen is associated with cognitive decline and risk for dementia in patients with mild cognitive impairment.

    PubMed

    Xu, G; Zhang, H; Zhang, S; Fan, X; Liu, X

    2008-07-01

    This study was aimed to investigate the relationship between plasma fibrinogen level and risk for cognitive decline and dementia in patients with mild cognitive impairment (MCI). Elderly patients with suspected cognitive impairment were screened and evaluated periodically. One hundred and eighty-five patients who met the criteria for MCI were enrolled. Blood coagulation functions and plasma fibrinogen levels were measured at baseline. Hyperfibrinogenaemia was defined as plasma fibrinogen > or =3.0 g/l. Global cognitive function was assessed serially with Mini-Mental State Examination (MMSE). The enrolled patients were followed for 2 years to observe if dementia was developed. There were 185 patients diagnosed as MCI, of which 17 (9.2%) deceased, 15 (8.1%) lost to follow-up, and 68 (36.8%) developed dementia during follow-up. Mean of MMSE score of the enrolled patients declined significantly during follow-up (22.0 +/- 3.0 vs. 18.1 +/- 5.8, p < 0.001). Patients with hyperfibrinogenaemia at baseline had greater MMSE decrement during follow-up than patients with normal fibrinogen level (-5.4 +/- 5.4 vs. -3.5 +/- 4.5, p < 0.05). Linear regression indicated that plasma fibrinogen level was associated with cognitive decline (R = 0.17, p < 0.05). Patients with hyperfibrinogenaemia had an increased risk for dementia and vascular dementia compared with patients with normal level of plasma fibrinogen (log rank test, p < 0.05). There was a trend that hyperfibrinogenaemia also increased risk for dementia of Alzheimer's type (p = 0.061). It can be concluded that plasma fibrinogen level may be associated with cognitive decline, and hyperfibrinogenaemia may increase risk for dementia in patients with MCI. PMID:17916180

  10. Fibrinogen is degraded and internalized during incubation with neutrophils, and fibrinogen products localize to electron lucent vesicles.

    PubMed Central

    Kirsch, Richard; Jaffer, Mohamed A; Woodburne, Vivienne E; Sewell, Trevor; Kelly, Sharon L; Kirsch, Ralph E; Shephard, Enid G

    2002-01-01

    A biologically relevant relationship exists between neutrophils and coagulation processes. Several studies have focused on the ability of neutrophil proteases (both intracellular and membrane-associated) to degrade fibrinogen. The present study investigates the events following the interaction of activated neutrophils with soluble fibrinogen. During incubation of PMA-stimulated neutrophils with fibrinogen at 37 degrees C, fibrinogenolysis occurred, and degraded fibrinogen became associated with the neutrophil. Immunoelectron microscopy identified these fibrinogen products to be located within electron lucent vesicles, and not on the surface of the cell, suggesting that they are internalized. Although a specific interaction between fibrinogen and the neutrophil membrane might assist uptake, in the presence of physiological concentrations of fibrinogen, internalization occurred largely via a non-specific pinocytic process. Studies at low temperature revealed that both intact and degraded forms of fibrinogen can associate with neutrophils. The fibrinogen products detected intracellularly in experiments performed at 37 degrees C might represent uptake of degraded as well as intact forms of fibrinogen, the latter being rapidly degraded intracellularly. This route of fibrinogenolysis contributes minimally to the overall extent of the degradation process, the majority occurring extracellularly. Neutrophils thus possess a proteolytic mechanism for preventing accumulation of surface ligand, perhaps allowing them to evade the immunomodulatory effects of such ligands during inflammation. PMID:12023883