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Wu YH, Lee YP, Chang JYF, Wang YP, Chiang CP, Sun A. High frequencies of vitamin B12 and folic acid deficiencies and hyperhomocysteinemia in Taiwanese male patients with oral submucous fibrosis. J Dent Sci 2023; 18:407-413. [PMID: 36643223 PMCID: PMC9831841 DOI: 10.1016/j.jds.2022.10.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Accepted: 10/21/2022] [Indexed: 11/09/2022] Open
Abstract
Background /purpose: Oral submucous fibrosis (OSF) is a betel quid chewing-caused oral mucosal disease with progressive collagen deposition. This study evaluated whether Taiwanese male OSF patients had high frequencies of vitamin B12 and folic acid deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody (GPCA) positivity. Materials and methods The blood hemoglobin (Hb), serum iron, vitamin B12, folic acid, homocysteine, and GPCA concentrations in 62 male OSF patients were measured and compared with the corresponding data in 124 age-matched male healthy control subjects. Results We found that 5 (8.1%), 12 (19.4%), 32 (51.6%), 31 (50.0%), 22 (35.5%), and 6 (9.7%) of the 62 male OSF patients had Hb (<13 g/dL), iron (≤70 μg/dL), vitamin B12 (≤450 pg/mL), and folic acid (≤6 ng/mL) deficiencies, hyperhomocysteinemia (>12 μM), and serum GPCA positivity, respectively. Furthermore, OSF patients had significantly higher frequencies of Hb (P = 0.006), vitamin B12 (P < 0.001), and folic acid (P < 0.001) deficiencies, hyperhomocysteinemia (P < 0.001), and serum GPCA positivity (P = 0.030) than 124 healthy control subjects. Of the 22 OSF patients with hyperhomocysteinemia, 4 had vitamin B12 deficiency only, 7 had folic acid deficiency only, and 11 had both vitamin B12 and folic acid deficiencies. Conclusion We conclude that Taiwanese male OSF patients have high frequencies of vitamin B12 and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity. The hyperhomocysteinemia in our OSF patients is predominantly due to deficiencies of either vitamin B12 or folic acid or both.
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Affiliation(s)
- Yu-Hsueh Wu
- Department of Stomatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan,Institute of Oral Medicine, School of Dentistry, National Cheng Kung University, Tainan, Taiwan
| | - Yi-Pang Lee
- Department of Dentistry, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Julia Yu-Fong Chang
- Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan,Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan,Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan
| | - Yi-Ping Wang
- Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan,Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan,Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan
| | - Chun-Pin Chiang
- Department of Dentistry, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan,Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan,Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan,Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan,Corresponding author. Department of Dentistry, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 707, Section 3, Chung-Yang Road, Hualien 970, Taiwan.
| | - Andy Sun
- Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan,Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan,Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan,Corresponding author. Department of Dentistry, National Taiwan University Hospital, No. 1, Chang-Te Street, Taipei 10048, Taiwan.
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Nieraad H, Pannwitz N, de Bruin N, Geisslinger G, Till U. Hyperhomocysteinemia: Metabolic Role and Animal Studies with a Focus on Cognitive Performance and Decline-A Review. Biomolecules 2021; 11:1546. [PMID: 34680179 PMCID: PMC8533891 DOI: 10.3390/biom11101546] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 10/05/2021] [Accepted: 10/09/2021] [Indexed: 12/18/2022] Open
Abstract
Disturbances in the one-carbon metabolism are often indicated by altered levels of the endogenous amino acid homocysteine (HCys), which is additionally discussed to causally contribute to diverse pathologies. In the first part of the present review, we profoundly and critically discuss the metabolic role and pathomechanisms of HCys, as well as its potential impact on different human disorders. The use of adequate animal models can aid in unravelling the complex pathological processes underlying the role of hyperhomocysteinemia (HHCys). Therefore, in the second part, we systematically searched PubMed/Medline for animal studies regarding HHCys and focused on the potential impact on cognitive performance and decline. The majority of reviewed studies reported a significant effect of HHCys on the investigated behavioral outcomes. Despite of persistent controversial discussions about equivocal findings, especially in clinical studies, the present evaluation of preclinical evidence indicates a causal link between HHCys and cognition-related- especially dementia-like disorders, and points out the further urge for large-scale, well-designed clinical studies in order to elucidate the normalization of HCys levels as a potential preventative or therapeutic approach in human pathologies.
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Affiliation(s)
- Hendrik Nieraad
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany; (N.P.); (N.d.B.); (G.G.)
| | - Nina Pannwitz
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany; (N.P.); (N.d.B.); (G.G.)
| | - Natasja de Bruin
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany; (N.P.); (N.d.B.); (G.G.)
| | - Gerd Geisslinger
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany; (N.P.); (N.d.B.); (G.G.)
- Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
| | - Uwe Till
- Former Institute of Pathobiochemistry, Friedrich-Schiller-University Jena, Nonnenplan 2, 07743 Jena, Germany;
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Chiang ML, Chiang CP, Sun A. Anemia, hematinic deficiencies, and gastric parietal cell antibody positivity in burning mouth syndrome patients with or without hyperhomocysteinemia. J Dent Sci 2020; 15:214-221. [PMID: 32595904 PMCID: PMC7305457 DOI: 10.1016/j.jds.2020.04.013] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Revised: 04/29/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND/PURPOSE Our previous study found that 170 of 884 burning mouth syndrome (BMS) patients have hyperhomocysteinemia. This study assessed whether these 170 BMS patients with hyperhomocysteinemia had significantly higher frequencies of anemia, hematinic deficiencies, and serum gastric parietal cell antibody (GPCA) positivity than 714 BMS patients without hyperhomocysteinemia or 442 healthy control subjects. MATERIALS AND METHODS The blood hemoglobin (Hb) and serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels in 170 BMS patients with hyperhomocysteinemia, 714 BMS patients without hyperhomocysteinemia, and 442 healthy control subjects were measured and compared. RESULTS We found that 170 BMS patients with hyperhomocysteinemia had significantly higher frequencies of macrocytosis, blood Hb and serum iron, vitamin B12, and folic acid deficiencies, and serum GPCA positivity than 442 healthy control subjects (all P-values < 0.001) or 714 BMS patients without hyperhomocysteinemia (all P-values < 0.05). Anemia was found in 77 of 170 BMS patients with hyperhomocysteinemia and in 98 of 714 BMS patients without hyperhomocysteinemia. Normocytic anemia (47 cases) and pernicious anemia (15 cases) were the two most common types of anemia in 170 BMS patients with hyperhomocysteinemia. Moreover, normocytic anemia (48 cases), iron deficiency anemia (21 cases), and thalassemia trait-induced anemia (21 cases) were the three most common types of anemia in 714 BMS patients without hyperhomocysteinemia. CONCLUSION BMS patients with hyperhomocysteinemia had significantly higher frequencies of macrocytosis, anemia, serum iron, vitamin B12, and folic acid deficiencies, and serum GPCA positivity than healthy control subjects or BMS patients without hyperhomocysteinemia.
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Affiliation(s)
- Meng-Ling Chiang
- Department of Pediatric Dentistry, Chang Gung Memorial Hospital, Taipei, Taiwan
- Department of Oral Pathology and Oral Diagnosis, Chang Gung Memorial Hospital, Taipei, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chun-Pin Chiang
- Department of Dentistry, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
- Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan
- Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan
- Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan
| | - Andy Sun
- Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan
- Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan
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Wang Y, Jin Y, Wang Y, Li L, Liao Y, Zhang Y, Yu D. The effect of folic acid in patients with cardiovascular disease: A systematic review and meta-analysis. Medicine (Baltimore) 2019; 98:e17095. [PMID: 31517834 PMCID: PMC6750242 DOI: 10.1097/md.0000000000017095] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND The effectiveness of folic acid supplementation in stroke risk has been investigated, however, the available results are inconclusive and conflicting. The purpose of this systemic review and meta-analysis was to assess the effect of folic acid in patients with cardiovascular disease (CVD). METHODS By searching the PubMed, EMBASE, and Cochrane library databases, we conducted a meta-analysis to evaluate effect of folic acid supplementation in patients with CVD. All-cause mortality, cardiovascular mortality, the risk of coronary heart disease (CHD) and stroke were summarized; hazard ratios (HR), the relative risk (RR) and its 95% confidence interval (CI) were also calculated. Fixed effects models were used to combine the data. A total of 12 randomized controlled trials, which involved 47,523 participants, met the inclusion criteria in this systematic review and meta-analysis. RESULTS Our meta-analysis showed that cardiovascular patients who received folic acid therapy had significantly decreased risk of stroke (RR = 0.85, 95% CI = 0.77-0.94, Pheterogeneity = .347, I = 10.6%) compared with patients who received control treatment. However, no significant difference in all-cause mortality (HR, 0.97, 95% CI, 0.86-1.10, Pheterogeneity = .315, I = 15.4%), cardiovascular mortality (HR, 0.87, 95% CI, 0.66-1.15, Pheterogeneity = .567, I = 0) and risk of CHD (RR, 1.04, 95% CI, 0.99-1.10, Pheterogeneity = .725, I = 0) were found between the 2 groups. CONCLUSION This meta-analysis suggested that folic acid supplementation significantly reduced the risk of stroke in patients with CVD.
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Affiliation(s)
- Yuan Wang
- Department of Geriatrics, Beijing Geriatric Hospital, Beijing
| | - Yang Jin
- Department of Respiratory, Beijing First Hospital of Integrated Chinese and Western Medicine, Beijing, China
| | - Yao Wang
- Department of Endocrinology, Zhejiang Hospital, Hangzhou
| | - Li Li
- Department of Endocrinology, Zhejiang Hospital, Hangzhou
| | - Yanhong Liao
- Department of Endocrinology, Zhejiang Hospital, Hangzhou
| | - Yun Zhang
- Department of Endocrinology, Zhejiang Hospital, Hangzhou
| | - Dan Yu
- Department of Endocrinology, Zhejiang Hospital, Hangzhou
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Chiang CP, Wu YC, Chang JYF, Wang YP, Wu YH, Sun A. Anemia, hematinic deficiencies, and gastric parietal cell antibody positivity in atrophic glossitis patients with or without hyperhomocysteinemia. J Formos Med Assoc 2019; 119:544-552. [PMID: 31444017 DOI: 10.1016/j.jfma.2019.08.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 08/02/2019] [Indexed: 01/27/2023] Open
Abstract
BACKGROUND/PURPOSE Our previous study found that 127 of 1064 atrophic glossitis (AG) patients have hyperhomocysteinemia. This study assessed whether the AG patients with hyperhomocysteinemia had significantly higher frequencies of anemia, hematinic deficiencies, and serum gastric parietal cell antibody (GPCA) positivity than AG patients without hyperhomocysteinemia or healthy control subjects. METHODS The blood hemoglobin (Hb) and serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels in 127 AG patients with hyperhomocysteinemia, 937 AG patients without hyperhomocysteinemia, and 532 healthy control subjects were measured and compared. RESULTS We found that 127 AG patients with hyperhomocysteinemia had significantly higher frequencies of blood Hb and serum iron, vitamin B12, and folic acid deficiencies and serum GPCA positivity than 532 healthy control subjects (all P-values < 0.001) and significantly higher frequencies of blood Hb and serum vitamin B12 and folic acid deficiencies and serum GPCA positivity than 937 AG patients without hyperhomocysteinemia (all P-values < 0.001). Moreover, 127 AG patients with hyperhomocysteinemia had significantly higher frequencies of macrocytic anemia and significantly lower frequencies of normocytic anemia than 937 AG patients without hyperhomocysteinemia (both P-values < 0.001). Pernicious anemia (22 cases) was found only in AG patients with hyperhomocysteinemia but not in AG patients without hyperhomocysteinemia. CONCLUSION AG patients with hyperhomocysteinemia had significantly higher frequencies of anemia, serum iron, vitamin B12, and folic acid deficiencies, and serum GPCA positivity than healthy control subjects and significantly higher frequencies of anemia, serum vitamin B12 and folic acid deficiencies, and serum GPCA positivity than AG patients without hyperhomocysteinemia.
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Affiliation(s)
- Chun-Pin Chiang
- Department of Dentistry, Far Eastern Memorial Hospital, New Taipei City, Taiwan; Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan
| | - Yang-Che Wu
- School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
| | - Julia Yu-Fong Chang
- Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan
| | - Yi-Ping Wang
- Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan
| | - Yu-Hsueh Wu
- Department of Dentistry, Far Eastern Memorial Hospital, New Taipei City, Taiwan; Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan
| | - Andy Sun
- Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
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Hematinic deficiencies and hyperhomocysteinemia in gastric parietal cell antibody-positive or gastric and thyroid autoantibodies-negative atrophic glossitis patients. J Formos Med Assoc 2019; 118:1114-1121. [PMID: 30979649 DOI: 10.1016/j.jfma.2019.03.017] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2019] [Accepted: 03/26/2019] [Indexed: 01/25/2023] Open
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Hasan T, Arora R, Bansal AK, Bhattacharya R, Sharma GS, Singh LR. Disturbed homocysteine metabolism is associated with cancer. Exp Mol Med 2019; 51:1-13. [PMID: 30804341 PMCID: PMC6389897 DOI: 10.1038/s12276-019-0216-4] [Citation(s) in RCA: 125] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Revised: 11/14/2018] [Accepted: 11/16/2018] [Indexed: 11/30/2022] Open
Abstract
Hyperhomocysteinemia/Homocysteinuria is characterized by an increased level of toxic homocysteine in the plasma. The plasma concentration of homocysteine is 5–15 μmol/L in healthy individuals, while in hyperhomocysteinemic patients, it can be as high as 500 μmol/L. While increased homocysteine levels can cause symptoms such as osteoporosis and eye lens dislocation, high homocysteine levels are most closely associated with cardiovascular complications. Recent advances have shown that increased plasma Hcy is also a fundamental cause of neurodegenerative diseases (including Alzheimer’s disease, Parkinson’s disease, and dementia), diabetes, Down syndrome, and megaloblastic anemia, among others. In recent years, increased plasma homocysteine has also been shown to be closely related to cancer. In this review, we discuss the relation between elevated plasma Hcy levels and cancer, and we conclude that disturbed homocysteine metabolism is associated with cancer. Future clinical perspectives are also discussed. Cancer can be added to the wide range of diseases known to be associated with elevated blood levels of the small amino acid homocysteine. Abnormally high levels of this compound are already known to contribute to conditions including cardiovascular problems, neurodegenerative diseases, neural tube defects, Down’s syndrome, diabetes and megaloblastic anemia. This review, by Laishram R. Singh and colleagues at the University of Delhi, India, concludes that disturbed homocysteine metabolism is associated with many forms of human cancer. The authors discuss a range of genetic, epigenetic and environmental factors that may be involved in the cause and effect relationships between homocysteine metabolism and cancer. It is particularly interesting that low folate (vitamin B9) levels result in high homocysteine levels, and vice versa. Further research may yield insights leading to new forms of cancer treatment and diagnosis.
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Affiliation(s)
- Tauheed Hasan
- Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, 110 007, India
| | - Reetika Arora
- Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, 110 007, India
| | - Aniket Kumar Bansal
- Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, 110 007, India
| | - Reshmee Bhattacharya
- Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, 110 007, India
| | - Gurumayum Suraj Sharma
- Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, 110 007, India
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Jakubowski H. Homocysteine Modification in Protein Structure/Function and Human Disease. Physiol Rev 2019; 99:555-604. [PMID: 30427275 DOI: 10.1152/physrev.00003.2018] [Citation(s) in RCA: 179] [Impact Index Per Article: 29.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Epidemiological studies established that elevated homocysteine, an important intermediate in folate, vitamin B12, and one carbon metabolism, is associated with poor health, including heart and brain diseases. Earlier studies show that patients with severe hyperhomocysteinemia, first identified in the 1960s, exhibit neurological and cardiovascular abnormalities and premature death due to vascular complications. Although homocysteine is considered to be a nonprotein amino acid, studies over the past 2 decades have led to discoveries of protein-related homocysteine metabolism and mechanisms by which homocysteine can become a component of proteins. Homocysteine-containing proteins lose their biological function and acquire cytotoxic, proinflammatory, proatherothrombotic, and proneuropathic properties, which can account for the various disease phenotypes associated with hyperhomocysteinemia. This review describes mechanisms by which hyperhomocysteinemia affects cellular proteostasis, provides a comprehensive account of the biological chemistry of homocysteine-containing proteins, and discusses pathophysiological consequences and clinical implications of their formation.
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Affiliation(s)
- Hieronim Jakubowski
- Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers-New Jersey Medical School, International Center for Public Health , Newark, New Jersey ; and Department of Biochemistry and Biotechnology, Poznań University of Life Sciences , Poznań , Poland
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Chiang CP, Wu YH, Chang JYF, Wang YP, Wu YC, Sun A. Hematinic deficiencies and hyperhomocysteinemia in gastric parietal cell antibody-positive or gastric and thyroid autoantibodies-negative Behcet's disease patients. J Formos Med Assoc 2019; 118:347-353. [PMID: 29898820 DOI: 10.1016/j.jfma.2018.05.017] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2018] [Revised: 05/16/2018] [Accepted: 05/24/2018] [Indexed: 12/31/2022] Open
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Chiang CP, Yu-Fong Chang J, Wang YP, Wu YH, Wu YC, Sun A. Recurrent aphthous stomatitis - Etiology, serum autoantibodies, anemia, hematinic deficiencies, and management. J Formos Med Assoc 2018; 118:1279-1289. [PMID: 30446298 DOI: 10.1016/j.jfma.2018.10.023] [Citation(s) in RCA: 70] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Accepted: 10/31/2018] [Indexed: 12/31/2022] Open
Abstract
Recurrent aphthous stomatitis (RAS) is one of the most common oral mucosal diseases characterized by recurrent and painful ulcerations on the movable or nonkeratinized oral mucosae. Clinically, three types of RAS, namely minor, major, and herpetiform types, can be identified. RAS more commonly affects labial mucosa, buccal mucosa, and tongue. Previous studies indicate that RAS is a multifactorial T cell-mediated immune-dysregulated disease. Factors that modify the immunologic responses in RAS include genetic predisposition, viral and bacterial infections, food allergies, vitamin and microelement deficiencies, systemic diseases, hormonal imbalance, mechanical injuries, and stress. Our previous study found the presence of serum gastric parietal cell antibody, thyroglobulin antibody, and thyroid microsomal antibody in 13.0%, 19.4%, and 19.7% of 355 RAS patients, respectively. We also found anemia, serum iron, vitamin B12, and folic acid deficiencies, and hyperhomocysteinemia in 20.9%, 20.1%, 4.8%, 2.6%, and 7.7% of 273 RAS patients, respectively. Therefore, it is very important to examine the complete blood count, serum autoantibody, hematinic, and homocysteine levels in RAS patients before we start to offer treatments for RAS. Because RAS is an immunologically-mediated disease, topical and systemic corticosteroid therapies are the main treatments of choice for RAS.
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Affiliation(s)
- Chun-Pin Chiang
- Department of Dentistry, Far Eastern Memorial Hospital, New Taipei City, Taiwan; Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan
| | - Julia Yu-Fong Chang
- Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan
| | - Yi-Ping Wang
- Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan
| | - Yu-Hsueh Wu
- Department of Dentistry, Far Eastern Memorial Hospital, New Taipei City, Taiwan; Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan
| | - Yang-Che Wu
- Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Andy Sun
- Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
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Majumder A, Singh M, George AK, Tyagi SC. Restoration of skeletal muscle homeostasis by hydrogen sulfide during hyperhomocysteinemia-mediated oxidative/ER stress condition 1. Can J Physiol Pharmacol 2018; 97:441-456. [PMID: 30422673 DOI: 10.1139/cjpp-2018-0501] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Elevated homocysteine (Hcy), i.e., hyperhomocysteinemia (HHcy), causes skeletal muscle myopathy. Among many cellular and metabolic alterations caused by HHcy, oxidative and endoplasmic reticulum (ER) stress are considered the major ones; however, the precise molecular mechanism(s) in this process is unclear. Nevertheless, there is no treatment option available to treat HHcy-mediated muscle injury. Hydrogen sulfide (H2S) is increasingly recognized as a potent anti-oxidant, anti-apoptotic/necrotic/pyroptotic, and anti-inflammatory compound and also has been shown to improve angiogenesis during ischemic injury. Patients with CBS mutation produce less H2S, making them vulnerable to Hcy-mediated cellular damage. Many studies have reported bidirectional regulation of ER stress in apoptosis through JNK activation and concomitant attenuation of cell proliferation and protein synthesis via PI3K/AKT axis. Whether H2S mitigates these detrimental effects of HHcy on muscle remains unexplored. In this review, we discuss molecular mechanisms of HHcy-mediated oxidative/ER stress responses, apoptosis, angiogenesis, and atrophic changes in skeletal muscle and how H2S can restore skeletal muscle homeostasis during HHcy condition. This review also highlights the molecular mechanisms on how H2S could be developed as a clinically relevant therapeutic option for chronic conditions that are aggravated by HHcy.
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Affiliation(s)
- Avisek Majumder
- a Department of Physiology, University of Louisville School of Medicine, Louisville, KY 40202, USA.,b Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY 40202, USA
| | - Mahavir Singh
- a Department of Physiology, University of Louisville School of Medicine, Louisville, KY 40202, USA.,c Eye and Vision Science Laboratory, University of Louisville School of Medicine, Louisville, KY 40202, USA
| | - Akash K George
- a Department of Physiology, University of Louisville School of Medicine, Louisville, KY 40202, USA.,c Eye and Vision Science Laboratory, University of Louisville School of Medicine, Louisville, KY 40202, USA
| | - Suresh C Tyagi
- a Department of Physiology, University of Louisville School of Medicine, Louisville, KY 40202, USA
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Mattia A, Azarpazhooh MR, Munoz C, Bogiatzi C, Quantz MA, Spence JD. Association of homocysteine and smoking with cerebral microemboli in patients with mechanical heart valves: a transcranial Doppler study. Stroke Vasc Neurol 2018; 2:198-203. [PMID: 29507780 PMCID: PMC5829912 DOI: 10.1136/svn-2017-000117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2017] [Revised: 10/31/2017] [Accepted: 11/01/2017] [Indexed: 11/03/2022] Open
Abstract
Objectives Microembolic signals (MES) on transcranial Doppler (TCD) predict stroke and cognitive decline. Plasma levels of total homocysteine (tHcy), a prothrombotic factor, are higher in patients with microemboli in carotid stenosis and in patients with paradoxical embolism. In this study we assessed the association between the level of tHcy and the number of MES in patients with mechanical heart valves (MHVs). Methods TCD monitoring was performed to detect MES before and after breathing 100% oxygen and repeated every 2-4 weeks up to six times. Results Twenty-five patients with MHVs (mean age: 63.60±10.15 years) participated in this study; 15 were men (66.47±7.25 years) and 10 were women (59.30±12.60 years). In total, there were 126 study visits. In multiple regression, higher tHcy was associated with more MES in both preoxygenation (OR 1.34 (95% CI 1.07 to 1.68, P=0.009)) and postoxygenation (OR 1.40 (95% CI 1.07 to 1.83, P=0.01)) phases. Current smoking and the length of time between the operation and monitoring also correlated with a higher number of MES before and after breathing oxygen, particularly in women. Conclusions Higher tHcy and smoking were associated with a higher MES count in both preoxygenation and postoxygenation phases. Because smoking can be stopped and hyperhomocysteinaemia is treatable, these are clinically important findings.
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Affiliation(s)
- Alicia Mattia
- Stroke Prevention and Atherosclerosis Research Centre, Robarts Research Institute, Western University, London, Ontario, Canada.,Department of Neurology, McMaster University, Hamilton, Ontario, Canada
| | - M Reza Azarpazhooh
- Division of Epidemiology and Biostatistics, Western University, London, Ontario, Canada.,Division of Neurology, Western University, London, Ontario, Canada
| | - Claudio Munoz
- Stroke Prevention and Atherosclerosis Research Centre, Robarts Research Institute, Western University, London, Ontario, Canada
| | - Chrysi Bogiatzi
- Stroke Prevention and Atherosclerosis Research Centre, Robarts Research Institute, Western University, London, Ontario, Canada.,Department of Neurology, McMaster University, Hamilton, Ontario, Canada
| | - Mackenzie A Quantz
- Division of Cardiac Surgery, Western University, London, Ontario, Canada
| | - J David Spence
- Stroke Prevention and Atherosclerosis Research Centre, Robarts Research Institute, Western University, London, Ontario, Canada.,Division of Neurology, Western University, London, Ontario, Canada.,Division of Clinical Pharmacology, Western University, London, Ontario, Canada
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13
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Chiang CP, Yu-Fong Chang J, Wang YP, Wu YH, Lu SY, Sun A. Oral lichen planus - Differential diagnoses, serum autoantibodies, hematinic deficiencies, and management. J Formos Med Assoc 2018; 117:756-765. [PMID: 29472048 DOI: 10.1016/j.jfma.2018.01.021] [Citation(s) in RCA: 114] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2018] [Revised: 01/26/2018] [Accepted: 01/30/2018] [Indexed: 01/06/2023] Open
Abstract
Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease that occurs more frequently in middle-aged and elderly female patients. Previous studies indicate that OLP is a T-cell dysfunction-induced localized autoimmune disease. Clinically, six types of OLP, namely reticular, papular, plaque-like, atrophic/erosive, ulcerative, and bullous types, can be identified. OLP more commonly affects buccal mucosa, tongue, and gingiva. It always has a bilateral and symmetric distribution of the oral lesions. Plaque-like and atrophic/erosive OLP may be misdiagnosed as oral leukoplakia and oral erythroleukoplakia, respectively. Our previous study found serum autoantibodies in 195 (60.9%) of the 320 OLP patients. Specific serum anti-nuclear, anti-smooth muscle, anti-mitochondrial, gastric parietal cell, thyroglobulin, and thyroid microsomal autoantibodies are present in 28.1%, 8.4%, 1.6%, 26.3%, 21.3%, and 24.4% of 320 OLP patients, respectively. Furthermore, we also discovered that 21.9%, 13.6%, 7.1%, 0.3%, and 14.8% of 352 OLP patients have hemoglobin, iron, vitamin B12, and folic acid deficiencies, and abnormally high serum homocysteine level, respectively. Therefore, it is very important to examine the serum autoantibody, hematinic and homocysteine levels in OLP patients before starting the treatments for OLP patients. Because OLP is an immunologically-mediated disease, corticosteroids are the drugs of choice for treatment of OLP.
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Affiliation(s)
- Chun-Pin Chiang
- Department of Dentistry, Far Eastern Memorial Hospital, New Taipei City, Taiwan; Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan
| | - Julia Yu-Fong Chang
- Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan
| | - Yi-Ping Wang
- Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan
| | - Yu-Hsueh Wu
- Department of Dentistry, Far Eastern Memorial Hospital, New Taipei City, Taiwan; Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan
| | - Shin-Yu Lu
- Oral Pathology and Family Dentistry Section, Department of Dentistry, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Andy Sun
- Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
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14
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Lin HP, Wu YH, Wang YP, Wu YC, Chang JYF, Sun A. Anemia and hematinic deficiencies in anti-gastric parietal cell antibody-positive or all autoantibodies-negative recurrent aphthous stomatitis patients. J Formos Med Assoc 2017; 116:99-106. [PMID: 27825815 DOI: 10.1016/j.jfma.2016.10.006] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2016] [Accepted: 10/09/2016] [Indexed: 01/17/2023] Open
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15
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Hematinic deficiencies and anemia statuses in recurrent aphthous stomatitis patients with or without atrophic glossitis. J Formos Med Assoc 2016; 115:1061-1068. [PMID: 27839675 DOI: 10.1016/j.jfma.2016.10.007] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2016] [Revised: 10/08/2016] [Accepted: 10/14/2016] [Indexed: 01/18/2023] Open
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16
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Hematinic deficiencies and anemia statuses in antigastric parietal cell antibody-positive erosive oral lichen planus patients with desquamative gingivitis. J Formos Med Assoc 2016; 115:860-866. [PMID: 27511590 DOI: 10.1016/j.jfma.2016.07.006] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2016] [Accepted: 07/05/2016] [Indexed: 01/02/2023] Open
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17
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Hainsworth AH, Yeo NE, Weekman EM, Wilcock DM. Homocysteine, hyperhomocysteinemia and vascular contributions to cognitive impairment and dementia (VCID). Biochim Biophys Acta Mol Basis Dis 2015; 1862:1008-17. [PMID: 26689889 DOI: 10.1016/j.bbadis.2015.11.015] [Citation(s) in RCA: 80] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2015] [Revised: 11/27/2015] [Accepted: 11/29/2015] [Indexed: 11/29/2022]
Abstract
Homocysteine is produced physiologically in all cells, and is present in plasma of healthy individuals (plasma [HCy]: 3-10μM). While rare genetic mutations (CBS, MTHFR) cause severe hyperhomocysteinemia ([HCy]: 100-200μM), mild-moderate hyperhomocysteinemia ([HCy]: 10-100μM) is common in older people, and is an independent risk factor for stroke and cognitive impairment. As B-vitamin supplementation (B6, B12 and folate) has well-validated homocysteine-lowering efficacy, this may be a readily-modifiable risk factor in vascular contributions to cognitive impairment and dementia (VCID). Here we review the biochemical and cellular actions of HCy related to VCID. Neuronal actions of HCy were at concentrations above the clinically-relevant range. Effects of HCy <100μM were primarily vascular, including myocyte proliferation, vessel wall fibrosis, impaired nitric oxide signalling, superoxide generation and pro-coagulant actions. HCy-lowering clinical trials relevant to VCID are discussed. Extensive clinical and preclinical data support HCy as a mediator for VCID. In our view further trials of combined B-vitamin supplementation are called for, incorporating lessons from previous trials and from recent experimental work. To maximise likelihood of treatment effect, a future trial should: supply a high-dose, combination supplement (B6, B12 and folate); target the at-risk age range; and target cohorts with low baseline B-vitamin status. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.
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Affiliation(s)
- Atticus H Hainsworth
- Cardiovascular and Cell Sciences Research Centre, St Georges University of London, London SW17 0RE, UK.
| | - Natalie E Yeo
- Cardiovascular and Cell Sciences Research Centre, St Georges University of London, London SW17 0RE, UK
| | - Erica M Weekman
- Sanders-Brown Center on Aging, University of Kentucky, Lexington KY 40536, USA
| | - Donna M Wilcock
- Sanders-Brown Center on Aging, University of Kentucky, Lexington KY 40536, USA.
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18
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Hematinic deficiencies and anemia statuses in oral mucosal disease patients with folic acid deficiency. J Formos Med Assoc 2015; 114:806-12. [PMID: 26187724 DOI: 10.1016/j.jfma.2015.06.006] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2015] [Accepted: 06/09/2015] [Indexed: 11/27/2022] Open
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19
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Hematinic deficiencies and pernicious anemia in oral mucosal disease patients with macrocytosis. J Formos Med Assoc 2015; 114:736-41. [PMID: 25935499 DOI: 10.1016/j.jfma.2015.03.015] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2014] [Revised: 02/07/2015] [Accepted: 03/17/2015] [Indexed: 11/20/2022] Open
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20
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Chang JYF, Wang YP, Wu YC, Cheng SJ, Chen HM, Sun A. Blood profile of oral mucosal disease patients with both vitamin B12 and iron deficiencies. J Formos Med Assoc 2015; 114:532-8. [PMID: 25886860 DOI: 10.1016/j.jfma.2015.03.002] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2015] [Revised: 03/10/2015] [Accepted: 03/17/2015] [Indexed: 10/23/2022] Open
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21
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Sun A, Chang JYF, Wang YP, Cheng SJ, Chen HM, Chiang CP. Do all the patients with vitamin B12 deficiency have pernicious anemia? J Oral Pathol Med 2015; 45:23-7. [PMID: 25990467 DOI: 10.1111/jop.12330] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/20/2015] [Indexed: 12/25/2022]
Affiliation(s)
- Andy Sun
- Graduate Institute of Clinical Dentistry; School of Dentistry; National Taiwan University; Taipei Taiwan
- Department of Dentistry; National Taiwan University Hospital; College of Medicine; National Taiwan University; Taipei Taiwan
| | - Julia Y.-F. Chang
- Graduate Institute of Clinical Dentistry; School of Dentistry; National Taiwan University; Taipei Taiwan
- Department of Dentistry; National Taiwan University Hospital; College of Medicine; National Taiwan University; Taipei Taiwan
| | - Yi-Ping Wang
- Graduate Institute of Clinical Dentistry; School of Dentistry; National Taiwan University; Taipei Taiwan
- Department of Dentistry; National Taiwan University Hospital; College of Medicine; National Taiwan University; Taipei Taiwan
| | - Shih-Jung Cheng
- Graduate Institute of Clinical Dentistry; School of Dentistry; National Taiwan University; Taipei Taiwan
- Department of Dentistry; National Taiwan University Hospital; College of Medicine; National Taiwan University; Taipei Taiwan
| | - Hsin-Ming Chen
- Graduate Institute of Clinical Dentistry; School of Dentistry; National Taiwan University; Taipei Taiwan
- Department of Dentistry; National Taiwan University Hospital; College of Medicine; National Taiwan University; Taipei Taiwan
- Graduate Institute of Oral Biology; School of Dentistry; National Taiwan University; Taipei Taiwan
| | - Chun-Pin Chiang
- Graduate Institute of Clinical Dentistry; School of Dentistry; National Taiwan University; Taipei Taiwan
- Department of Dentistry; National Taiwan University Hospital; College of Medicine; National Taiwan University; Taipei Taiwan
- Graduate Institute of Oral Biology; School of Dentistry; National Taiwan University; Taipei Taiwan
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22
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Raut SC, Patil VW, Dalvi SM, Bakhshi GD. Helicobacter pylori gastritis, a presequeale to coronary plaque. Clin Pract 2015; 5:717. [PMID: 25918633 PMCID: PMC4387345 DOI: 10.4081/cp.2015.717] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2014] [Revised: 01/19/2015] [Accepted: 02/02/2015] [Indexed: 12/11/2022] Open
Abstract
Helicobacter pylori are considered the most common human pathogen colonizing gastric mucosa. Gastritis with or without H. pylori infection is associated with increase in levels of homocysteine and high-sensitivity C-reactive protein (hs-CRP) but a more pronounced increase is noted in gastritis with H. pylori infection. Increasing level of homocysteine, due to decreased absorption of vitamin B12 and folic acid, together with increased CRP levels in gastritis with H. pylori infection may be the earliest event in the process of atherosclerosis and plaque formation. Retrospective study conducted at tertiary care hospital in Mumbai by Department of Biochemistry in association with Department of Surgery. Eighty patients who underwent gastroscopy in view of gastritis were subjected to rapid urease test for diagnosis of H. pylori infection. Vitamin B12, folic acid, homocysteine and hs-CRP were analyzed using chemiluminescence immuno assay. Student’s t-test, Pearson’s correlation and linear regression used for statistical analysis. Patients with H. pylori gastritis had significantly lower levels of vitamin B12 (271.6±101.3 vs 390.6±176.7 pg/mL; P=0.0005), as well as higher levels of homocysteine (17.4±7.4 vs 13.8±7.8 µmol/L; P=0.037) and hs-CRP (2.5±2.9 vs 1.2±1.1 mg/L; P=0.017), than in patients without H. pylori gastritis. However, folic acid showed (8.9±3.2 vs 10.0±3.6 ng/mL; P=0.171) no significant difference. Elevated homocysteine and hs-CRP in H. pylori gastritis may independently induce endothelial dysfunction, leading to cardiovascular pathology.
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Affiliation(s)
- Shrikant C Raut
- Department of Biochemistry, Grant Government Medical College and Sir JJ Group of Hospitals , Byculla, Mumbai, India
| | - Vinayak W Patil
- Department of Biochemistry, Grant Government Medical College and Sir JJ Group of Hospitals , Byculla, Mumbai, India
| | - Shubhangi M Dalvi
- Department of Biochemistry, Grant Government Medical College and Sir JJ Group of Hospitals , Byculla, Mumbai, India
| | - Girish D Bakhshi
- Department of Surgery, Grant Government Medical College and Sir JJ Group of Hospitals , Byculla, Mumbai, India
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23
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Chen HM, Wang YP, Chang JYF, Wu YC, Cheng SJ, Sun A. Significant association of deficiencies of hemoglobin, iron, folic acid, and vitamin B12 and high homocysteine level with oral lichen planus. J Formos Med Assoc 2015; 114:124-9. [DOI: 10.1016/j.jfma.2014.10.004] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2014] [Revised: 10/12/2014] [Accepted: 10/15/2014] [Indexed: 10/24/2022] Open
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24
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Sun A, Chen HM, Cheng SJ, Wang YP, Chang JYF, Wu YC, Chiang CP. Significant association of deficiencies of hemoglobin, iron, vitamin B12, and folic acid and high homocysteine level with recurrent aphthous stomatitis. J Oral Pathol Med 2014; 44:300-5. [PMID: 25048341 DOI: 10.1111/jop.12241] [Citation(s) in RCA: 85] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/02/2014] [Indexed: 01/21/2023]
Affiliation(s)
- Andy Sun
- Department of Dentistry; School of Dentistry; National Taiwan University; Taipei Taiwan
- National Taiwan University Hospital; College of Medicine; National Taiwan University; Taipei Taiwan
| | - Hsin-Ming Chen
- Department of Dentistry; School of Dentistry; National Taiwan University; Taipei Taiwan
- National Taiwan University Hospital; College of Medicine; National Taiwan University; Taipei Taiwan
- Graduate Institute of Clinical Dentistry; National Taiwan University; Taipei Taiwan
- Graduate Institute of Oral Biology; School of Dentistry; National Taiwan University; Taipei Taiwan
| | - Shih-Jung Cheng
- Department of Dentistry; School of Dentistry; National Taiwan University; Taipei Taiwan
- National Taiwan University Hospital; College of Medicine; National Taiwan University; Taipei Taiwan
- Graduate Institute of Clinical Dentistry; National Taiwan University; Taipei Taiwan
| | - Yi-Ping Wang
- Department of Dentistry; School of Dentistry; National Taiwan University; Taipei Taiwan
- National Taiwan University Hospital; College of Medicine; National Taiwan University; Taipei Taiwan
- Graduate Institute of Clinical Dentistry; National Taiwan University; Taipei Taiwan
| | - Julia Yu-Fong Chang
- Department of Dentistry; School of Dentistry; National Taiwan University; Taipei Taiwan
- National Taiwan University Hospital; College of Medicine; National Taiwan University; Taipei Taiwan
- Graduate Institute of Clinical Dentistry; National Taiwan University; Taipei Taiwan
| | - Yang-Che Wu
- Department of Dentistry; School of Dentistry; National Taiwan University; Taipei Taiwan
- National Taiwan University Hospital; College of Medicine; National Taiwan University; Taipei Taiwan
- Graduate Institute of Clinical Dentistry; National Taiwan University; Taipei Taiwan
| | - Chun-Pin Chiang
- Department of Dentistry; School of Dentistry; National Taiwan University; Taipei Taiwan
- National Taiwan University Hospital; College of Medicine; National Taiwan University; Taipei Taiwan
- Graduate Institute of Clinical Dentistry; National Taiwan University; Taipei Taiwan
- Graduate Institute of Oral Biology; School of Dentistry; National Taiwan University; Taipei Taiwan
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25
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High plasma homocysteine increases risk of metabolic syndrome in 6 to 8 year old children in rural Nepal. Nutrients 2014; 6:1649-61. [PMID: 24763111 PMCID: PMC4011057 DOI: 10.3390/nu6041649] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2013] [Revised: 03/21/2014] [Accepted: 04/02/2014] [Indexed: 01/18/2023] Open
Abstract
Little attention has been given to the association of plasma homocysteine (Hcy) and metabolic syndrome (MetS) in children. We have evaluated the risk of MetS with plasma Hcy in a cohort of 6 to 8 year old rural Nepalese children, born to mothers who had participated in an antenatal micronutrient supplementation trial. We assessed Hcy in plasma from a random selection of n = 1000 children and determined the relationship of elevated Hcy (>12.0 μmol/L) to MetS (defined as the presence of any three of the following: abdominal adiposity (waist circumference ≥ 85th percentile of the study population), high plasma glucose (≥85th percentile), high systolic or diastolic blood pressure (≥90th percentile of reference population), triglyceride ≥ 1.7 mmol/L and high density lipoprotein < 0.9 mmol/L.) and its components. There was an increased risk of low high-density lipoproteins (HDL), [odds ratios (OR) = 1.77, 95% confidence intervals (CI) = 1.08–2.88; p = 0.020], high blood pressure [OR = 1.60, 95% CI = 1.10–2.46; p = 0.015] and high body mass index (BMI) [OR = 1.98, 95% CI = 1.33–2.96; p = 0.001] with elevated Hcy. We observed an increased risk of MetS (OR = 1.75, 95% CI = 1.06–2.90; p = 0.029) with elevated Hcy in age and gender-adjusted logistic regression models. High plasma Hcy is associated with increased risk of MetS and may have implications for chronic disease later in life.
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Wang YP, Lin HP, Chen HM, Kuo YS, Lang MJ, Sun A. Hemoglobin, iron, and vitamin B12 deficiencies and high blood homocysteine levels in patients with anti-thyroid autoantibodies. J Formos Med Assoc 2014; 113:155-60. [DOI: 10.1016/j.jfma.2012.04.003] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2012] [Accepted: 04/09/2012] [Indexed: 11/26/2022] Open
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Ozuguz P, Karabulut AA, Tulmac M, Kisa U, Kocak M, Gunduz O. Markers of Endothelial Dysfunction and Evaluation of Vascular Reactivity Tests in Behçet Disease. Angiology 2013; 65:937-43. [DOI: 10.1177/0003319713512413] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
We assessed endothelial dysfunction (ED) in patients with Behcet disease (BD; n = 40) and healthy controls (n = 20). Serum lipid, homocysteine, asymmetric dimethylarginine (ADMA) and high-sensitivity C-reactive protein (hsCRP) levels, erythrocyte sedimentation rates (ESRs), and ultrasonographic flow-mediated dilatation (FMD) were measured. Mean hsCRP, ESR, homocysteine, and ADMA were significantly higher in the BD group ( P < .001 for all). Patients with active BD had higher serum levels of hsCRP, homocysteine, and ESR compared with those in remission ( P < .001, P < .001, and P = .005, respectively). Flow-mediated dilatation was significantly lower in patients with BD than in controls ( P = .001). Flow-mediated dilatation correlated negatively with BD duration and serum ADMA levels ( P < .001, r = −.745 and P < .001, r = −.682); a positive correlation was seen between serum ADMA levels and BD duration ( P < .001, r = .552). Only stepwise multivariate regression analysis revealed BD duration to have a significant effect on FMD. Flow-mediated dilatation, in conjunction with markers of inflammation, may evaluate ED in patients with BD.
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Affiliation(s)
- Pinar Ozuguz
- Department of Dermatology, Faculty of Medicine, Kocatepe University, Afyon Turkey
| | - Ayse Anil Karabulut
- Department of Dermatology, Faculty of Medicine, Kirikkale University, Kirikkale, Turkey
| | - Murat Tulmac
- Department of Cardiology, Faculty of Medicine, Kirikkale University, Kirikkale, Turkey
| | - Ucler Kisa
- Department of Biochemistry, Faculty of Medicine, Kirikkale University, Kirikkale, Turkey
| | - Mukadder Kocak
- Department of Dermatology, Faculty of Medicine, Kirikkale University, Kirikkale, Turkey
| | - Ozgur Gunduz
- Department of Dermatology, Faculty of Medicine, Kirikkale University, Kirikkale, Turkey
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28
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Lin HP, Wang YP, Chen HM, Kuo YS, Lang MJ, Sun A. Significant association of hematinic deficiencies and high blood homocysteine levels with burning mouth syndrome. J Formos Med Assoc 2013; 112:319-25. [DOI: 10.1016/j.jfma.2012.02.022] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2012] [Revised: 02/13/2012] [Accepted: 02/17/2012] [Indexed: 10/28/2022] Open
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29
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Sun A, Lin HP, Wang YP, Chen HM, Cheng SJ, Chiang CP. Significant reduction of serum homocysteine level and oral symptoms after different vitamin-supplement treatments in patients with burning mouth syndrome. J Oral Pathol Med 2013; 42:474-9. [DOI: 10.1111/jop.12043] [Citation(s) in RCA: 68] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/04/2012] [Indexed: 11/28/2022]
Affiliation(s)
- Andy Sun
- Graduate Institute of Clinical Dentistry; School of Dentistry, National Taiwan University; Taipei Taiwan
- School of Dentistry; National Taiwan University; Taipei Taiwan
- Department of Dentistry; National Taiwan University Hospital, College of Medicine; National Taiwan University; Taipei Taiwan
| | - Hung-Pin Lin
- Graduate Institute of Clinical Dentistry; School of Dentistry, National Taiwan University; Taipei Taiwan
- School of Dentistry; National Taiwan University; Taipei Taiwan
- Department of Dentistry; National Taiwan University Hospital, College of Medicine; National Taiwan University; Taipei Taiwan
| | - Yi-Ping Wang
- Graduate Institute of Clinical Dentistry; School of Dentistry, National Taiwan University; Taipei Taiwan
- School of Dentistry; National Taiwan University; Taipei Taiwan
- Department of Dentistry; National Taiwan University Hospital, College of Medicine; National Taiwan University; Taipei Taiwan
| | - Hsin-Ming Chen
- School of Dentistry; National Taiwan University; Taipei Taiwan
- Department of Dentistry; National Taiwan University Hospital, College of Medicine; National Taiwan University; Taipei Taiwan
- Graduate Institute of Oral Biology; School of Dentistry, National Taiwan University; Taipei Taiwan
| | - Shih-Jung Cheng
- School of Dentistry; National Taiwan University; Taipei Taiwan
- Department of Dentistry; National Taiwan University Hospital, College of Medicine; National Taiwan University; Taipei Taiwan
| | - Chun-Pin Chiang
- Graduate Institute of Clinical Dentistry; School of Dentistry, National Taiwan University; Taipei Taiwan
- School of Dentistry; National Taiwan University; Taipei Taiwan
- Department of Dentistry; National Taiwan University Hospital, College of Medicine; National Taiwan University; Taipei Taiwan
- Graduate Institute of Oral Biology; School of Dentistry, National Taiwan University; Taipei Taiwan
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30
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Sun A, Wang YP, Lin HP, Chen HM, Cheng SJ, Chiang CP. Significant reduction of homocysteine level with multiple B vitamins in atrophic glossitis patients. Oral Dis 2012; 19:519-24. [DOI: 10.1111/odi.12035] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2012] [Revised: 10/07/2012] [Accepted: 10/12/2012] [Indexed: 11/28/2022]
Affiliation(s)
- A Sun
- Graduate Institute of Clinical Dentistry; National Taiwan University; Taipei Taiwan
- School of Dentistry; National Taiwan University; Taipei Taiwan
- Department of Dentistry; National Taiwan University Hospital; College of Medicine; National Taiwan University; Taipei Taiwan
| | - Y-P Wang
- Graduate Institute of Clinical Dentistry; National Taiwan University; Taipei Taiwan
- School of Dentistry; National Taiwan University; Taipei Taiwan
- Department of Dentistry; National Taiwan University Hospital; College of Medicine; National Taiwan University; Taipei Taiwan
| | - H-P Lin
- Graduate Institute of Clinical Dentistry; National Taiwan University; Taipei Taiwan
- School of Dentistry; National Taiwan University; Taipei Taiwan
- Department of Dentistry; National Taiwan University Hospital; College of Medicine; National Taiwan University; Taipei Taiwan
| | - H-M Chen
- School of Dentistry; National Taiwan University; Taipei Taiwan
- Department of Dentistry; National Taiwan University Hospital; College of Medicine; National Taiwan University; Taipei Taiwan
- Graduate Institute of Oral Biology; School of Dentistry; National Taiwan University; Taipei Taiwan
| | - S-J Cheng
- School of Dentistry; National Taiwan University; Taipei Taiwan
- Department of Dentistry; National Taiwan University Hospital; College of Medicine; National Taiwan University; Taipei Taiwan
| | - C-P Chiang
- Graduate Institute of Clinical Dentistry; National Taiwan University; Taipei Taiwan
- School of Dentistry; National Taiwan University; Taipei Taiwan
- Department of Dentistry; National Taiwan University Hospital; College of Medicine; National Taiwan University; Taipei Taiwan
- Graduate Institute of Oral Biology; School of Dentistry; National Taiwan University; Taipei Taiwan
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Sun A, Wang YP, Lin HP, Chia JS, Chiang CP. Do all the patients with gastric parietal cell antibodies have pernicious anemia? Oral Dis 2012; 19:381-6. [DOI: 10.1111/odi.12014] [Citation(s) in RCA: 62] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2012] [Revised: 07/17/2012] [Accepted: 07/27/2012] [Indexed: 12/01/2022]
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MTHFR C677T polymorphism and its relationship to myocardial infarction in the Eastern Black Sea region of Turkey. Arch Med Res 2012; 42:709-12. [PMID: 22222489 DOI: 10.1016/j.arcmed.2011.12.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2011] [Accepted: 12/12/2011] [Indexed: 11/23/2022]
Abstract
BACKGROUND AND AIMS An association of homozygous MTHFR 677T genotypes with elevated plasma homocysteine level has been documented, but results are still controversial. We aimed to investigate prevalence of the C677T polymorphism in patients with acute myocardial infarction (MI) in the Eastern Black Sea region of Turkey. METHODS We studied genomic DNA of 231 unrelated patients (aged 59 ± 13 years; 175 male, 56 female) with first anterior acute MI and 242 healthy controls (aged 54 ± 19 years; 182 male, 60 female) using real-time polymerase chain reaction kits for the MTHFR C677T mutation. RESULTS Prevalence of MTHFR C677T mutant genotype was 49.1% (CT: 45.8%, TT: 3.3%) in controls and 48.45% (CT: 38.5%, TT: 9.95%) in patients with acute MI. The TT mutation was more frequent in patients with acute MI than in controls (9.95 vs. 3.3%) (OR; 3.23, 95% CI; [1.34-8.05], p = 0.003). CONCLUSIONS The MTHFR gene homozygote TT mutation is a risk factor for patients with MI in the eastern Black Sea Turkish Population.
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Sun A, Lin HP, Wang YP, Chiang CP. Significant association of deficiency of hemoglobin, iron and vitamin B12, high homocysteine level, and gastric parietal cell antibody positivity with atrophic glossitis. J Oral Pathol Med 2011; 41:500-4. [DOI: 10.1111/j.1600-0714.2011.01122.x] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Kolling J, Scherer EB, da Cunha AA, da Cunha MJ, Wyse ATS. Homocysteine induces oxidative-nitrative stress in heart of rats: prevention by folic acid. Cardiovasc Toxicol 2011; 11:67-73. [PMID: 21076891 DOI: 10.1007/s12012-010-9094-7] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Hyperhomocysteinemia is a risk factor for cardiovascular disease, stroke, and thrombosis; however, the mechanisms by which homocysteine triggers these dysfunctions are not fully understood. In the present study, we investigated the effect of chronic hyperhomocysteinemia on some parameters of oxidative stress, namely thiobarbituric acid reactive substances, an index of lipid peroxidation, 2',7'-dichlorofluorescein (H(2)DCF) oxidation, activities of antioxidant enzymes named superoxide dismutase and catalase, as well as nitrite levels in heart of young rats. We also evaluated the effect of folic acid on biochemical alterations elicited by hyperhomocysteinemia. Wistar rats received daily subcutaneous injection of homocysteine (0.3-0.6 μmol/g body weight) and/or folic acid (0.011 μmol/g body weight) from their 6th to the 28th day of life. Controls and treated rats were killed 1 h and/or 12 h after the last injection. Results showed that chronic homocysteine administration increases lipid peroxidation and reactive species production and decreases enzymatic antioxidant defenses and nitrite levels in the heart of young rats killed 1 h, but not 12 h after the last injection of homocysteine. Folic acid concurrent administration prevented homocysteine effects probable by its antioxidant properties. Our data indicate that oxidative stress is elicited by chronic hyperhomocystenemia, a mechanism that may contribute, at least in part, to the cardiovascular alterations characteristic of hyperhomocysteinemic patients. If confirmed in human beings, our results could propose that the supplementation of folic acid can be used as an adjuvant therapy in cardiovascular alterations caused by homocysteine.
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Affiliation(s)
- Janaína Kolling
- Laboratório de Neuroproteção e Doenças Metabólicas, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, CEP, Porto Alegre, RS, Brazil
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Kritz H, Schmid P, Karanikas G, Rodrigues M, Sinzinger H. Detection of early atherosclerotic lesions in the carotid artery: Experimental and preliminary human data. Int J Angiol 2011. [DOI: 10.1007/bf01616229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
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Abstract
AbstractHyperhomocysteinemia represents elevated homocysteine (Hcys) concentrations in blood above the normal range. In humans, the normal range of homocysteine is 5.0–15.9 mM/ml. High levels of homocysteine disturb the normal epithelial functions and correlate with cardiovascular diseases even at slightly increased concentrations. In homocysteine metabolism, vitamins play an important role. The mechanism through which homocysteine triggers these effects is not yet elucidated, but the involvement of reactive species may be the answer. It is not known whether the intra- or extracellular antioxidant system is more affected by elevated homocysteine levels. We studied the effects of hyperhomocysteinemia on the intra- and extracellular antioxidant defense systems in two different types of diet in rats. Type I was food with low folic acid and vitamin B12 content and type II was food with normal amounts of these two vitamins. Hyperhomocysteinemia was experimentally induced by oral administration of methionine 2 mg/kg body weight, single daily dose, for a 15-day period. Plasma concentrations of homocysteine were measured using an HPLC method. In the response of the intracellular antioxidant defense system against hyperhomocysteinemia, we determined the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in red blood cells, using RANDOX kits for manual use. For the extracellular response we determined the plasma total antioxidant status (TAS) also using a RANDOX kit for manual use. Our data show that methionine load induces hyperhomocysteinemia despite normal vitamin supply in rats. SOD activity rose with simultaneous decrease in GPx activity independently of diet; this might suggest that the intracellular defense system was disturbed by the rise in homocysteine level. TAS decrease suggests that the extracellular antioxidant defense was also affected. We assume that hyperhomocysteinemia is directly linked to reactive species generation and the intracellular space seems to be more affected than the extracellular one.
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Koubaa N, Nakbi A, Hammami S, Mehri S, Attia N, Ben Farhat M, Hammami M. Association of the C677T MTHFR Polymorphism With Homocysteine, Ox-LDL Levels, and Thiolactonase Activities in the Severity of Coronary Syndrome. Clin Appl Thromb Hemost 2010; 16:515-21. [DOI: 10.1177/1076029610369798] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Coronary artery diseases (CAD) are influenced by multiple genes of modest effect as the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, related to MTHFR activity and total plasma homocysteine (tHcy) concentration. This study was designed to evaluate tHcy, oxidized low-density lipoprotein (LDL) (ox-LDL), high-sensibility C-reactive protein (Hs CRP) levels, and homocysteine thiolactonase (HTase) activities as new risk factors for CAD and to investigate an association between MTHFR polymorphism tHcy concentrations and coronary syndrome severity. Our results showed significantly higher levels of tHcy and ox-LDL in patients associated with lower HTase activities. These levels increased proportionally to disease severity. Total plasma Hcy levels were negatively correlated to HTase activities in patients where the TT genotype was significantly more frequent. In a multivariate analysis, tHcy level was the only independent factor affecting the coronary syndrome severity. High tHcy levels are associated with coronary syndrome severity and may be explained either by the elevated prevalence of TT genotype or by the diminished HTase activities.
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Affiliation(s)
- Nadia Koubaa
- Laboratory of Biochemistry, UR Human Nutrition and Metabolic Disorders, Faculty of Medicine, Monastir, Tunisia
| | - Amel Nakbi
- Laboratory of Biochemistry, UR Human Nutrition and Metabolic Disorders, Faculty of Medicine, Monastir, Tunisia
| | - Sonia Hammami
- Department of Internal Medicine, CHU F Bourguiba, Monastir, Tunisia
| | - Sounira Mehri
- Laboratory of Biochemistry, UR Human Nutrition and Metabolic Disorders, Faculty of Medicine, Monastir, Tunisia
| | - Nabil Attia
- Laboratory of Biochemistry, UR Human Nutrition and Metabolic Disorders, Faculty of Medicine, Monastir, Tunisia
| | | | - Mohamed Hammami
- Laboratory of Biochemistry, UR Human Nutrition and Metabolic Disorders, Faculty of Medicine, Monastir, Tunisia,
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38
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Abdulle AM, Pathan JY, Moussa N, Gariballa S. Association between homocysteine and endothelial dysfunction markers in stroke disease. Nutr Neurosci 2010; 13:2-6. [PMID: 20132648 DOI: 10.1179/147683010x12611460763562] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
Abstract
BACKGROUND Evidence shows that there is an increase in concentrations of markers of endothelial dysfunction immediately following acute ischaemic stroke. Several studies suggest that endothelial dysfunction may be partly caused by oxidation related to the effects of raised total plasma homocysteine. OBJECTIVE The aim of this study was to measure changes in total plasma homocysteine and markers of endothelial dysfunction in stroke disease within a known period of time post infarct. SUBJECTS AND METHODS We studied 40 acute ischaemic stroke patients (mean age +/- SD, 50.2 +/- 9.5 years) and 42 hospitalised non-stroke patients (mean age, 44.3 +/- 14.9 years). Fasting venous blood was obtained within 24 h, 3 days and 7 days after the stroke onset and hospitalisation for non-stroke patients for measurements of total plasma homocysteine, markers of endothelial dysfunction including intracellular adhesion molecule (i-CAM), vascular cell adhesion molecule-1 (v-CAM) and leukocyte adhesion molecule-1 (E-selectin) and C-reactive proteins (CRPs). RESULTS We found no significant differences in baseline total plasma homocysteine, E-selectin, v-CAM, vitamin B(12), and folate concentrations between ischaemic stroke patients and non-stroke controls. i-CAM concentrations were significantly higher and CRPs non-significantly lower at baseline in stroke patients compared with controls. Although all endothelial dysfunction markers increased significantly during the study period, the rise in E-selectin levels was less than that seen in i-CAM, and v-CAM. Total plasma homocysteine concentrations showed positive correlations with creatinine (r = 0.537; P < 0.02), and inverse correlations with both vitamin B(12) (r = -0.560; P < 0.001) and folate (r = -0.469; P < 0.002); however, there were no significant correlations between total plasma homocysteine or B-vitamins and markers of endothelial dysfunction in ischaemic stroke patients or controls. CONCLUSIONS We found evidence of an increase in markers of endothelial dysfunction following acute ischaemic stroke but this had no relationship with total plasma homocysteine concentrations.
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Affiliation(s)
- Abdishakur M Abdulle
- Department of Internal Medicine, Faculty of Medicine and Health Sciences, United Arab Emirates (UAE) University, Al-Ain, United Arab Emirates
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Kartal Durmazlar SP, Akgul A, Eskioglu F. Hyperhomocysteinemia in patients with stasis dermatitis and ulcer: A novel finding with important therapeutic implications. J DERMATOL TREAT 2009; 20:336-9. [DOI: 10.3109/09546630902775069] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Sucker C, Kurschat C, Farokhzad F, Hetzel GR, Grabensee B, Maruhn-Debowski B, Loncar R, Scharf RE, Zotz RB. The TT genotype of the C677T polymorphism in the methylentetrahydrofolate reductase as a risk factor in thrombotic microangiopathies: results from a pilot study. Clin Appl Thromb Hemost 2009; 15:283-8. [PMID: 19448163 DOI: 10.1177/1076029607308865] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
In this study, we assessed the potential role of the TT genotype of the gene of the methylenetetrahydrofolate reductase for the manifestation of thrombotic microangiopathies, enrolling 40 affected patients (mean age [+/- standard deviation] 35 +/- 11 years). As a result, the methylenetetrahydrofolate reductase 677TT genotype was more prevalent in patients with thrombotic microangiopathies compared with controls (adjusted odds ratio = 2.58, 95% confidence interval = 1.2-5.7, P = .018), particularly in those suffering from the hemolytic uremic syndrome. A hemolytic more severe clinical course of thrombotic microangiopathies in carriers of the methylenetetrahydrofolate reductase 677TT genotype was not observed. In summary, our findings suggest a significant influence of the methylenetetrahydrofolate reductase genotype on the manifestation of thrombotic microangiopathies. The 677 TT genotype of this polymorphism appears to be a risk factor for manifestation of these rare thrombotic disorders, possibly explained by endothelial activation and increased oxidative stress.
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Affiliation(s)
- Christoph Sucker
- Department of Hemostasis and Transfusion Medicine, Heinrich Heine University Medical Center, Dusseldorf, Germany.
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41
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Koubaa N, Nakbi A, Hammami S, Attia N, Mehri S, Ben Hamda K, Ben Farhat M, Miled A, Hammami M. Association of homocysteine thiolactonase activity and PON1 polymorphisms with the severity of acute coronary syndrome. Clin Biochem 2009; 42:771-6. [PMID: 19269283 DOI: 10.1016/j.clinbiochem.2009.02.017] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2008] [Revised: 02/12/2009] [Accepted: 02/15/2009] [Indexed: 10/21/2022]
Abstract
INTRODUCTION Excess of total homocysteine (tHcy) and decrease of thiolactonase activities (HTase) have been proposed as risk factors for coronary artery diseases (CAD). OBJECTIVES We evaluated the relationship of tHcy and HTase with paraoxonase 1 (PON1) gene polymorphism according to CAD severity. DESIGN AND METHODS 118 healthy volunteers and 91 CAD patients were compared. RESULTS Serum levels of tHcy and oxidized LDL (ox-LDL) increased significantly by 26% and 48% in CAD patients and were associated with significantly lower levels of HDL cholesterol (p=0.02) and 42% of decrease in HTase activities (p<0.05). In these patients the HTase activity was negatively associated with tHcy and Hs CRP levels (r=-0.622, p=0.00 and r=-0.355, p=0.007 respectively) but positively associated with apoB and triglyceride levels (r=0.35, p=0.042 and r=0.308, p=0.003 respectively). HTase activity decreased inversely to the number of affected vessels and according to PON1 polymorphism. PON1 Q192R RR and PON1 L55M MM genotypes were associated with higher HTase activities. Only PON1 L55M (MM) genotype frequency was significantly higher in CAD patients than in controls (P<0.05), while its frequency was similar between the two subgroups according to CAD severity. In a multivariate analysis, tHcy levels were the only independent factor affecting the severity of cardiovascular disease (p=0.029). CONCLUSIONS High tHcy levels are associated with the severity of cardiovascular disease and may be partly explained by the diminished HTase activities in these patients.
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Affiliation(s)
- Nadia Koubaa
- Faculty of Medicine, Laboratory of Biochemistry, UR Human Nutrition and Metabolic Disorders, Avicene st 5019 Monastir, Tunisia
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42
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Zhou J, Austin RC. Contributions of hyperhomocysteinemia to atherosclerosis: Causal relationship and potential mechanisms. Biofactors 2009; 35:120-9. [PMID: 19449439 DOI: 10.1002/biof.17] [Citation(s) in RCA: 99] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Hyperhomocysteinemia (HHcy) is considered an independent risk factor for cardiovascular disease, including ischemic heart disease, stroke, and peripheral vascular disease. Mutations in the enzymes and/or nutritional deficiencies in B vitamins required for homocysteine metabolism can induce HHcy. Studies using genetic- or diet-induced animal models of HHcy have demonstrated a causal relationship between HHcy and accelerated atherosclerosis. Oxidative stress and activation of proinflammatory factors have been proposed to explain the atherogenic effects of HHcy. Recently, HHcy-induced endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) have been found to play a role in HHcy-induced atherogenesis. This review will focus on the cellular mechanisms of HHcy in atherosclerosis from both in vivo and in vitro studies. The contributions of ER stress and the UPR in atherogenesis will be emphasized. Results from recent clinical trials assessing the cardiovascular risk of lowering total plasma homocysteine levels and new findings examining the atherogenic role of HHcy in wild-type C57BL/6J mice will also be discussed. (c) 2009 International Union of Biochemistry and Molecular Biology, Inc.
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Affiliation(s)
- Ji Zhou
- Department of Medicine, McMaster University, Hamilton, ON, Canada
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Homocysteine may involve in the pathogenesis of Behcet's disease by inducing inflammation. Mediators Inflamm 2009; 2008:407972. [PMID: 19197380 PMCID: PMC2633607 DOI: 10.1155/2008/407972] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2008] [Revised: 11/02/2008] [Accepted: 11/17/2008] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVE Our aim was to evaluate the significance of homocysteine (Hcy) in Behcet's disease (BD) and the association of elevated Hcy levels associated with the indices of inflammation in BD. METHODS Untreated 70 patients with BD and 33 healthy individuals were included into the study. Hcy, tumor necrosis alpha (TNF-alpha), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were evaluated with respect to activity and specific individual clinical manifestations of the disease. RESULTS Hcy levels were found significantly elevated in active BD when compared to inactive BD and healthy controls. Hcy levels were found to have high correlation with the number of active clinical manifestations increased. A significant positive correlation was found between serum Hcy and TNF-alpha levels, CRP, and ESR. Hcy was found to be the best predictor of TNF-alpha among other parameters. CONCLUSION Hcy may involve in the pathogenesis of BD by inducing inflammation.
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Lijfering WM, Coppens M, Veeger NJ, Middeldorp S, Hamulyák K, Prins MH, Büller HR, van der Meer J. Hyperhomocysteinemia is not a risk factor for venous and arterial thrombosis, and is associated with elevated factor VIII levels. Thromb Res 2008; 123:244-50. [DOI: 10.1016/j.thromres.2007.12.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2007] [Revised: 12/06/2007] [Accepted: 12/18/2007] [Indexed: 12/20/2022]
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45
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Held C, Sumner G, Sheridan P, McQueen M, Smith S, Dagenais G, Yusuf S, Lonn E. Correlations between plasma homocysteine and folate concentrations and carotid atherosclerosis in high-risk individuals: baseline data from the Homocysteine and Atherosclerosis Reduction Trial (HART). Vasc Med 2008; 13:245-53. [DOI: 10.1177/1358863x08092102] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Abstract Homocysteine has been proposed as a risk factor for atherosclerosis. The association between plasma total homocysteine (tHcy) concentration and carotid atherosclerosis has not been thoroughly studied in high-risk populations with vascular disease. For this study, carotid atherosclerosis was assessed by measurements of carotid intima-media thickness (IMT) and plaque calcification in 923 patients with vascular disease or diabetes. Associations with tHcy and plasma folate concentrations were examined. The mean and single maximum carotid IMT were 1.27 ± 0.34 mm and 2.41 ± 0.83 mm, respectively. The mean segment plaque calcification score was 27.8%. tHcy correlated with mean ( r = 0.13; p < 0.001) and single maximum ( r = 0.12; p < 0.001) carotid IMT. There was a progressive increase in mean and single maximum carotid IMT across quartiles of tHcy ( p < 0.0001 for trend). These associations were no longer significant after adjusting for other CV risk factors. A trend towards an inverse association between plasma folate and mean max carotid IMT was found in both univariate and multivariable analyses. However, the plaque calcification score increased across quartiles of tHcy ( p < 0.01) and decreased across quartiles of plasma folate concentrations ( p < 0.05) after multiple adjustments. In conclusion, in high-risk individuals, tHcy and low folate concentrations were only weakly associated with carotid IMT. In contrast, we found an independent association with the plaque calcification score, a measure of more advanced atherosclerosis. The effect of tHcy lowering on carotid atherosclerosis and stroke prevention warrants further investigation.
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Affiliation(s)
- Claes Held
- Uppsala Clinical Research Centre and Department of Cardiology, Uppsala University Hospital, Uppsala, Sweden; Population Health Research Institute, Hamilton General Hospital, McMaster Clinic, Hamilton, Ontario, Canada
| | - Glen Sumner
- Population Health Research Institute, Hamilton General Hospital, McMaster Clinic, Hamilton, Ontario, Canada
| | - Patrick Sheridan
- Population Health Research Institute, Hamilton General Hospital, McMaster Clinic, Hamilton, Ontario, Canada
| | - Mathew McQueen
- Population Health Research Institute, Hamilton General Hospital, McMaster Clinic, Hamilton, Ontario, Canada
| | - Sandra Smith
- Population Health Research Institute, Hamilton General Hospital, McMaster Clinic, Hamilton, Ontario, Canada
| | - Gilles Dagenais
- Laval University and Hospital Heart and Lung Institute, Quebec, Quebec, Canada
| | - Salim Yusuf
- Population Health Research Institute, Hamilton General Hospital, McMaster Clinic, Hamilton, Ontario, Canada
| | - Eva Lonn
- Population Health Research Institute, Hamilton General Hospital, McMaster Clinic, Hamilton, Ontario, Canada
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Abstract
Morphological and immunocytochemical studies have elucidated the complex processes involved in atherogenesis. The notion of plaque instability has emerged from this work and underscored the importance of inflammation in determining clinical complications associated with atherosclerosis, such as acute coronary syndrome. Cells of the immune system have been detected within atherosclerotic lesions and auto-antibodies directed against modified LDL and heat-shock proteins have been identified in the blood of individuals with atherosclerosis. The use of risk 'engines', e.g. the Framingham coronary risk score, has facilitated the identification of individuals at high risk, but the constituent classical risk factors used in these algorithms do not adequately differentiate individuals at moderate risk. As age is a major component of the equations used in these algorithms they are not particularly useful in young adults, and their applicability to non-Caucasian populations has been questioned. Biomarkers of early disease and plaque instability have therefore both been sought. Although some of these markers have been shown individually to be associated with a significant hazard ratio, no substantial improvement in discrimination has been demonstrated when they are incorporated into a risk 'engine'. The latter has generally been assessed by receiver operator characteristic curve analysis, although this approach has been criticised. Other modalities, including imaging and functional assessments of vascular function, are now being developed for clinical use.
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Trabetti E. Homocysteine,MTHFR gene polymorphisms, and cardio-cerebrovascular risk. J Appl Genet 2008; 49:267-82. [DOI: 10.1007/bf03195624] [Citation(s) in RCA: 85] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Ross R, Bowen-Pope DF, Raines EW. Platelet-derived growth factor: its potential roles in wound healing, atherosclerosis, neoplasia, and growth and development. CIBA FOUNDATION SYMPOSIUM 2008; 116:98-112. [PMID: 3000710 DOI: 10.1002/9780470720974.ch7] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Platelet-derived growth factor (PDGF) has been found to be derived not only from platelets that have been induced to release their contents, but also from a number of transformed cells (including cells transformed by both DNA and RNA viruses, spontaneous transformation, and cells from various human tumours), from activated macrophages, from embryonic rat aortic smooth muscle cells, and from rat aortic smooth muscle cells derived from experimentally induced intimal proliferative lesions. The studies discussed demonstrate the potential role of platelets and macrophages in atherosclerosis and in wound repair, and indicate the ability of anti-PDGF IgG to inhibit proliferative responses in vitro. With the demonstration that the transforming protein derived from the oncogene from the simian sarcoma virus is highly homologous with PDGF, it was possible to show that a number of transformed cells secrete PDGF and show markedly decreased binding of PDGF. The same is true for embryonic rat aortic smooth muscle cells and for cells from experimentally induced proliferative lesions in the rat carotid artery. All these findings point to the role of PDGF in the formation of these lesions and can be correlated with the capacity of the cells noted above, as well as injured endothelial cells, to secrete PDGF or PDGF-like molecules. The biological significance of these observations is discussed and a model for atherogenesis is proposed.
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49
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Jamaluddin MS, Yang X, Wang H. Hyperhomocysteinemia, DNA methylation and vascular disease. Clin Chem Lab Med 2008; 45:1660-6. [PMID: 18067449 DOI: 10.1515/cclm.2007.350] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
Hyperhomocysteinemia (HHcy) has been established as a potent independent risk factor for cardiovascular disease (CVD) and the underlying mechanism is largely unknown. We were the first to propose that hypomethylation is the key biochemical mechanism by which homocysteine (Hcy) inhibits endothelial cell (EC) growth. We reported that clinically relevant concentrations of Hcy (10-50 micromol/L) exerts highly selective inhibitory effects on cyclin A transcription and EC growth through a hypomethylation related mechanism, which blocks cell cycle progression and endothelium regeneration. Recently, we demonstrated that Hcy reduces DNA methyltransferase 1 (DNMT1) activity and demethylates cyclin A promoter leading to cyclin A chromatin remodeling. We found that adenovirus-transduced DNMT1 gene expression reverses the inhibitory effect of Hcy on cyclin A expression and EC growth inhibition. We hypothesize that DNA hypomethylation is a key biochemical mechanism responsible for Hcy-induced cyclin A suppression and growth inhibition in EC and contributes to CVD.
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Affiliation(s)
- Md S Jamaluddin
- Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140, USA
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50
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Fernandez F, Colson NJ, Griffiths LR. Pharmacogenetics of migraine: genetic variants and their potential role in migraine therapy. Pharmacogenomics 2008; 8:609-22. [PMID: 17559350 DOI: 10.2217/14622416.8.6.609] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Migraine is a paroxysmal neurological disorder affecting up to 6% of males and 18% of females in the general population, and has been demonstrated to have a strong, but complex, genetic component. Genetic investigation of migraine provides hope that new targets for medications and individual specific therapy will be developed. The identification of polymorphisms or genetic biomarkers for disease susceptibility and treatment should aid in providing a better understanding of migraine pathology and, consequently, more appropriate and efficient treatment for migraineurs. In this review, we will discuss results investigating genetic biomarkers for migraine and their potential role in future therapy planning.
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Affiliation(s)
- F Fernandez
- Genomics Research Centre, School of Medical Science, Griffith University, Gold Coast, Queensland, 9726 Australia
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