S. Tournis - Academia.edu (original) (raw)
Papers by S. Tournis
Annals of the Rheumatic Diseases
BackgroundMyostatin is expressed in skeletal muscles and exerts a negative feedback in myogenesis... more BackgroundMyostatin is expressed in skeletal muscles and exerts a negative feedback in myogenesis. Chronic inflammation has been associated with increased serum myostatin levels (Baig MH, Front Physiol. 2022).ObjectivesThe calculation of serum myostatin levels in patients with rheumatoid arthritis (RA) and association with disease parameters.MethodsA cross-sectional study of 30 post-menopausal women with RA, classified according to the 1987 ACR criteria. Blood samples were collected and inflammatory markers (erythrocyte sedimentation rate, ESR, and C-reactive protein, CRP) were calculated. Serum myostatin levels were assessed using the ELISA method. Seropositive disease was defined according to a positive history of antibodies against rheumatoid factor (RF) or against citrullinated proteins (ACPA). Disease activity and patient functionality were expressed by using the DAS28 (ESR) and the HAQ-DI scores respectively.ResultsIn our cohort, 47% (n=14) had seropositive disease. Mean value...
Clinical Cardiology, 2000
Annals of the New York Academy of Sciences, 2006
American journal of hypertension, 2009
The mechanisms by which menopause may influence the systemic subclinical atherosclerosis are unex... more The mechanisms by which menopause may influence the systemic subclinical atherosclerosis are unexplained. The aim of this cross-sectional study was to evaluate the associations between early menopause, established cardiovascular (c-v) risk factors, metabolic parameters (insulin secretion and sensitivity, plasma adiponectin), and carotid intima-media thickness (IMT) in healthy women. In 74 menopausal women (mean age = 51 +/- 3 years, mean duration of menopause = 2.9 +/- 1.2 years) and in 74 nonmenopausal women comparable for age and body mass index (BMI), common carotid artery (CCA) luminal diameter, and IMT in different carotid segments were measured in digitized ultrasound images. Insulin sensitivity and secretion were assessed using the euglycemic hyperinsulinemic clamp technique and oral glucose tolerance test (OGTT). Insulin secretion was reconstructed by mathematical modeling. CCA diameter (5.55 +/- 0.46 vs. 5.21+/- 0.51 mm, P < 0.001), CCA IMT (608 +/- 78 vs. 576 +/- 74 mic...
Calcified Tissue International, 2006
The mitochondrial theory of ageing proposes that the lifetime accumulation of mutations in mitoch... more The mitochondrial theory of ageing proposes that the lifetime accumulation of mutations in mitochondrial DNA leads to the progressive loss of cellular viability, via some combination of bioenergy insufficiency, enhanced production of reactive oxygen species (ROS) and apoptosis. It has also been suggested that this could entrain a vicious cycle of ROS damage and mutagenesis. Mitochondrial DNA mutations do indeed accumulate with age, albeit to a very low level. Debate rages as to whether this could have any physiological significance, even if mitotic segregation is substantial. However, in stem cells, where mtDNA copy number may be relatively low, and the number of rounds of cell division high, segregation of mutants could result in eventual loss of precisely those cells that provide the body with the repair capacity needed to stave off functional decline and eventual death. Until recently, our ability to evaluate the role of mtDNA mutations in ageing was based purely on correlative data. However, the introduction of germline mutations into the nuclear genome which affect the mtDNA replication apparatus has allowed us to manipulate the mitochondrial genome experimentally, and provide a more formal test of the hypothesis. By crippling the proofreading exonuclease activity of the mitochondrial DNA polymerase (DNA polymerase gamma, POLG) we were able to induce the progressive accumulation of mtDNA point mutations to high levels. In cultured human cells this results in a selective crisis, once a critical mutation load is crossed, manifesting after some 60-90 cell divisions. When such a mutator was introduced into the mouse, a similar accumulation of mtDNA mutations in all tissues was found, associated with a phenotype of premature ageing, including many features reminiscent of human ageing: loss of mineral bone density and kyphosis, megalocytic anemia, loss of muscle mass, adipose tissue and hair, loss of fertility in both sexes and early death. The accumulation of mtDNA mutations in Polg mutator mice appears to be approximately linear with age, refuting the idea of a mutagenic vicious cycle, and instead consistent with the idea of a selective crisis brought about progressively by a constant rate of mutagenesis and the effects of mitotic segregation. A recent analysis of mtDNA from hair roots of young and aged humans supports this interpretation.
European Geriatric Medicine, 2014
Diabetes Care, 2007
We sought to compare the effects of combined calcium and vitamin D supplementation versus placebo... more We sought to compare the effects of combined calcium and vitamin D supplementation versus placebo on blood glucose and markers of inflammation in nondiabetic adults aged &amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =65 years. A total of 314 Caucasian adults without diabetes received either 500 mg calcium citrate and 700 IU vitamin D(3) or placebos daily for 3 years in a double-blind, randomized, controlled trial designed for bone-related outcomes. In a post hoc analysis, fasting plasma glucose (FPG), insulin sensitivity (estimated by homeostasis model assessment of insulin resistance [HOMA-IR]), plasma C-reactive protein, and interleukin-6, were measured at baseline and 3 years. The effects of combined calcium-vitamin D supplementation on 3-year change in FPG depended on baseline FPG (P = 0.02 for interaction). Therefore, we conducted analyses separately in participants with normal fasting glucose (NFG) (FPG &amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;5.6 mmol/l, n = 222) and impaired fasting glucose (IFG) (FPG 5.6-6.9 mmol/l, n = 92) at baseline. Among participants with IFG at baseline, those who took combined calcium-vitamin D supplements had a lower rise in FPG at 3 years compared with those on placebo (0.02 mmol/l [0.4 mg/dl] vs. 0.34 mmol/l [6.1 mg/dl], respectively, P = 0.042) and a lower increase in HOMA-IR (0.05 vs. 0.91, P = 0.031). In the NFG subgroup, there was no difference in the change in FPG or HOMA-IR between the two treatment arms. There were no differences in C-reactive protein or interleukin-6 between the two treatment arms in either subgroup. In healthy, older adults with IFG, supplementation with calcium and vitamin D may attenuate increases in glycemia and insulin resistance that occur over time. However, our findings should be considered hypothesis generating and need to be confirmed in randomized trials specifically designed for the outcomes of interest.
Clinical Cardiology, 1999
Backgroundand hypothesis: Although it is well established that diabetes mellitus (DM) induces mor... more Backgroundand hypothesis: Although it is well established that diabetes mellitus (DM) induces more severe coronary artery disease (CAD), it is not known whether it contributes to the development of coronary collateral circulation. The present study examines coronary Collateral Circulation in diabetic and nondiabetic patients with angiographically verified CAD.
Endocrinology, Diabetes & Metabolism Case Reports, 2015
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused primarily by benign mes... more Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused primarily by benign mesenchymal tumors. These tumors typically follow a benign clinical course and local recurrence occurs in !5% of cases. We investigated a 49-year-old man with a recurrent mesenchymal phosphaturic tumor showing no signs of malignancy. The patient suffered from chronic muscle weakness, myalgia and cramps. His medical record included the diagnosis of oncogenic osteomalacia, for which he was submitted to tumor resection in the left leg three times before. Laboratory examination showed hypophosphatemia, hyperphosphaturia and an elevated serum FGF23 level. A radical surgical approach (amputation) was advised, however, complete biochemical and clinical remission was not reached. Molecular analysis of the tumor cells demonstrated overexpression of growth factor receptors implicated in tumor angiogenesis and metastatic potential (platelet derived growth factor type A (PDGFRA), PDGFRB and vascular endothelial growth factor receptor) together with increased expression of FGF23, x-linked-phosphate-regulating endopeptidase and KLOTHO. TIO is usually associated with benign phosphauturic tumors and, when identified, resection of the tumor leads to complete remission in the majority of cases. The underlying pathophysiology of recurrences in these tumors is not known. This is the first report showing increased expression of growth factor receptors in a locally aggressive but histopathologically benign phosphaturic mesenchymal tumor.
Metabolism, 2014
Increased fracture risk, traditionally associated with type 1 diabetes, has lately been of great ... more Increased fracture risk, traditionally associated with type 1 diabetes, has lately been of great concern in patients with type 2 diabetes. A variable increase in fracture risk has been reported, ranging from 20% to 3-fold, depending on skeletal site, diabetes duration and study design. Longer disease duration, the presence of diabetic complications, inadequate glycemic control, insulin use and increased risk for falls are all reported to increase fracture risk. Patients with type 2 diabetes display a unique skeletal phenotype with either normal or more frequently increased, bone mineral density and impaired structural and geometric properties. Recently, alterations in bone material properties seem to be the predominant defect leading to increased bone fragility. Accumulation of advanced glycation end-products and changes in collagen cross-linking along with suppression of bone turnover seem to be significant factors impairing bone strength. FRAX score has been reported to underestimate fracture risk and lumbar spine BMD is inadequate in predicting vertebral fractures. Anti-diabetic medications, apart from thiazolidinediones, appear to be safe for the skeleton, although more data are needed. Optimal strategies to reduce skeletal fragility in type 2 diabetic patients are yet to be determined.
Journal of long-term effects of medical implants, 2011
Aseptic loosening after total hip arthroplasty is related to bone loss of the operated leg. The a... more Aseptic loosening after total hip arthroplasty is related to bone loss of the operated leg. The aim of the present study was to investigate the effect of aseptic loosening on volumetric bone mineral density (vBMD) and bone geometry in the operated leg, in postmenopausal women with a loosened cemented femoral implant using peripheral quantitative computed tomography (pQCT). We matched 12 postmenopausal women with aseptic loosening of cemented femoral implant, with 12 women without aseptic loosening (control group) according to age, BMI, and years from operation. All patients underwent pQCT of both tibias, DXA of the lumbar spine, and determination of biochemical markers of bone turnover. pQCT values in the control group as well as the nonoperated legs between groups had no significant difference. In the aseptic loosening group, there was significant reduction of cortical vBMD (cort vBMD) at 14% and 38% sites (cortical site), cortical thickness at 38% site, and of polar stress strengt...
Hormones (Athens, Greece)
Anorexia nervosa is a serious psychiatric disorder accompanied by high morbidity and mortality. I... more Anorexia nervosa is a serious psychiatric disorder accompanied by high morbidity and mortality. It is characterized by emaciation due to self-starvation and displays a unique hormonal profile. Alterations in gonadal axis, growth hormone resistance with low insulin-like growth factor I levels, hypercortisolemia and low triiodothyronine levels are almost universally present and constitute an adaptive response to malnutrition. Bone metabolism is likewise affected resulting in low bone mineral density, reduced bone accrual and increased fracture risk. Skeletal deficits often persist even after recovery from the disease with serious implications for future skeletal health. The pathogenetic mechanisms underlying bone disease are quite complicated and treatment is a particularly challenging task.
The Journal of Clinical Endocrinology & Metabolism, 2006
Annals of the Rheumatic Diseases
BackgroundMyostatin is expressed in skeletal muscles and exerts a negative feedback in myogenesis... more BackgroundMyostatin is expressed in skeletal muscles and exerts a negative feedback in myogenesis. Chronic inflammation has been associated with increased serum myostatin levels (Baig MH, Front Physiol. 2022).ObjectivesThe calculation of serum myostatin levels in patients with rheumatoid arthritis (RA) and association with disease parameters.MethodsA cross-sectional study of 30 post-menopausal women with RA, classified according to the 1987 ACR criteria. Blood samples were collected and inflammatory markers (erythrocyte sedimentation rate, ESR, and C-reactive protein, CRP) were calculated. Serum myostatin levels were assessed using the ELISA method. Seropositive disease was defined according to a positive history of antibodies against rheumatoid factor (RF) or against citrullinated proteins (ACPA). Disease activity and patient functionality were expressed by using the DAS28 (ESR) and the HAQ-DI scores respectively.ResultsIn our cohort, 47% (n=14) had seropositive disease. Mean value...
Clinical Cardiology, 2000
Annals of the New York Academy of Sciences, 2006
American journal of hypertension, 2009
The mechanisms by which menopause may influence the systemic subclinical atherosclerosis are unex... more The mechanisms by which menopause may influence the systemic subclinical atherosclerosis are unexplained. The aim of this cross-sectional study was to evaluate the associations between early menopause, established cardiovascular (c-v) risk factors, metabolic parameters (insulin secretion and sensitivity, plasma adiponectin), and carotid intima-media thickness (IMT) in healthy women. In 74 menopausal women (mean age = 51 +/- 3 years, mean duration of menopause = 2.9 +/- 1.2 years) and in 74 nonmenopausal women comparable for age and body mass index (BMI), common carotid artery (CCA) luminal diameter, and IMT in different carotid segments were measured in digitized ultrasound images. Insulin sensitivity and secretion were assessed using the euglycemic hyperinsulinemic clamp technique and oral glucose tolerance test (OGTT). Insulin secretion was reconstructed by mathematical modeling. CCA diameter (5.55 +/- 0.46 vs. 5.21+/- 0.51 mm, P < 0.001), CCA IMT (608 +/- 78 vs. 576 +/- 74 mic...
Calcified Tissue International, 2006
The mitochondrial theory of ageing proposes that the lifetime accumulation of mutations in mitoch... more The mitochondrial theory of ageing proposes that the lifetime accumulation of mutations in mitochondrial DNA leads to the progressive loss of cellular viability, via some combination of bioenergy insufficiency, enhanced production of reactive oxygen species (ROS) and apoptosis. It has also been suggested that this could entrain a vicious cycle of ROS damage and mutagenesis. Mitochondrial DNA mutations do indeed accumulate with age, albeit to a very low level. Debate rages as to whether this could have any physiological significance, even if mitotic segregation is substantial. However, in stem cells, where mtDNA copy number may be relatively low, and the number of rounds of cell division high, segregation of mutants could result in eventual loss of precisely those cells that provide the body with the repair capacity needed to stave off functional decline and eventual death. Until recently, our ability to evaluate the role of mtDNA mutations in ageing was based purely on correlative data. However, the introduction of germline mutations into the nuclear genome which affect the mtDNA replication apparatus has allowed us to manipulate the mitochondrial genome experimentally, and provide a more formal test of the hypothesis. By crippling the proofreading exonuclease activity of the mitochondrial DNA polymerase (DNA polymerase gamma, POLG) we were able to induce the progressive accumulation of mtDNA point mutations to high levels. In cultured human cells this results in a selective crisis, once a critical mutation load is crossed, manifesting after some 60-90 cell divisions. When such a mutator was introduced into the mouse, a similar accumulation of mtDNA mutations in all tissues was found, associated with a phenotype of premature ageing, including many features reminiscent of human ageing: loss of mineral bone density and kyphosis, megalocytic anemia, loss of muscle mass, adipose tissue and hair, loss of fertility in both sexes and early death. The accumulation of mtDNA mutations in Polg mutator mice appears to be approximately linear with age, refuting the idea of a mutagenic vicious cycle, and instead consistent with the idea of a selective crisis brought about progressively by a constant rate of mutagenesis and the effects of mitotic segregation. A recent analysis of mtDNA from hair roots of young and aged humans supports this interpretation.
European Geriatric Medicine, 2014
Diabetes Care, 2007
We sought to compare the effects of combined calcium and vitamin D supplementation versus placebo... more We sought to compare the effects of combined calcium and vitamin D supplementation versus placebo on blood glucose and markers of inflammation in nondiabetic adults aged &amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =65 years. A total of 314 Caucasian adults without diabetes received either 500 mg calcium citrate and 700 IU vitamin D(3) or placebos daily for 3 years in a double-blind, randomized, controlled trial designed for bone-related outcomes. In a post hoc analysis, fasting plasma glucose (FPG), insulin sensitivity (estimated by homeostasis model assessment of insulin resistance [HOMA-IR]), plasma C-reactive protein, and interleukin-6, were measured at baseline and 3 years. The effects of combined calcium-vitamin D supplementation on 3-year change in FPG depended on baseline FPG (P = 0.02 for interaction). Therefore, we conducted analyses separately in participants with normal fasting glucose (NFG) (FPG &amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;5.6 mmol/l, n = 222) and impaired fasting glucose (IFG) (FPG 5.6-6.9 mmol/l, n = 92) at baseline. Among participants with IFG at baseline, those who took combined calcium-vitamin D supplements had a lower rise in FPG at 3 years compared with those on placebo (0.02 mmol/l [0.4 mg/dl] vs. 0.34 mmol/l [6.1 mg/dl], respectively, P = 0.042) and a lower increase in HOMA-IR (0.05 vs. 0.91, P = 0.031). In the NFG subgroup, there was no difference in the change in FPG or HOMA-IR between the two treatment arms. There were no differences in C-reactive protein or interleukin-6 between the two treatment arms in either subgroup. In healthy, older adults with IFG, supplementation with calcium and vitamin D may attenuate increases in glycemia and insulin resistance that occur over time. However, our findings should be considered hypothesis generating and need to be confirmed in randomized trials specifically designed for the outcomes of interest.
Clinical Cardiology, 1999
Backgroundand hypothesis: Although it is well established that diabetes mellitus (DM) induces mor... more Backgroundand hypothesis: Although it is well established that diabetes mellitus (DM) induces more severe coronary artery disease (CAD), it is not known whether it contributes to the development of coronary collateral circulation. The present study examines coronary Collateral Circulation in diabetic and nondiabetic patients with angiographically verified CAD.
Endocrinology, Diabetes & Metabolism Case Reports, 2015
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused primarily by benign mes... more Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused primarily by benign mesenchymal tumors. These tumors typically follow a benign clinical course and local recurrence occurs in !5% of cases. We investigated a 49-year-old man with a recurrent mesenchymal phosphaturic tumor showing no signs of malignancy. The patient suffered from chronic muscle weakness, myalgia and cramps. His medical record included the diagnosis of oncogenic osteomalacia, for which he was submitted to tumor resection in the left leg three times before. Laboratory examination showed hypophosphatemia, hyperphosphaturia and an elevated serum FGF23 level. A radical surgical approach (amputation) was advised, however, complete biochemical and clinical remission was not reached. Molecular analysis of the tumor cells demonstrated overexpression of growth factor receptors implicated in tumor angiogenesis and metastatic potential (platelet derived growth factor type A (PDGFRA), PDGFRB and vascular endothelial growth factor receptor) together with increased expression of FGF23, x-linked-phosphate-regulating endopeptidase and KLOTHO. TIO is usually associated with benign phosphauturic tumors and, when identified, resection of the tumor leads to complete remission in the majority of cases. The underlying pathophysiology of recurrences in these tumors is not known. This is the first report showing increased expression of growth factor receptors in a locally aggressive but histopathologically benign phosphaturic mesenchymal tumor.
Metabolism, 2014
Increased fracture risk, traditionally associated with type 1 diabetes, has lately been of great ... more Increased fracture risk, traditionally associated with type 1 diabetes, has lately been of great concern in patients with type 2 diabetes. A variable increase in fracture risk has been reported, ranging from 20% to 3-fold, depending on skeletal site, diabetes duration and study design. Longer disease duration, the presence of diabetic complications, inadequate glycemic control, insulin use and increased risk for falls are all reported to increase fracture risk. Patients with type 2 diabetes display a unique skeletal phenotype with either normal or more frequently increased, bone mineral density and impaired structural and geometric properties. Recently, alterations in bone material properties seem to be the predominant defect leading to increased bone fragility. Accumulation of advanced glycation end-products and changes in collagen cross-linking along with suppression of bone turnover seem to be significant factors impairing bone strength. FRAX score has been reported to underestimate fracture risk and lumbar spine BMD is inadequate in predicting vertebral fractures. Anti-diabetic medications, apart from thiazolidinediones, appear to be safe for the skeleton, although more data are needed. Optimal strategies to reduce skeletal fragility in type 2 diabetic patients are yet to be determined.
Journal of long-term effects of medical implants, 2011
Aseptic loosening after total hip arthroplasty is related to bone loss of the operated leg. The a... more Aseptic loosening after total hip arthroplasty is related to bone loss of the operated leg. The aim of the present study was to investigate the effect of aseptic loosening on volumetric bone mineral density (vBMD) and bone geometry in the operated leg, in postmenopausal women with a loosened cemented femoral implant using peripheral quantitative computed tomography (pQCT). We matched 12 postmenopausal women with aseptic loosening of cemented femoral implant, with 12 women without aseptic loosening (control group) according to age, BMI, and years from operation. All patients underwent pQCT of both tibias, DXA of the lumbar spine, and determination of biochemical markers of bone turnover. pQCT values in the control group as well as the nonoperated legs between groups had no significant difference. In the aseptic loosening group, there was significant reduction of cortical vBMD (cort vBMD) at 14% and 38% sites (cortical site), cortical thickness at 38% site, and of polar stress strengt...
Hormones (Athens, Greece)
Anorexia nervosa is a serious psychiatric disorder accompanied by high morbidity and mortality. I... more Anorexia nervosa is a serious psychiatric disorder accompanied by high morbidity and mortality. It is characterized by emaciation due to self-starvation and displays a unique hormonal profile. Alterations in gonadal axis, growth hormone resistance with low insulin-like growth factor I levels, hypercortisolemia and low triiodothyronine levels are almost universally present and constitute an adaptive response to malnutrition. Bone metabolism is likewise affected resulting in low bone mineral density, reduced bone accrual and increased fracture risk. Skeletal deficits often persist even after recovery from the disease with serious implications for future skeletal health. The pathogenetic mechanisms underlying bone disease are quite complicated and treatment is a particularly challenging task.
The Journal of Clinical Endocrinology & Metabolism, 2006