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Biomedical subjects

Fotini Boufidou

Publications and source records attributed to Fotini Boufidou.

10 recordsLinked to original sources
PubMed2006

Telomerase activity is decreased in peripheral blood mononuclear cells of hemodialysis patients.

BACKGROUND: Telomerase preserves telomere length and structure, preventing cellular senescence, which is associated with alteration of the chromosomal ends. We hypothesized that telomerase activity is altered in peripheral blood mononuclear cells (PBMCs) of hemodialysis (HD) patients. To investigate this hypothesis as well as the relationship between telomerase and inflammation, we measured the activity of this reverse transcriptase as well as the level of several inflammatory markers in PBMCs and serum of an end-stage renal failure (ESRF) population and a non-renal-failure group of subjects. METHODS: In PBMCs isolated from 42 HD and 39 non-renal-failure subjects of the same age (51.0 +/- 12.4 and 51.4 +/- 12.1 years, respectively) telomerase activity was measured using PCR-ELISA; the method was based on the telomeric repeat amplification protocol. RESULTS: Telomerase activity in PBMCs was detected in 18 (42.9%) HD and 28 (71.8%) non-renal-failure subjects (p = 0.013). Among positive subjects, percent telomerase activity in PBMCs was significantly higher in non-renal- failure (117 +/- 112 %) than in HD (47.6 +/- 57.1 %) subjects (p = 0.008). Detectable telomerase activity was lower in long-term than in short-term HD patients (13.3 +/- 8.9 vs. 75.0 +/- 64.8%, respectively, p = 0.015). Although higher in HD group, inflammatory indexes (C-reactive protein, interleukin-6, IL-6, soluble IL-6 and soluble gp130) were not correlated to telomerase activity in PBMCs. CONCLUSION: Telomerase activity in PBMCs is reduced in HD patients. It seems that, at least in this type of cell in this population, defense from senescence, as assessed by telomerase activity, is altered and associated with the chronicity of uremia/HD procedure.

Adult↗
PubMed2006

Serum oxidized low-density lipoprotein is inversely correlated to telomerase activity in peripheral blood mononuclear cells of haemodialysis patients.

BACKGROUND: Telomerase preserves telomeres' function and structure preventing cellular senescence. Its activity is reduced in peripheral blood mononuclear cells (PBMC) of haemodialysis (HD) patients. The purpose of this study is to investigate the potential correlation between increased oxidative stress/inflammation and telomerase activity in PBMC of HD patients. METHODS: Telomerase activity was measured by PCR-ELISA in PBMC isolated from a group of 42 HD patients and 39 subjects with estimated glomerular filtration rate >or=80 mL/min (control group). Serum oxidized low-density lipoprotein (ox-LDL), tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) were also measured in both groups by ELISA. RESULTS: Ox-LDL was negatively correlated to percentage telomerase activity in PBMC (r = -0.506, P = 0.000 in the whole group of 81 HD and normal subjects and r = -0.559, P < 0.001 in HD patients). TNF was also inversely associated with percentage telomerase activity in the whole group studied (r = -0.492, P = 0.000) while IL-10 was not. In stepwise multiple linear regression, taking into consideration the most important characteristics of the HD patients and control group, the only significant predictors for percentage telomerase activity in PBMC were ox-LDL and TNF (beta = -0.421, t = -4.083, P = 0.000 and beta = -0.381, t = -3.691, P = 0.000, respectively) while examining separately HD patients, the predictors for the same parameter were ox-LDL and HD duration (beta = -0.671, t = -4.709, P = 0.000 and beta = -0.349, t = -2.447, P = 0.023, respectively). CONCLUSION: Ox-LDL serum level is inversely correlated to telomerase activity in PBMC of HD patients. Our study proposes a new consequence of increased oxidative stress in HD patients: the premature cellular senescence potentially related to atherosclerosis through LDL oxidation.

Adult↗
PubMed2005

Release of interleukin-6 and its soluble receptors by activated peripheral blood monocytes is elevated in hypocholesterolemic hemodialysis patients.

BACKGROUND: A reverse association between cholesterol level and cardiovascular disease mortality is observed in hemodialysis (HD) patients; this paradoxical relationship may be explained by the coexistence of inflammation. Interleukin-6 (IL-6) is a central regulator of inflammation; its action is augmented by the soluble IL-6 receptor (sIL-6R) and inhibited by the soluble gp130 (sgp130). In order to investigate the potential association of inflammation with cholesterol levels in the HD population, release of soluble IL-6 components by peripheral blood mononuclear cells (PBMCs) was measured in two groups of HD patients with distinctly different lipid profile and in a control group. METHODS: Twenty-two HD patients with low serum cholesterol (range 85-171 mg/dl), 23 HD patients with high cholesterol (189-342 mg/dl) and 21 normolipidemic non-renal failure subjects were enrolled in the study. IL-6, sIL-6R and sgp130 were measured by ELISA in the serum and in the supernatant collected from cell cultures of activated or resting PBMCs isolated from all three groups. RESULTS: Serum IL-6 and sgp130 level was higher while sIL-6R was lower in both groups of HD patients compared to the control group. The ex-vivo release of the IL-6 and sgp130 by unstimulated PBMCs did not differ significantly between the three groups but that of the sIL-6R was higher in non-renal failure than in hypercholesterolemic HD subjects. Production of sIL-6R by stimulated PBMCs was higher in low-cholesterol HD patients (p < 0.001) and the same was valid for the sgp130 release (p = 0.034). Release of IL-6 by activated PBMCs was higher in the low-cholesterol compared to the high-cholesterol HD patients group (p = 0.011 for post hoc test). Major serum lipid fractions were inversely correlated to IL-6 and sIL-6R production from stimulated PBMCs in HD but not in non-renal failure subjects. Finally, release of the sgp130 by PBMCs was significantly reduced in 13 hypertriglyceridemic--and hypercholesterolemic--HD patients. CONCLUSION: Production of soluble components of a crucial pro-inflammatory and potentially atherogenic cytokine, namely the IL-6, by stimulated PBMCs appears to be inversely correlated with the serum cholesterol levels in HD patients.

Adult↗
PubMed2005

Serum and peripheral blood mononuclear cells infectious burden: correlation to inflammation and atherosclerosis in haemodialysis patients.

BACKGROUND: Infectious agents may be implicated in the inflammatory atherosclerotic process. Not only specific microorganisms but also the infectious burden, defined as the number of pathogens to which a patient is exposed, has been associated with atherosclerosis. In the present study, the infectious burden, determined directly (by identification of viable pathogens in peripheral blood mononuclear cells (PBMC)) and indirectly (by serum antibodies detection) is correlated to the inflammatory and atherosclerotic status in haemodialysis (HD) patients, a population at high risk for cardiovascular disease. METHODS: The viable forms of four microorganisms (Chlamydia pneumoniae, herpes virus 1 and 2 and cytomegalovirus) were identified in patients PBMC by cell cultures and subsequent polymerase chain reaction. Serum IgG against the above pathogens and Helicobacter pylori were also determined. Inflammation was assessed by measurement of C-reactive protein (CRP), serum amyloid A (SAA), three pro- and one anti-inflammatory cytokines and four adhesion molecules. Atherosclerosis was defined by a scoring system using medical history data. RESULTS: The number of viable pathogens identified in PBMC in the 122 HD patients included in the study were zero in 22.1% of them, one in 33.6%, two in 43.4% and three in one patient. The number of IgG antibodies determined was one in 6.6% of patients, two in 32%, three in 48.4% and four in 13.1%. Seropositivity was not significantly different between patients with or without the respective viable pathogen identified in PBMC. Atherosclerosis was present in 40.2% of patients, and CRP, SAA and interleukin-6 were all increased in these patients. Neither inflammatory indexes nor atherosclerosis were significantly different in patients with a higher number of viable pathogens detected in PBMC or in those with a higher antibodies number. CONCLUSIONS: The direct infectious burden determination (the number of viable pathogens in PBMC) does not coincide with the serum (by IgG detection) infectious burden. Although inflammation correlates to atherosclerosis, neither PBMC nor the serum infectious burden is associated with these two entities in the inflamed and atherosclerotic HD patients.

Adolescent↗
PubMed2004

Treatment with fluvastatin rapidly modulates, via different pathways, and in dependence on the baseline level, inflammation in hemodialysis patients.

BACKGROUND: Hemodialysis (HD) patients are frequently in an elevated inflammatory state which is correlated to the atherosclerosis-related and overall morbidity and mortality in this population. Statins, beyond their antilipidemic effects, are also considered to have anti-inflammatory, immunomodulating and antioxidant properties. The individual response of HD patients to a short course of fluvastatin, the mechanisms involved in the immunomodulating and anti-inflammatory effects of this drug and the time interval to the appearance of these effects are investigated in this longitudinal study. METHODS: In a group of 51 HD patients, fluvastatin 40 mg/day was administered for 4 weeks. Serial measurements of the lipid profile, C-reactive protein (CRP), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), interleukin-10 (IL-10), and serum oxidized LDL (ox-LDL), were performed before, during, and after the treatment period. RESULTS: Total cholesterol was significantly reduced after 14 days of treatment with fluvastatin (from mean +/- SD 216.7 +/- 34.3 to 179.2 +/- 42.3 mg/dl, p < 0.001). IL-6 and ox-LDL were reduced on day 28 (p < 0.001 and p < 0.01, respectively) and IL-10 was increased on day 14 (p = 0.05); CRP did not change significantly during the treatment period while sIL-6R was increased on day 28 of fluvastatin administration (p < 0.05). In a subgroup of patients with CRP, IL-6, sIL-6R, and ox-LDL baseline serum values > or = the median and IL-10 < or = the median, CRP was reduced on day 28 of fluvastatin treatment (p < 0.01), IL-6 and ox-LDL were reduced earlier, on day 14 (p = 0.05 and p < 0.05, respectively) while sIL-6R did not change significantly during the treatment period. CONCLUSIONS: Treatment with fluvastatin rapidly modulates inflammation in HD patients. Enhancement of anti-inflammatory mechanisms and attenuation of the inflammatory and oxidative state contribute to this modulation. Patients in an elevated baseline inflammatory state respond more rapidly and effectively to the treatment. This immediate and multi-potent action of the statins could be clinically useful in acute atherosclerosis complications or in the treatment of chronic inflammation in HD patients.

Aged↗
PubMed2004

Cytokine production in bipolar affective disorder patients under lithium treatment.

BACKGROUND: Our knowledge concerning immune functioning in bipolar affective disorder (BAD) is limited, while lithium's immunomodulatory effects seem multiple and conflicting. Our aim was to evaluate cytokine production and lithium's effect on it in BAD patients, using ELISPOT technique as a sensitive tool. METHODS: Cytokine (IL-2, IL-6, IL-10 and IFN-gamma) production from isolated peripheral blood lymphocytes (PBLs) was evaluated (ELISPOT technique) in 40 euthymic BAD patients under chronic lithium treatment, in 20 healthy volunteers, and in 10 never medicated BAD patients before and after the introduction of lithium therapy. In all cases, cytokine plasma levels were also measured using ELISA. RESULTS: BAD patients under chronic lithium treatment had significantly lower numbers of IL-2, IL-6, IL-10 and IFN-gamma secreting cells compared to healthy volunteers. The number of cytokine secreting cells decreased in never medicated patients after 3 months of lithium treatment. In vitro stimulation of PBLs with lithium did not affect the number of cytokine secreting cells either in the patients or in the healthy volunteers. CONCLUSIONS: The significantly lower number of PBLs producing cytokines (IL-2, IL-6, IL-10 and IFN-gamma) in euthymic BAD patients under chronic lithium treatment result from the long-term (over 3 months) lithium administration. In vitro stimulation of PBLs with lithium did not change the number of cytokine producing cells. Our findings may be useful in elucidating possible downregulatory effects of lithium in humans.

Adult↗
PubMed2004

Serum cytokine concentrations in alcohol-dependent individuals without liver disease.

In the current study, our aim was to evaluate and investigate the influence of heavy alcohol intake on serum interleukin (IL)-6, IL-8, IL-10, IL-12, and tumor necrosis factor-alpha (TNF-alpha) concentrations. The selection of cytokines was based on their presumptive role in the pathophysiology of alcohol dependence. On admission to the Drug-Free Substance Addiction Detoxification clinic ("ATHENA"), blood samples were obtained from study participants, and serum cytokine concentrations were measured by using a commercial sandwich enzyme-linked immunosorbent assay technique. Alcohol dependence, as diagnosed according to DSM-IV [Diagnostic and Statistical Manual of Mental Disorders (4th ed.)] criteria for alcohol dependence and estimated by using the Composite International Diagnostic Interview (CIDI), was characterized by increased serum IL-6 concentration. Interleukin-8, IL-10, IL-12, and TNF-alpha concentrations were comparable to those found in control subjects (P>.05). These results indicate that in alcohol-dependent individuals there is a significant increase in the serum IL-6 concentration (P <.05).

Adolescent↗
PubMed2003

Analysis of polymorphisms in the alpha-subunit of the olfactory G-protein Golf in lithium-treated bipolar patients.

OBJECTIVE: This study examines the alpha-subunit of the olfactory G-protein (G(olf)) as a possible candidate gene for bipolar disorder. The alpha-subunit of the G(olf) gene maps to a region on chromosome 18p that has been implicated in several linkage studies as a potential site of a bipolar disorder susceptibility loci. METHODS: We investigated whether two polymorphisms in the alpha-subunit of the G(olf) gene (A-->G in intron 3 and T-->G in intron 10) are associated with bipolar disorder in a sample of 149 bipolar patients under lithium treatment compared with 139 healthy controls using haplotype analysis. RESULTS: There was no evidence for an association between the investigated polymorphisms in the G(olf) gene and bipolar disorders, as well as to response to lithium treatment or common side effects, like hand tremor, weight gain and cognitive dysfunction. CONCLUSION: The results of the present study do not support the hypothesis that the G(olf) gene is a major susceptibility factor for bipolar disorders.

Adult↗
PubMedDate not supplied

Interrelationship of hepatic function, thyroid activity and mood status in alcohol-dependent individuals.

BACKGROUND: Alcohol-induced changes in thyroid function may contribute to the development of mood disorders such as depression and anxiety that almost invariably coexist in alcohol-dependent individuals. The aim of the present study was to investigate the severity of liver dysfunction and thyroid activity in correlation with anxiety and depressive-like symptomatology before and after a detoxification period. PATIENTS AND METHODS: In a sample of 100 alcohol-abusing/dependent subjects treated on an in-patient basis according to a standard detoxification protocol, measurements of the serum levels of hepatic enzymes (ASAT, ALAT, gammaGT) and thyroid hormones (T3, T4, TSH) as well as measures of anxiety, depression and global functioning were obtained at baseline and at weekly intervals over the period of 4-5 weeks. RESULTS: After completion of the alcohol detoxification, most measurements returned to normal levels and correlations were observed between the levels of hepatic enzymes and thyroid hormones. Additionally, a significant correlation was obtained between the levels of thyroid hormones and the mood status scales. CONCLUSION: Our results indicated a dysfunction of the hypothalamic-pituitary-thyroid axis in alcohol dependence with possible implications in the diagnosis and treatment of mood disorders associated with alcohol abuse.

Adult↗