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Biomedical subjects

Anastasios Kalofoutis

Publications and source records attributed to Anastasios Kalofoutis.

At least 19 recordsLinked to original sources

Interleukin-1 alpha and beta, TNF-alpha and HTTLPR gene variants study on alcohol toxicity and detoxification outcome.

Genetic factors may influence the liability to treatment outcome and medical complications in alcoholism. In the present study we investigated the IL-1A rs1800587, IL-1B rs3087258, TNF-alpha rs1799724 and the HTTLPR variants in a sample of 64 alcohol dependents and 47 relatives versus a set of clinical parameters and outcome measures. Alcohol dependents had a less favorable clinical profile compared to relatives (higher cholesterol, triglycerides, glucose, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, gamma-glutamyltransferase). After detoxification, all clinical indexes improved and hepatic enzyme levels were similar in alcohol dependents and relatives, except for the GGT that remained significantly higher in alcohol dependents. Alcoholic depressive and anxiety scores were significantly reduced after detoxification. IL-1A, IL-1B, TNF-alpha and HTTLPR variants were not associated with any baseline clinical index or change after detoxification. In our sample IL-1A, IL-1B, TNF-alpha and HTTLPR do not appear as liability factors for alcohol toxicity or detoxification outcome, however the small sample size may influence the observed results.

Adult↗

Indices of low-grade chronic inflammation correlate with early cognitive deterioration in an elderly Greek population.

Elevated serum levels of adhesion molecules (AM) reflect low-grade chronic inflammation and have been associated with several conditions of neuronal damage. The aim of the present study was the investigation of possible correlation between early cognitive decline and inflammatory processes in the elderly as indicated by plasma C-reactive protein (CRP) and AM levels. Thirty-seven subjects with dementia were selected from a community-dwelling, genetically isolated, geriatric population (above 60 years of age) based on the Mini Mental State Examination scale (MMSE) and the Diagnostic and Statistical Manual (DSM-IV) criteria. In parallel, a group of 33 age-matched healthy controls were selected from the same population. The levels of CRP (mg/l), sICAM-1 (ng/ml) and sVCAM-1 (ng/ml) were measured in the serum samples of both groups. Serum concentrations of all three molecules sICAM-1, sVCAM-1 and CRP were significantly higher in the dementia group when compared to controls (656.78 +/- 161.51 versus 467.05 +/- 231.26, p < 0.01; 631.64 +/- 149.76 versus 449.04 +/- 285.27, p < 0.01; 1.53 +/- 0.97 versus 0.7221 +/- 0.61, p < 0.01, respectively). Furthermore, a positive correlation was observed between the three molecules studied and the degree of severity of cognitive impairment. The findings of this study enhance the hypothesis of the presence of an underlying inflammatory process leading to cognitive deterioration and predisposing dementia in the elderly. The present work supports the evaluation of inflammatory molecules as early indicators of cognitive decline in elderly individuals.

Adult↗

Prognostic significance of microalbuminuria in non-diabetic patients with acute myocardial infarction.

BACKGROUND: The aim of this study was to examine whether the presence of microalbuminuria (20-200 microg/min) can predict in-hospital morbidity and mortality in non-diabetic patients with acute myocardial infarction. METHODS: Two hundred twenty-three (172 men and 51 women) non-diabetic patients with acute myocardial infarction were studied prospectively. The main outcome measures of the study were based on a comparison of in-hospital mortality and major non-fatal in-hospital events (pulmonary edema, post-infarction angina, infarct extension, mechanical complications, conduction disturbances and ventricular arrhythmias) between microalbuminuric and normoalbuminuric patients. RESULTS: A significant proportion of patients (33.6%) had microalbuminuria. Seventy-six patients (34%) developed an in-hospital event (fatal or non-fatal). Six patients (2.7%) with acute myocardial infarction died in the hospital. Patients with microalbuminuria had a higher mortality rate in comparison with normoalbuminuric patients (6.6% vs. 0.68%, p = 0.01). For non-fatal events, the incidence of pulmonary edema and ventricular arrhythmias was significantly higher in patients with microalbuminuria (14.6% vs. 3.4%, p < 0.001 and 12% vs. 3.4%, p = 0.01, respectively). The combined end-point of the total number of fatal and non-fatal events was significantly higher in patients with microalbuminuria (57.3% vs. 22.3%, p < 0.001). In multiple logistic regression analysis, microalbuminuria (p < 0.001) and ejection fraction (p = 0.01) were independently related to the occurrence of major in-hospital events. CONCLUSIONS: Microalbuminuria is a significant predictor of in-hospital morbidity and mortality in non-diabetic patients with acute myocardial infarction.

Aged↗

Elevation of plasma concentration of adhesion molecules in late-life depression.

OBJECTIVES: Late-life depression may be associated with vascular disease. The purpose of the study was to investigate this association by determining the levels of soluble adhesion molecules (sICAM-1 and sVCAM-1) which represent markers of ischemia-induced inflammation in elderly individuals with depression. METHODS: Blood samples were obtained from 33 subjects with depression selected from a community-dwelling population after screening with the Geriatric Depression Scale, and 33 matched controls. Serum concentrations of sICAM-1 (ng/mL) and sVCAM-1 (ng/mL) were measured in both groups. RESULTS: Depressed patients (Group A) possessed significantly higher sICAM-1 levels compared to healthy controls (Group B) (674.94 +/- 166.90 ng/ml vs 467.05 +/- 231.26 ng/ml, respectively, p < 0.01). Similarly the same groups demonstrated elevated sVCAM-1 levels compared to controls (572.14 +/- 182.20 ng/ml vs 449.04 +/- 285.27 ng/ml, p < 0.05); a difference that in both cases remained significant after adjustment for potential confounders (gender, smoking, presence of metabolic syndrome). CONCLUSION: These findings indicate an association between high serum levels of VCAM-1, and ICAM-1 and depression in the elderly and further support the vascular depression hypothesis, which has important implications for the understanding and management of late-life depression.

Age of Onset↗

Short-term effect of orlistat on dietary glycotoxins in healthy women and women with polycystic ovary syndrome.

Exogenous advanced glycation endproducts (AGEs, known atherogenic molecules) abundant in everyday precooked, rich in fat, overheated meals can possibly contribute to the increased risk for diabetes and cardiovascular disease in women with polycystic ovary syndrome (PCOS). The aim of the present study was to investigate the effect of a lipase inhibitor on absorbed food glycotoxins in healthy women and those with PCOS. A 2-day protocol was followed. In the first day, a meal rich in AGE was provided, which on the second day was followed by two 120-mg capsules of lipase inhibitor, orlistat. Serum AGE levels were evaluated at baseline (0 hours), and at 3 and 5 hours postmeal during the study. Thirty-six women were studied, 15 controls (mean age, 28.80 +/- 5.47 years; body mass index, 25.85 +/- 6.73 kg/m(2)) and 21 with PCOS (mean age, 25.29 +/- 5.06 years; body mass index, 30.40 +/- 7.51 kg/m(2)) (University Hospital, Athens, Greece, institutional practice). Serum AGE levels, on day 1, were significantly increased both in the control group and in the PCOS group as compared with basal values (control group, 14.1%; PCOS group, 6.0%; P < .001). The corresponding rise was significantly lower on day 2 when the same meal was combined with orlistat (control group, 4.1%; PCOS group, 2.0%; P < .01). A limitation of the study is that it is a nonplacebo, nonrandomized therapeutic trial where each subject is considered as its own control. In conclusion, this study demonstrated the beneficial effect of orlistat on the absorption of food glycotoxins.

Absorption↗

Differences in expression of cardiovascular risk factors among type 2 diabetes mellitus patients of different age.

Atherosclerotic coronary heart disease and other forms of cardiovascular disease (CVD) are the major cause of mortality in type II diabetes (T2DM) as well as a major contributor to morbidity and lifetime costs. The purpose of this article is the identification of the biochemical parameters in plasma, which may serve as predisposition factors to CVD in T2DM patients of different ages. The variability of hyperglycemia, dyslipidemia, and inflammation with age progression was also studied for comparison. Four different diabetic groups allocated on the basis of the subjects' age (Group A: 15-25 years old; Group B: 26-40 years old; Group C: 40-60 years old; Group D: 60-80 years old) and consisting of 10 patients each, in parallel with 10 healthy controls matched for age, sex, and ethnic origin were screened for glucose, insulin, lipid profile (total cholesterol, triglycerides, LDL, and HDL), and inflammatory mediators (CRP, IL-6, and TNF-alpha). Significant differences were observed among the expressions of biochemical markers among different age groups. Hyperglycemia showed no variability with age whereas dyslipidemia correlated positively with age progression, as well as obesity, low physical activity, and family history of heart disease or diabetes. Marked inflammation was prominent only in Groups C and D. This article indicates that different biochemical parameters may be used for the assessment of CVD risk in T2DM patients of variable age.

Adolescent↗

Inflammatory process in type 2 diabetes: The role of cytokines.

Population-based studies have shown strong relationship between inflammatory markers and metabolic disturbances, obesity, and atherosclerosis, whereas inflammation has been considered as a "common soil" between these clinical entities and type 2 diabetes (T2D). The accumulation of macrophages in adipose tissue (AT), the common origin of macrophages and adipocytes, the prevalent presence of peripheral mononuclear cells, and apoptotic beta cells by themselves seem to be the sources of inflammation present in T2D, since they generate the mediators of the inflammatory processes, namely cytokines. The main cytokines involved in the pathogenesis of T2D are interleukin-1beta (IL-1beta), with an action similar to the one present in type 1 diabetes, tumor necrosis factor-alpha (TNF-alpha), and IL-6, considered as the main regulators of inflammation, leptin, more recently introduced, and several others, such as monocyte chemoattractant protein-1, resistin, adiponectin, with either deleterious or beneficial effects in diabetic pathogenesis. The characterization of these molecules targeted diabetes treatment beyond the classical interventions with lifestyle changes and pharmaceutical agents, and toward the determination of specific molecular pathways that lead to low grade chronic inflammatory state mainly due to an immune system's unbalance.

Animals↗

Evidence for nonautonomous effect of p53 tumor suppressor in carcinogenesis.

Prostate, breast, and probably other epithelial tumors harbor inactivating mutations in the p53 tumor suppressor gene in the stromal cells, implying the nonautonomous action of p53 in carcinogenesis. We have tested this hypothesis by evaluating the tumorigenicity of MCF7 human breast cancer cells in severe combined immunodeficient mice that differ in their p53 status. Our results showed that, indeed, p53 ablation in the hosts reduced the latency for the development of MCF7 tumors. Furthermore, we show that heterozygous hosts frequently undergo loss of heterozygosity at the p53 locus in the tumor stroma tissue by mechanism that resembles the inactivation of p53 in primary tumors. To evaluate the impact of p53 ablation in the stromal fibroblasts, in tumorigenesis, tumors were reconstituted in mice bearing wild-type p53 alleles, by mixing MCF7 cells with fibroblasts isolated from mutant or wild-type p53 mice. Our results suggest that tumors containing p53-deficient fibroblasts developed faster and were more aggressive than their counterparts with wild-type fibroblasts, although their neoplastic component, namely MCF7 mammary carcinoma cells, was identical in both cases. These data strongly support the notion for the operation of a nonautonomous mechanism for p53 action in primary tumors and provide a mechanistic association between p53 mutations in the stromal component of epithelial tumors and carcinogenesis.

Animals↗

Hypermethylation of CpG islands in the promoter region of the p15INK4B gene in childhood acute leukaemia.

It has been reported that the cyclin-dependent kinase inhibitor (CDKI) gene p15INK4B is frequently inactivated by genetic alterations and may be responsible for various malignant tumours. Another way of inactivation of this CDKI is by hypermethylation of 5'CpG islands in the promoter region of the p15INK4B gene and this inactivation seems to be a frequent event in various haematological malignancies. In the present study, we investigated the methylation status of the p151NK4B gene to clarify its role in the pathogenesis of childhood acute myeloid (AML) and acute lymphoblastic leukaemia (ALL). The study included 23 cases of B-cell origin ALL, 13 cases of T-cell origin ALL, 32 cases of AML, and 10 apparently healthy controls. Hypermethylation was studied by methylation-specific polymerase chain reaction. Hypermethylation of the p15INK4B gene was more frequent in cases with T-cell origin ALL (46.2%), but similar among children with B-cell origin ALL (13.0%) and AML (18.8%). Hypermethylation of p15INK4B may be involved in the pathogenesis of T-cell origin ALL, but not in that of AML or B-cell origin ALL.

Child↗

Evidence of reduced plasma HDL subfractions in patients with cutaneous discoid lupus erythematosus.

OBJECTIVES: The aim of the present study was to evaluate the dyslipidemic profile of patients with Cutaneous Discoid Lupus Erythematosus (DLE) with particular emphasis on the levels of High Density Lipoprotein (HDL) Cholesterol and its subfractions, HDL2 and HDL3. DESIGN AND METHOD: The study involved characterization of the lipid profile of 30 patients with diagnosed DLE (11 male and 19 female) and 34 age- and BMI-matched healthy individuals. RESULTS: Patients with DLE presented increased serum cholesterol, triglycerides and LDL-Cholesterol levels (P < 0.001, respectively) compared to the control group, while the levels of HDL-Cholesterol (P < 0.001), as well as its subfractions, HDL2 (P < 0.001) and HDL3 (P < 0.02) were markedly decreased. In addition, the ratio of CHOL/HDL was increased in patients with DLE (P < 0.001), whereas a reduction was observed in the ratio of HDL2/HDL3 (P < 0.001) in the same group. CONCLUSIONS: Our findings suggest that patients with cutaneous discoid lupus erythematosus have an increased risk of atherosclerosis due to the marked dyslipidemia associated with the disease. The reduced levels of HDL subfractions, HDL2 and HDL3, are believed to contribute to the dyslipidemic profile and further provide an important target for therapeutic intervention.

Adult↗

Extrapituitary effects of the growth hormone-releasing hormone.

Growth hormone-releasing hormone (GHRH) is a neuropeptide secreted by the hypothalamus that stimulates the synthesis and release of growth hormone (GH) in the pituitary. Accumulating evidence suggests that in addition to GHRH's neuroendocrine action, GHRH is present in several extrahypothalamic tissues and is involved in a variety of cellular processes. Its function is related to the regulation of cell proliferation and differentiation of various nonpituitary cell types. In certain cases, ectopic production of GHRH has also been implicated in carcinogenesis. The mechanisms by which GHRH affects the peripheral extrapituitary tissues remain poorly understood, but it is likely that classic neuroendocrine action as well as paracrine and autocrine pathways are involved. Some headway has been made in the identification of extrapituitary receptors for GHRH and cDNA as splice variants of these GHRH receptors found in various tumors. The fact that the nonpituitary GHRH receptors are not fully identified, however, remains the major obstacle in studying, at a more mechanistic level, the action of local GHRH. This review summarizes the information available regarding the role of GHRH in the extrapituitary tissues with emphasis on its potential therapeutic and diagnostic applications.

Animals↗

Increased levels of serum advanced glycation end-products in women with polycystic ovary syndrome.

OBJECTIVE: Women with polycystic ovary syndrome (PCOS) carry a number of cardiovascular risk factors and are considered to be at increased risk for atherosclerosis. Elevated concentrations of advanced glycation end-products (AGE), which exert their effects through interaction with specific receptors (RAGE), have been implicated in the cellular and tissue damage during atherosclerotic processes. DESIGN/PATIENTS: We investigated serum AGE levels in 29 young women with PCOS as well as the expression of their receptor, RAGE, in circulating monocytes and compared them levels with 22 healthy control women. MEASUREMENTS/RESULTS: Women with PCOS had higher levels of serum AGE proteins compared to healthy individuals (9.81 +/- 0.16 vs. 5.11 +/- 0.16, P < 0.0001), and increased RAGE expression was observed in monocytes of PCOS women compared to controls (30.91 +/- 10.11 vs. 7.97 +/- 2.61, P < 0.02). A positive correlation was observed between AGE proteins and testosterone (T) levels (r = 0.73, P < 0.0001). The correlation between AGE proteins and T levels remained high (partial correlation coefficient = 0.61, P = 0.0001) after controlling for body mass index (BMI), insulin levels and the area under the curve for glucose (AUCGLU) during an oral glucose tolerance test (OGTT). A positive correlation was also observed between AGE proteins and the free androgen index (FAI) (r = 0.58, P < 0.0001), waist-to-hip ratio (WHR) (r = 0.31, P < 0.02), insulin (r = 0.46, P < 0.001), homeostasis model assessment (HOMA) (r = 0.47, P < 0.0001), AUCGLU (r = 0.52, P < 0.002) and RAGE (r = 0.59, P < 0.01). A negative correlation was observed between AGE proteins and glucose/insulin ratio (GLU/INS) (r = -0.35, P < 0.01), and the quantitative insulin sensitivity check index (QUICKI) (r =-0.50, P < 0.01). In multiple regression analysis T was the only independent predictor of AGE levels (P < 0.0001, b = 0.044) between BMI, insulin, SHBG and AUCGLU (adjusted R2 = 0.59, F = 44.41, P < 0.0001). CONCLUSION: These data clearly demonstrate, for the first time, that PCOS women without overt hyperglycaemia have increased AGE levels and elevated RAGE expression when compared with controls.

Adult↗

Comparison of the extent and severity of coronary artery disease in patients with acute myocardial infarction with and without microalbuminuria.

The extent and severity of coronary atherosclerosis were compared between 43 microalbuminuric and 87 normoalbuminuric nondiabetic patients with acute myocardial infarction. Patients with microalbuminuria had significantly greater scores of the severity (Gensini score) and extent (Hamsten score) of coronary artery disease (p <0.001).

Age Distribution↗

The significance of serum HDL phospholipid levels in angiographically defined coronary artery disease.

OBJECTIVES: To evaluate discriminant serum lipid components associated with the presence and extent of coronary artery disease, with particular emphasis on the role of HDL phospholipids as an important predictor for disease severity. DESIGN AND METHODS: Total serum lipoprotein and phospholipids levels of 157 adult male patients (grouped based on degree of coronary artery occlusion) who underwent coronary angiography were analyzed. RESULTS: Patients showed elevated triglyceride (P < 0.001) and VLDL (P < 0.001) levels whereas a significant reduction was observed at LDL (P < 0.01), HDL (P < 0.01), and HDL-phospholipids (P < 0.001) concentrations. Correlation with disease progression (from one to three occluded vessels) showed significant rise in levels (P < 0.001) and markedly decreased HDL phospholipids (P < 0.001). CONCLUSIONS: Triglyceride levels and HDL phospholipids are better indicators of the presence and extent of coronary artery disease compared to the other lipoproteins studied. Furthermore, the HDL phospholipids/Total Cholesterol ratio is proposed as additional information of the degree of coronary artery occlusion.

Aged↗

Comparison of raloxifene and atorvastatin effects on serum lipids composition of healthy post-menopausal women.

The aim of this study was to evaluate the effects of the selective oestrogen receptor modulator, raloxifene, and those of statin, atorvastatin, in reducing the cardiovascular risks associated with the post-menopausal status. A detailed study of serum lipid concentrations was performed in four groups of post-menopausal women receiving either placebo, raloxifene or atorvastatin alone or their combination for the period of three months. Group A (raloxifene) showed significant decrease in total cholesterol levels (P < 0.05) and an increase in phospholipids concentration (P < 0.05), followed by a marked reduction in low-density lipoprotein cholesterol (LDL-C) levels (P < 0.01) and ApoB amounts (P < 0.001). Additionally, ApoA-I concentration was significantly increased (P < 0.01). Group B (atorvastatin) presented decreased cholesterol (P < 0.05) and triglycerides levels (P < 0.01), followed by elevated high-density lipoprotein cholesterol (HDL-C) concentration (P < 0.05) and low LDL-C amounts (P < 0.001). ApoA-I was significantly increased (P < 0.001) whereas ApoB was reduced (P < 0.001). The combined treatment in Group C (raloxifene and atorvastatin) showed significant changes in the majority of serum lipids. In particular, total cholesterol was reduced (P < 0.001), as well as triglycerides (P < 0.001) levels. Phospholipids were raised (P < 0.01) whereas LDL-C was reduced (P < 0.001) as was ApoB (P < 0.001). Furthermore, ApoA-I was elevated (P < 0.001). A further attempt to evaluate each treatment group was performed and the significance of these results is discussed.

Adult↗

The effect of valacyclovir treatment on natural killer cells of infertile women.

PROBLEM: The aim of this study was to investigate the effect of valacyclovir treatment on natural killer (NK) cell concentration in the peripheral blood of infertile women. METHOD OF STUDY: Peripheral blood NK cell concentration of 104 non-pregnant women with a history of infertility was determined by flow cytometry. The controls were 14 fertile non-pregnant women. A cohort of 42 out of 104 women--whose NK cell levels were 175/microL or higher--was prospectively studied for the presence of HSV-1, 2, VZV, cytomegalovirus, HHV-6, HHV-7 and HHV-8 DNA in the peripheral blood and was orally administered valacyclovir (open label study). RESULTS: Herpes virus DNA was detected in 64.3% of the 42 women examined. Prior to valacyclovir treatment mean NK cell concentration in herpes-negative group was statistically higher from control group but lower from herpes positive group (P = 0.0007, ANOVA). Following valacyclovir treatment the mean NK cell concentration was statistically decreased in all studied women (P = 0.000453), in herpes-negative (P = 0.01622) and in herpes positive group (P = 0.0056). Sufficient decrease was observed in 31 (73.8%) of 42 women who received the drug. CONCLUSIONS: Valacyclovir treatment is associated with a decrease of NK cell levels in most of the women with a history of infertility.

Acyclovir↗

Immunohistochemical detection of GHRH and its receptor splice variant 1 in primary human breast cancers.

OBJECTIVE: GHRH is secreted by the hypothalamus and, upon binding to specific GHRH receptors in the pituitary, stimulates growth hormone (GH) production and release from the pituitary. In addition to this neuroendocrine action, accumulated evidence implies additional roles for GHRH in carcinogenesis in non-pituitary tissues. In vitro and in vivo studies have shown that splice variant 1 (SV1) of the GHRH receptor, which is widely expressed in non-pituitary tissues and cancers, can mediate the proliferative effects of GHRH. The aim of the present study was to investigate the operation of an autocrine stimulatory loop between GHRH and SV1 in primary breast tumors. DESIGN: Fifty-three primary breast tumors were evaluated for GHRH and SV1 expression. METHODS: Expression of GHRH and SV1 was assessed by immunohistochemistry using anti-GHRH SV95 and anti-SV1 2317/5 polyclonal antibodies. RESULTS: About 40% of the specimens tested express GHRH and/or SV1 (approx. 25% each), while in 35% of these positive specimens co-expression of these antigens was detected (P<0.01). Furthermore, a correlation of GHRH, but not SV1, expression was detected in lobular compared with ductal carcinomas. CONCLUSIONS: These results constitute the first demonstration for the expression of GHRH and SV1 in primary breast cancers, and provide evidence for the operation of an autocrine stimulatory loop between GHRH and SV1 in primary cancers. Our findings indicate that GHRH analogs could have diagnostic and therapeutic applications for the management of breast cancer.

Adenocarcinoma↗

Ligand-dependent and -independent effects of splice variant 1 of growth hormone-releasing hormone receptor.

Existing evidence indicates that, in addition to its neuroendocrine action, growth hormone-releasing hormone (GHRH) acts directly on several nonpituitary tissues, especially neoplasms, and stimulates cell proliferation. We have recently reported that a splice variant of the receptor (SV1) is expressed in various normal tissues and particularly in tumor tissues, producing mitogenic effects on GHRH binding. By using HEC-1A human endometrial carcinoma cells, which express endogenous SV1, we show that, in addition to its ability to mediate the mitogenic effects of GHRH, SV1 also possesses relatively high intrinsic, ligand-independent activity. By using an antisense RNA-based approach we found that SV1 ablation reduces the efficacy of colony formation and the rate of cell proliferation of HEC-1A cells in the absence of exogenous GHRH, and decreases their sensitivity to GHRH when the neurohormone is added to the culture media. This ligand-independent stimulation of cell proliferation appears to be a characteristic property of the truncated form of the receptor, because the expression of SV1 and not of the full-length GHRH receptor stimulated the proliferation of 3T3 fibroblasts in the absence of exogenous GHRH, whereas both forms mediated the proliferative effects of GHRH. Evaluation of 21 specimens of human primary endometrial carcinoma for expression of SV1 by immunohistochemistry indicated that in contrast to the GHRH receptor, which is absent, SV1 is expressed in approximately 43% of the specimens. These findings indicate that SV1 can operate in a ligand-independent as well as a ligand-dependent manner. The overexpression of this form of GHRH receptor may be associated with carcinogenesis.

3T3 Cells↗