Biomedical subjects

C Piperi

Publications and source records attributed to C Piperi.

8 recordsLinked to original sources

PubMed2006

Inflammatory and endothelial markers in women with polycystic ovary syndrome.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) carry a pattern of cardiovascular risk factors. Endothelial dysfunction and chronic inflammation are early findings in the atherosclerotic process. The purpose of the study was to investigate the coexistence of active inflammation markers and endothelial dysfunction in young women with PCOS, and their relationship with metabolic and hormonal abnormalities of the syndrome. MATERIALS AND METHODS: Twenty-five young women with PCOS and 25 controls of similar age and body mass index (BMI) were studied. Endothelial function was assessed by flow-mediated dilatation (FMD) on the brachial artery and smooth muscle cells injury was excluded by nitrate-induced dilatation (NID). Plasma levels of endothelin-1 (ET-1), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and high sensitivity C-reactive protein (hsCRP) were measured. Hormonal and metabolic profiles were determined in both groups. RESULTS: Flow-mediated dilatation (FMD) was statistically lower in PCOS (P < 0.001), whereas nitrate-induced dilatation (NID) was similar within the two groups. Polycystic ovary syndrome (PCOS) had statistically higher levels of ET-1 (P = 0.03), sICAM-1 (P = 0.01), sVCAM-1 (P = 0.02) and hsCRP (P = 0.01). Furthermore FMD was statistically higher in PCOS population with hsCRP 1 mg L(-1) when compared with PCOS population with hsCRP > 1 mg L(-1) (P = 0.02). Flow-mediated dilatation (FMD) was negatively related to hsCRP (r = -0.512, P = 0.015); ET-1 was positively related to free androgen index (r = 0.27, P = 0.05) and negatively to sex hormone-binding globulin (r = -0.465, P = 0.022); sVCAM-1 was positively related to total testosterone (r = 0.431, P = 0.036); hsCRP was positively related to BMI (r = 0.647, P = 0.001), and negatively related to FMD (r = -0.512, P = 0.015), quantitative insulin sensitivity check index (QUICKI) (r = -0.499, P = 0.018), and MATSUDA index (r = -0.445, P = 0.038). CONCLUSIONS: The present study demonstrates that endothelial dysfunction coexists and is influenced by the presence of increased serum levels of inflammation and endothelial activation markers in young women with PCOS. These parameters appear to be interrelated with hyperandrogenaemia in this insulin-resistant population.

Adult↗

PubMed2005

Evaluation of serum lipids and high-density lipoprotein subfractions (HDL2, HDL3) in postmenopausal patients with breast cancer.

Breast cancer patients are known to be at increased risk for developing other chronic diseases including cardiovascular disease. Studies by different investigators have shown a correlation between increased dietary fat or hypercholesterolemia and the occurrence of breast cancer. Since previous studies on lipoprotein subfractions in this type of cancer have been inconsistent, we evaluated the lipids and lipoprotein subfraction levels in postmenopausal patients with breast cancer in an attempt to identify the risk for the development of cardiovascular disease. The study included 132 patients, 56 of which were suffering from breast cancer, 32 from pancreatic and 44 age-matched controls. Total cholesterol (TC), triglycerides and lipoprotein fractions as well as TC/High density lipoprotein (HDL) and HDL2/HDL3 ratios were estimated by standard laboratory techniques. An increase in triglycerides and a decrease in HDL-cholesterol, especially in the HDL2 subfraction, were observed in patients with breast cancer as compared to the controls (P < 0.05). The maximum changes in TC, and HDL concentrations were observed in patients with advanced disease. Analysis of indexes of atherosclerosis (TC/HDL, and HDL2/HDL3 ratios) demonstrated that breast cancer patients had significantly higher TC/HDL ratio (6.44+/-1.24) compared with controls (3.43+/-0.57, p = 0.001), and patients with pancreatic cancer (3.79+/-0.15, p = 0.027). The results have demonstrated an unfavourable lipid profile in untreated breast cancer patients with high atherosclerosis indexes. This observation is of great importance, considering the potential use of endocrine therapy that could result in further deterioration of lipid indexes. We propose the evaluation and monitoring of lipid profile prior and after the induction of hormonal therapy in breast cancer patients, as a routine in clinical setting.

Aged↗

PubMed2005

Evidence of improved serum fatty acid profile of postmenopausal women receiving atorvastatin and raloxifene.

Raloxifene and atorvastatin have been shown to reduce the risk of cardiovascular disease associated with postmenopausal status and it has been postulated that their effects may be partly mediated by favourable changes in serum lipids and fatty acid composition. In the present study, individual administration of either raloxifene (Group A) or atorvastatin (Group B) or both (Group C) was compared for a period of 3 months and their effects on total lipids and fatty acids composition was evaluated. Postmenopausal women receiving both raloxifene and atorvastatin showed significant changes in the majority of serum lipids with important reductions in total cholesterol (p < 0.001), triglycerides (p < 0.001), LDL-C (p < 0.001) and Apo B levels (p < 0.001). Phospholipids concentrations (p < 0.01) as well as Apo A-I were also significantly raised (p < 0.001). Furthermore, oleic acid (18:1) and linoleic acid (18:2) levels were significantly increased (p < 0.01 and p < 0.001 respectively) followed by a marked reduction in palmitic acid (16:0) and arachidonic acid (20:4) concentrations (p < 0.01 and p < 0.001 respectively). The results of the study indicate that the serum lipid and fatty acid composition in postmenopausal women is influenced by the combined treatment of raloxifene and atorvastatin and a further attempt to evaluate the significance of these results is discussed.

Adult↗

PubMed2005

Metformin administration improves endothelial function in women with polycystic ovary syndrome.

OBJECTIVE: The aim of this study was to investigate the endothelial status in young women with polycystic ovary syndrome (PCOS), using a simple and easily reproducible hemodynamic method combined with a biological marker and to evaluate the effect of metformin treatment on these parameters. DESIGN: Descriptive clinical trial. METHODS: Forty young women, 20 with PCOS and 20 normal women of similar age and body mass index were studied. Metformin (1700 mg daily) was administered for 6 months to the PCOS group. The endothelium status and the metabolic and hormonal profile were studied in both groups, as well as after metformin, by flow-mediated dilatation (FMD) on the brachial artery and by measurements of plasma endothelin-1 (ET-1) levels. RESULTS: FMD was impaired in the PCOS group when compared with controls (3.24+/-0.71% vs 8.81+/-1.07% respectively, P<0.0001), but this difference normalized after metformin treatment (PCOS(post-metformin) vs controls: 8.17+/-1.26 vs 8.81+/-1.07%, P = 0.70) since the values significantly improved after metformin treatment (PCOS(pre-metformin) vs PCOS(post-metformin): 3.24+/-0.71 vs 8.17+/-1.26%, P=0.003). ET-1 levels were significantly higher in the PCOS women compared with the control group (7.23+/-0.50 vs 4.99+/-0.69 fmol/l, P=0.01), they improved significantly after metformin treatment (PCOS(pre-metformin) vs PCOS(post-metformin): 7.23+/-0.50 vs 3.57+/-0.60 fmol/l, P<0.0001) and their difference compared with the control group was reversed (PCOS(post-metformin) vs controls: 3.57+/-0.60 vs 4.99+/-0.69 fmol/l, P=0.13). Metformin administration improved hyperandrogenemia. However, in this study, mathematical methods used to assess insulin resistance failed to show any detected alteration after treatment with metformin. CONCLUSIONS: PCOS women were found to exhibit endothelial dysfunction compared with controls, which was reversed 6 months after metformin administration.

Adult↗

PubMed2004

Effects of hemodialysis on serum lipids and phospholipids of end-stage renal failure patients.

Patients with chronic renal failure undergoing periodic maintenance hemodialysis frequently present dyslipoproteinaemia which has been linked to the sharply increased risk of cardiovascular disease in these subjects. Reported defects on lipoprotein-related enzyme activities suggest a possible influence of hemodialysis not just to plasma lipid and lipoprotein levels but also to the composition of cell membranes. In this study, it was investigated whether the reported lipid abnormalities are accompanied by changes in serum phospholipids levels. Blood samples were obtained from 140 patients undergoing maintenance hemodialysis treatment and 122 normolipidemic healthy controls and analyzed for total serum phospholipids and their individual subclasses, as well as for total cholesterol and triglycerides, HDL-cholesterol and its subclasses. A significant decrease was observed in serum HDL cholesterol levels (p < 0.001) and its subclasses, HDL2-cholesterol (p < 0.01) and HDL3-cholesterol (p < 0.01) in patients when compared with healthy controls. A critical increase in the serum triglyceride content (p < 0.001) of patients was also observed. In addition, the serum levels of sphingomyelin (p < 0.01) and diphosphatidylglycerol (p < 0.001) were increased in the patient group, while the levels of phosphatidylcholine (p < 0.01) and phosphatidylinositol (p < 0.01) were significantly decreased in the patient group compared to healthy controls. In conclusion, this work clearly demonstrates that hemodialysis treatment contributes significantly to the dyslipidemic profile of end-stage renal failure patients by altering serum lipoprotein and phospholipids concentrations.

Adult↗

PubMed2004

Comparative analysis of oestrogen and raloxifene effects on the phospholipid composition of high density lipoproteins in healthy postmenopausal women.

The beneficial effect of selective oestrogen receptor modulators such as raloxifene in cardiovascular disease may be mediated partly by favourable changes in the phospholipid composition of high density lipoprotein (HDL) subclasses. In Group A (oestrogen alone) HDL2 phosphatidylcholine increased (P<0.001), while there was a decrease in HDL2 phosphatidylinositol (P<0.05) and HDL2 phosphatidylethanolamine (P<0.05) compared to controls (baseline). In the same group, HDL3 phosphatidylcholine increased (P<0.001) and HDL3 phosphatidylethanolamine decreased (P<0.01). In Group B (raloxifene) HDL2 phosphatidylcholine increased (P<0.001) as well as HDL2 diphosphatidylglycerol (P<0.01) while there were decreases in HDL2 sphingomyelin (P<0.01) and HDL2 phosphatidylethanolamine (P<0.05). In the same group, an increase in HDL3 phosphatidylcholine (P<0.001) and a reduction in HDL3 phosphatidylinositol (P<0.05) were observed as well as a decrease in HDL3 phosphatidylethanolamine (P<0.01) and HDL3 diphosphatidylglycerol (P<0.05). The significance of these results is discussed.

Age Factors↗

PubMed2001

A structure-function study of ligand recognition by CD22beta.

B-cell-specific CD22 is a member of a group of cell adhesion molecules within the immunoglobulin superfamily that display binding to glycans with terminal sialic acid residues. Binding of endogenous ligands to CD22 triggers B-cell activation and proliferation. It is therefore conceivable that high affinity ligands for CD22 may be of value as inhibitors of B-cell activation in allergy and chronic inflammation. In this study, we aimed to delineate the structural requirements for ligand binding to CD22. A library of 20 mono-, di-, and trisaccharide analogs of the basic binding motif Neu5Ac(alpha2,6)Lac was synthesized and screened for affinity for CD22beta. In general, CD22 ligand recognition appeared to be rather tolerant with respect to structural modifications of the anomeric sugar on a mono-, di-, and trisaccharide level, although affinity was increased by the presence of a nitro aromatic group at C-2. The most potent monovalent ligand, Neu5Ac-4-nitrobenzoyl-Glc, was selected to generate multivalent ligands based on either a glutamate or Tris cluster core. All multivalent ligands displayed at least a 10-fold increased affinity for CD22 compared with the corresponding monovalent glycoside. Interestingly, a maximal gain in affinity was already obtained for bivalent ligands, regardless of the terminal glycoside. A trivalent Tris-based cluster of Neu5Ac-4-nitrobenzoyl-Glc displayed a 300-fold higher affinity compared with the basic binding motif, which makes it, to our knowledge, the most potent antagonist for CD22 yet synthesized. As our in vitro fluorescence-activated cell sorting studies demonstrated efficient cellular uptake of a CD22 substrate, the most potent ligand in this study may hold promise as a homing device for immunomodulatory compounds and cytostatics.

Animals↗

PubMed2001

Design and synthesis of a multivalent homing device for targeting to murine CD22.

CD22 is a cell-surface glycoprotein uniquely located on mature B-cells and B-cell derived tumour cells. Current evidence suggests that binding of endogenous ligands to CD22 leads to modulation of B-cell activation by antigen. Incidentally, however, B-cell activation may derail. and lead to an undesired immune response, for example in cases of allergy, rheumatoid arthritis and Crohn's disease. In this situation, synthetic high-affinity ligands for CD22 may be of therapeutic value as inhibitors of B-cell activation. Recent studies have revealed that natural ligands for CD22 contain the trisaccharide NeuAc alpha-2,6-Lac as the basic binding motif. In addition, it has been demonstrated that binding to CD22 is strongly enhanced by multivalent presentation of the basic binding motif (cluster effect). In this paper. the stepwise development of a novel multivalent high-affinity ligand for CD22 is described. In the first stage, a series of monovalent NeuAc alpha-2,6-Glc(Y)X type binding motifs was prepared, and their affinity for murine CD22 was monitored, to obtain more insight into the effect of separate structure elements on ligand recognition. In the second stage, we prepared a trivalent cluster, based on the monovalent motif that displayed the highest affinity for CD22, NeuAc alpha-2,6-GlcNBzNO2OMe (7). This cluster, TRIS(NeuAc alpha-2,6-GlcNBzNO2)3 (52), displayed a more than 58-fold higher affinity for CD22 than the reference structure NeuAc alpha-2,6-LacOMe (10). To our knowledge, the cluster 52 is one of the most potent antagonists for CD22 yet synthesised.

Animals↗