23 research outputs found

    The influence of PON1 192 polymorphism on endothelial function in diabetic subjects with or without hypertension.

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    Hypertension and type 2 diabetes mellitus (T2DM) cause endothelial dysfunction probably through increased oxidant stress. Paraoxonase (PON1) is an high-density lipoprotein (HDL)-linked anti-oxidant enzyme whose capacity is influenced by a genetic polymorphism at codon 192. In the present study we have investigated the role of PON1 polymorphism on endothelial function in subjects with T2DM with or without hypertension. Three groups of male subjects were enrolled: 65 healthy control subjects without T2DM or hypertension (CON), 51 with only T2DM (DM), and 67 with both hypertension and T2DM (HYP+DM). The PON1 Gln192Arg polymorphism was determined by polymerase chain reaction (PCR) amplification and restriction analysis. Endothelial function was evaluated as flow-mediated vasodilatation (FMD) of the brachial artery after forearm ischemia. Data were analyzed according to the presence or absence of the Arg allele. Subjects with T2DM had markedly impaired FMD, compared with those of the CON group. In the CON and HYP+DM groups no difference was observed in FMD between subjects homozygous for the Gln allele and those carrying the Arg allele. In the DM group FMD was lower among those carrying the Arg allele compared with Gln/Gln homozygotes (2.1+/-2.4% vs. 6.2+/-5.2%, p=0.002). In conclusion, the present findings demonstrated that FMD was less impaired in normotensive diabetic subjects homozygous for the Gln allele, consistent with the notion that this isoform has a more effective antioxidant action that serves to protect circulating low-density lipoprotein (LDL). Hypertension seems to abolish the protective effect of the Gln isoform. These findings, however, warrant further investigation to clarify their clinical import

    Body mass index, metabolic syndrome and carotid atherosclerosis.

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    OBJECTIVE: Body fatness and fat distribution are widely accepted as coronary heart disease risk factors. In this study, we have evaluated the contribution of generalized adiposity, assessed by body mass index (BMI), to carotid atherosclerosis, in participants with or without metabolic syndrome (MetS). METHODS: We have analysed 840 female and 1002 male participants in a regional Cardiovascular Disease Prevention Campaign. Blood glucose and lipids were analysed by standard methods. According to BMI, calculated as weight (in kilograms)/height (in square metres), participants were divided into normal weight (BMI <25 kg/m2), overweight (BMI between 25 and 29.9 kg/m2) and obese (BMI>29.9 kg/m2). Carotid atherosclerosis was evaluated by echo Doppler. RESULTS: Blood pressure, waist circumference, triglycerides and glucose were significantly higher, and high-density lipoprotein was lower, in overweight and obese participants, compared with normal weight. MetS was more frequent among obese and overweight than normal-weight participants (51.7 vs. 21.5 vs. 9.8%, respectively). The prevalence of carotid atherosclerosis was 45.29% in participants with MetS, significantly higher than in participants without MetS (33.04%, P<0.0001), but it was similar across the three weight categories. Furthermore, in multiple regression analyses BMI was not significantly associated with carotid atherosclerosis. CONCLUSION: The present findings suggest that increasing body weight favours the clustering of coronary heart disease risk factors. Overweight and obesity, however, do not independently associate with carotid atherosclerosis

    Lymphatics at crossroads of angiogenesis and lymphangiogenesis

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    The lymphatic system is implicated in interstitial fluid balance regulation, immune cell trafficking, oedema and cancer metastasis. However, the sequence of events that initiate and coordinate lymphatic vessel development (lymphangiogenesis) remains obscure. In effect, the understanding of physiological regulation of lymphatic vasculature has been overshadowed by the greater emphasis focused on angiogenesis, and delayed by a lack of specific markers, thereby limiting this field to no more than a descriptive characterization. Recently, new insights into lymphangiogenesis research have been due to the discovery of lymphatic-specific markers and growth factors of vascular endothelial growth factor (VEGF) family, such as VEGF-C and VEGF-D. Studies using transgenic mice overexpressing VEGF-C and VEGF-D have demonstrated a crucial role for these factors in tumour lymphangiogenesis. Knowledge of lymphatic development has now been redefined at the molecular level, providing an interesting target for innovative therapies. This review highlights the recent insights and advances into the field of lymphatic vascular research, outlining the most important aspects of the embryo development, structure, specific markers and methods applied for studying lymphangiogenesis. Finally, molecular mechanisms involved in the regulation of lymphangiogenesis are described. © Anatomical Society of Great Britain and Ireland 2004

    The potential of glucose management indicator for the estimation of glucose disposal rate in people with type 1 diabetes

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    Background and aims: Insulin resistance is a growing feature in type 1 diabetes (T1D). It can be quantified by calculating the estimated glucose disposal rate (eGDR) with the Epstein's formula, which includes laboratory-measured glycated hemoglobin (HbA1c). We aimed the current research to assess the agreement between the conventional eGDR formula and an alternative one (eGDR-GMI) incorporating the glucose management indicator (GMI) derived from continuous glucose monitoring (CGM). We also explored the relationship between eGDR-GMI, cardiovascular risk factors, and the prevalence of diabetes-related complications. Methods and results: We designed a cross-sectional study that included adults with T1D. eGDRGMI and eGDR (mg/kg/min) were calculated using GMI or HbA1c, waist circumference, and hypertensive state. Clinical data were collected from electronic medical records. The analyses encompassed 158 participants with a mean age of 39 f 13 years. The BlandAltman analysis showed a good agreement between eGDR-GMI and eGDR. When we divided participants in eGDR-GMI tertiles we found a higher prevalence of diabetes-related complications and a less favorable metabolic profile in the lowest eGDR-GMI tertile. The relative risk of retinopathy, nephropathy, and neuropathy significantly increased by approximately 1 unit with each decrease in eGDR-GMI, regardless of age, sex, disease duration, lipids, and smoking habit. Conclusions: eGDR-GMI represents a valid and robust alternative to the eGDR to assess insulin resistance in T1D. Low eGDR-GMI is associated with diabetes complications and a less favorable metabolic profile. Incorporating the eGDR-GMI into clinical practice can enhance the characterization of T1D people and allow for a more personalized treatment approach. (c) 2024 The Author(s). Published by Elsevier B.V. on behalf of The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

    Intensive cardiac care unit admission trends during the COVID-19 outbreak in Italy: a multi-center study

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    A significant decline in the admission to intensive cardiac care unit (ICCU) has been noted in Italy during the COVID-19 outbreak. Previous studies have provided data on clinical features and outcome of these patients, but information is still incomplete. In this multicenter study conducted in six ICCUs, we enrolled consecutive adult patients admitted to ICCU in three specific time intervals: from February 8 to March 9, 2020 [before national lockdown (pre-LD)], from March 10 to April 9, 2020 [during the first period of national lockdown (in-LD)] and from May 18 to June 17, 2020 [soon after the end of all containment measures (after-LD)]. Compared to pre-LD, in-LD was associated with a significant drop in the admission to ICCU for all causes (- 35%) and acute coronary syndrome (ACS; - 49%), with a rebound soon after-LD. The in-LD reduction was greater for women (- 49%) and NSTEMI (- 61%) compared to men (- 28%) and STEMI (- 33%). Length-of-stay, and in-hospital mortality did not show any significant change from to pre-LD to in-LD in the whole population as well as in the ACS group. This study confirms a notable reduction in the admissions to ICCUs from pre-LD to in-LD followed by an increment in the admission rates after-LD. These data strongly suggest that people, particularly women and patients with NSTEMI, are reluctant to seek medical care during lockdown, possibly due to the fear of viral infection. Such a phenomenon, however, was not associated with a rise in mortality among patients who get hospitalization

    Thalidomide downregulates angiogenic genes in bone marrow endothelial cells of patients with active multiple myeloma

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    PurposeTo study the antiangiogenic effect of thalidomide.Patients and MethodsThe expression of key angiogenic genes was studied in bone marrow endothelial cells (ECs) of patients with active and nonactive multiple myeloma (MM), monoclonal gammopathies unattributed/unassociated (MG[u]), diffuse large B-cell non-Hodgkin's lymphoma, in a Kaposi's sarcoma (KS) cell line, and in healthy human umbilical vein ECs (HUVECs) following exposure to therapeutic doses of thalidomide.ResultsThalidomide markedly downregulates the genes in a dose-dependent fashion in active MMECs and KS cell line, but upregulates them or is ineffective in nonactive MMECs, MG(u)ECs, NHL-ECs, and in HUVECs. Secretion of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and hepatocyte growth factor also diminishes according to the dose in culture conditioned media (CM) of active MMECs and KS, whereas it does not change in the other CM.ConclusionInhibition by thalidomide is probably confined to the genes of active MMECs and KS. This would account for its higher efficacy in these diseases
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