[Show abstract][Hide abstract] ABSTRACT: Background:
Some patients experience statin-induced side effects or prefer nutraceutical approaches for the treatment of dyslipidemia. This has led to a search for alternative therapeutic approaches for dyslipidemia management. In recent studies Citrus bergamia (known as Bergamot) juice was able to reduce serum levels of lipids. Such benefit may be attributed to high amounts of flavonoids contained in Bergamot fruit juice (neoeriocitrin, neohesperidin, naringin). The aim of the present study was to fully investigate the effects of a Bergamot extract on cardio-metabolic parameters, including plasma lipids, atherogenic lipoproteins and subclinical atherosclerosis.
Eighty subjects (42 men and 38 women, mean age: 55 ± 13 years) with moderate hypercholesterolemia [e.g., with plasma LDL-cholesterol concentrations between 160 and 190 mg/dl (between 4.1 and 4.9 mmol/l)] were included. A Bergamot-derived extract (Bergavit R(®)) was given at a fixed dose daily (150 mg of flavonoids, with 16% of neoeriocitrin, 47% of neohesperidin and 37% of naringin) for 6 months. Lipoprotein subfractions were assessed by gel electrophoresis. With this methodology low density lipoprotein (LDL) subclasses are distributed as seven bands (LDL-1 and -2 as large LDL, and LDL-3 to -7 as atherogenic small, dense LDL). Subclinical atherosclerosis was assessed by carotid intima-media thickness (cIMT) using B-mode ultrasound.
After 6 months, Bergavit R(®) reduced total cholesterol (from 6.6 ± 0.4 to 5.8 ± 1.1 mmol/l, p < 0.0001), triglycerides (from 1.8 ± 0.6 to 1.5 ± 0.9 mmol/l, p = 0.0020), and LDL-cholesterol (from 4.6 ± 0.2 to 3.7 ± 1.0 mmol/l, p < 0.0001), while HDL- cholesterol increased (from 1.3 ± 0.2 to 1.4 ± 0.4 mmol/l, p < 0.0007). In addition, a significant increase in LDL-1 (from 41.2 ± 0.2 to 49.6 ± 0.2%, p < 0.0001) was accompanied by decreased small, dense LDL-3, -4, and 5 particles (from 14.5 ± 0.1 to 9.0 ± 0.1% p < 0.0001; 3.2 ± 0.1 to 1.5 ± 0.1% p = 0.0053; 0.3 ± 0.0% to 0.1 ± 0.0% p = 0.0133, respectively). cIMT also decreased from 1.2 ± 0.4 to 0.9 ± 0.1 mm (p < 0.0001).
This is the first study investigating the effects of Bergamot flavonoids supplementation on cardio-metabolic risk in dyslipidemic subjects. Bergavit R(®) (Bergamot juice extract) supplementation significantly reduced plasma lipids and improved the lipoprotein profile. cIMT was also reduced significantly over a relatively short time frame of 6 months.
Preview · Article · Jan 2016 · Frontiers in Pharmacology
[Show abstract][Hide abstract] ABSTRACT: Background:
Statins are the most common used lipid lowering drugs but they may cause adverse effects and despite their well-established therapeutic benefits residual cardiovascular (CV) risk remains. The use of other lipid lowering drugs and nutraceuticals alone or as add-on lipid-modifying therapy can be an option in such cases. Several studies have reported health-related properties of the Citrus fruits, among which bergamot (Citrus bergamia Risso) differs from others by particularly high content of certain compounds.
This narrative review summarizes the current evidence on the effects of bergamot on lipid parameters based on studies involving animals and humans.
This natural supplement may lead to effective lipid-lowering treatment. Its lipid-lowering activity is attributed to different flavonoids. However, the exact mechanisms involved remain unclear.
It is expected that ongoing and future studies will confirm the benefit of bergamot in dyslipidemic and other cardiometabolic disorders, potentially leading to reduced overall CV risk.
No preview · Article · Dec 2015 · Phytomedicine: international journal of phytotherapy and phytopharmacology
[Show abstract][Hide abstract] ABSTRACT: To explore the effects of the glucagon-like peptide-1 receptor analogue liraglutide on subclinical atherosclerosis in diabetic subjects with non-alcoholic fatty liver disease (NAFLD).
In this 8-month prospective study, 29 subjects with type 2 diabetes (T2DM) and NAFLD (16 men and 13 women, mean age: 61 ± 10 years) were matched for age and gender with 29 subjects with T2DM without NAFLD (16 men and 13 women, mean age: 61 ± 8 years). Liraglutide 0.6 mg/day for 2 weeks, followed by 1.2 mg/day, was given in addition to metformin.
Anthropometric variables, glucometabolic parameters and carotid intima-media thickness (IMT) using B-mode real-time ultrasound were assessed at baseline and 4 and 8 months.
Glycated hemoglobin reduced significantly in both groups. No significant changes were found in body weight, waist circumference and lipids. Carotid IMT decreased significantly in the T2DM patients with NAFLD (from 0.96 ± 0.27 to 0.82 ± 0.17 to 0.85 ± 0.12 mm, p = 0.0325), but not in the T2DM patients without NAFLD (from 0.91 ± 0.23 to 0.88 ± 0.17 to 0.85 ± 0.15 mm, p = 0.4473).
Eight months of liraglutide use in patients with T2DM and NAFLD significantly reduced carotid IMT, a surrogate marker of atherosclerosis, independently of glucometabolic changes.
[Show abstract][Hide abstract] ABSTRACT: This work reports a clinical trial performed at Palermo University Hospital "Paolo Giaccone". From January 2004 to December 2011, 79 patients were enrolled (40 men and 39 women). All patients suffered from Inflammatory Bowel Disease (IBD) and were subjected to orthopedic consultation at the Institute of Orthopaedics, University Hospital of Palermo, for arthropathy secondary to IBD. The patients were divided into two groups (A and B) and dealt with different therapies for the resolution of the inflammatory picture of the colonic mucosa and the treatment of the extraintestinal articular manifestations. Group A was treated with drug therapy: Diclofenac (75 mg im/day for 10 days) and Mesalazine (800 mg gastro-resistant tablets, one tablet twice a day in mild forms, and one tablet three times per day in moderate forms). In group B, in addition to the previous treatment protocol, two probiotic mixtures were added in a time of two weeks: in the first week, twice a day, one capsule containing a mixture of Enterococcus faecium and Saccharomyces boluard was administered, with the main purpose to mitigate the intestinal inflammation; in the second week, twice a day too, one capsule containing a mixture of Lactobacillus salivarius and Lactobacillus acidophilus was administered, with the aim to promote the restoration of a normal intestinal microenvironment. The attenuation of intestinal inflammation, improved by the presence of probiotics, could have important effects on the articular manifestations, resulting in a significant improvement of the arthropathy. All patients were evaluated with the Harvey-Bradshaw Index. Both Crohn Disease and Ulcerative Cholitis diagnosis was made with clinical, laboratory, endoscopic and instrumental tests; the degree of disease activity was evaluated using the criteria of Truelove and Witts. The WOMAC-Score (Western Ontario McMaster) was used in our study to investigate the degree of articular involvement of the patients. The data were statistically evaluated and these are shown that the B group of patients treated with conventional therapy + probiotic mixture had a better resolution of the clinical and of this post-treatment parameters: WOMAC score, ESR, CRP and white blood cells; and also the B group of patients have a better response to standard therapy compared with patients who did not receive the probiotic with a remarkable statistic significance (p≤0.0001).
Full-text · Article · Sep 2014 · Progress in Nutrition
[Show abstract][Hide abstract] ABSTRACT: Lipid-lowering drugs may cause adverse effects and, although lipid targets may be achieved, a substantial residual cardiovascular (CV) risk remains. Treatment with agents mimicking proteins present in the body, such as incretin-based therapies, provided promising results. However, in order to improve lipids and CV risk, lifestyle measures remain important. Some researchers focused on nutraceuticals that may beneficially affect metabolic parameters and minimize CV risk. Chitosan, a dietary fiber, can regulate lipids with benefit on anthropometric parameters. The beneficial properties of dietary supplements (such as green tea extract, prebiotics, plant sterols, and stanols) on plasma lipids, lipoproteins, blood pressure, glucose, and insulin levels and their anti-inflammatory and anti-oxidant effects are documented. However, larger, prospective clinical trials are required to confirm such benefits. Such treatments may be recommended when lipid-lowering drugs are neither indicated nor tolerated as well as in order to achieve therapeutic targets and/or overcome residual CV risk.
[Show abstract][Hide abstract] ABSTRACT: Liraglutide, a long-acting glucagon-like peptide-1 (GLP-1) analog, has several non- glycemic properties, but its effect on carotid intima-media thickness (IMT), a recognized marker of subclinical atherosclerosis, is still unknown.
A prospective study of 8 months duration in 64 patients with type-2 diabetes and no prior history of coronary artery disease evaluated whether adding liraglutide to metformin affects carotid IMT, measured by color doppler ultrasound.
After 8 months, fasting glucose decreased by 2.1 mmol/l and HbA1c by 1.9% (p < 0.01 for all). Liraglutide reduced total-cholesterol and triglycerides by 10%, and LDL-cholesterol by 19%, whereas HDL-cholesterol increased by 18% (p < 0.01 for all lipid changes). Carotid IMT decreased from 1.19 +/- 0.47 to 0.94 +/- 0.21 mm (p < 0.01). Yet, changes in carotid IMT did not correlate with changes in any other variable studied.
Liraglutide decreases carotid IMT after 8 months treatment independently of its effect on plasma glucose and lipids concentrations.Trial registration: ClinicalTrials.gov: NCT01715428.
Preview · Article · Feb 2014 · Cardiovascular Diabetology
[Show abstract][Hide abstract] ABSTRACT: Small, dense low-density lipoproteins (LDLs) are more susceptible to oxidation than their larger, more buoyant counterparts and therefore the biological modification of these LDL particles may, in part, be responsible for their atherogenic properties. Kotani et al. found that at multiple regression analysis there was an independent and significant inverse correlation between the mean LDL particle size and the oxidative stress status; notably, the authors adjusted not only for the traditional cardiovascular risk factors, but also for drug treatments. Higher levels of small, dense LDL concentrations significantly contribute to atherosclerosis, and lipoprotein size and subfractions may refine cardiovascular disease risk assessment.
No preview · Article · Jan 2014 · Expert Review of Endocrinology & Metabolism
[Show abstract][Hide abstract] ABSTRACT: Probiotics and conventional terapy: new fronter in therapeutic approach in articular mani-festations of IBD» Summary. This work reports a clinical trial performed at Palermo University Hospital "Paolo Giaccone". From January 2004 to December 2011, 79 patients were enrolled (40 men and 39 women). All patients suffe-red from Inflammatory Bowel Disease (IBD) and were subjected to orthopedic consultation at the Institute of Orthopaedics, University Hospital of Palermo, for arthropathy secondary to IBD. The patients were divided into two groups (A and B) and dealt with different therapies for the resolution of the inflammatory picture of the colonic mucosa and the treatment of the extraintestinal articular manifestations. Group A was treated with drug therapy: Diclofenac (75 mg im/day for 10 days) and Mesalazine (800 mg gastro-resistant tablets, one tablet twice a day in mild forms, and one tablet three times per day in moderate forms). In group B, in addition to the previous treatment protocol, two probiotic mixtures were added in a time of two weeks: in the first week, twice a day, one capsule containing a mixture of Enterococcus faecium and Saccharomyces boluard was administered, with the main purpose to mitigate the intestinal inflammation; in the second week, twice a day too, one capsule containing a mixture of Lactobacillus salivarius and Lactobacillus acidophilus was admini-stered, with the aim to promote the restoration of a normal intestinal microenvironment. The attenuation of intestinal inflammation, improved by the presence of probiotics, could have important effects on the articular manifestations, resulting in a significant improvement of the arthropathy. All patients were evaluated with the Harvey-Bradshaw Index. Both Crohn Disease and Ulcerative Cholitis diagnosis was made with clinical, laboratory, endoscopic and instrumental tests; the degree of disease activity was evaluated using the criteria of Truelove and Witts. The WOMAC-Score (Western Ontario McMaster) was used in our study to investigate the degree of articular involvement of the patients. The data were statistically evaluated and these are shown that the B group of patients treated with conventional therapy + probiotic mixture had a better resolution of the clinical and of this post-treatment parameters: WOMAC score, ESR, CRP and white blood cells; and also the B group of patients have a better response to standard therapy compared with patients who did not receive the probiotic with a remarkable statistic significance (p≤0.0001).
[Show abstract][Hide abstract] ABSTRACT: Incretin peptides are a group of gastrointestinal hormones that play a prominent role in the regulation of glucose metabolism. Incretin-based therapies (IBTs) have recently emerged as an important treatment option for patients with type 2 diabetes mellitus (T2DM). These pharmaceutical agents may be especially well suited for patients who are overweight or obese with primarily post-meal glucose peaks, and in whom traditional first-line oral agents have failed to maintain adequate glycemic control. There are 2 classes of IBTs: the dipeptidyl peptidase-4 (DPP-4) inhibitors and the glucagon-like peptide 1 (GLP-1) receptor agonists. The ultimate effect of both types of agents is to augment GLP-1 signaling, which results in enhanced glucose-dependent insulin secretion, inhibition of glucagon secretion and decreased appetite. This leads to improved regulation of glucose homeostasis accompanied by either no increase in body weight (with DPP-4 inhibitors) or a reduction (with GLP-1 receptor agonists). GLP-1 inhibits food intake and the increased GLP-1 response may contribute as a satiety signal. Although data regarding the effect of GLP agonists and DPP-4 inhibitors on levels of peptides involved in the regulation of food intake in T2DM are few, an indirect effect of IBT on weight loss is possible (e.g. Exendin-4 induces adiponectin secretion in vitro). Results from animal models indicate reduction of food intake and body weight by GLP-1 agonists, but follow-up studies are required. A growing amount of evidence suggests that these peptides may also impact the cardiovascular system, including beneficial effects on myocardial cells, lipid profiles and blood pressure as well as reduced markers of systemic inflammation and improved endothelial dysfunction. The potential role of these agents in improving components of the metabolic syndrome and retardation of atherosclerosis needs to be fully elucidated. Although IBTs are currently recommended only for use in the early treatment of T2DM, the 'non-glycemic' actions of these drugs may have far reaching therapeutic implications. It is hoped that future studies will elucidate their potential strengths and weaknesses for use in various metabolic conditions.
Full-text · Article · Dec 2013 · Current pharmaceutical design
[Show abstract][Hide abstract] ABSTRACT: The role Hsp60 might play in various inflammatory and autoimmune diseases is under investigation, but little information exists pertaining to Hashimoto's thyroiditis (HT). With the aim to fill this gap, in the present work, we directed our attention to Hsp60 participation in HT pathogenesis. We found Hsp60 levels increased in the blood of HT patients compared to controls. The chaperonin was immunolocalized in thyroid tissue specimens from patients with HT, both in thyrocytes and oncocytes (Hurthle cells) with higher levels compared to controls (goiter). In oncocytes, we found Hsp60 not only in the cytoplasm but also on the plasma membrane, as shown by double immunofluorescence performed on fine needle aspiration cytology. By bioinformatics, we found regions in the Hsp60 molecule with remarkable structural similarity with the thyroglobulin (TG) and thyroid peroxidase (TPO) molecules, which supports the notion that autoantibodies against TG and TPO are likely to recognize Hsp60 on the plasma membrane of oncocytes. This was also supported by data obtained by ELISA, showing that anti-TG and anti-TPO antibodies cross-react with human recombinant Hsp60. Antibody-antigen (Hsp60) reaction on the cell surface could very well mediate thyroid cell damage and destruction, perpetuating inflammation. Experiments with recombinant Hsp60 did not show stimulation of cytokine production by peripheral blood mononuclear cells from HT patients. All together, these results led us to hypothesize that Hsp60 may be an active player in HT pathogenesis via an antibody-mediated immune mechanism.
[Show abstract][Hide abstract] ABSTRACT: Chitosan can favorably modulate plasma lipids, but the available data are not conclusive. We evaluated the effect of chitosan on plasma lipids and lipoproteins in 28 patients with plasma triglyceride levels >150 mg/dL (mean age: 63 ± 12 years), not taking other lipid-lowering agents. All patients received a chitosan derived from fungal mycelium (Xantonet, Bromatech, Italy) at a fixed dose of 125 mg/d in addition to their current medications for 4 months. Polyacrylamide gel electrophoresis was used to measure low-density lipoprotein (LDL) subclasses. After treatment, total cholesterol reduced by 8%, LDL cholesterol by 2%, and triglycerides by 19%, with a concomitant 14% increase in high-density lipoprotein cholesterol. We also found a beneficial effect of chitosan on LDL subclasses, with a significant increase in LDL-2 particles (from 37 ± 8% to 47 ± 8%, P = .0001) and a decrease (although not significant) in atherogenic small, dense LDL. Whether these findings may affect cardiovascular risk remains to be established in future studies.
[Show abstract][Hide abstract] ABSTRACT: Estrogens are secreted primarily by the ovaries and placenta, by the testes in men and also produced by peripheral steroidogenic conversion. The 3 major naturally occurring estrogens are: 17β-estradiol (E2), estrone and estriol, of which E2 is the predominant and most active. The actions of E2 are mediated by at least 3 different receptors - the classical ERs (ERα and ERβ) and G-protein coupled receptor 30 (GPR30). E2 signaling in cardiomyocytes involves ERα- and ERβ-independent pathways, and treatment with the E2 receptor antagonists (Selective Estrogen Receptor Modulators- SERMs), which are agonists of GPR30, inhibits cardiac cell growth. Effects of E2 in preventing endothelial dysfunction, a prerequisite of atherosclerosis, are well recognized. Atherosclerosis involves interaction between the cells of the arterial wall endothelial cells (EC) and vascular smooth muscle cell (VSMC), as well as migration of macrophages into wall tunica media. It is predominantly developed at sites with abnormally high shear stress, such as bifurcations or branching of arteries, initiated by an injury to the endothelium and exposure to atherogenic lipids and toxins, such as those contained in tobacco smoke or infectious agents. Animal studies have shown effects of E2 in preventing atherosclerosis, inflammation and endothelial or vascular dysfunction. Gender differences along this pathogenic pathway have been also described. We review the data from the available animal and human studies, which focus on anti-atherogenic effects of E2. These studies represent evidence, albeit indirect, for an inhibitory effect of E2 on the progression of coronary artery atherosclerosis.
No preview · Article · May 2013 · Hormone and Metabolic Research
[Show abstract][Hide abstract] ABSTRACT: Glucagon-like peptide-1 is an incretin secreted in response to nutrient ingestion. Derangements in the incretin system may contribute to the onset and progression of hyperglycemia in Type 2 diabetes. Liraglutide is a long-acting human glucagon-like peptide-1-receptor agonist suitable for once-daily administration. Blood glucose- and weight-reducing effects, improvements in pancreatic beta-cell function and a low risk of hypoglycemic events have been demonstrated with this agent. There is a trend towards improvement in the proinflammatory milieu. Liraglutide also appears to have beneficial effects on plasma lipids and lipoproteins in the form of a reduction in total cholesterol, triglycerides and LDL cholesterol, and a concomitant increase in HDL cholesterol. These favorable effects of liraglutide on multiple metabolic pathways may contribute to a retardation of atherosclerosis and possibly a reduction in cardiovascular risk. However, prospective studies are still needed to elucidate the clinical impact of liraglutide on cardiovascular outcomes in patients with Type 2 diabetes.
No preview · Article · Apr 2013 · Clinical Lipidology
[Show abstract][Hide abstract] ABSTRACT: The presence of the metabolic syndrome (MS) increases cardiovascular morbidity and mortality and we aimed to assess the outcome in subjects with the MS and subclinical atherosclerosis.
We followed-up for five years 339 Mediterranean subjects with asymptomatic carotid intima-media thickness >0.9 mm (men: 60%; age: 66±5 years), of whom 130 had the MS (men: 59%; age: 66±5 years), evaluating at baseline traditional cardiovascular risk factors (including male gender, older age, obesity, hypertension, diabetes, smoking, family history of cardiovascular diseases, dyslipidemia) and plasma levels of C-reactive protein and fibrinogen.
Cardio- and cerebrovascular events were registered in the 29% of subjects with the MS and in the 20% of those without it and the presence of more criteria for the diagnosis of the MS was significantly associated with vascular morbidity and mortality. By multivariate analysis, including all baseline variables, independent predictive roles for the events were found for elevated markers of inflammation (OR 3.8), elevated fasting glucose (OR 2.1) and elevated triglycerides (OR 1.4).
These findings confirm a worst vascular outcome in subjects with more criteria for the diagnosis of the MS and further suggest the need of future research to understand the combined role of inflammation and the MS in the progression from subclinical to clinical atherosclerosis.
No preview · Article · Jun 2012 · International angiology: a journal of the International Union of Angiology
[Show abstract][Hide abstract] ABSTRACT: Autoimmune hepatitis (AIH) is a chronic liver disease characterized by clinical features analogue to viral and non-autoimmune liver disorders, but with distinct sero-autoimmunologic properties. The disease results from a network of complex interactions involving genetic predisposition, triggering factors, autoantigens and immunoregulatory system. Diagnosis of AIH relies on positive autoantibodies determination and on liver core biopsy histological appearance. Corticosteroid and immunosuppressive drugs are generally useful in the treatment of disease. However, when inflammation cannot be controlled, progression from chronic hepatitis to cirrhosis is often observed and hepatocellular carcinoma may appear at the end stage. Here we reported a case of a woman, affected with AIH. The patient presented features of chronic liver disease of neither viral nor alcoholic aetiology. Serum evidence of hypertraminasemia, hypergammaglobulinemia and specific autoantibodies were the leading points to final diagnosis, which was validated by liver biopsy. The patient was, finally, successfully treated with steroids.
No preview · Article · Jan 2012 · Acta Medica Mediterranea
[Show abstract][Hide abstract] ABSTRACT: Type 2 diabetes is associated with a cluster of inter-related plasma lipid and lipoprotein abnormalities, including reduced HDL-C, a predominance of small, dense LDL and elevated triglycerides. These abnormalities occur even in prediabetes, before blood sugars rise sufficiently in order to confirm a diagnosis of diabetes, and this transition phase incurs important cardiovascular risk. This is the rationale for paying attention to dyslipidemia through the use of the hypolipidemic, rather than hypoglycemic drugs only. A literature search (by Medline and Scopus) was performed. The authors also manually reviewed the references of selected articles for any pertinent material. Beyond the 'quantity' of LDL, several lipid-lowering agents and particularly statins, are only in part beneficial on the 'quality' of LDL, so that their net effect on small, dense LDL is moderate. Among hypoglycemic agents, insulin and metformin have shown a limited role on small, dense LDL, while pioglitazone is more beneficial. The efficacy of incretin-based therapies on LDL subclasses remains to be tested by future studies, considering that preliminary studies have reported significant improvements by these agents on triglycerides and HDL-C plasma concentrations. Beyond hypolipidemic drugs, hypoglycemic agents have been found to be significantly effective in modulating levels of small, dense LDL, towards less atherogenic particles in patients with Type 2 diabetes. This may be linked to the reduction in cardiovascular risk obtained by these agents in this category of high-risk subjects.
No preview · Article · Oct 2011 · Clinical Lipidology