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1.
Eat Weight Disord ; 21(2): 269-76, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26395273

ABSTRACT

PURPOSE: The aim of this study was to investigate the possible correlation between epicardial adipose tissue (EAT) thickness and predictive parameters for metabolic syndrome (MS) in overweight/obese prepubertal children. METHODS: 73 prepubertal children, average age of 8.22Ā years, with no endocrine or syndromic causes of obesity or under drug therapy for chronic disease were enrolled. Weight, height, body circumferences and skinfolds' thickness were measured. BMI, BMI z score (z-BMI) and waist-to-height ratio (WtHR) were calculated. Standard MS-related laboratory parameters were assessed. Finally, all children underwent echocardiographic measurement of EAT. RESULTS: A positive correlation between EAT and z-BMI was found only among overweight/obese children (rĀ =Ā 0.43, pĀ =Ā 0.001). In particular, data showed that 89Ā % of our sample had a waist (W) >90th percentile. Statistical differences in diastolic blood pressure (DBP; pĀ <Ā 0.01) and EAT (pĀ =Ā 0.02) were observed on comparing WĀ <90th percentile vs WĀ >90th percentile patients. Besides, in patients with W >90th percentile and family history of risk factors for MS, the value of EAT correlated positively with z-BMI, W, WtHR, triglycerides (Tg), insulin and homeostatic model assessment of insulin resistance and negatively with HDL. CONCLUSIONS: The EAT and the markers of MS probably share the same pathogenetic factors. Further studies might elucidate whether EAT deserves to be included among the diagnostic factors of MS.


Subject(s)
Adipose Tissue/metabolism , Body Weight/physiology , Metabolic Syndrome/diagnosis , Overweight/diagnosis , Adipose Tissue/diagnostic imaging , Child , Echocardiography , Female , Humans , Insulin Resistance/physiology , Male , Metabolic Syndrome/diagnostic imaging , Metabolic Syndrome/metabolism , Obesity/diagnosis , Obesity/diagnostic imaging , Obesity/metabolism , Overweight/diagnostic imaging , Overweight/metabolism , Risk Factors , Waist Circumference/physiology
2.
Eat Weight Disord ; 24(1): 1-2, 2019 02.
Article in English | MEDLINE | ID: mdl-30109494

Subject(s)
Adiposity , Obesity , Humans
3.
Sci Rep ; 13(1): 3400, 2023 02 28.
Article in English | MEDLINE | ID: mdl-36854960

ABSTRACT

Several theories have tried to elucidate the mechanisms behind the pathophysiology of chronic subdural hematoma (CSDH). However, this process is complex and remains mostly unknown. In this study we performed a retrospective randomised analysis comparing the cortical atrophy of 190 patients with unilateral CSDH, with 190 healthy controls. To evaluate the extent of cortical atrophy, CT scan images were utilised to develop an index that is the ratio of the maximum diameter sum of 3 cisterns divided by the maximum diameter of the skull at the temporal lobe level. Also, we reported, for the first time, the ultrastructural analyses of the CSDH using a combination of immunohistochemistry methods and transmission electron microscopy techniques. Internal validation was performed to confirm the assessment of the different degrees of cortical atrophy. Relative Cortical Atrophy Index (RCA index) refers to the sum of the maximum diameter of three cisterns (insular cistern, longitudinal cerebral fissure and cerebral sulci greatest) with the temporal bones' greatest internal distance. This index, strongly related to age in healthy controls, is positively correlated to the preoperative and post-operative maximum diameter of hematoma and the midline shift in CSDH patients. On the contrary, it negatively correlates to the Karnofsky Performance Status (KPS). The Area Under the Receiver Operating Characteristics (AUROC) showed that RCA index effectively differentiated cases from controls. Immunohistochemistry analysis showed that the newly formed CD-31 positive microvessels are higher in number than the CD34-positive microvessels in the CSDH inner membrane than in the outer membrane. Ultrastructural observations highlight the presence of a chronic inflammatory state mainly in the CSDH inner membrane. Integrating these results, we have obtained an etiopathogenetic model of CSDH. Cortical atrophy appears to be the triggering factor activating the cascade of transendothelial cellular filtration, inflammation, membrane formation and neovascularisation leading to the CSDH formation.


Subject(s)
Hematoma, Subdural, Chronic , Neurodegenerative Diseases , Humans , Hematoma, Subdural, Chronic/diagnostic imaging , Retrospective Studies , Physical Phenomena , Filtration , Inflammation , Atrophy
4.
BMC Gastroenterol ; 12: 162, 2012 Nov 16.
Article in English | MEDLINE | ID: mdl-23157720

ABSTRACT

BACKGROUND: The impact of viral subtype on the rate of sustained virological response (SVR) to antiviral therapy in patients chronically infected with hepatitis C genotype 1 subtype 1a and 1b has not been extensively investigated. The aim of this study is to determine whether the HCV genotype 1 subtypes 1a and 1b respond differently to treatment with PEGylated interferon (PEG-IFN) plus ribavirin. METHODS: For 48 weeks, 388 "naĆÆve"genotype 1 patients were treated weekly with PEG-IFN α-2a or PEG-INF α-2b combined with daily ribavirin (1000-1200 mg/day). The numbers of patients in whom HCV-RNA was undetectable were compared after 4 (rapid virological response, RVR), 12 (early virological response, EVR), and 48 (end treatment virological response, ETR) weeks of treatment as well as 24 weeks after the last treatment (sustained virological response, SVR). RESULTS: The rate of SVR was higher in subtype 1a patients than subtype 1b patients (55% vs. 43%; p < 0.02). Multiple logistic regression analysis showed that infection with genotype 1a (odds ratio(OR) : 1.8; 95% confidence interval (CI): 1.4 to 4.1), age < 50 years (OR:7.0; 95% CI 1.1 to 21.2), alanine aminotransferase level (ALT)<100 IU/ml (OR:2.1; 95% CI: 1.3 to3.5), HCV-RNA < 5.6 log10 IU/ml (OR: 3.2; 95% CI: 2.7 to 6.9) and fibrosis score < S3 (OR: 3.8; 95% CI:3.2 to 7.4), were all independent predictors of SVR. CONCLUSION: Dual antiviral therapy is more effective against HCV subtype 1a than against subtype 1b and this difference is independent of other factors that may favour viral clearance. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01342003.


Subject(s)
Antiviral Agents/therapeutic use , Hepacivirus/drug effects , Hepacivirus/genetics , Hepatitis C, Chronic/drug therapy , Interferon-alpha/therapeutic use , Polyethylene Glycols/therapeutic use , Adult , Alanine Transaminase/blood , Biopsy , Drug Therapy, Combination , Female , Genotype , Hepatitis C, Chronic/pathology , Humans , Interferon alpha-2 , Liver Cirrhosis/drug therapy , Liver Cirrhosis/pathology , Liver Cirrhosis/virology , Male , Middle Aged , RNA, Viral/blood , Recombinant Proteins/therapeutic use , Ribavirin/therapeutic use , Treatment Outcome
5.
Cells ; 11(15)2022 08 04.
Article in English | MEDLINE | ID: mdl-35954264

ABSTRACT

Obesity is associated with increased cardiovascular morbidity. Adult patients with growth hormone deficiency (GHD) show morpho-functional cardiological alterations. A total of 353 overweight/obese patients are enrolled in the period between 2009 and 2019 to assess the relationships between GH secretory capacity and the metabolic phenotype, cardiovascular risk factors, body composition and cardiac echocardiographic parameters. All patients underwent GHRH + arginine test to evaluate GH secretory capacity, DEXA for body composition assessment and transthoracic echocardiography. Blood samples are also collected for the evaluation of metabolic parameters. In total, 144 patients had GH deficiency and 209 patients had normal GH secretion. In comparing the two groups, we found significant differences in body fat distribution with predominantly visceral adipose tissue accumulation in GHD patients. Metabolic syndrome is more prevalent in the GHD group. In particular, fasting glycemia, triglycerides and systolic and diastolic blood pressure are found to be linearly correlated with GH secretory capacity. Epicardial fat thickness, E/A ratio and indexed ventricular mass are worse in the GHD group. In the population studied, metabolic phenotype, body composition, cardiovascular risk factors and cardiac morphology are found to be related to the GH secretory capacity. GH secretion in the obese patient seems to be an important determinant of metabolic health.


Subject(s)
Human Growth Hormone , Overweight , Body Composition , Cross-Sectional Studies , Human Growth Hormone/metabolism , Humans , Obesity/metabolism
6.
Indian J Med Res ; 134(6): 898-903, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22310821

ABSTRACT

Highly active antiretroviral therapy (HAART) significantly changed the prevalence of the cardiovascular manifestations of human immunodeficiency virus (HIV)/AIDS. In developed countries, a 30 per cent reduction in the prevalence of cardiomyopathy and pericardial effusion was observed, possibly related to a reduction of opportunistic infections and myocarditis. In developing countries, however, where the availability of HAART is limited, and the pathogenic impact of nutritional factors is significant, a 32 per cent increase was seen in the prevalence of cardiomyopathy and related high mortality rate from congestive heart failure. Also, some HAART regimens in developed countries, especially those including protease inhibitors, may cause, in a high proportion of HIV-infected patients, a lipodystrophy syndrome that is associated with an increased risk of cardiovascular events related to a process of accelerated atherosclerosis. Careful cardiac screening is warranted for patients who are being evaluated for, or who are receiving HAART regimens, particularly for those with known underlying cardiovascular risk factors, according to the most recent clinical guidelines.


Subject(s)
Acquired Immunodeficiency Syndrome/drug therapy , Antiretroviral Therapy, Highly Active/adverse effects , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Developing Countries , HIV-Associated Lipodystrophy Syndrome/complications , HIV-Associated Lipodystrophy Syndrome/etiology , Humans , Myocarditis/epidemiology , Prevalence , Risk Factors
7.
BMC Gastroenterol ; 10: 21, 2010 Feb 19.
Article in English | MEDLINE | ID: mdl-20170514

ABSTRACT

BACKGROUND: In patients with chronic hepatitis C virus (HCV) genotype 2 or 3, 24 weeks' treatment with pegylated interferon alfa (PEG-IFN-alpha) and ribavirin induces a sustained virological response (SVR) in almost 80% of cases. Evidence suggests that a similar response rate may be obtained with shorter treatment periods, especially in patients with a rapid virological response (RVR). The aim of this study was to compare the efficacy of 12 or 24 weeks of treatment in patients with chronic HCV genotype 2 or 3 and to identify patients suitable for 12 weeks treatment. METHODS: Two hundred and ten patients received PEG-IFN-alpha-2a (180 ug/week) and ribavirin (800-1200 mg/day) for 4 weeks. Patients with a RVR (HCV RNA not detectable) were randomized (1:1) to either 12 (group A1) or 24 (group A2) weeks of combination therapy. Patients without a RVR continued with 24-weeks' combination therapy (group B). HCV RNA was monitored at weeks 4, 8, 12, and 24, and at week 24 post-treatment. RESULTS: At study end, end of treatment response (ETR) was observed in 62 (86%) patients of group A1 and in 55 (77%) patients of group A2 (p < 0.05) Relapse rate was 3% each in groups A1 and A2, and 6% in group B. Among patients with a HCVRNA test 24 weeks after the end of treatment, SVR was observed in 60 (83%) of group A1 patients and in 53 (75%) of group A2 patients. Rapid virological response, low baseline HCV RNA levels, elevated alanine aminotransferase levels and low fibrosis score, were the strongest covariates associated with SVR, independent of HCV genotype. No baseline characteristic was associated with relapse. CONCLUSION: In HCV patients with genotype 2 or 3, 12-week combination therapy is as efficacious as 24-week therapy and several independent covariates were predictive of SVR. TRIAL REGISTRATION: Trial number ISRCTN29259563.


Subject(s)
Antiviral Agents/administration & dosage , Hepacivirus/genetics , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/virology , Interferon-alpha/administration & dosage , Polyethylene Glycols/administration & dosage , Ribavirin/administration & dosage , Adult , Aged , Drug Administration Schedule , Drug Therapy, Combination , Female , Genotype , Humans , Interferon alpha-2 , Logistic Models , Male , Middle Aged , Recombinant Proteins , Recurrence , Treatment Outcome , Young Adult
8.
J Clin Monit Comput ; 24(2): 101-5, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20058057

ABSTRACT

BACKGROUND: Takotsubo cardiomyopathy was described for the first time in Japan in the 1990s. It is very similar to the ischemic cardiopathy both for clinical and instrumental characteristics. His peculiarity is an alteration of the ventricular contraction mechanism with hypo-akinesis of the apex and lateral segments of the left ventricle, associated with hyper-kinesis of the heart base which is responsible for the typical echocardiographic aspect of a cruet during the systole. However, the etiology of this cardiomyopathy is still unknown despite the fact that numerous hypothesis have been made. A single study of 16 patients proved multivasal damage by a BLASH SCORE analysis of the coronary radiography. In our study, performed on 24 patients, we intended to assess the actual implication of the microcirculation by analyzing the TIMI frame count (TFC), so as reporting correlations between alterations of each single artery and its respective myocardial area. METHODS AND RESULTS: Six Cardiology Centres performed an International multi-centre collection of a consecutive series of 24 patients, of which 20 were women and four men. The average age was 67.4 years. All patients admitted to one of the Cardiology divisions were previously listed for symptoms and signs of Takotsubo cardiomyopathy. An electrocardiographic (ECG), echocardio-gram and a hemodynamic study were carried out on each patient. The patients were evaluated with a follow up lasting 7 weeks. On the coronary radiography film, the microcirculation was examined by an analysis of the TFC according to the Gibson technique. The value obtained was considered pathological if it was >30 frames. The evaluation of the microcirculation by the TFC analysis showed that in 23 of the 24 patients there was a pathological slow down of the flow in the coronary micro- circulation. By analysing the number of involved vessels it was noted that nine patients had a slowdown of the general flow in all three vessels, six patients in only two vessels and the remaining nine in one vessel. In particular: in 14 patients there was an abnormal TFC in left anterior descending coronary artery (LAD), 16 in the right coronary artery (RCA) and 18 in the left circumflex coronary artery (LCX), while in one patient the picture quality in the acute phase did not allow an evaluation of the score in the RCA and in another patient in the LDA. None of the explored vessels that was responsible for the disorder of the microcirculation showed any stenosis. CONCLUSION: From the data evaluated by us, microcirculatory dysfunction seems to be present very often during acute phases of Takotsubo illness, but it is not the only determining factor of the illness.


Subject(s)
Coronary Angiography/methods , Coronary Circulation , Microcirculation , Radiographic Image Interpretation, Computer-Assisted/methods , Takotsubo Cardiomyopathy/diagnostic imaging , Takotsubo Cardiomyopathy/physiopathology , Aged , Blood Flow Velocity , Female , Humans , Male
9.
Nutrients ; 12(11)2020 Nov 14.
Article in English | MEDLINE | ID: mdl-33202604

ABSTRACT

Sirtuin 1 (SIRT1) is a sensor of cell energy availability, and with leptin and adiponectin, it regulates metabolic homeostasis. Widely studied in tissues, SIRT1 is under evaluation as a plasmatic marker. We aimed at assessing whether circulating SIRT1 behaves consistently with leptin and adiponectin in conditions of deficiency, excess or normal fat content. Eighty subjects were evaluated: 27 with anorexia nervosa (AN), 26 normal-weight and 27 with obesity. Bloodstream SIRT1, leptin and adiponectin (ELISA), total and trunk fat mass (FM) %, abdominal visceral adipose tissue, liver steatosis and epicardial fat thickness (EFT) were assessed. For each fat store, the coefficient of determination (R2) was used to evaluate the prediction capability of SIRT1, leptin and adiponectin. Plasma SIRT1 and adiponectin coherently decreased with the increase of FM, while the opposite occurred with leptin. Mean levels of each analyte were different between groups (p < 0.005). A significant association between plasma variables and FM depots was observed. SIRT1 showed a good predictive strength for FM, particularly in the obesity group, where the best R2 was recorded for EFT (R2 = 0.7). Blood SIRT1, adiponectin and leptin behave coherently with FM and there is synchrony between them. The association of SIRT1 with FM is substantially superimposable to that of adiponectin and leptin. Given its homeostatic roles, SIRT1 may deserve to be considered as a plasma clinical/biochemical parameter of adiposity and metabolic health.


Subject(s)
Adiponectin/blood , Anorexia Nervosa/blood , Leptin/blood , Obesity/blood , Sirtuin 1/blood , Absorptiometry, Photon , Adolescent , Adult , Anorexia Nervosa/physiopathology , Biomarkers/blood , Cross-Sectional Studies , Echocardiography, Doppler , Enzyme-Linked Immunosorbent Assay , Female , Humans , Intra-Abdominal Fat/metabolism , Intra-Abdominal Fat/physiopathology , Linear Models , Male , Middle Aged , Obesity/physiopathology , Pericardium/physiopathology , Young Adult
10.
Curr Diab Rep ; 9(1): 37-42, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19192423

ABSTRACT

The introduction of highly active antiretroviral therapy (HAART) has significantly improved the clinical outcome of HIV disease with increased survival rates. However, some HAART regimens, especially those including protease inhibitors, have been shown to cause in a high proportion of HIV-infected patients metabolic (dyslipidemia, insulin resistance) and somatic (lipodystrophy/lipoatrophy) changes that are associated with an increased risk of cardiovascular disease (coronary artery disease and stroke). The pathogenesis of HAART-associated metabolic syndrome and of its atherogenic profile is complex, and several factors are involved, including direct effects of HAART on lipid metabolism, endothelial and adipocyte cell function, activation of proinflammatory cytokines, and mitochondrial dysfunction. A better understanding of the molecular mechanisms responsible for this syndrome will lead to the discovery of new drugs that will reduce the incidence of lipodystrophy and related metabolic complications in HIV-infected patients facing long-term HAART.


Subject(s)
Antiretroviral Therapy, Highly Active/adverse effects , HIV Infections/drug therapy , Metabolic Syndrome/chemically induced , Adipokines/physiology , Cardiovascular Diseases/chemically induced , Cardiovascular Diseases/physiopathology , HIV Infections/complications , Humans , Hypertension/etiology , Hypertension/physiopathology , Lipodystrophy/etiology , Lipodystrophy/metabolism , Metabolic Syndrome/physiopathology , Mitochondria/physiology , Protease Inhibitors/adverse effects , Protease Inhibitors/therapeutic use , Risk Assessment , Syndrome , Tumor Necrosis Factor-alpha/physiology
11.
Rev Assoc Med Bras (1992) ; 55(5): 621-30, 2009.
Article in English | MEDLINE | ID: mdl-19918668

ABSTRACT

The introduction of highly active antiretroviral therapy (HAART) has significantly improved the clinical outcome of HIV disease, with increased survival rates. However, the introduction of HAART has generated a contrast in the cardiac manifestations of AIDS. In developed countries, we observed an approximate 30% reduction in the prevalence of HIV-associated cardiomyopathy, possibly related to a reduction of opportunistic infections and myocarditis. In developing countries, however, where the availability of HAART is limited and the pathogenic impact of nutritional factors is significant, we observed an increase of approximately 32% in the prevalence of HIV-associated cardiomyopathy and a related high mortality rate from congestive heart failure. Also, some HAART regimens in developed countries, especially those including protease inhibitors, have been shown to cause, in a high proportion of HIV-infected patients, a iatrogenic metabolic syndrome (HIV-lipodystrophy syndrome).This is associated with an increased risk of atherosclerosis-related cardiovascular events even in young HIV-infected people. A better understanding of the molecular mechanisms responsible for this syndrome will lead to the discovery of new drugs that will reduce cardiovascular risk in HIV-infected patients receiving HAART.


Subject(s)
Acquired Immunodeficiency Syndrome/complications , Antiretroviral Therapy, Highly Active/adverse effects , Cardiomyopathies/etiology , Acquired Immunodeficiency Syndrome/drug therapy , Acquired Immunodeficiency Syndrome/metabolism , Humans
12.
Nutrition ; 59: 1-6, 2019 03.
Article in English | MEDLINE | ID: mdl-30415157

ABSTRACT

Epicardial adipose tissue is a particular visceral fat depot with unique anatomic, biomolecular, and genetic features. Epicardial fat displays both physiological and pathological properties. Epicardial fat expresses genes and secretes cytokines actively involved in the thermogenesis and regulation of lipid and glucose metabolism of the adjacent myocardium. A disequilibrium between epicardial fat feeding and overfeeding the myocardium with free fatty acids leads to intramyocardial fat infiltration causing organ damage and clinical consequences. The upregulation of epicardial fat proinflammatory and lipogenic genes contributes to the fat build up in the proximal coronary arteries. Epicardial fat is a measurable and modifiable risk factor that can serve as a novel and additional tool for cardiovascular risk stratification. Pharmacologically targeting epicardial fat with drugs such as glucagon peptide-like 1 analogs or sodium glucose transport 2 inhibitors reduces the epicardial fat burden and induces beneficial cardiometabolic effects. Assessment and manipulation of epicardial fat transcriptome might open new avenues in the prevention of cardiometabolic diseases.


Subject(s)
Adipose Tissue/metabolism , Pericardium/metabolism , Coronary Artery Disease/etiology , Cytokines/metabolism , Glucose/metabolism , Humans , Lipid Metabolism/physiology , Myocardium/metabolism , Risk Factors , Thermogenesis/physiology
13.
Int J Cardiol ; 265: 195-203, 2018 Aug 15.
Article in English | MEDLINE | ID: mdl-29885686

ABSTRACT

Human Immunodeficiency Virus (HIV) infection affects 36.7 million people worldwide, it accounted for 1.1 million deaths in 2015. The advent of combined antiretroviral therapy (cART) has been associated with a decrease in HIV-related morbidity and mortality. However, there are increasing concerns about long-lasting effects of chronic inflammation and immune activation, leading to premature aging and HIV-related mortality. Cardiovascular diseases, especially coronary artery disease, are among the leading causes of death in HIV-infected patients, accounting for up to 15% of total deaths in high income countries. Furthermore, as cART availability expands to low-income countries, the burden of cardiovascular related mortality is likely to rise. Hence, over the next decade HIV-associated cardiovascular disease burden is expected to increase globally. In this review, we summarize our understanding of the pathogenesis and risk factors associated with HIV infection and cardiovascular disease, in particular coronary artery disease.


Subject(s)
Anti-Retroviral Agents/administration & dosage , Cardiovascular Diseases/epidemiology , Cost of Illness , HIV Infections/epidemiology , Anti-Retroviral Agents/adverse effects , Cardiovascular Diseases/chemically induced , Cardiovascular Diseases/diagnosis , Drug Therapy, Combination , HIV Infections/diagnosis , HIV Infections/drug therapy , Humans , Risk Factors
14.
Article in English | MEDLINE | ID: mdl-30131769

ABSTRACT

Context: Sirtuins (SIRTs) are NAD+-dependent deacetylases, cellular sensors to detect energy availability, and modulate metabolic processes. SIRT1, the most studied family member, influences a number of tissues including adipose tissue. Expression and activity of SIRT1 reduce with weight gain and increase in conditions of starvation. Objective: To focus on SIRT1 plasma concentrations in different conditions of adiposity and to correlate SIRT1 with fat content and distribution, energy homeostasis and inflammation in under-weight, normal-weight, and obese individuals. Materials and Methods: 21 patients with anorexia nervosa, 26 normal-weight and 75 patients with obesity were evaluated. Body fat composition by dual-energy X-ray absorptiometry, ultrasound liver adiposity, echocardiographic epicardial fat thickness (EFT), inflammatory (ESR, CRP, and fibrinogen), and metabolic (FPG, insulin, LDL- and HDL-cholesterol, triglycerides) parameters, calculated basal metabolic rate (BMR) and plasma SIRT1 (ELISA) were measured. Results: SIRT1 was significantly higher in anorexic patients compared to normal-weight and obese patients (3.27 Ā± 2.98, 2.27 Ā± 1.13, and 1.36 Ā± 1.31 ng/ml, respectively). Linear regression models for each predictor variable adjusted for age and sex showed that SIRT1 concentration was inversely and significantly correlated with EFT, fat mass %, liver fat content, BMR, weight, BMI, WC, LDL-cholesterol, insulin, ESR. Stepwise multiple regression analysis revealed that age and EFT were the best independent correlates of SIRT1 (Ɵ = -0.026 Ā± 0.011, p = 0.025, and Ɵ = -0.516 Ā± 0.083, p < 0.001, respectively). Conclusions: Plasma SIRT1 shows a continuous pattern that inversely follows the whole spectrum of adiposity. SIRT1 significantly associates with EFT, a strong index of visceral fat phenotype, better than other indexes of adiposity studied here.

15.
Curr Med Chem ; 14(26): 2734-48, 2007.
Article in English | MEDLINE | ID: mdl-18045120

ABSTRACT

The introduction of highly active antiretroviral therapy (HAART) in 1996 dramatically changed the course of HIV infection. This therapy involves the use of at least three agents from two distinct classes of antivirals: a protease inhibitor (PI) in combination with two nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTIs), or a non-nucleoside reverse transcriptase inhibitor (NNRTI) in combination with NRTIs. Nine drugs containing PIs are clinically available: the first generation ones, saquinavir, ritonavir, indinavir, nelfinavir, and amprenavir, and the second generation ones, fosamprenavir (the amprenavir prodrug), lopinavir, atazanavir, and tipranavir. Many other compounds are in advanced clinical evaluation, such as among others TMC-114, whereas a lot of different other effective HIV protease inhibitors were reported, mainly by using amprenavir and TMC-114 as lead molecules. The main goals of research in this field are: (i) the design of better pharmacological agents, devoid of severe side effects, resistance problems and with simple administration schedules (preferably once daily), and (ii) achieving eradication of the virus, and possibly, a definitive cure of the disease. A review on the pharmacology and interactions of these agents with other drugs is presented here, with emphasis on how these pharmacological interferences may improve the clinical use of antivirals, or how side effects due to PI drugs may be managed better by taking them into account (such as for example ritonavir boosting of other PIs which reduces dosages and administration schedules of these drugs). Except for being highly effective in the treatment of HIV infection, recent reports showed this class of drugs to be effective as antitumor agents, as antibacterials (for example against Mycobacterium tuberculosis infection), antifungals (against Candida albicans), antimalarials, antiSARS and anti-influenza agents.


Subject(s)
HIV Infections/drug therapy , HIV Protease Inhibitors/therapeutic use , Anti-Bacterial Agents/therapeutic use , Anti-Retroviral Agents/pharmacology , Antifungal Agents/therapeutic use , Antineoplastic Agents/therapeutic use , Antiretroviral Therapy, Highly Active , Aspartic Acid Endopeptidases/antagonists & inhibitors , Drug Design , HIV Infections/virology , HIV Protease Inhibitors/adverse effects , HIV Protease Inhibitors/chemistry , HIV-1/drug effects , Humans , Molecular Structure
16.
Am J Cardiol ; 99(10): 1470-2, 2007 May 15.
Article in English | MEDLINE | ID: mdl-17493483

ABSTRACT

Patients infected with human immunodeficiency virus (HIV) are at increased risk for subclinical atherosclerosis. Whether increased cardiac adiposity may be related to HIV subclinical atherosclerosis is still unexplored. The objective of this study was to evaluate whether echocardiographically determined subepicardial adipose tissue, an index of cardiac adiposity, is related to carotid intima-media thickness (IMT), an index of subclinical atherosclerosis, in HIV-infected patients receiving highly active antiretroviral therapy. Echocardiographic epicardial fat thickness and ultrasonographic IMT were measured in 103 consecutive HIV-infected Caucasian subjects receiving highly active antiretroviral therapy. Echocardiographic subepicardial adipose tissue showed an excellent correlation with IMT (r = 0.92, p <0.01). Multiple regression analysis showed that IMT was best predicted by epicardial fat thickness (r(2) = 0.81, p <0.01). In conclusion, this study suggests, for the first time, that epicardial adipose tissue, an index of cardiac adiposity, may be significantly related to subclinical atherosclerosis in HIV-infected patients.


Subject(s)
Adipose Tissue/pathology , Carotid Artery Diseases/etiology , Carotid Artery, Common/pathology , Pericardium/pathology , Tunica Intima/pathology , Tunica Media/pathology , Adipose Tissue/diagnostic imaging , Adipose Tissue/virology , Adiposity , Adolescent , Adult , Aged , Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly Active , Blood Pressure , Body Mass Index , Carotid Artery Diseases/diagnostic imaging , Carotid Artery Diseases/pathology , Carotid Artery Diseases/virology , Carotid Artery, Common/diagnostic imaging , Carotid Artery, Common/physiopathology , Carotid Artery, Common/virology , Echocardiography , Female , HIV Infections/complications , HIV Infections/diagnostic imaging , HIV Infections/drug therapy , HIV Infections/pathology , Humans , Male , Middle Aged , Pericardium/diagnostic imaging , Pericardium/virology , Predictive Value of Tests , Regression Analysis , Treatment Outcome , Tunica Intima/diagnostic imaging , Tunica Intima/virology , Tunica Media/diagnostic imaging , Tunica Media/virology , Waist-Hip Ratio
17.
Oncol Rep ; 17(5): 1121-6, 2007 May.
Article in English | MEDLINE | ID: mdl-17390054

ABSTRACT

The majority of cancers affecting HIV-infected subjects are those established as acquired immunodeficiency syndrome (AIDS)-defining: Kaposi's sarcoma (KS), non-Hodgkin's lymphoma (NHL), and invasive cervical cancer (ICC). However, other types of cancer, such as Hodgkin's disease (HD), anal cancer, lung cancer and testicular germ cell tumors appear to be more common among HIV-infected subjects compared to the general population. While not classified as AIDS-defining, these malignancies have been referred to as AIDS-associated malignancies. The mechanisms by which depressed immunity could increase the risk for cancer are unclear, except for in KS and most subtypes of NHL, where it is strictly associated with a low CD4 count. Although it remains unclear whether HIV-1 acts directly as an oncogenic agent, it may contribute to the development of malignancies through several mechanisms (e.g., infection by oncogenic viruses, impaired immune surveillance, imbalance between cellular proliferation and differentiation). Studies of the effect of highly active antiretroviral therapy (HAART) on the incidence and progression of HIV/AIDS-associated cancers provided contrasting data. While a significant decrease in the incidence of KS has been observed, HAART has not had a significant impact on NHL incidence, particularly systemic NHL, or on ICC, HD, anal cancers and other non-AIDS-defining cancers. Regardless of whether these cancers are directly related to HIV-induced immunodeficiency, treating cancer in HIV-infected patients remains a challenge because of drug interactions, compounded side effects, and the potential effect of chemotherapy on CD4 count and HIV-1 viral load. A better knowledge of viral mechanisms of immune evasion and manipulation will provide the basis for a better management and treatment of the malignancies associated with chronic viral infections.


Subject(s)
HIV Infections/complications , HIV Infections/drug therapy , HIV-1 , Neoplasms/virology , Antiretroviral Therapy, Highly Active , HIV Infections/virology , Humans
18.
Expert Opin Drug Metab Toxicol ; 3(3): 451-64, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17539751

ABSTRACT

Erectile dysfunction frequently represents a neurovascular complication of diabetes mellitus, and it has been calculated that almost 50% of diabetic men will have erectile dysfunction within 6 years after diagnosis. Penile endothelial and smooth muscle cell dysfunction are due to molecular pathway abnormalities (i.e., activation of PKC, increased oxidative stress and overproduction of advanced-glycosylation end products). The response rate to oral drug therapies, such as sildenafil, is lower than in most other groups. Because therapeutic alternatives (i.e., intracavernous injections with vasoactive agents) are not curative, clinical trials aimed to demonstrate rehabilitative effects with daily phosphodiesterase type-5 inhibitors are ongoing. If this approach proves successful, it will determine many advantages over the intracavernosal treatment and potentially induce sexual rehabilitation.


Subject(s)
Diabetes Complications/drug therapy , Erectile Dysfunction/drug therapy , Piperazines/therapeutic use , Sulfones/therapeutic use , 3',5'-Cyclic-GMP Phosphodiesterases/antagonists & inhibitors , 3',5'-Cyclic-GMP Phosphodiesterases/metabolism , Cyclic Nucleotide Phosphodiesterases, Type 5 , Diabetes Complications/physiopathology , Endothelium, Vascular/drug effects , Endothelium, Vascular/physiopathology , Erectile Dysfunction/complications , Erectile Dysfunction/physiopathology , Humans , Male , Models, Biological , Phosphodiesterase Inhibitors/administration & dosage , Phosphodiesterase Inhibitors/pharmacology , Phosphodiesterase Inhibitors/therapeutic use , Piperazines/administration & dosage , Piperazines/pharmacology , Purines/administration & dosage , Purines/pharmacology , Purines/therapeutic use , Sildenafil Citrate , Sulfones/administration & dosage , Sulfones/pharmacology
19.
Curr HIV Res ; 4(1): 79-85, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16454713

ABSTRACT

Highly active antiretroviral therapy (HAART) regimens, especially those including protease inhibitors have been shown to cause, in a high proportion of HIV-infected patients, a metabolic syndrome (lipodystrophy/lipoatrophy, dyslipidemia, type 2 diabetes mellitus, insulin resistance) that may be associated with an increased risk of cardiovascular disease. A careful stratification of the cardiovascular risk of HIV-infected patients under HAART is needed according to the most recent clinical guidelines.


Subject(s)
Antiretroviral Therapy, Highly Active/adverse effects , Cardiovascular Diseases/chemically induced , HIV Infections/drug therapy , HIV-Associated Lipodystrophy Syndrome/chemically induced , Metabolic Diseases/chemically induced , Cardiovascular Diseases/epidemiology , Diabetes Mellitus, Type 2/chemically induced , Diabetes Mellitus, Type 2/epidemiology , Dyslipidemias/chemically induced , Dyslipidemias/epidemiology , HIV-Associated Lipodystrophy Syndrome/epidemiology , Humans , Insulin Resistance , Male , Metabolic Diseases/epidemiology , Risk Factors , Syndrome
20.
Curr HIV Res ; 4(2): 239-41, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16611062

ABSTRACT

Takotsubo cardiomyopathy (in Japanese language "takotsubo" is a fishing pot with a round bottom and a neck that is used for trapping octopuses) is a new syndrome, which is characterized by transient left ventricular dysfunction and by a typical left ventriculogram showing transient extensive akinesis of the apical and mid portions of the left ventricle with hypercontraction of the basal segment, from which this disease takes its name. Since 1990 sporadic cases of takotsubo cardiomyopathy were reported by Japanese authors, and only a few European reports are available. We report a case of takotsubo-like left ventricular dysfunction in an human immunodeficiency virus (HIV)-infected caucasian patient.


Subject(s)
HIV Infections/complications , HIV/growth & development , Ventricular Dysfunction, Left/virology , Adrenergic beta-Antagonists/therapeutic use , Adult , Echocardiography , Humans , Male , Ventricular Dysfunction, Left/diagnosis , Ventricular Dysfunction, Left/drug therapy
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