Alexandre José Faria Carrilho

Prevalência da lipodistrofia associada ao HIV em pacientes ambulatoriais brasileiros: relação com síndrome metabólica e fatores de risco cardiovascular

Lipodystrophy in HIV-infected patients (LDHIV) affects 40-50% of HIV-infected patients, but there are no data on its prevalence in Brazil. The aim of this study was to assess the LDHIV prevalence among HIV-infected adult Brazilian individuals, as well as to evaluate LDHIV association with cardiovascular risk factors and the metabolic syndrome (MS). It was included 180 adult HIV-infected outpatients consecutively seen in the Infectology Clinic of Universidade Estadual de Londrina. Anthropometric and clinical data (blood pressure, family and personal comorbidities, duration of HIV infection/AIDS, antiretroviral drugs used, CD4+ cells, viral load, fasting glycemia and plasma lipids) were obtained both from a clinical interview as well as from medical charts. LDHIV was defined as the presence of body changes self-reported by the patients and confirmed by clinical exam. MS was defined using the NCEP-ATPIII criteria, reviewed and modified by AHA/NHLBI. A 55% prevalence of LDHIV was found. Individuals with LDHIV presented a longer infected period since HIV infection, longer AIDS duration and longer use of antiretroviral drugs. In multivariate analysis, women (p=0.006) and AIDS duration >8 years (p 25 kg/m(2) (p 40 years on HIV first detection (p=0.002). There was a trend to higher frequency of LDHIV among patients with MS (65% versus 50%, p=0.051). LDHIV prevalence among our patients (55%) was similar to previous reports from other countries. MS prevalence in these HIV-infected individuals seems to be similar to the prevalence reported on Brazilian non-HIV-infected adults.

Lipoproteins and CETP levels as risk factors for severe sepsis in hospitalized patients

Eur J Clin Invest 2010; 40 (4): 330–338

Metformin increases HDL3-cholesterol and decreases subcutaneous truncal fat in nondiabetic patients with HIV-associated lipodystrophy.

The purpose of this study was to assess metformin effects on high-density lipoprotein (HDL) composition of patients with HIV-associated lipodystrophy (LDHIV). Twenty-four adult outpatients were enrolled to receive metformin (1700 mg/d) during 6 months, but 2 were lost to follow-up and 6 stopped the drug due to adverse events (gastrointestinal in 5, and excessive weight loss in 1). From the 16 subjects who completed the study, 69% were female. At baseline, 3 and 6 months, we assessed: weight, waist and hip circumferences, blood pressure, fasting glucose and insulin, homeostasis model assessment of insulin resistance (HOMA2-IR), lipids, and HDL subfractions by microultracentrifugation. At 0 and 6 months, body fat distribution was assessed by computed tomography (CT) scan (L4 and middle femur). Metformin use was associated with reduction of mean weight (-2.4Kg at 6 months; p < 0.001), body mass index, waist, waist-to-hip ratio and a marked decrease in blood pressure (p < 0.001). Subcutaneous (p = 0.01) and total abdominal fat (p = 0.002) were reduced, but no change was found in visceral or thigh fat. No difference was detected on plasma glucose, insulin, HOMA2-IR, cholesterol or triglycerides, except for an increase in HDL3-cholesterol (from 21 mg/dL to 24 mg/dL, p = 0.002) and a reduction of nascent HDL (the fraction of plasma HDL-cholesterol not associated to subfractions HDL2 or HDL3) (p = 0.008). Adverse effects were very common, but most were gastrointestinal and mild. Thus, metformin use in LDHIV increases HDL3-cholesterol (probably due to improved maturation of HDL) and decreases blood pressure, weight, waist, and subcutaneous truncal fat, making this an attractive option for preventing cardiovascular disease in this population.

Prevalência de auto-imunidade tireoidiana em um grupo de pacientes com diabetes mellitus tipo 1 em Londrina, PR

Thyroid autoimmunity is a frequent comorbid condition subjects with in type 1 diabetes mellitus (DM1). We evaluated the prevalence of antithyroid autoantibodies (antimicrosomal, antithyroglobulin and antithyroid peroxidase), in addition to clinical (gender, age, DM duration) and laboratory (TSH, HbA1) characteristics of 101 patients (mean age 20 ± 9.6 years; 62 female) followed at the HC/UEL. RESULTS: Autoantibodies were found in 31 subjects (30.7%). In the age group 18 years, 35.7% (p= 0.22). Among the patients with positive antibodies, 40% had some thyroid dysfunction vs only 4.4% of those without antibodies (p<0.001). The average TSH was higher in the positive than in negative group (3.75 and 2.32µU/mL, respectively; p= 0.01). CONCLUSIONS: The prevalence of thyroid antibodies was 30.7%, in accordance to the literature.

Regulation of hepatic cholesterol metabolism in CETP/LDLr mice by cholesterol feeding and by drugs (cholestyramine and lovastatin) that lower plasma cholesterol.

1 The hepatic mechanisms involved in the simultaneous regulation of plasma cholesterol concentration and cholesteryl ester transfer protein (CETP) activity were investigated by sharply modifying the hepatic rates of cholesterol synthesis. This was accomplished by cholestyramine, lovastatin and cholesterol feeding in human CETP transgenic mice cross‐bred with low‐density lipoprotein receptor (LDLr)‐knockout mice, generating CETP+/–/LDLr+/– mice, which present a plasma lipoprotein profile resembling that of humans. 2 Analyses of pooled data showed that the plasma CETP activity correlated positively with plasma total cholesterol concentration, hepatic CETP mRNA and the liver microsomal cholesterol content; a negative correlation was found between plasma CETP activity and the liver 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase and LDLr mRNA levels. These coordinated events represent an efficient control system that stabilizes the cell cholesterol content. 3 Nonetheless, not all cholesterol metabolism regulatory systems seem to fit into a coherent pattern of responses, suggesting that other unknown cellular mechanisms play roles depending on the type of pharmacological intervention. 4 For example, microsomal cholesterol content was not affected by cholestyramine, but was increased on cholesterol feeding (as predicted), and, surprisingly, on lovastatin treatment. Furthermore, although both plasma cholesterol‐lowering drugs increased CYP7A1 mRNA and had no effect on CYP27 mRNA, other metabolic components were differentially modified. Cholestyramine and lovastatin, respectively, did not modify and increased both HMG‐CoA and sterol responsive element binding protein 1c mRNA, did not modify and lowered liver X receptor α mRNA, lowered and increased ATP binding cassette A1 mRNA and lowered and did not modify scavenger receptor B1 mRNA. 5 That is, different to unabsorbed cholestyramine, lovastatin, as an absorbed plasma cholesterol‐lowering drug, may have modified the activity of other unknown genes that play roles in the interaction of CETP with the metabolism of hepatic cholesterol.

Impaired antioxidant action of high density lipoprotein in patients with type 1 diabetes with normoalbuminuria and microalbuminuria

AIMS Patients with type 1 diabetes, in the absence of chronic complications, have serum concentrations of high density lipoprotein cholesterol (HDL-C) similar to the general population. However, their HDL particles may be dysfunctional. We aimed to evaluate the antioxidant effect of HDL2 and HDL3 obtained from Caucasian males with type 1 diabetes with normoalbuminuria and microalbuminuria. METHODS Twenty Caucasian men with type 1 diabetes (10 with normoalbuminuria and 10 with microalbuminuria) and 10 healthy Caucasian men participated in the study. Lipoproteins were obtained by density gradient ultracentrifugation. The antioxidant effect of HDL was assessed by measuring lipid hydroperoxide (LOOH) concentration after 3h of pooled LDL oxidation catalyzed by 5μM CuSO4 in the absence or presence of HDL2 or HDL3. RESULTS The control, normoalbuminuria, and microalbuminuria groups had similar HDL-C concentration and estimated glomerular filtration rate. Glycemic control was similar between diabetes groups (HbA1c 8.1±0.9% and 8.3±0.7%, P=0.70), but estimated glucose disposal rate was lower in patients with microalbuminuria (8.0±0.6 and 4.5±1.1mg/kg/min, P<0.01). The relative antioxidant effect of HDL2 from control, normoalbuminuria, and microalbuminuria groups were 92.8±2.4%, 85.4±1.7%, and 74.2±4.6%, respectively (P<0.01), and the HDL3 effect were 95.0±2.2%, 86.4±4.4%, and 75.3±4.2%, respectively (P<0.01). CONCLUSION Both HDL2 and HDL3 inhibited LOOH formation in copper-catalyzed oxidation of LDL in vitro. Overall, this antioxidant effect was lower in Caucasian men with type 1 diabetes, and was further compounded in those with microalbuminuria.

Adrenocorticotropic hormone but not high-density lipoprotein cholesterol or salivary cortisol was a predictor of adrenal insufficiency in patients with septic shock.

ABSTRACT Relative adrenal insufficiency in sepsis has been extensively debated on; however, accurate diagnosis and therapeutic intervention remain controversial. The authors aimed to evaluate adrenocorticotropic hormone (ACTH), salivary cortisol, total cortisol and estimated plasma-free cortisol, cholesterol, and lipoproteins as predictors of adrenal insufficiency in patients within 24 h of septic shock diagnosis. This prospective study evaluated all hospitalized patients older than 18 years who developed septic shock and were using vasoactive drugs within 24 h of diagnosis. Blood and saliva samples were drawn at baseline and 60 min (T60) after 250 &mgr;g tetracosactide intravenous injection. Patients were divided into two groups: responders (&Dgr; [T60 minus baseline] total cortisol >9 &mgr;g/dL) and nonresponders (&Dgr; total cortisol ⩽9 &mgr;g/dL or baseline total cortisol <10 &mgr;g/dL). The latter group was considered to have adrenal insufficiency. A total of 7,324 hospitalized patients were monitored, and 34 subjects with septic shock were included in the analysis. Adrenal insufficiency was found in 32.4%. Total cholesterol, high-density lipoprotein cholesterol, triglycerides, and salivary cortisol did not differ between groups. Estimated plasma-free cortisol was not better than total plasma cortisol in estimating adrenal function. Baseline endogenous ACTH was higher in nonresponders than responders (55.5 pg/mL vs. 18.3 pg/mL, respectively; P = 0.01). The cutoff ACTH value that discriminated patients with adrenal insufficiency was 31.5 pg/mL. Thus, endogenous ACTH measured within 24 h of septic shock diagnosis could predict adrenal response to tetracosactide.

A boy with Prader-Willi syndrome: unmasking precocious puberty during growth hormone replacement therapy

Prader-Willi syndrome (PWS) is a genetic disorder frequently characterized by obesity, growth hormone deficiency, genital abnormalities, and hypogonadotropic hypogonadism. Incomplete or delayed pubertal development as well as premature adrenarche are usually found in PWS, whereas central precocious puberty (CPP) is very rare. This study aimed to report the clinical and biochemical follow-up of a PWS boy with CPP and to discuss the management of pubertal growth. By the age of 6, he had obesity, short stature, and many clinical criteria of PWS diagnosis, which was confirmed by DNA methylation test. Therapy with recombinant human growth hormone (rhGH) replacement (0.15 IU/kg/day) was started. Later, he presented psychomotor agitation, aggressive behavior, and increased testicular volume. Laboratory analyses were consistent with the diagnosis of CPP (gonadorelin-stimulated LH peak 15.8 IU/L, testosterone 54.7 ng/dL). The patient was then treated with gonadotropin-releasing hormone analog (GnRHa). Hypothalamic dysfunctions have been implicated in hormonal disturbances related to pubertal development, but no morphologic abnormalities were detected in the present case. Additional methylation analysis (MS-MLPA) of the chromosome 15q11 locus confirmed PWS diagnosis. We presented the fifth case of CPP in a genetically-confirmed PWS male. Combined therapy with GnRHa and rhGH may be beneficial in this rare condition of precocious pubertal development in PWS.

Research update for articles published in EJCI in 2012

Department of Cardiology and Coronary Unit, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain, Biomarkers Research Program, Biochemistry Department, College of Science, , Prince Mutaib Chair for Biomarkers of Osteoporosis, Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia, Cardiovascular Research Center (CSIC-ICCC), Barcelona, Spain, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain, Cardiovascular Research Chair, UAB, Barcelona, Spain, Cardiology Department, Hospital Clinico Universitario, INCLIVA, University of Valencia, Valencia, Spain, First Clinical of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy, Department of Cardiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China, Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands, Health Research Institute, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain, Liver Research Unit, Santa

Research update for articles published in EJCI in 2010: RESEARCH UPDATE

Christopher Adlbrecht, Elmar Aigner, Juan M. Bellón, Izolde Bouloukaki, Alberto Bouzas-Mosquera, Alexandre J. F. Carrilho, Kuo-Chu Chang, Nipon Chattipakorn, Siriporn C. Chattipakorn, Yi-Jen Chen, Yuan-Chiang Chung, Roshan Colah, Christian Datz, Jens B. Frøkjær, Shunji Fujimori, Panagiota Georgiadou, Cintia M. Grion, Chih-Ping Hsu, Martin Hülsmann, Ming-Jui Hung, Ming-Yow Hung, Efstathios K. Iliodromitis, Irene M. Lang, TingI. Lee, Winfried März, Sona B. Nair, Gemma Pascual, Jesús Peteiro, Choitsu Sakamoto, Atsushi Satomura, Sophia E. Schiza, Peter Stärkel, Tatjana Stojakovic, David L. Vesely, Darren L.Walters and Yusuf Yilmaz Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria, First Department of Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria, Detartment of Medical Specialities and Surgery, University of Alcala, Alcalá de, Spain, Networking Research Centre on Biomaterials, Bioengineering and Nanomedicine (CIBER-BBN), Madrid, Spain, Sleep Disorders Unit, Department of Thoracic Medicine, Medical School, University of Crete, Heraklion, Greece, Department of Cardiology, Hospital Universitario A Coruña, A Coruña, Spain, Department of Internal Medicine, Londrina State University, Londrina, PR, Brazil, Department of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan, Cardiac Electrophysiology Research and Training Center, Chiang Mai University, Chiang Mai, Thailand, Graduate Institute of Clinical Medicine, College of Medicine, Taipei, Taiwan, Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, Department of Surgery, Cheng-Ching General Hospital, Taichung, Taiwan, National Institute of Immunohematology (I.C.M.R.), K.E.M Hospital Campus, Parel, Mumbai, India, Department of Internal Medicine, General Hospital Oberndorf, Oberndorf, Austria, Mech-Sense, Department of Radiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark, Department of Gastroenterology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan, 2nd Division of Interventional Cardiology, Onassis Cardiac Surgery Center, Athens, Greece, Department of Medical Laboratory Science and Biotechnology, Yuanpei University, Hsinchu, Taiwan, Department of Cardiology, Chang Gung Memorial Hospital, Keelung, Chang Gung University College of Medicine, Gueishan, Taoyuan, Taiwan, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei, Taiwan, Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan, 2nd University Department of Cardiology, Medical School, Attikon University General Hospital, Athens, Greece, Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria, Institute of Public Health, Social and Preventive Medicine, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany, Synlab Academy, Synlab Services GmbH, Mannheim, Germany, Division of Laboratory Medicine, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan, Institut de recherche expérimentale et clinique (IREC), Université Catholique de Louvain, Brussels, Belgium, Department of Gastroenterology, St. Luc University Hospital, Brussels, Belgium, Departments of Internal Medicine and Molecular Pharmacology and Physiology, James A. Haley Veterans Hospital, Tampa, FL, USA, University of South Florida Health Sciences Cardiac Hormone Center, Tampa, FL, USA, The Prince Charles Hospital, University of Queensland, Brisbane, Qld, Australia, Institute of Gastroenterology, Istanbul, Turkey, Department of Gastroenterology, School of Medicine, Marmara University, Istanbul, Turkey