RESUMO
Ureteropelvic junction obstruction (UPJO) is a congenital or acquired functionally significant impairment of urinary transport from the renal pelvis to the ureter. Congenital UPJO typically results from intrinsic disease such as the presence of an aperistaltic segment of the ureter, aberrant vessels or kidney abnormalities. Rare conditions can sometimes mimic an UPJO. We present a case of an 86-year-old woman with a UPJO diagnosed on CT. The patient was counseled on treatment options and elected to undergo a left uretherorenoscopy (URS) plus left laparoscopic pyeloplasty. The definitive histopathologic diagnosis was perinephric myxoid pseudotumor of fat, an extremely rare neoplasm, mass-forming. To the best of our knowledge, this is the first known case of a pseudotumor of fat causing UPJO. 6-month follow-up showed neither recurrence nor residual UPJO. We describe a rare presentation of extrinsic perinephric myxoid pseudotumor of fat causing UPJ obstruction. In elderly patients with no history of malignancy, UPJ obstruction can occur because of atypical masses.
Assuntos
Laparoscopia , Ureter , Obstrução Ureteral , Feminino , Humanos , Idoso , Idoso de 80 Anos ou mais , Laparoscopia/métodos , Ureter/cirurgia , Pelve Renal/patologia , Pelve Renal/cirurgia , Rim/anormalidadesRESUMO
AIM: Aortic stenosis is a frequent valvular disease, with transcatheter aortic valve implantation (TAVI) being performed when surgical replacement is at increased risk. However, TAVI-induced effects on myocardial efficiency are unknown. We aimed to investigate changes in LV mechano-energetic pre-/post-TAVI and their prognostic impact. METHODS: A total of 46 patients (25 males) received transesophageal and simultaneous radial pressure plus transaortic gradient monitoring before/immediately after prosthesis deployment. Efficiency was computed as external work/potential energy, as derived from LV pressure-volume plots; myocardial oxygen consumption (MVO2) was estimated as PWImod, i.e. a noninvasively validated alternative for MVO2 estimation. RESULTS: TAVI was successful in all patients, peak transaortic gradient decreasing - 40 ± 20 mmHg (p < 0.001). Efficiency improved post-TAVI (+ 0.6 ± 0.12; p = 0.004), with a concomitant PWImod reduction (- 16 ± 31%; p < 0.001). When contextualized to fixed PWImod value (5 ml/min/100 g), efficiency significantly affected survival (p = 0.029). Over 1026 ± 450-day follow-up, a change in efficiency pre-/post-TAVI ≤ 0.021 (median of the difference) predicted more deaths from any cause (30%) as compared with a change > 0.021 (17%), particularly in those patients with a pre-TAVI mean high-gradient (HG ≥ 40 mmHg) phenotype (p < 0.05). In particular, HG patients exhibited the lowest efficiency/PWImod ratio pre-/post-TAVI (p = 0.048), relative to the other aortic stenosis patients, suggestive of an unfavourable matching between cardiac function and metabolic demand, which foreshortens some intrinsic damaged muscle condition in these patients. CONCLUSION: LV mechanical efficiency improves immediately post-TAVI, notwithstanding an inhomogeneous mechano-energetic matching among the aortic stenosis patients, which can impact negatively on their long-term prognosis, particularly in those with the HG phenotype.
Assuntos
Estenose da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/cirurgia , Substituição da Valva Aórtica Transcateter , Função Ventricular Esquerda/fisiologia , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/mortalidade , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Volume Sistólico/fisiologia , Taxa de Sobrevida , Resultado do Tratamento , Pressão Ventricular/fisiologiaRESUMO
STUDY QUESTION: Can high resolution array-CGH analysis on a cohort of women showing a primary ovarian insufficiency (POI) phenotype in young age identify copy number variants (CNVs) with a deleterious effect on ovarian function? SUMMARY ANSWER: This approach has proved effective to clarify the role of CNVs in POI pathogenesis and to better unveil both novel candidate genes and pathogenic mechanisms. WHAT IS KNOWN ALREADY: POI describes the progression toward the cessation of ovarian function before the age of 40 years. Genetic causes are highly heterogeneous and despite several genes being associated with ovarian failure, most of genetic basis of POI still needs to be elucidated. STUDY DESIGN, SIZE, DURATION: The current study included 67 46,XX patients with early onset POI (<19 years) and 134 control females recruited between 2012 and 2016 at the Medical Cytogenetics and Molecular Genetics Lab, IRCCS Istituto Auxologico Italiano. PARTICIPANTS/MATERIALS, SETTING, METHODS: High resolution array-CGH analysis was carried out on POI patients' DNA. Results of patients and female controls were analyzed to search for rare CNVs. All variants were validated and subjected to a gene content analysis and disease gene prioritization based on the present literature to find out new ovary candidate genes. Case-control study with statistical analysis was carried out to validate our approach and evaluate any ovary CNVs/gene enrichment. Characterization of particular CNVs with molecular and functional studies was performed to assess their pathogenic involvement in POI. MAIN RESULTS AND THE ROLE OF CHANCE: We identified 37 ovary-related CNVs involving 44 genes with a role in ovary in 32 patients. All except one of the selected CNVs were not observed in the control group. Possible involvement of the CNVs in POI pathogenesis was further corroborated by a case-control analysis that showed a significant enrichment of ovary-related CNVs/genes in patients (P = 0.0132; P = 0.0126). Disease gene prioritization identified both previously reported POI genes (e.g. BMP15, DIAPH2, CPEB1, BNC1) and new candidates supported by transcript and functional studies, such as TP63 with a role in oocyte genomic integrity and VLDLR which is involved in steroidogenesis. LARGE SCALE DATA: ClinVar database (http://www.ncbi.nlm.nih.gov/clinvar/); accession numbers SCV000787656 to SCV000787743. LIMITATIONS, REASONS FOR CAUTION: This is a descriptive analysis for almost all of the CNVs identified. Inheritance studies of CNVs in some non-familial sporadic cases was not performed as the parents' DNA samples were not available. Addionally, RT-qPCR analyses were carried out in few cases as RNA samples were not always available and the genes were not expressed in blood. WIDER IMPLICATIONS OF THE FINDINGS: Our array-CGH screening turned out to be efficient in identifying different CNVs possibly implicated in disease onset, thus supporting the extremely wide genetic heterogeneity of POI. Since almost 50% of cases are negative rare ovary-related CNVs, array-CGH together with next generation sequencing might represent the most suitable approach to obtain a comprehensive genetic characterization of POI patients. STUDY FUNDING/COMPETING INTEREST(S): Supported by Italian Ministry of Health grants 'Ricerca Corrente' (08C203_2012) and 'Ricerca Finalizzata' (GR-2011-02351636, BIOEFFECT) to IRCCS Istituto Auxologico Italiano.
Assuntos
Hibridização Genômica Comparativa , Variações do Número de Cópias de DNA , Dosagem de Genes , Ovário/fisiologia , Insuficiência Ovariana Primária/genética , Adolescente , Idade de Início , Estudos de Casos e Controles , Criança , Bases de Dados Genéticas , Feminino , Genoma Humano , Humanos , Menopausa Precoce/genética , Mutação , Doenças Ovarianas/genética , Fenótipo , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genéticaRESUMO
Primary ovarian insufficiency (POI) is characterized by a loss of ovarian function before the age of 40 and account for one major cause of female infertility. POI relevance is continuously growing because of the increasing number of women desiring conception beyond 30 years of age, when POI prevalence is >1%. POI is highly heterogeneous and can present with ovarian dysgenesis and primary amenorrhea, or with secondary amenorrhea, and it can be associated with other congenital or acquired abnormalities. In most cases POI remains classified as idiopathic. However, the age of menopause is an inheritable trait and POI has a strong genetic component. This is confirmed by the existence of several candidate genes, experimental and natural models. The variable expressivity of POI defect may indicate that, this disease may frequently be considered as a multifactorial or oligogenic defect. The most common genetic contributors to POI are the X chromosome-linked defects. Here, we review the principal X-linked and autosomal genes involved in syndromic and non-syndromic forms of POI with the expectation that this list will soon be upgraded, thus allowing the possibility to predict the risk of an early age at menopause in families with POI.
Assuntos
Amenorreia/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Disgenesia Gonadal/genética , Insuficiência Ovariana Primária/genética , Adulto , Amenorreia/patologia , Feminino , Genes Ligados ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Disgenesia Gonadal/patologia , Humanos , Menopausa/genética , Ovário/metabolismo , Ovário/patologia , Insuficiência Ovariana Primária/patologiaRESUMO
It has been reported that patients with Down syndrome (DS) frequently develop transient myeloproliferative disorder (TMD) and less commonly myeloid leukemia in DS (ML-DS). We examined the pathogenetic relationship of these conditions with somatic mutations of the GATA1 gene in children with both TMD and ML-DS. To determine the incidence of GATA1 mutations in a cohort of DS patients and the applicability of these mutations as a clonal marker to detect minimal residual disease, we screened 198 samples of 169 patients with DS for mutations in GATA1 exon 2 by direct sequencing. Novel mutations were detected in four of the 169 DS patients (2 with TMD and 2 with ML-DS). We examined spontaneous remission and response to therapy in TMD and ML-DS patients and concluded that these mutations can be used as stable markers in PCR analysis to monitor these events.
Assuntos
Síndrome de Down/genética , Mutação da Fase de Leitura , Fator de Transcrição GATA1/genética , Leucemia Mieloide/genética , Transtornos Mieloproliferativos/genética , Sequência de Bases , Análise Mutacional de DNA , Síndrome de Down/tratamento farmacológico , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Lactente , Recém-Nascido , Leucemia Mieloide/tratamento farmacológico , Masculino , Transtornos Mieloproliferativos/tratamento farmacológico , Resultado do TratamentoRESUMO
We report on a patient carrying a 17q21.31 microdeletion and exhibiting many common syndrome features, together with other clinical signs which have rarely or never been described to date. The detected 695-kb 17q21.31 deletion is larger than in most previously reported cases but is still probably the result of recombination between flanking low-copy repeats. Due to the complexity of the patient's clinical condition, together with the presence of 3 previously unreported symptoms, namely chronic anemia, cervical vertebrae arthrosis and vertebrae fusion, this case is an important addition to the existing knowledge about the 17q21.31 microdeletion syndrome.
RESUMO
We analyzed the results of treatment with imatinib mesylate in 70 patients with chronic-phase chronic myeloid leukemia who had previously been treated (with second-line or higher imatinib), many of them in a late chronic phase. The median follow-up period was 60.5 months (range 3-100 months). Our objective was to assess the efficacy and safety of treatment. The mean dose was 400 mg per day. The hematologic response rate was 92.1% at six months, while the cumulative rates of major and complete cytogenetic responses were 73.6 and 66.3%, respectively. Molecular response rate improved slowly and steadily over time, reaching 65.8% at 60 months, remaining stable for up to 96 months. The five-year progression-free survival and overall survival were 84 and 89%, respectively. Cytogenetic response by 12 months significantly correlated with overall survival (P = 0.0007) and progression-free survival (P = 0.0280). Sokal risk score did not differ significantly between subgroups. The medication was well tolerated, with only 16% of patients showing hematologic toxicity grades 3 and 4. At the end of the assessment, 57% of the patients were still on imatinib mesylate; most of those who discontinued treatment (17/30) did so because of unsatisfactory response. Treatment with imatinib mesylate in previously treated chronic-phase chronic myeloid leukemia induced durable responses in a high proportion of patients and was related to satisfactory long-term and event-free survival.
Assuntos
Antineoplásicos/uso terapêutico , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Benzamidas , Brasil , Intervalo Livre de Doença , Feminino , Humanos , Mesilato de Imatinib , Leucemia Mieloide de Fase Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Piperazinas/administração & dosagem , Piperazinas/efeitos adversos , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Resultado do TratamentoRESUMO
The role played by genetic components in the etiology of the Class III phenotype, a class of dental malocclusion, is not yet understood. Regions that may be related to the development of Class III malocclusion have been suggested previously. The aim of this study was to search for genetic linkage with 6 microsatellite markers (D1S234, D4S3038, D6S1689, D7S503, D10S1483, and D19S566), near previously proposed candidate regions for Class III. We performed a two-point parametric linkage analysis for 42 affected individuals from 10 Brazilian families with a positive Class III malocclusion segregation. Analysis of our data indicated that there was no evidence for linkage of any of the 6 microsatellite markers to a Class III locus at = zero, with data supporting exclusion for 5 of the 6 markers evaluated. The present work reinforces that Class III is likely to demonstrate locus heterogeneity, and there is a dependency of the genetic background of the population in linkage studies.
Assuntos
Má Oclusão Classe III de Angle/genética , Prognatismo/genética , Brasil , Genes Dominantes , Heterogeneidade Genética , Ligação Genética , Loci Gênicos , Mandíbula/anormalidades , Repetições de Microssatélites , LinhagemRESUMO
WHAT IS KNOWN AND OBJECTIVE: The efficacy of sibutramine has been demonstrated in randomized trials in obese/overweight patients including those with type 2 diabetes mellitus (T2DM). Our objective was to evaluate the effects of 1-year treatment with sibutramine compared to placebo on body weight, glycaemic control, lipid profile, and inflammatory parameters in type 2 diabetic patients. METHODS: Two hundred and forty-six patients with uncontrolled T2DM [glycated haemoglobin (HbA(1c) ) > 8·0%] in therapy with different oral hypoglycaemic agents or insulin were randomized to take 10 mg of sibutramine or placebo for 12 months. We evaluated at baseline, and after 3, 6, 9, and 12 months these parameters: body weight, body mass index (BMI), HbA(1c) , fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), leptin, tumour necrosis factor-α (TNF-α), adiponectin (ADN), vaspin, high sensitivity C-reactive protein (Hs-CRP). RESULTS AND DISCUSSION: We observed a decrease of body weight after 9 and 12 months in the group treated with sibutramine, but not in the control group. Regarding glycaemic and lipid profile, although there are differences seen over time within each of the groups, we did not obtain any significant differences between the two groups. Both placebo and sibutramine gave a similar improvement of HOMA-IR, leptin, TNF-α, ADN, and Hs-CRP. No vaspin variations were observed in either group. WHAT IS NEW AND CONCLUSION: Sibutramine resulted in a decrease in body weight at 9 months and at 12 months that was not observed with placebo. Although there were differences seen over time within each of the groups, there were no significant differences between groups for any other parameter that we measured.
Assuntos
Depressores do Apetite/farmacologia , Ciclobutanos/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Inflamação/tratamento farmacológico , Obesidade/tratamento farmacológico , Obesidade/epidemiologia , Adiponectina/sangue , Depressores do Apetite/efeitos adversos , Glicemia , Índice de Massa Corporal , Peso Corporal , Proteína C-Reativa/metabolismo , Comorbidade , Ciclobutanos/efeitos adversos , Diabetes Mellitus Tipo 2/metabolismo , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/farmacologia , Inflamação/metabolismo , Inflamação/patologia , Inflamação/fisiopatologia , Insulina/sangue , Resistência à Insulina , Leptina/sangue , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/patologia , Obesidade/fisiopatologia , Placebos , Ensaios Clínicos Controlados Aleatórios como Assunto , Tiazolidinedionas/farmacologia , Fatores de TempoRESUMO
WHAT IS KNOWN: The increased risk of cardiovascular events in diabetic patients has been related to numerous metabolic and haemoreological factors. Some of these factors appear to be particularly evident during the post-prandial phases and to be related to peak plasma glucose level. AIM: To compare the effect of addition of pioglitazone and acarbose to sulphonylureas and metformin therapy on metabolic parameters and on markers of endothelial dysfunction and vascular inflammation in type 2 diabetic patients. MATERIALS AND METHODS: We enrolled 473 caucasian type 2 diabetic patients. All patients underwent measurements of height and body weight, body mass index (BMI), glycated haemoglobin (HbA1c) , fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), post-prandial plasma insulin (PPI), homeostasis model assessment (HOMA index), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), sICAM-1, IL-6, high-sensitivity C reactive protein (hsCRP), sVCAM-1, sE-selectin and tumour necrosis factor (TNF-α). Assessments were made at start of titration, after 3 months [before a first oral glucose tolerance test (OGTT)], after 6 months and at the study end (before a second OGTT). RESULTS: Two-hundred and seventy four patients completed the study: 138 were randomized to double-blind treatment with pioglitazone and 136 with acarbose. Significant BMI and weight increase were observed after full treatment in the pioglitazone group relative to the acarbose group. A decrease in glycated haemoglobin was observed after the titration period in the pioglitazone group compared to both baseline value and the acarbose group. A decrease in glycated haemoglobin was also obtained after full treatment in the pioglitazone group when compared to the end of titration period and to the acarbose group. Significant decrease in FPG was obtained in the pioglitazone group after full treatment compared to the end of titration period. Post-prandial plasma glucose decrease was observed in acarbose group compared to the baseline value and to the end of titration period. Fasting plasma insulin decreased in the pioglitazone group after both the titration period and the full treatment period compared to both the baseline value and the acarbose group. The HOMA index decreased significantly after the full treatment in pioglitazone group compared to the end of titration period and to the acarbose group. Interleukin-6 and tumour necrosis factor-α decreased after full treatment in the pioglitazone group relative to the end of titration period. Significant hsCRP decrease was obtained after the titration period when compared to the baseline value in the pioglitazone group. High-sensitivity C reactive protein decreased in the pioglitazone group after full treatment compared to the end of titration period and to the acarbose group. WHAT IS NEW AND CONCLUSION: Pioglitazone reduces the inflammatory response to a glucose challenge more than acarbose in type 2 diabetic patients, already treated with maximal doses of sulphonylureas and metformin.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Tiazolidinedionas/uso terapêutico , Acarbose/administração & dosagem , Acarbose/uso terapêutico , Biomarcadores , Glicemia , Pressão Sanguínea/efeitos dos fármacos , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/administração & dosagem , Inflamação/sangue , Interleucina-6/sangue , Lipídeos/sangue , Masculino , Metformina/administração & dosagem , Metformina/uso terapêutico , Pessoa de Meia-Idade , Pioglitazona , Compostos de Sulfonilureia/administração & dosagem , Tiazolidinedionas/administração & dosagem , Fator de Necrose Tumoral alfa/sangueRESUMO
We looked for genotoxic effects in laboratory personnel routinely exposed to petroleum derivate compounds in an indoor environment. The exposed group of 21 workers from the Fuel Quality Control Laboratory of the Brazilian Petroleum Agency was matched with a group of 10 people from the staff of the Brazilian Ministry of Health. Chromosome aberrations in peripheral blood lymphocytes, micronuclei in exfoliated cells in the urine and hematological parameters were examined. There was a significantly increased level of chromosome aberrations and micronuclei in the exposed group compared with controls. A high correlation between chromosome aberrations and micronuclei was observed in the exposed group (Spearman rank test, r = 0.73, P = 0.0001). The hematological parameters in these exposed individuals did not differ from reference values.
Assuntos
Aberrações Cromossômicas , Linfócitos/efeitos dos fármacos , Mutagênicos , Petróleo/toxicidade , Adulto , Brasil , Dano ao DNA , Feminino , Humanos , Masculino , Testes para Micronúcleos , Exposição Ocupacional , Petróleo/efeitos adversos , Controle de Qualidade , Valores de Referência , Bexiga Urinária/metabolismoRESUMO
The aim of the study was to compare the effects of vildagliptin added to pioglitazone or glimepiride on metabolic and insulin resistance related-indices in poorly controlled type 2 diabetic patients (T2DM). 168 patients with T2DM were randomized to take either pioglitazone 30 mg once a day plus vildagliptin 50 mg twice a day or glimepiride 2 mg 3 times a day plus vildagliptin 50 mg twice a day. We evaluated body weight, body mass index (BMI), glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), homeostasis model assessment beta-cell function index (HOMA-beta), fasting plasma proinsulin (FPPr), proinsulin/fasting plasma insulin ratio (Pr/FPI ratio), adiponectin (ADN), resistin (R), tumor necrosis factor-alpha (TNF-alpha), and high sensitivity C-reactive protein (Hs-CRP) at their baseline values, and after 3, 6, 9, and 12 months of treatment. We observed a similar improvement of HbA1c, FPG, PPG, and Hs-CRP compared to baseline in the 2 groups. Fasting plasma insulin, FPPr, Pr/FPI ratio, R, and TNF-alpha were significantly decreased and ADN was significantly increased with pioglitazone plus vildagliptin, but not with glimepiride plus vildagliptin. HOMA-IR, and HOMA-beta values obtained with pioglitazone plus vildagliptin were significantly better than the values obtained with glimepiride plus vildagliptin. Pioglitazone plus vildagliptin were found to be more effective in preserving beta-cell function, and in reducing insulin resistance, and inflammatory state parameters.
Assuntos
Adamantano/análogos & derivados , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Nitrilas/uso terapêutico , Pirrolidinas/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Tiazolidinedionas/uso terapêutico , Adamantano/uso terapêutico , Índice de Massa Corporal , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Quimioterapia Combinada , Feminino , Humanos , Hipoglicemiantes/farmacologia , Inflamação/complicações , Inflamação/patologia , Resistência à Insulina , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Masculino , Pessoa de Meia-Idade , Pioglitazona , Compostos de Sulfonilureia/farmacologia , Tiazolidinedionas/farmacologia , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/metabolismo , VildagliptinaRESUMO
BACKGROUND: Incretin-based therapies have provided additional options for the treatment of type 2 diabetes mellitus. The aim of our study was to evaluate the effects of exenatide compared to glibenclamide on body weight, glycemic control, beta-cell function, insulin resistance, and inflammatory state in patients with diabetes. METHODS: One hundred twenty-eight patients with uncontrolled type 2 diabetes mellitus receiving therapy with metformin were randomized to take exenatide 5 microg twice a day or glibenclamide 2.5 mg three times a day and titrated to exenatide 10 microg twice a day or glibenclamide 5 mg three times a day. We evaluated body weight, body mass index (BMI), glycated hemoglobin (HbA(1c)), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance (HOMA-IR) index, homeostasis model assessment beta-cell function (HOMA-beta) index, plasma proinsulin (PPr), PPr/FPI ratio, resistin, retinol binding protein-4 (RBP-4), and high-sensitivity C-reactive protein (Hs-CRP) at baseline and after 3, 6, 9, and 12 months. RESULTS: Body weight and BMI decreased with exenatide and increased with glibenclamide. A similar improvement of HbA(1c), FPG, and PPG was obtained in both groups, whereas FPI decreased with exenatide and increased with glibenclamide. The HOMA-IR index decreased and the HOMA-beta index increased with exenatide but not with glibenclamide. A decrease of PPr was reported in both groups, but only glibenclamide decreased the PPr/FPI ratio. Resistin and RBP-4 decreased with exenatide and increased with glibenclamide. A decrease of Hs-CRP was obtained with exenatide, whereas no variations were observed with glibenclamide. CONCLUSIONS: Both exenatide and glibenclamide gave a similar improvement of glycemic control, but only exenatide gave improvements of insulin resistance and beta-cell function, giving also a decrease of body weight and of inflammatory state.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Glibureto/uso terapêutico , Hipoglicemiantes/uso terapêutico , Peptídeos/uso terapêutico , Peçonhas/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/efeitos dos fármacos , Índice de Massa Corporal , Peso Corporal/efeitos dos fármacos , Proteína C-Reativa/análise , Exenatida , Feminino , Hemoglobinas Glicadas/análise , Humanos , Hiperglicemia/tratamento farmacológico , Incretinas/agonistas , Resistência à Insulina/fisiologia , Células Secretoras de Insulina/efeitos dos fármacos , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Proinsulina/sangue , Resistina/sangue , Proteínas Plasmáticas de Ligação ao Retinol/análise , Adulto JovemRESUMO
The aim of this study was to evaluate the effect of an oral glucose tolerance test (OGTT) on the level of endothelial dysfunction and vascular inflammation markers in healthy subjects (H) and diabetic overweight patients (D). We enrolled 256 healthy subjects and 274 type 2 diabetic patients. We evaluated blood glucose (BG), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), high-sensitivity C reactive protein (hsCRP), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), and tumor necrosis factor-alpha (TNF-alpha) at baseline and after OGTT. We observed that BG, sICAM-1, IL-6, hs-CRP, sVCAM-1, sE-selectin, and TNF-alpha values were higher in D group than in H group. In a large sample of adult healthy subjects and type 2 diabetics we observed that both answer to an OGTT with a significant increase in biomarkers of systemic low-grade inflammation and endothelial dysfunction such as hsCRP, IL-6, TNF-alpha, sICAM-1, sVCAM-1, and sE-selectin. Type 2 diabetics experienced, however, a more significant increase in TNF-alpha, and sE-selectin.
Assuntos
Biomarcadores/sangue , Doenças Cardiovasculares/imunologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Endotélio Vascular/imunologia , Endotélio/imunologia , Adulto , Glicemia , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/imunologia , Feminino , Teste de Tolerância a Glucose , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/sangue , Molécula 1 de Adesão de Célula Vascular/sangueRESUMO
The aim of this study was to compare the effect of telmisartan and eprosartan on insulin sensitivity in overweight hypertensive patients. Fifty overweight (BMI > or = 25 and <30 kg/m (2)) outpatients, aged 41-65 years, with mild to moderate hypertension [systolic blood pressure (SBP) >140 and diastolic blood pressure (DBP) > or = 90 and < or = 110 mmHg], after a 4-week placebo period, were randomized to receive telmisartan 80 mg or eprosartan 600 mg for 8 weeks. Following another 4-week placebo period, patients were crossed to the alternative regimen for further 8 weeks. At the end of each placebo and active treatment period, blood pressure (BP), insulin sensitivity (by euglycemic hyperinsulinemic clamp), fasting plasma glucose (FPG), insulin (FPI), total cholesterol (TC), LDL-C, HDL-C, and triglycerides (Tg) were evaluated. Insulin sensitivity was expressed as the amount of glucose infused during the last 30 min (glucose infusion rate, GIR) in micromol/min/kg. Both telmisartan and eprosartan significantly reduced SBP/DBP values (by a mean of 19.4/13.3 mmHg and 17.9/12.1 mmHg respectively, all p<0.001 vs. placebo), with no significant difference between the two treatments. GIR was significantly increased by telmisartan (2.25+/-0.61 micromol/min/kg, p<0.05 vs. placebo) but not by eprosartan (0.25+/-0.14 micromol/min/kg, p=ns), the difference between the two drugs being statistically significant (p<0.02). No change in FPG, FPI, HDL-C, and Tg was observed with either treatment. Telmisartan significantly reduced TC (-9.9 mg/dl, -5%, p<0.04 vs. placebo) and LDL-C (-8.8 mg/dl, -7%, p<0.03 vs. placebo), whereas eprosartan did not influence them. These findings indicate a superiority regarding an improvement of insulin sensitivity and plasma lipid profile in overweight hypertensives by telmisartan as compared to eprosartan, possibly related to the selective stimulating PPAR-gamma property of telmisartan.
Assuntos
Acrilatos/uso terapêutico , Benzimidazóis/uso terapêutico , Benzoatos/uso terapêutico , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Imidazóis/uso terapêutico , Insulina/metabolismo , Sobrepeso/complicações , Sobrepeso/tratamento farmacológico , Tiofenos/uso terapêutico , Adulto , Idoso , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Glicemia , Feminino , Humanos , Hipertensão/sangue , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Sobrepeso/sangue , Sobrepeso/fisiopatologia , TelmisartanRESUMO
Acute lymphoblastic leukemia (ALL) accounts for approximately 80% of all acute leukemias during childhood. Chromosomal anomalies resulting from gene fusion, which are frequent in leukemias, create hybrid transcripts, the great majority of which encode transcription factors. We analyzed 88 pediatric patients (median age 7.3 years) who had B-lineage acute lymphoblastic leukemia (B-ALL), using reverse transcriptase-polymerase chain reaction, to look for gene fusion transcripts of TEL/AML1, E2A/PBX1, BCR/ABL p190, and MLL/AF4. The frequencies of these transcripts were 21.21, 9.68, 3.03, and 0%, respectively. All positive cases had a common B-ALL immunophenotype. The low frequency of the TEL/AML1 transcript that is found in developing countries, such as Brazil, may be due to the low incidence of leukemia; this would support Greaves' hypothesis.
Assuntos
Aberrações Cromossômicas , Mutação , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Brasil , Linhagem da Célula , Criança , Bases de Dados Genéticas , Feminino , Humanos , Imunofenotipagem , Masculino , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismoRESUMO
We evaluate the effect of a standardized dietary supplementation with omega-3 polyunsaturated fatty acids (n-3 PUFAs) on the level of some markers of vascular remodeling in patients with combined dyslipidemia. Three hundred and thirty-three patients received placebo or n-3 PUFAs for 6 months. We evaluated body mass index, glycemic profile, blood pressure, lipid profile, lipoprotein(a), plasminogen activator inhibitor-1, homocysteine, fibrinogen, high-sensitivity C reactive protein, ADP, MMP-2 and MMP-9, and tissue inhibitors of metalloproteinase-1 and -2. A significant increase of high-density lipoprotein-cholesterol, and a significant decrease of triglycerides were present after 3 and 6 months with n-3 PUFAs intake. A significant plasminogen activator inhibitor-1, fibrinogen and high-sensitivity C reactive protein decrease was obtained after 3 and 6 months and a significant ADP increase was observed after 3 and 6 months of n-3 PUFAs. A significant MMP-2, MMP-9, tissue inhibitors of metalloproteinase-1 and tissue inhibitors of metalloproteinase-2 decrease was obtained after 6 months compared to the baseline value with n-3 PUFAs intake. n-3 PUFAs give a better lipid profile and a better improvement of coagulation, fibrinolytic and inflammatory parameters than placebo. Furthermore, lowers levels of MMP-2, MMP-9 and their tissue inhibitors are obtained with n-3 PUFAs compared to placebo.
Assuntos
Dislipidemias/tratamento farmacológico , Ácidos Graxos Ômega-3/uso terapêutico , Metaloproteases/metabolismo , Inibidores de Proteases/uso terapêutico , Estudos de Casos e Controles , Feminino , Fibrinólise , Humanos , Masculino , Metaloproteases/antagonistas & inibidores , PlacebosRESUMO
BACKGROUND AND OBJECTIVE: Most antidiabetic agents target only one of several underlying causes of diabetes. The complementary actions of the glinides and the biguanides may give optimal glycemic control in patients with type 2 diabetes mellitus. The aim of the present study was to compare the effects of nateglinide plus metformin with glibenclamide plus metformin on glucose and lipid metabolism, and haemodynamic parameters in patients with type 2 diabetes mellitus. METHODS: We enrolled 248 type 2 diabetic patients. Patients were randomly assigned to receive nateglinide (n = 124) or glibenclamide (n = 124), after 6 months of run-in, in which we titrated nateglinide (starting dose 180 mg/day), glibenclamide (starting dose 7.5 mg/day), and metformin (starting dose 1500 mg/day). The final doses were (mean +/- standard deviation), 300 +/- 60, 12.5 +/- 2.5, and 2500 +/- 500 mg/day, respectively. We followed these patients for 1 year after titration. We assessed body mass index (BMI), fasting (FPG) and post-prandial (PPG) plasma glucose, glycosylated haemoglobin (HbA(1c)), fasting (FPI) and post-prandial (PPI) plasma insulin, homeostasis model assessment (HOMA) index, and lipid profile [total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), apolipoprotein A-I (Apo A-I), and apolipoprotein B (Apo B)], systolic blood pressure (SBP), and diastolic blood pressure (DBP). All variables were evaluated at baseline and after 3 and 6 months in the run-in period, and at baseline, and after 3, 6, 9 and 12 months for both treatment groups. RESULTS AND DISCUSSION: Body mass index did not show any significant change during the study. We observed a significant improvement from baseline to 1 year on HbA(1c) (P < 0.01 vs. baseline and vs. glibenclamide group, respectively), FPG (P < 0.01 vs. baseline), PPG (P < 0.01 vs. baseline), and on HOMA index (P < 0.05 vs. baseline) in the nateglinide group. In the glibenclamide group, we found significant changes in HbA(1c) (P < 0.05 vs. baseline), FPG (P < 0.01 vs. baseline), PPG (P < 0.05 vs. baseline), and HOMA index (P < 0.05 vs. baseline). No significant change was observed in TC, LDL-C, HDL-C, Tg, Apo A-I, Apo B, SBP, DBP and HR in either group after 3, 6, 9 and 12 months. These effects of nateglinide and glibenclamide on insulin-resistance parameters are in agreement with previous reports. Contrarily to previous reports, we did not observe any significant BP change in patients treated with glibenclamide. Although both nateglinide and glibenclamide attenuated PPG and HOMA index, they did not have significant effects on lipid metabolism, as already shown in subjects with type 2 diabetes and good glycemic control. CONCLUSION: Nateglinide improved glycemic control better than glibenclamide in combination with metformin.
Assuntos
Cicloexanos/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glibureto/farmacologia , Hipoglicemiantes/farmacologia , Metformina/uso terapêutico , Fenilalanina/análogos & derivados , Glicemia/análise , Índice de Massa Corporal , Cicloexanos/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Glibureto/uso terapêutico , Hemoglobinas Glicadas/análise , Hemodinâmica/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/sangue , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Nateglinida , Fenilalanina/farmacologia , Fenilalanina/uso terapêuticoRESUMO
The data reported in literature revealed a novel function for matrix metalloproteinases (MMPs) as modulators of adipogenesis. However, their expression profile and role in the cellular microenvironment during obesity-mediated adipose tissue development remain poorly defined. The authors hypothesized that MMP-2 and MMP-9 levels might be abnormal in obesity, reflecting alterations in extracellular matrix (ECM) turnover. One hundred and sixty three obese patients and 165 controls were enrolled. The following were measured: body mass index (BMI), waist circumference (WC), fasting plasma glucose (FPG), fasting plasma insulin (FPI), homeostasis model assessment (HOMA) index, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (Tg), lipoprotein(a) (Lp(a)), and plasma levels of MMP-2 and MMP-9. A significant increase of BMI and WC (p< .0001) was observed in obese patients. No FPG change was present in obese group, whereas FPI and HOMA index increases (p< .0001) were obtained in obese patients compared to control subjects. No SBP and DBP variations were observed in obese group. Significant TC and LDL-C increases (p< .0001) were present in obese patients, whereas no HDL-C, Tg, and Lp(a) changes were obtained in both groups. MMP-2 and MMP-9 levels were significantly higher in obese group (p< .0001). Plasma levels of MMP-2 and MMP-9 are increased in obese patients which may reflect abnormal ECM metabolism.
Assuntos
Resistência à Insulina/fisiologia , Metaloproteinase 2 da Matriz/sangue , Metaloproteinase 9 da Matriz/sangue , Obesidade/enzimologia , Adulto , Pressão Sanguínea , Índice de Massa Corporal , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/enzimologia , Feminino , Humanos , Itália , Lipídeos/sangue , Lipoproteína(a)/sangue , Masculino , Obesidade/sangue , Obesidade/fisiopatologiaRESUMO
BACKGROUND AND OBJECTIVE: Angiotensin II receptor blockers represent a class of effective and well-tolerated orally active antihypertensive drugs in the general hypertensive population and in diabetic patients. The aim of our study was to investigate the metabolic effects of telmisartan and irbesartan in diabetic subjects treated with rosiglitazone. METHODS: We evaluated 188 type 2 diabetic patients with metabolic syndrome. All patients took a fixed dose of 4 mg rosiglitazone/day. We administered 40 mg telmisartan/day or 150 mg irbesartan/day and evaluated their body mass index, glycosylated haemoglobin (HbA(1c)), fasting plasma glucose (FPG), fasting plasma insulin (FPI), homeostasis model assessment-index (Homa-IR), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol, triglycerides, systolic blood pressure, diastolic blood pressure, adiponectin and resistin during 12 months of this treatment. RESULTS AND DISCUSSION: In addition to a comparable antihypertensive effect for telmisartan and irbesartan after 6 and 12 months, both treatments were associated with a significant reduction in TC and LDL-C plasma levels compared with baseline. After 6 months of treatment, only the telmisartan group experienced a significant improvement in (HbA(1c)), FPG, Homa-IR, adiponectin and resistin compared with the baseline values, whereas both drug regimens were associated with a significant improvement in these parameters after 12 months. However, the improvements observed in the telmisartan group were significantly larger than that noted in the irbesartan group after 12 months of treatment. FPI significantly decreased only after 12 months of treatment in both groups, but again, the reduction was significantly larger in the telmisartan-treated subjects. CONCLUSIONS: Telmisartan seemed to improve glycaemic and lipid control and metabolic parameters of the metabolic syndrome better than irbesartan. These differences could be relevant in the choice of therapy for this condition and diabetes.