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1.
Eur Rev Med Pharmacol Sci ; 26(1 Suppl): 127-137, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36448870

RESUMO

OBJECTIVE: Sub-trochanteric fractures are among the most challenging for trauma surgeons. The purpose of this study was to analyze our own experience about subtrochanteric fractures. We focused on functional and radiographic outcomes after intramedullary locked nail fixation with or without cerclage assist. PATIENTS AND METHODS: A retrospective analysis on subtrochanteric fractures managed from January 2016 to April 2021 was conducted. Patients treated by closed reduction and intramedullary nail fixation were enrolled in Group A, while Group B included those patients who underwent wire-assisted intramedullary nail fixation. All patients performed clinical and radiological follow-up and complications were analyzed. The significance was established for a value of p < 0.05. RESULTS: 80 patients were included in the present study. The mean age was 74.2 (+/-19.2) years. The mean surgical time was 84.7 (+/-24.6) and 254.7 (+/-80.2) minutes in Group A and Group B, respectively. The mean blood loss was 87.3 (+/-18.3) ml in Group A and 224.4 (+/-37.8) ml in Group B. Quality of reduction was mainly superior in Group B. The mean time of union was 4.2 (+/-1.4) months in Group A and 3.4 (+/-2.1) months in Group B. Statistical differences were observed in Visual Analogue Scale (VAS) and in the Short Form 12 (SF-12) after 6 and 12 months of follow-up with better results in Group B. The complication rate was 18.2% in Group A and 12.2% in Group B. CONCLUSIONS: We recommend the use of wires when acceptable closed reduction cannot be obtained because its use may be useful for medial wall stability. For elderly patients, closed reduction may be more appropriate as the quality of life and functional recovery between the two methods is almost overlapped.


Assuntos
Fraturas do Quadril , Procedimentos de Cirurgia Plástica , Cirurgiões , Idoso , Humanos , Qualidade de Vida , Estudos Retrospectivos , Fraturas do Quadril/diagnóstico por imagem , Fraturas do Quadril/cirurgia
2.
Diabetes Metab ; 48(4): 101323, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35045332

RESUMO

We tested the hypothesis that common genetic variability of beta-cell genes responsible for monogenic diabetes may affect beta cell function in type 2 diabetes mellitus (T2DM). We studied 794 drug- naïve GAD-negative patients with newly diagnosed T2DM (age: median=59 years; I.Q. range: 52-66; body mass index: 29.3 kg/m2; 26.6-32.9). Beta-cell function was assessed by state-of-art mathematical modeling of glucose/C-peptide curves during a 240'-300' frequently sampled oral glucose tolerance test, to provide the beta-cell responses to the rate of increase in glucose concentration (derivative control: DC) and to glucose concentration (proportional control: PC). Forty-two single nucleotide polymorphism (SNPs), selected to cover over 90% of common genetic variability, were genotyped in nine monogenic diabetes genes: HNF4A, GCK, HNF1A, PDX1, HNF1B, NEUROD1, KLF11, KCNJ11 and ABCC8. Allelic variants of four SNPs (rs1303722 and rs882019 of GCK, rs7310409 of HNF1A and rs5219 of KCNJ11) were significantly associated with DC of beta-cell secretion (all P < 0.036). Allelic variants of four other SNPs (rs2868094 and rs6031544 of HNF4A, and rs1801262 and rs12053195 of NEUROD1) were associated with PC of beta-cell secretion (P < 0.02). In multivariate models, GCK, HNF1A and KCNJ11 SNPs explained 2.5% of the DC variability of beta-cell secretion, whereas HNF4A and NEUROD1 SNPs explained 3.6% of the PC variability of beta-cell secretion. We conclude that common variability of monogenic diabetes genes is significantly associated with an impaired beta-cell function in patients with newly diagnosed T2DM; thereby, these genes might be targeted by specific treatments in T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Idoso , Peptídeo C , Glucose , Teste de Tolerância a Glucose , Humanos , Pessoa de Meia-Idade , Mutação
3.
J Endocrinol Invest ; 44(12): 2567-2574, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34128214

RESUMO

BACKGROUND: Elevated fasting plasma glucose has been associated with increased risk for development of type 2 diabetes (T2D). The balance between glucokinase (GCK) and glucose-6-phosphate catalytic subunit 2 (G6PC2) activity are involved in glucose homeostasis through glycolytic flux, and subsequent insulin secretion. AIM: In this study, we evaluated the association between the genetic variability of G6PC2 and GCK genes and T2D-related quantitative traits. METHODS: In 794 drug-naïve, GADA-negative, newly diagnosed T2D patients (VNDS; NTC01526720) we performed: genotyping of 6 independent tag-SNPs within GCK gene and 5 tag-SNPs within G6PC2 gene; euglycaemic insulin clamp to assess insulin sensitivity; OGTT to estimate beta-cell function (derivative and proportional control; DC, PC) by mathematical modeling. Genetic association analysis has been conducted using Plink software. RESULTS: Two SNPs within GCK gene (rs882019 and rs1303722) were associated to DC in opposite way (both p < 0.004). Two G6PC2 variants (rs13387347 and rs560887) were associated to both parameters of insulin secretion (DC and PC) and to fasting C-peptide levels (all p < 0.038). Moreover, subjects carrying the A allele of rs560887 showed higher values of 2h-plasma glucose (2hPG) (p = 0.033). Haplotype analysis revealed that GCK (AACAAA) haplotype was associated to decreased fasting C-peptide levels, whereas, the most frequent haplotype of G6PC2 (GGAAG) was associated with higher fasting C-peptide levels (p = 0.001), higher PC (ß = 6.87, p = 0.022) and the lower 2hPG (p = 0.012). CONCLUSION: Our findings confirmed the role of GCK and G6PC2 in regulating the pulsatility in insulin secretion thereby influencing insulin-signaling and leading to a gradual modulation in glucose levels in Italian patients with newly diagnosed T2D.


Assuntos
Diabetes Mellitus Tipo 2 , Quinases do Centro Germinativo/genética , Glucose-6-Fosfatase/genética , Glucose/metabolismo , Secreção de Insulina/genética , Insulina , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Glucose-6-Fosfato/metabolismo , Haplótipos , Humanos , Insulina/biossíntese , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/patologia , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
4.
J Biol Regul Homeost Agents ; 34(3 Suppl. 2): 63-69. ADVANCES IN MUSCULOSKELETAL DISEASES AND INFECTIONS - SOTIMI 2019, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32856442

RESUMO

Implant-associated infections remain one of the main problems in trauma surgery, particularly for treatment of open tibial fractures. The role of systemic antibiotic prophylaxis is now established and accepted, but recent literature also seems to emphasize the importance of local antibiotic prophylaxis. Antibiotic coated nails play a crucial role, allowing at the same time the prevention of infections and favoring the stabilization of fractures. These devices appear to be a clinically effective and safe solution. The purpose of the study was to investigate the role of antibiotic coated nails in the treatment of tibia fractures. A literature review was performed on MEDLINE through PubMed to identify scientific publications relevant to the use of antibiotic coated nails in tibial fractures. Primary outcomes were infection rate and bone union rate. This review present numerous limits due primarily to the small number and different nature of studies published; the heterogeneity of the devices used.


Assuntos
Antibacterianos/uso terapêutico , Fixação Intramedular de Fraturas , Fraturas da Tíbia , Pinos Ortopédicos , Consolidação da Fratura , Humanos , Fraturas da Tíbia/diagnóstico por imagem , Fraturas da Tíbia/cirurgia , Resultado do Tratamento
5.
Injury ; 51 Suppl 3: S34-S38, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32430196

RESUMO

INTRODUCTION: Humerus fractures are frequent, accounting for about 3-4% of all fractures in adults. Treatment for fractures of the diaphyseal and proximal meta-epiphyseal regions remains controversial: there is no unanimity in the scientific community about the superiority of surgical treatment over non-surgical treatment and which is the best between possible surgical treatments. Among the choices for surgical treatment the most commonly used implants are the locking-compression plate and the intramedullary nailing. The purpose of this study was to perform a clinical and radiographic follow-up in patients who underwent surgical procedures for reduction and osteosynthesis of proximal or diaphyseal humeral fractures by means of anterograde intramedullary nailing with a straight-shaped nail. PATIENTS AND METHODS: A clinical and radiographic follow-up was performed in 56 patients who underwent surgical procedures for reduction and osteosynthesis of proximal or diaphyseal humeral fractures by means of antegrade intramedullary nailing using Synthes MultiLoc® system. Clinical data were collected using subjective quality of life assessment forms (SF12-v2), quality of life related to specific disabilities assessment forms (Quick-DASH, ASES score, WORC) and objective functional assessment forms (Constant-Murley score). The radiographic Follow-Up was performed at 30, 90 and 180 days from the date of the surgery. RESULTS: Almost all patients were able to return to a satisfactory quality of life, comparable with the one before the traumatic episode. The functional results were assessed as excellent or good with almost complete recovery of the range of motion and moderate recovery of strength. The residual pain encountered was moderate or zero. The average QuickDASH score was 17.7 ± 4.3 (range 9.1 - 27.3). The average ASES score was 73.8 ± 8.1 (range 58.3 - 88.3). The average WORC score was 543.3 ± 100 [74% ± 4.8%] (range 310 - 740). The mean Constant-Murley score was 69.6 ± 4.6 (range 61 - 84). All patients had a fair or good consolidation of the fracture on radiographic examinations. The calculated RUST score was 4.2 ± 0.4 (range 4-5) 30 days after surgery, 6.1 ± 0.9 (range 4- 8) 90 days after surgery and 9.8 ± 1.5 (range 7-12) to 180 days after surgery. No major complications were found. CONCLUSIONS: Treatment of the diaphyseal and proximal meta-epiphyseal humeral fractures with antegrade intramedullary nail provides excellent subjective and objective clinical results and good radiographic results. However, clinical studies with larger number of patients and longer follow-up are necessary.


Assuntos
Fixação Intramedular de Fraturas , Fraturas do Úmero , Fraturas do Ombro , Adulto , Pinos Ortopédicos , Placas Ósseas , Humanos , Fraturas do Úmero/diagnóstico por imagem , Fraturas do Úmero/cirurgia , Qualidade de Vida , Fraturas do Ombro/diagnóstico por imagem , Fraturas do Ombro/cirurgia , Resultado do Tratamento
6.
Malays Orthop J ; 14(3): 177-179, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33403082

RESUMO

Isolated apophyseal avulsion of the greater trochanter is a rare condition in the paediatric population, frequently related to avascular necrosis of the femoral head. Since there are few cases in the literature, there is no consensus regarding the best treatment of this injury. Our study describes the case of a 9-year-old patient with an avulsion of the right greater trochanter. A minimally invasive osteosynthesis was performed, achieving complete clinical and radiographic healing of the patient and no long-term complications after four years.

7.
Int J Biochem Cell Biol ; 106: 74-83, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30468920

RESUMO

Regulation of alternative splicing events is an essential step required for the expression of functional cytoskeleton and sarcomere proteins in cardiomyocytes. About 3% of idiopathic dilated cardiomyopathy cases present mutations in the RNA binding protein RBM20, a tissue specific regulator of alternative splicing. Transcripts expressed preferentially in skeletal and cardiac muscle, including TTN, CAMK2D, LDB3, LMO7, PDLIM3, RTN4, and RYR2, are RBM20-dependent splice variants. In the present study, we investigated the RBM20 involvement in post-transcriptional regulation of splicing variants expressed by Formin homology 2 domain containing 3 (FHOD3) gene. FHOD3 is a sarcomeric protein highly expressed in the cardiac tissue and required for the assembly of the contractile apparatus. Recently, FHOD3 mutations have been found associated with heart diseases. We identified novel FHOD3 splicing variants differentially expressed in human tissues and provided evidences that FHOD3 transcripts are specific RBM20 and PTBP1 targets. Furthermore, we demonstrated that the expression of RBM20 and PTBP1 promoted the alternative shift, from inclusion to exclusion, of selected FHOD3 exons. These results indicate that RBM20 and PTBP1 play a role in the actin filament functional organization mediated by FHOD3 isoforms and suggest their possible involvement in heart diseases.


Assuntos
Processamento Alternativo , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Proteínas dos Microfilamentos/biossíntese , Proteína de Ligação a Regiões Ricas em Polipirimidinas/metabolismo , Proteínas de Ligação a RNA/metabolismo , Forminas , Células HeLa , Ribonucleoproteínas Nucleares Heterogêneas/genética , Humanos , Proteínas dos Microfilamentos/genética , Proteína de Ligação a Regiões Ricas em Polipirimidinas/genética , Isoformas de Proteínas/biossíntese , Isoformas de Proteínas/genética , Proteínas de Ligação a RNA/genética
8.
Rhinology ; 53(4): 359-64, 2015 12.
Artigo em Inglês | MEDLINE | ID: mdl-26397160

RESUMO

BACKGROUND: Nasal polyposis (NP) is an inflammatory disease of the upper nasal airways frequently present in CF patients. Interferon-Related Developmental Regulator 1 (IFRD1) gene was reported as a possible modifier of CF lung disease severity. Three IFRD1 SNPs were analyzed to investigate a possible effect on the development of NP in CF patients. METHODS AND PATIENTS: The DNA of 143 patients with CF (40 with and 103 without NP) was purified from peripheral blood samples. IFRD1 SNPs (rs7817, rs3807213, rs6968084) were genotyped by restriction enzyme analysis. RESULTS: The T allele of the common polymorphisms rs7817 and the rs7817-rs3807213 haplotype were associated with NP (p = 0.002 and 0.004, respectively). CONCLUSIONS: These results showed the association of the IFRD1-rs7817 polymorphism with NP in CF patients.


Assuntos
Fibrose Cística/complicações , Proteínas Imediatamente Precoces/genética , Pólipos Nasais/genética , Adulto , Fibrose Cística/genética , Feminino , Haplótipos , Humanos , Masculino , Polimorfismo de Nucleotídeo Único
9.
Clin Genet ; 87(5): 440-7, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-24735133

RESUMO

Heterozygous loss-of-function mutations in the glucokinase (GCK) gene cause maturity-onset diabetes of the young (MODY) subtype GCK (GCK-MODY/MODY2). GCK sequencing revealed 16 distinct mutations (13 missense, 1 nonsense, 1 splice site, and 1 frameshift-deletion) co-segregating with hyperglycaemia in 23 GCK-MODY families. Four missense substitutions (c.718A>G/p.Asn240Asp, c.757G>T/p.Val253Phe, c.872A>C/p.Lys291Thr, and c.1151C>T/p.Ala384Val) were novel and a founder effect for the nonsense mutation (c.76C>T/p.Gln26*) was supposed. We tested whether an accurate bioinformatics approach could strengthen family-genetic evidence for missense variant pathogenicity in routine diagnostics, where wet-lab functional assays are generally unviable. In silico analyses of the novel missense variants, including orthologous sequence conservation, amino acid substitution (AAS)-pathogenicity predictors, structural modeling and splicing predictors, suggested that the AASs and/or the underlying nucleotide changes are likely to be pathogenic. This study shows how a careful bioinformatics analysis could provide effective suggestions to help molecular-genetic diagnosis in absence of wet-lab validations.


Assuntos
Biologia Computacional , Diabetes Mellitus Tipo 2/genética , Glucoquinase/genética , Mutação de Sentido Incorreto , Fenótipo , População Branca/genética , Adolescente , Sequência de Aminoácidos , Substituição de Aminoácidos , Criança , Pré-Escolar , Biologia Computacional/métodos , Análise Mutacional de DNA , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Humanos , Masculino , Dados de Sequência Molecular , Linhagem , Alinhamento de Sequência
10.
Acta Diabetol ; 50(3): 401-8, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23161442

RESUMO

We investigated cross-sectionally whether the type 2 diabetes (T2DM) risk alleles of rs1801282 (PPARG2) and rs4607103 (ADAMTS9) were associated with T2DM and/or insulin sensitivity (IS) and beta cell function (ßF) in Italians without and with newly diagnosed T2DM. In 676 nondiabetic subjects (336 NGR and 340 IGR) from the GENFIEV study and in 597 patients from the Verona Newly Diagnosed Type 2 Diabetes Study (VNDS), we (1) genotyped rs1801282 and rs4607103, (2) assessed ßF by C-peptide/glucose modeling after OGTT, and (3) assessed IS by HOMA-IR in both studies and by euglycemic insulin clamp in VNDS only. Logistic, linear, and two-stage least squares regression analyses were used to test (a) genetic associations with T2DM and with pathophysiological phenotypes, (b) causal relationships of the latter ones with T2DM by a Mendelian randomization design. Both SNPs were associated with T2DM. The rs4607103 risk allele was associated to impaired ßF (p < 0.01) in the GENFIEV study and in both cohorts combined. The rs1801282 genotype was associated with IS both in the GENFIEV study (p < 0.03) and in the VNDS (p < 0.03), whereas rs4607103 did so in the VNDS only (p = 0.01). In a Mendelian randomization design, both HOMA-IR (instrumental variables: rs1801282, rs4607103) and ßF (instrumental variable: rs4607103) were related to T2DM (p < 0.03-0.01 and p < 0.03, respectively). PPARG2 and ADAMTS9 variants are both associated with T2DM and with insulin resistance, whereas only ADAMTS9 may be related to ßF. Thus, at least in Italians, they may be considered bona fide "insulin resistance genes".


Assuntos
Proteínas ADAM/genética , Diabetes Mellitus Tipo 2/genética , Resistência à Insulina/genética , PPAR gama/genética , Proteína ADAMTS9 , Adulto , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Genótipo , Humanos , Insulina/metabolismo , Secreção de Insulina , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Mutação Puntual , Fatores de Risco
11.
Blood Cancer J ; 2(3): e61, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22829256

RESUMO

Although the pathogenesis of BCR-ABL1-positive acute lymphoblastic leukemia (ALL) is mainly related to the expression of the BCR-ABL1 fusion transcript, additional cooperating genetic lesions are supposed to be involved in its development and progression. Therefore, in an attempt to investigate the complex landscape of mutations, changes in expression profiles and alternative splicing (AS) events that can be observed in such disease, the leukemia transcriptome of a BCR-ABL1-positive ALL patient at diagnosis and at relapse was sequenced using a whole-transcriptome shotgun sequencing (RNA-Seq) approach. A total of 13.9 and 15.8 million sequence reads was generated from de novo and relapsed samples, respectively, and aligned to the human genome reference sequence. This led to the identification of five validated missense mutations in genes involved in metabolic processes (DPEP1, TMEM46), transport (MVP), cell cycle regulation (ABL1) and catalytic activity (CTSZ), two of which resulted in acquired relapse variants. In all, 6390 and 4671 putative AS events were also detected, as well as expression levels for 18 315 and 18 795 genes, 28% of which were differentially expressed in the two disease phases. These data demonstrate that RNA-Seq is a suitable approach for identifying a wide spectrum of genetic alterations potentially involved in ALL.

12.
J Neurol Sci ; 319(1-2): 37-41, 2012 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-22664156

RESUMO

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common form of familial vascular dementia, is caused by mutations of the NOTCH3 gene. Approximately two hundred pathogenic mutations have been reported within five exons (exons 3, 4, 6, 11 and 19) which accounted for 78% of known mutations in worldwide series. We reported twenty-one NOTCH3 pathogenic mutations (including five novel ones) identified in 53 index Italian patients. Exons 4 (28%), 7 (21%) and 19 (24%) were the most frequently involved. To dissect genetic heterogeneity, we analyzed five haplotyped tagging single nucleotide polymorphisms (rs1044009, rs4809030, rs10426042, rs10423702 and rs3815188) in 95 patients, 39 unaffected pedigree members and 50 healthy controls. SNPs were analyzed using the Illumina VeraCode Universal Capture Beads technology by Allele Specific Primer Extension (ASPE). We identified ten different haplotypes named H1-H10; H1 was the most common haplotype in patients and controls and it was associated with at least twelve out of the twenty-one mutations. Detected mutations were not associated to specific haplotypes while genotyping was compatible with a possible founder effect for the novel p.S396C mutation which clustered in a restricted geographical area of northeast Italy. The results added on to the genetic heterogeneity of CADASIL and emphasized difficulties in designing algorithms for molecular diagnosis.


Assuntos
CADASIL/genética , Haplótipos , Mutação , Receptores Notch/genética , População Branca/genética , Estudos de Coortes , Análise Mutacional de DNA , Efeito Fundador , Genótipo , Humanos , Itália , Polimorfismo de Nucleotídeo Único , Receptor Notch3
13.
Balkan J Med Genet ; 15(Suppl): 51-5, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24052744

RESUMO

The development of thoracic aortic aneurysms (TAAs) involves a multifactorial process resulting in alterations of the structure and composition of the extracellular matrix (ECM). Recently, modifications in microRNA (miRNA) expression were implicated in the pathogenesis of TAA. This study presents a preliminary miRNA microarray analysis conducted on pooled ascending aorta RNAs obtained from non familial non syndromic TAA patients (five males and five females) compared to matched control pools. Ninety-nine differentially expressed miRNAs with >1.5-fold-up- or down-regulation in TAAs compared to controls were identified, 16.0% of which were similarly regulated in the two sexes. Genes putatively targeted by differentially expressed miRNAs belonged preferentially to focal adhesion and adherens junction pathways. The results indicate an altered regulation of miRNA-mediated gene expression in the cellular interactions of aneurysmal aortic wall.

14.
Aliment Pharmacol Ther ; 33(10): 1162-72, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21443535

RESUMO

BACKGROUND: Hepatitis C virus (HCV) is a major cause of chronic liver disease, cirrhosis and hepatocellular carcinoma and the identification of the predictors of response to antiviral therapy is an important clinical issue. AIM: To determine the independent contribution of factors including IL28B polymorphisms, IFN-gamma inducible protein-10 (IP-10) levels and the homeostasis model assessment of insulin resistance (HOMA-IR) score in predicting response to therapy in chronic hepatitis C (CHC). METHODS: Multivariate analysis of factors predicting rapid (RVR) and sustained (SVR) virological response in 280 consecutive, treatment-naive CHC patients treated with peginterferon alpha and ribavirin in a prospective multicentre study. RESULTS: Independent predictors of RVR were HCV RNA <400 000 IU/mL (OR 11.37; 95% CI 3.03-42.6), rs12980275 AA (OR 7.09; 1.97-25.56) and IP-10 (OR 0.04; 0.003-0.56) in HCV genotype 1 patients and lower baseline γ-glutamyl-transferase levels (OR=0.02; 0.0009-0.31) in HCV genotype 3 patients. Independent predictors of SVR were rs12980275 AA (OR 9.68; 3.44-27.18), age <40 years (OR=4.79; 1.50-15.34) and HCV RNA <400 000 IU/mL (OR 2.74; 1.03-7.27) in HCV genotype 1 patients and rs12980275 AA (OR=6.26; 1.98-19.74) and age <40 years (OR 5.37; 1.54-18.75) in the 88 HCV genotype 1 patients without a RVR. RVR was by itself predictive of SVR in HCV genotype 1 patients (OR 33.0; 4.06-268.32) and the only independent predictor of SVR in HCV genotype 2 (OR 9.0, 1.72-46.99) or genotype 3 patients (OR 7.8, 1.43-42.67). CONCLUSIONS: In HCV genotype 1 patients, IL28B polymorphisms, HCV RNA load and IP-10 independently predict RVR. The combination of IL28B polymorphisms, HCV RNA level and age may yield more accurate pre-treatment prediction of SVR. HOMA-IR score is not associated with viral response.


Assuntos
Antivirais/uso terapêutico , Quimiocina CXCL10/sangue , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Interleucinas/genética , Polimorfismo Genético , Carga Viral , Adulto , Estudos de Coortes , Quimioterapia Combinada , Ensaio de Imunoadsorção Enzimática , Feminino , Genótipo , Hepatite C Crônica/sangue , Hepatite C Crônica/genética , Humanos , Interferon-alfa/uso terapêutico , Interferons , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/uso terapêutico , Estudos Prospectivos , RNA Viral/sangue , Proteínas Recombinantes/uso terapêutico , Ribavirina/uso terapêutico
15.
Eur J Vasc Endovasc Surg ; 41(3): 358-63, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21236709

RESUMO

OBJECTIVES: An inflammatory process following stroke in human brains and systemic inflammatory responses after stroke in humans have been reported by numerous investigators. The aim of the study was to investigate if genes involved in the cyclooxygenase 2 (COX-2) pathway are upregulated at peripheral level in patients after transient ischaemic attack (TIA) and stroke. DESIGN OF STUDY: Blood samples were obtained from two groups of patients undergoing carotid endarterectomy. The first group included 25 patients who presented TIA or ischaemic stroke. The second group included 35 patients who had an asymptomatic internal carotid artery stenosis. Total RNA was isolated and the expression of Toll-like Receptor 4 (TLR4), COX-2, membrane-associated Prostaglandin E synthase (mPGES-1), Prostaglandin E2 receptors (EP3 and EP4) was analysed by real time RT-PCR. RESULTS: Expression of COX-2 and TLR4 were significantly increased in symptomatic patients (p < 0.001). Correlation analysis showed that TLR4 expression significantly correlated with COX-2 expression (R = 0.65; p < 0.01) in ischaemic stroke patients. This correlation was not observed in TIA and asymptomatic patients. CONCLUSIONS: Our results suggest that the peripheral mechanism of inflammatory injury after stroke may be mediated by TLR4 through a COX-2-dependent pathway.


Assuntos
Isquemia Encefálica/genética , Estenose das Carótidas/genética , Ciclo-Oxigenase 2/genética , RNA/sangue , Acidente Vascular Cerebral/genética , Receptor 4 Toll-Like/genética , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/enzimologia , Isquemia Encefálica/imunologia , Estenose das Carótidas/enzimologia , Estenose das Carótidas/imunologia , Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas , Feminino , Humanos , Oxirredutases Intramoleculares/genética , Ataque Isquêmico Transitório/enzimologia , Ataque Isquêmico Transitório/genética , Ataque Isquêmico Transitório/imunologia , Itália , Masculino , Pessoa de Meia-Idade , Prostaglandina-E Sintases , Receptores de Prostaglandina E Subtipo EP3/genética , Receptores de Prostaglandina E Subtipo EP4/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Acidente Vascular Cerebral/enzimologia , Acidente Vascular Cerebral/imunologia , Regulação para Cima
16.
Acta Biomed ; 82(2): 154-9, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22480071

RESUMO

Total Hip Arthroplasty (THA) is one of the most common orthopedic operations in the world. The number of THA is expected to grow and with it the number of associated complications. Although improved surgical technique and the development of more scrupulous asepsis has decreased the incidence of periprosthetic joint infection (PJI), it remains one of the most feared complications of joint arthroplasty. The purpose of this study is to present the use of antibiotic-loaded collagen sponges (Collatamp EG) in the prophylaxis and treatment of PJI. For this scope a case report is described. The advantages offered by the antibiotic loaded sponges in terms of high and sustained concentration of antibiotic at the site of infection, diffused by the fully reabsorbable carrier, showed to be a an important adjuvant therapy in the treatment of PJI. Low systemic concentration of the drug and a wide versatility in surgical application are other advantages of this dispositive.


Assuntos
Antibacterianos/administração & dosagem , Antibioticoprofilaxia/métodos , Artroplastia de Quadril , Infecções Relacionadas à Prótese/prevenção & controle , Artroplastia de Quadril/efeitos adversos , Colágeno , Humanos , Complicações Pós-Operatórias/prevenção & controle , Tampões de Gaze Cirúrgicos
17.
J Clin Endocrinol Metab ; 96(2): E389-93, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21159844

RESUMO

CONTEXT: Intronic variants of TCF7L2 are confirmed genetic risk factors for type 2 diabetes and are associated to alterations in beta cell function in nondiabetic individuals. OBJECTIVE: The objective of the study was to test whether TCF7L2 variability may affect ß-cell function also in patients with type 2 diabetes. DESIGN: This was a cross-sectional association study. SETTING: The study was conducted at a university hospital referral center for diabetes. PATIENTS: Patients included 464 (315 males and 149 females) glutamic acid decarboxylase-negative patients [age: median 59 yr (interquartile range: 52-65); body mass index: 29.3 kg/m(2) (26.5-32.9); fasting plasma glucose: 7.0 mmol/liter (6.1-8.0)] with newly diagnosed type 2 diabetes. INTERVENTION(S): Interventions included frequently sampled oral glucose tolerance test and euglycemic insulin clamp. MAIN OUTCOME MEASURE(S): ß-Cell function (derivative control and proportional control); insulin sensitivity; genotypes of the following TCF7L2 single-nucleotide polymorphisms: rs7901695, rs7903146, rs11196205, and rs12255372. RESULTS: Both rs7901695 and rs7903146 diabetes risk alleles were associated with reduced proportional control of ß-cell function (P = 0.019 and P = 0.022, respectively). Two low-frequency haplotypes were associated with extreme (best and worst) phenotypes of ß-cell function (P < 0.01). No associations between TCF7L2 genotypes and insulin sensitivity were detected. CONCLUSIONS: TCF7L2 diabetes risk variants, either as single-nucleotide polymorphisms or as haplotypes, detrimentally influence ß-cell function and might play a role in determining the metabolic phenotype of patients with newly diagnosed type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatologia , Células Secretoras de Insulina/fisiologia , Proteína 2 Semelhante ao Fator 7 de Transcrição/genética , Idoso , Alelos , Glicemia/metabolismo , Índice de Massa Corporal , Peptídeo C/metabolismo , Estudos de Coortes , Estudos Transversais , Bases de Dados Factuais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Variação Genética , Teste de Tolerância a Glucose , Haplótipos , Humanos , Hipoglicemiantes/uso terapêutico , Resistência à Insulina/genética , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Testes de Função Pancreática , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco
18.
J Biomed Biotechnol ; 2010: 321082, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20379347

RESUMO

Urinary tract infections (UTIs) are a frequent cause of morbidity in children and adults and affect up to 10% of children; its recurrence rate is estimated at 30-40%. UTI may occur in up to 50% of all women in their lifetimes and frequently require medication. Recent advances have suggested that a deregulation of candidate genes in humans may predispose patients to recurrent UTI. The identification of a genetic component of UTI recurrences will make it possible to diagnose at-risk adults and to predict genetic recurrences in their offspring. Six out of 14 genes investigated in humans may be associated with susceptibility to recurrent UTI in humans. In particular, the HSPA1B, CXCR1 & 2, TLR2, TLR4, TGF-beta1 genes seem to be associated with an alteration of the host response to UTIs at various levels.


Assuntos
Predisposição Genética para Doença , Infecções Urinárias/genética , Proteínas de Choque Térmico HSP72/genética , Humanos , Viés de Publicação , Receptores CXCR/genética , Recidiva , Receptores Toll-Like/genética , Fator de Crescimento Transformador beta1/genética , Fator A de Crescimento do Endotélio Vascular/genética
19.
Br J Dermatol ; 163(2): 364-70, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20346027

RESUMO

BACKGROUND: Basal cell carcinoma (BCC) is 10 times more frequent in organ transplant recipients (OTRs) than in the general population. Factors in OTRs conferring increased susceptibility to BCC include ultraviolet radiation exposure, immunosuppression, viral infections such as human papillomavirus, phototype and genetic predisposition. The PTCH1 gene is a negative regulator of the hedgehog pathway, that provides mitogenic signals to basal cells in skin. PTCH1 gene mutations cause naevoid BCC syndrome, and contribute to the development of sporadic BCC and other types of cancers. Associations have been reported between PTCH1 polymorphisms and BCC susceptibility in nontransplanted individuals. OBJECTIVES: To search for novel common polymorphisms in the proximal 5' regulatory region upstream of PTCH1 gene exon 1B, and to investigate the possible association of PTCH1 polymorphisms and haplotypes with BCC risk after organ transplantation. METHODS: Three PTCH1 single nucleotide polymorphisms (rs2297086, rs2066836 and rs357564) were analysed by restriction fragment length polymorphism analysis in 161 northern Italian OTRs (56 BCC cases and 105 controls). Two regions of the PTCH1 gene promoter were screened by heteroduplex analysis in 30 cases and 30 controls. RESULTS: Single locus analysis showed no significant association. Haplotype T(1686)-T(3944) appeared to confer a significantly higher risk for BCC development (odds ratio 2.98, 95% confidence interval 2.55-3.48; P = 0.001). Two novel rare polymorphisms were identified at positions 176 and 179 of the 5'UTR. Two novel alleles of the -4 (CGG)(n) microsatellite were identified. No association of this microsatellite with BCC was observed. CONCLUSIONS: Haplotypes containing T(1686)-T(3944) alleles were shown to be associated with an increased BCC risk in our study population. These data appear to be of great interest for further investigations in a larger group of transplant individuals. Our results do not support the hypothesis that common polymorphisms in the proximal 5' regulatory region of the PTCH1 gene could represent an important risk factor for BCC after organ transplantation.


Assuntos
Carcinoma Basocelular/genética , Haplótipos/genética , Transplante de Órgãos , Polimorfismo Genético , Receptores de Superfície Celular/genética , Neoplasias Cutâneas/genética , Adolescente , Adulto , Idoso , Éxons/genética , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Receptores Patched , Receptor Patched-1 , Adulto Jovem
20.
Br J Dermatol ; 157(1): 49-57, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17578436

RESUMO

BACKGROUND: Overexpression of cyclooxygenase-2 (COX-2), resulting in excessive prostaglandin production, has been observed in human epidermal keratinocytes after ultraviolet B injury, in squamous cell skin carcinoma (SCC), in actinic keratoses, and in the early stages of carcinogenesis in a wide variety of tissues. The dysregulation of COX-2 expression can in part be due to functional changes affecting regulatory elements in the promoter or 3' untranslated region (UTR) of the gene. Two common polymorphisms (-765G-->C, and -1195A-->G) in the promoter region of the COX-2 gene (now PTGS2), and one common polymorphism in the 3' UTR (8473T-->C) have been described, and reported as associated with various malignancies. OBJECTIVES: To determine if common known polymorphisms in the regulatory region of the COX-2 gene (PTGS2) can be associated with nonmelanoma skin cancer (NMSC) predisposition after organ transplantation, to evaluate if cancer risks are associated with specific COX-2 gene (PTGS2) haplotypes containing these polymorphisms, and to identify possible new genetic polymorphisms in the proximal 5' or 3' regulatory regions of the gene associated with disease. METHODS: The frequency of the three polymorphisms was determined in 240 Northern Italian transplant recipient patients (107 cases and 133 controls) with polymerase chain reaction-restriction fragment length polymorphism analysis. The proximal 5' and 3' regulatory regions of the gene were screened by heteroduplex analysis. RESULTS: Stratification by age at transplant and type of tumours [SCC or basal cell carcinoma (BCC)] demonstrated that allele -765C represented a protective factor in BCC cases undergoing transplantation before 50 years of age (CC + CG vs. GG, Fisher exact test P = 0.003). One rare polymorphism, -62C-->G, was detected in the 5' flanking region. The allele frequency of -62G was 0.019, and no difference in genotype between cases and controls was observed. No other variants were found, suggesting that sequence variations in these regions are not likely to contribute to NMSC risk in this population. Haplotype analysis showed that the haplotype containing all major alleles represents a protective factor in patients with SCC undergoing transplantation after 50 years of age [P = 0.009; OR = 0.37 (0.18-0.79)] and that variant -1195A-->G may represent a risk factor in this subgroup of patients [P = 0.01; OR = 4.77 (1.47-16.41)]. Haplotype analysis in patients with BCC revealed that variant -765C might be a protective factor in patients undergoing transplantation before 50 years of age. Variant 8473T-->C, located in the 3' UTR region of the gene, showed no association with NMSC risk after transplantation. CONCLUSIONS: COX-2 common variants -765G-->C and -1195A-->G appear to be associated with risk of NMSC, although in different ways in the SCC and BCC subgroups, indicating that environmental and genetic risk factors may play different roles in the outcome leading to these two phenotypes.


Assuntos
Ciclo-Oxigenase 2/genética , Frequência do Gene/genética , Proteínas de Membrana/genética , Transplante de Órgãos/fisiologia , Polimorfismo Genético/genética , Sequências Reguladoras de Ácido Nucleico/genética , Neoplasias Cutâneas/genética , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
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