RESUMO
Hypophosphatasia (HPP) is a rare genetic disorder in which pathogenic variants of the ALPL gene lead to a marked decrease of tissue non-specific alkaline phosphatase (TNSALP) activity. Although HPP is a systemic disorder, its clinical manifestations are more evident on bones, teeth, muscle and central nervous system. The clinical spectrum ranges from severe forms with extreme skeletal deformities, respiratory impairment, seizures, to very mild forms with onset in late adulthood and few clinical signs. The diagnosis can be suspected by measurement of TNSALP activity, but the insufficient awareness among health professionals and the lack of official guidelines are responsible for delayed diagnosis in children with HPP. The purpose of the current document is to provide an expert opinion directed at optimizing the diagnostic pathway of pediatric HPP. From April to December 2022, a multidisciplinary working group of 6 experts including two pediatric endocrinologists, a pediatric neurologist, a pediatric odontologist, a clinical geneticist, and a molecular biologist gathered in a series of periodic meetings to discuss the main issues related to the diagnosis of HPP in children and formalize an Expert Opinion statement. The experts agreed on a diagnostic trail that begins with the recognition of specific clinical signs, leading to biochemical analyses of TNSALP activity and vitamin B6 serum concentration. Very important are the neurological and dental manifestation of the disease that should be thoroughly investigated. The evaluation of TNSALP activity must consider sex and age variability and low activity must be persistent. Repeated blood measurements are thus necessary. The molecular analysis is then mandatory to confirm the diagnosis and for genetic counseling.
Assuntos
Hipofosfatasia , Insuficiência Respiratória , Humanos , Criança , Adulto , Hipofosfatasia/diagnóstico , Hipofosfatasia/genética , Prova Pericial , Fosfatase Alcalina/genética , Sistema Nervoso Central , Pessoal de Saúde , MutaçãoRESUMO
A kidney-transplanted patient, unvaccinated against yellow fever (YF), developed high fever, progressed rapidly to hepatic insufficiency and coma, and died 8 days later. Real-time polymarase chain reaction for YF virus collected on the seventh day of symptoms was positive. Autopsy showed disseminated infection and midzonal hepatitis with apoptotic hepatocytes and minimal inflammatory reaction.
Assuntos
Transplante de Rim , Vacina contra Febre Amarela , Febre Amarela , Humanos , Transplante de Rim/efeitos adversos , Febre Amarela/diagnóstico , Vírus da Febre Amarela/genéticaRESUMO
We determined peripheral blood (PB) and biopsy (Bx) RNA expression signatures in a Brazilian and US cohort of kidney transplant patients. Phenotypes assigned by precise histology were: acute rejection (AR), interstitial fibrosis/tubular atrophy/chronic rejection (CR), excellent functioning transplants (TX), and glomerulonephritis recurrence (GN). Samples were analyzed on microarrays and profiles from each cohort were cross-validated on the other cohort with similar phenotypes. We discovered signatures for each tissue: (1) AR vs TX, (2) CR vs TX, and (3) GN vs TX using the Random Forests algorithm. We validated biopsies signatures of AR vs TX (area under the curve [AUC] 0.97) and CR vs TX (AUC 0.87). We also validated both PB and Bx signatures of AR vs TX and CR vs TX with varying degrees of accuracy. Several biological pathways were shared between AR and CR, suggesting similar rejection mechanisms in these 2 clinical phenotypes. Thus, we identified gene expression signatures for AR and CR in transplant patients and validated them in independent cohorts of significantly different racial/ethnic backgrounds. These results reveal that there are strong unifying immune mechanisms driving transplant diseases and identified in the signatures discovered in each cohort, suggesting that molecular diagnostics across populations are feasible despite ethnic and environmental differences.
Assuntos
Biomarcadores/análise , Etnicidade/genética , Rejeição de Enxerto/diagnóstico , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Leucócitos Mononucleares/metabolismo , Transcriptoma , Adolescente , Adulto , Idoso , Biópsia , Estudos de Coortes , Feminino , Seguimentos , Perfilação da Expressão Gênica , Rejeição de Enxerto/sangue , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto JovemAssuntos
COVID-19 , Transplante de Rim , Brasil , Hospitalização , Humanos , Rim , Dados Preliminares , SARS-CoV-2 , TransplantadosRESUMO
Rational-designed multimerization of targeting ligands can be used to improve kinetic and thermodynamic properties. Multimeric targeting ligands may be produced by tethering multiple identical or two or more monomeric ligands of different binding specificities. Consequently, multimeric ligands may simultaneously bind to multiple receptor molecules. Previously, multimerization has been successfully applied on radiolabeled RGD peptides, which resulted in an improved tumor targeting activity in animal models. Multimerization of peptide-based ligands may improve the binding characteristics by increasing local ligand concentration and by improving dissociation kinetics. Here, we present a preclinical study on a novel radiolabeled bombesin (BN) homodimer, designated (111)In-DOTA-[(Aca-BN(7-14)]2, that was designed for enhanced targeting of gastrin-releasing peptide receptor (GRPR)-positive prostate cancer cells. A BN homodimer was conjugated with DOTA-NHS and labeled with (111)In. After HPLC purification, the GRPR targeting ability of (111)In-DOTA-[Aca-BN(7-14)]2 was assessed by microSPECT imaging in SCID mice xenografted with the human prostate cancer cell line PC-3. (111)In labeling of DOTA-[(Aca-BN(7-14)]2 was achieved within 30 min at 85 °C with a labeling yield of >40%. High radiochemical purity (>95%) was achieved by HPLC purification. (111)InDOTA-[Aca-BN(7-14)]2 specifically bound to GRPR-positive PC-3 prostate cancer cells with favorable binding characteristics because uptake of 111In-DOTA-[Aca-BN(7-14)]2 in GRPR-positive PC-3 cells increased over time. A maximum peak with 30% radioactivity was observed after 2 h of incubation. The log D value was -1.8 ± 0.1. (111)In-DOTA-[Aca-BN(7-14)]2 was stable in vitro both in PBS and human serum for at least 4 days. In vivo biodistribution analysis and microSPECT/CT scans performed after 1, 4, and 24 h of injection showed favorable binding characteristics and tumor-to-normal tissue ratios. This study identifies (111)In-DOTA-[(Aca-BN(7-14)]2 as a promising radiotracer for nuclear imaging of GRPR in prostate cancer.
Assuntos
Bombesina , Radioisótopos de Índio , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/metabolismo , Receptores da Bombesina/metabolismo , Animais , Linhagem Celular Tumoral , Compostos Heterocíclicos com 1 Anel , Humanos , Masculino , Camundongos , Camundongos Nus , Compostos Radiofarmacêuticos , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
Psoriatic arthritis (PsA) is described as a multifactorial autoimmune rheumatic disease although its development is surely linked to some specific HLA genes (especially the HLA-Cw*06:02 allele). To date, its complex immunopathogenetic mechanism is not well clarified. Actually, increasing evidence suggest that qualitative and quantitative interplays between some PsA-susceptibility HLA alleles and other genetic, regulatory and environmental factors, may develop distinct subphenotypes of PsA. We first provide a brief summary of current knowledge about the various PsA conditions. Then, we consider the reasons why further analysis of the clinical course of patients affected by distinct PsA subsets, and who receive different therapeutic treatments, should be carried out in conjunction with deeper investigations about the identification of key genes and immunoregulatory agents by applying the most recent advances in biotechnology. This approach could better explain the molecular mechanisms responsible for both the onset and progression of this multi-faceted pathology with the purpose of significantly improving the management of PsA patients.
Assuntos
Artrite Psoriásica/genética , Predisposição Genética para Doença , Antígenos HLA/genética , Polimorfismo de Nucleotídeo Único , Artrite Psoriásica/imunologia , Antígenos HLA-C/genética , HumanosRESUMO
Genetic investigations on ancient human remains affected by rheumatological pathologies are a research field of particular interest for identifying origins and the etiopathology of diseases, especially those having an autoimmune background such as rheumatoid arthritis (RA). We wish to demonstrate how reliable studies concerning this topic require collaboration between multiple disciplines, usually starting from paleopathologic observations up to immunogenetic screening, even involving analytical chemistry. Here, we focused our investigation on the skeleton of Cardinal Carlo de'Medici (1595-1666) for whom RA and psoriatic arthritis (PsA) were postulated after paleopathologic examination. RA susceptibility is linked to specific HLA alleles belonging to DRB1 04 locus, such as DRB1 0401, while Cw 0602 and DRB1 07 predispose to PsA. Thus, we genotyped the Cardinal?s remains to search for RA or PsA risk genes. Ancient DNA is often subjected to hydrolysis followed by fragmentation. For this reason, all immunogenetic tests were preceded by an original RP-HPLC-FL method able to inform on the ancient DNA preservation and the extent of contamination, with the purpose of avoiding the risk of false positive results. After DNA isolation from a piece of bone from the Cardinal, PCR-SSP and reverse-SSO hybridization assays were applied to perform genomic HLA-typing. RP-HPLC-FL analysis revealed a good preservation of DNA without contamination by exogenous genomes. Molecular tests assigned to the Cardinal the genotype DRB1 0401/1102 for HLA-DRB locus and Cw 04/ 12 for HLA-C locus, data that support a genetic predisposition for RA but not for PsA. This multidisciplinary study has allowed us: (i) to ascertain that the remains undoubtedly belonged to the specific subject, Cardinal Carlo de?Medici; (ii) to sustain that the subject suffered from RA rather then that PsA, and (iii) to state that RA was already widespread in Europe at the Renaissance age, despite some authors claiming that the disease was introduced to the Old Continent from America after colonization during the 18th century.
Assuntos
Artrite Reumatoide/etiologia , Cromatografia Líquida de Alta Pressão/métodos , DNA/análise , Imunogenética/métodos , Paleopatologia , Artrite Psoriásica/etiologia , Artrite Psoriásica/genética , Artrite Reumatoide/genética , Cadeias HLA-DRB1/genética , HumanosRESUMO
INTRODUCTION: Rhamnus alpinus L. (Rhamnaceae), a traditional plants in the flora of the Abruzzo region, is known to contain active anthraquinone secondary metabolites. However, the content of anthraquinones varies among R. alpinus samples depending on collection season and site. Thus, using simple, reliable and accurate analytical methods for the determination of anthraquinones in R. alpinus extracts allows comparative study of different methods of extraction. OBJECTIVE: After a partial validation of an HPLC method for the simultaneous determination of five anthraquinones, aloe-emodine, rheine, emodine, chrysophanol and physcione, in the bark of R. alpinus, we compared three different methods of extraction. METHODOLOGY: Anthraquinones were extracted from the bark of R. alpinus using different techniques (methanol maceration, ultrasonic and supercritical CO(2) extraction). Separation and quantification of anthraquinones were accomplished using a reversed-phase C(18) column with the mobile phase of H(2)O-methanol (40 : 60, v/v, 1% formic acid) at a wavelength of 254 nm. The qualitative analyses were also achieved at wavelength of 435 nm. RESULTS: All calibration curves were linear over the concentration range tested (10-200 mM) with the determination coefficients >or=0.991. The detection limits (S/N = 3) were 5 mM for each analytes. All five anthraquinones were found in the samples tested at concentrations reported in experimental data. CONCLUSION: The described HPLC method and optimised extraction procedure are simple, accurate and selective for separation and quantification of anthraquinones in the bark of R. alpinus and allow evaluation of the best extraction procedure between the tested assays.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Casca de Planta/química , Extratos Vegetais/análise , Antraquinonas/análise , Dióxido de Carbono/química , Cromatografia com Fluido Supercrítico/métodos , Emodina/análogos & derivados , Emodina/análise , Metanol/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Reprodutibilidade dos Testes , Rhamnus/química , UltrassomRESUMO
BACKGROUND AND OBJECTIVES: FSGS recurrence after kidney transplantation is a major risk factor for graft loss. However, the natural history, clinical predictors, and response to treatment remain unclear because of small sample sizes and poor generalizability of single-center studies, and disease misclassification in registry-based studies. We therefore aimed to determine the incidence, predictors, and treatment response of recurrent FSGS in a large cohort of kidney transplant recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Post-Transplant Glomerular Disease (TANGO) project is an observational, multicenter, international cohort study that aims to investigate glomerular disease recurrence post-transplantation. Transplant recipients were screened for the diagnosis of idiopathic FSGS between 2005 and 2015 and details were recorded about the transplant, clinical outcomes, treatments, and other risk factors. RESULTS: Among 11,742 kidney transplant recipients screened for FSGS, 176 had a diagnosis of idiopathic FSGS and were included. FSGS recurred in 57 patients (32%; 95% confidence interval [95% CI], 25% to 39%) and 39% of them lost their graft over a median of 5 (interquartile range, 3.0-8.1) years. Multivariable Cox regression revealed a higher risk for recurrence with older age at native kidney disease onset (hazard ratio [HR], 1.37 per decade; 95% CI, 1.09 to 1.56). Other predictors were white race (HR, 2.14; 95% CI, 1.08 to 4.22), body mass index at transplant (HR, 0.89 per kg/m2; 95% CI, 0.83 to 0.95), and native kidney nephrectomies (HR, 2.76; 95% CI, 1.16 to 6.57). Plasmapheresis and rituximab were the most frequent treatments (81%). Partial or complete remission occurred in 57% of patients and was associated with better graft survival. CONCLUSIONS: Idiopathic FSGS recurs post-transplant in one third of cases and is associated with a five-fold higher risk of graft loss. Response to treatment is associated with significantly better outcomes but is achieved in only half of the cases.
Assuntos
Glomerulosclerose Segmentar e Focal/cirurgia , Sobrevivência de Enxerto , Transplante de Rim/efeitos adversos , Adulto , Brasil , Europa (Continente) , Feminino , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/fisiopatologia , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Plasmaferese , Recidiva , Retratamento , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Rituximab/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a sensitive functional marker in heart disease, including left ventricular hypertrophy (LVH) secondary to valvular aortic stenosis (AS). We evaluated the association between NT-proBNP changes, oxidative stress, energy status and severity of LVH in patients with AS. Ten patients undergoing aortic valve replacement for AS were studied. Plasma NT-proBNP concentrations were performed by electroluminescence immunoassay 15min after the induction of anesthesia (t0), before aortic cross-clamping (t1), before clamp removal (t2), 15min after myocardial reperfusion (t3), and 24h after surgery (t4). Heart biopsies were obtained and high energy phosphates (ATP, ADP, AMP) were analyzed by capillary electrophoresis (CE). In plasma samples from the coronary sinus, nitrate plus nitrite (NOx) concentrations were also analyzed by CE. Echocardiographic measurements were acquired and correlations between biochemical markers and severity of AS were assessed. NT-proBNP peaked significantly at t4 (p<0.001). A linear correlation between NT-proBNP values measured at t0 and t4 was found (R(2)=0.89; p<0.001). A negative correlation between NT-proBNP production and phosphorylation potential (ATP/ADP ratio) was observed (R(2)=0.62; p<0.01). NOx values positively correlated with NT-proBNP levels (p<0.01). NT-proBNP inversely correlated with aortic valvular area (r=81, p<0.01), positively correlated with mean (r=0.82, p<0.01) and maximum left ventricle-to-aortic gradients (r=0.80, p<0.01), and with left ventricular mass (r=0.69, p<0.01). NT-proBNP is a useful marker of LVH and severity of AS. It may complement echocardiographic evaluation of patients with AS in identifying the optimum time for surgery.
Assuntos
Estenose da Valva Aórtica/fisiopatologia , Cardiomiopatia Hipertrófica/fisiopatologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Peptídeo Natriurético Encefálico/sangue , Estresse Oxidativo , Fragmentos de Peptídeos/sangue , Difosfato de Adenosina/metabolismo , Monofosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/cirurgia , Biomarcadores/sangue , Eletroforese Capilar , Metabolismo Energético , Circulação Extracorpórea , Feminino , Parada Cardíaca Induzida , Implante de Prótese de Valva Cardíaca , Humanos , Hipertrofia Ventricular Esquerda/metabolismo , Imunoensaio , Medições Luminescentes , Masculino , Nitratos/sangue , Nitritos/sangue , Fosforilação , Índice de Gravidade de DoençaRESUMO
BACKGROUND/AIM: Onychomycosis (OM) is one of the commonest superficial fungal infections. Patients undergoing hemodialysis (HD) treatment and kidney transplant recipients (KTR) are considered at risk of contracting fungal infections, but the few published data do not reach the conclusion of whether they are predisposed to OM. This study aimed to determine the prevalence and etiology of OM in these patients and to determine the antifungal susceptibility profile of the isolated fungal species. METHODS: We recruited 149 HD patients, 187 KTR, and a control group comprising 174 patients attending an internal medicine service with other diseases than renal diseases. All patients underwent an examination of all toenails to check for the presence of OM. Antifungal susceptibility tests were performed following the Clinical and Laboratory Standards Institute (CLSI) recommendations. RESULTS: The prevalence rates of OM in HD patients (23.4%) and KTR (23.0%) were significantly higher than those in age- and sex-matched control groups (13.2%). In HD patients, OM was associated with diabetes but not with the duration of dialysis. In KTR, OM was more prevalent in those without diabetes and likely also in those using mycophenolate mofetil or azathioprine but was not associated with the duration of transplantation. Trichophyton rubrum was the most prevalent species (45.9%) followed by T. mentagrophytes (24.5%) and Candida parapsilosis (18.0%). Fluconazole, itraconazole, voriconazole, and terbinafine were all efficient against the isolates of dermatophyte, with terbinafine showing the lowest and fluconazole the highest minimal inhibitory concentrations. All isolates of C. parapsilosis were sensitive to the antifungals according to the CLSI criteria. CONCLUSION: We found a high prevalence of OM in HD and KTR patients and suggest that these conditions should be considered a risk factor of OM. All 4 antifungals evaluated in the study showed good in vitro activity against the etiologic agents.
Assuntos
Dermatoses do Pé/etiologia , Transplante de Rim/efeitos adversos , Onicomicose/etiologia , Diálise Renal/efeitos adversos , Adulto , Antifúngicos/farmacologia , Candida parapsilosis/efeitos dos fármacos , Candidíase/tratamento farmacológico , Candidíase/etiologia , Candidíase/microbiologia , Suscetibilidade a Doenças , Feminino , Dermatoses do Pé/tratamento farmacológico , Dermatoses do Pé/microbiologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Onicomicose/tratamento farmacológico , Onicomicose/microbiologia , Fatores de Risco , Tinha/tratamento farmacológico , Tinha/etiologia , Tinha/microbiologiaRESUMO
Ketoprofen lysine salt(Artrosilene injectable solution) is a non-steroidal anti-inflammatory agent frequently administered by slow intravenous infusion with portable elastomeric infusion systems in association regimen with other analgesic drugs. The aim of this study was to investigate the physicochemical compatibility between ketoprofen lysine salt(Artrosilene injectable solution) and other injectable drugs frequently used in association, such as tramadol hydrochloride, keterolac tromethamine and morphine hydrochloride, into the Infusor LV5, Baxter elastomeric infusion system. Physicochemical properties of drug mixture, including colour, clarity, pH and drug content were observed or measured by a reversed-phase HPLC method with UV detection, before and after (up to 7 days) mixing at room temperature and under light protection. The results obtained demonstrated the physicochemical compatibility of ketoprofen lysine salt(Artrosilene injectable solution) with all drug formulations at every tested mixing ratios into Baxer Infusor LV5 infusion devices.
Assuntos
Anti-Inflamatórios não Esteroides/química , Cetoprofeno/análogos & derivados , Lisina/análogos & derivados , Analgésicos Opioides/análise , Analgésicos Opioides/química , Anti-Inflamatórios não Esteroides/análise , Fenômenos Químicos , Físico-Química , Cromatografia Líquida de Alta Pressão , Cor , Combinação de Medicamentos , Incompatibilidade de Medicamentos , Embalagem de Medicamentos , Elastômeros , Concentração de Íons de Hidrogênio , Bombas de Infusão , Cetoprofeno/análise , Cetoprofeno/química , Cetorolaco de Trometamina/análise , Cetorolaco de Trometamina/química , Lisina/análise , Lisina/química , Morfina/análise , Morfina/química , Soluções Farmacêuticas , Tramadol/análise , Tramadol/químicaRESUMO
The fourth-order derivative spectrum from the alcoholic sample is used. HCT can be determined by a specific peak-trough, of low intensity, at 330-340 nm. For IST evaluation, a peak-trough around 250-310 nm is available, common to both products, whose amplitude increases linearly only for low concentration values, while it decreases at higher values. The most difficult aspect of the analysis lies in how to find the optimal concentration range, so that both signals can be evaluated simultaneously. The best results were achieved by using a linear regression for HCT and a regression plane for IST.
Assuntos
Compostos de Bifenilo/análise , Hidroclorotiazida/análise , Preparações Farmacêuticas/química , Tetrazóis/análise , Irbesartana , Estrutura Molecular , Espectrofotometria Ultravioleta/métodosRESUMO
The gastrin-releasing peptide receptor (GRPR) is overexpressed in a variety of human malignancies, including prostate cancer. Bombesin (BBN) is a 14 amino acids peptide that selectively binds to GRPR. In this study, we developed two novel Al(18)F-labeled lanthionine-stabilized BBN analogs, designated Al(18)F-NOTA-4,7-lanthionine-BBN and Al(18)F-NOTA-2,6-lanthionine-BBN, for positron emission tomography (PET) imaging of GRPR expression using xenograft prostate cancer models. (Methyl)lanthionine-stabilized 4,7-lanthionine-BBN and 2,6-lanthionine-BBN analogs were conjugated with a NOTA chelator and radiolabeled with Al(18)F using the aluminum fluoride strategy. Al(18)F-NOTA-4,7-lanthionine-BBN and Al(18)F-NOTA-2,6-lanthionine-BBN was labeled with Al(18)F with good radiochemical yield and specific activity>30 GBq/µmol for both radiotracers. The logD values measured for Al(18)F-NOTA-4,7-lanthionine-BBN and Al(18)F-NOTA-2,6-lanthionine-BBN were -2.14 ± 0.14 and -2.34 ± 0.15, respectively. In athymic nude PC-3 xenografts, at 120 min post injection (p.i.), the uptake of Al(18)F-NOTA-4,7-lanthionine-BBN and Al(18)F-NOTA-2,6-lanthionine-BBN in prostate cancer (PC-3) mouse models was 0.82 ± 0.23% ID/g and 1.40 ± 0.81% ID/g, respectively. An excess of unlabeled É-aminocaproic acid-BBN(7-14) (300-fold) was co-injected to assess GRPR binding specificity. Tumor uptake of Al(18)F-NOTA-4,7-lanthionine-BBN and Al(18)F-NOTA-2,6-lanthionine-BBN in PC-3 tumors was evaluated by microPET (µPET) imaging at 30, 60 and 120 min p.i. Blocking studies showed decreased uptake in PC-3 bearing mice. Stabilized 4,7-lanthionine-BBN and 2,6-lanthionine-BBN peptides were rapidly and successfully labeled with (18)F. Both tracers may have potential for GRPR-positive tumor imaging.
Assuntos
Neoplasias da Próstata/diagnóstico por imagem , Receptores da Bombesina/metabolismo , Alanina/análogos & derivados , Alanina/farmacocinética , Animais , Bombesina/farmacocinética , Linhagem Celular Tumoral , Radioisótopos de Flúor/farmacocinética , Humanos , Masculino , Camundongos Nus , Transplante de Neoplasias , Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Sulfetos/farmacocinética , Distribuição Tecidual , Microtomografia por Raio-XRESUMO
FLAIR and diffusion-weighted MRI were obtained twice (mean interval 20 +/- 4 months) in 10 patients with leukoaraiosis. At follow-up, visual extension of leukoaraiosis was unchanged, whereas the median of whole brain apparent diffusion coefficient (WB-ADC) histogram was increased (p= 0.008) and brain volume index (BVI) was decreased (p = 0.006). WB-ADC histogram and BVI are sensitive to leukoaraiosis and might be considered for monitoring progression of the disease.
Assuntos
Encéfalo/patologia , Transtornos Cerebrovasculares/patologia , Imageamento por Ressonância Magnética/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Transtornos Leucocíticos/patologia , Estudos Longitudinais , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estatísticas não ParamétricasRESUMO
Neuroimaging changes in the cerebral subcortical white matter (WMC) are recognized with the highest frequency in elderly subjects, particularly in those with vascular risk factors. WMC have been consistently reported to be associated with global or selective cognitive deficits, depression, motor and gait impairment. All these deficits are main contributors to disability in the elderly. Moreover, subjects with WMC have an increased risk of cardiovascular events and death from vascular causes. Functional status in subjects with WMC is variable, from normal to severely (physically or cognitively) disable. The association of WMC with age and with some of the clinical manifestations of aging suggests that WMC could be one of the age-related processes involved in the transition to disability in the elderly. Large cohorts of patients with WMC of different severity and detailed follow-up observation may help elucidating this issue. If WMC are shown to have an impact on disability in the aged population, efforts could be made to prevent WMC and WMC-related motor and cognitive deficits, and to identify measures aimed to halt or slow their progression.
Assuntos
Envelhecimento/fisiologia , Encéfalo/patologia , Idoso , Transtornos Cognitivos/patologia , Depressão/patologia , Pessoas com Deficiência , Humanos , Transtornos dos Movimentos/patologiaRESUMO
High-performance liquid chromatographic methods for the analysis of fluoroquinolones in biological fluids are reviewed. In particular, sample preparation and handling procedures, chromatographic conditions, and detection methods are discussed. A summary of published high-performance liquid chromatographic assays for individual fluoroquinolones is included.
Assuntos
Anti-Infecciosos/análise , Animais , Cromatografia Líquida de Alta Pressão , Fluoroquinolonas , HumanosRESUMO
A simple, specific and sensitive high-performance liquid chromatographic method has been developed for the determination of tocopherols in malt sprouts. A supercritical fluid extraction (SFE) procedure was used to isolate tocopherols from the vegetal matrix before quantitative analysis. The analytes were separated on a Zorbax reversed-phase column using methanol-water as mobile phase and quantified by measuring its fluorescence at lambda(em)=328 nm after excitation of the analytes at lambda(exc)=303 nm. The limits of detection for alpha-, gamma- and delta-tocopherols were 0.04, 0.05, and 0.05 microg/ml, respectively. The calibration graphs of the method were linear from 0.1 to 1.5, 0.2 to 2.5, and 0.2 to 2.0 microg/ml, for alpha-, gamma- and delta-tocopherols, respectively. This SFE and HPLC procedure is simple, precise and accurate for the determination of tocopherols in malt sprouts.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Cromatografia com Fluido Supercrítico/métodos , Grão Comestível/química , Tocoferóis/análise , Calibragem , Sensibilidade e Especificidade , Espectrometria de FluorescênciaRESUMO
Simvastatin (SV), an analogue of lovastatin, is the lactone form of 1',2',6',7',8',8a'-hexahydro-3,5-dihydroxy-2',6'-dimethyl-8'(2'',2''-di met hyl-1''-oxobutoxy)-1'-naphthalene-heptanoic acid (SVA) which lowers plasma cholesterol by inhibiting 3-hydroxy-3-methylglutaryl-CoA reductase. A fast, simple and accurate method for determining SV and SVA concentrations in human plasma has been developed and validated for use in the analysis of plasma samples from patients and healthy volunteers. This method involves an extraction procedure using a mixture of acetonitrile-water and reversed-phase high-performance liquid chromatography with UV detection. The procedure was linear from 20 to 1000 ng ml-1 for SV and from 25 to 1000 ng ml-1 for SVA, respectively. The method was accurate with relative errors of 5.0, 2.1 and 3.2% for human plasma controls containing 50, 250 and 500 ng ml-1 of SV, respectively. The corresponding precision was 2.3, 1.8 and 1.0% (RSD%). Similarly, relative standard deviations less than 2.3% and relative errors of less than 5.2% were obtained from human plasma controls containing SVA at identical concentrations. The method is suitable for pharmacology and pharmacokinetic studies of simvastatin.