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1.
Epilepsy Behav ; 101(Pt B): 106370, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31300386

RESUMO

Between 3 and 12% of all adult status epilepticus (SE) are caused by a brain tumor. Gliomas, and in particular, high-grade gliomas (HGGs), are at high risk of SE development. In this study, we aimed to describe the clinical characteristic and outcomes of tumor-associated SE (TASE) in a population of adult patients with glioma prospectively collected between 2013 and 2019. In the aforementioned period, we observed 26 TASE (median age: 68 years). Overall, 22 patients (85%) presented a HGG (one anaplastic astrocytoma and 21 a glioblastoma) while 4 had a LGG (two diffuse astrocytoma and two ganglioglioma). All the lesions were supratentorial, and the temporal lobe was the most frequently involved (20 patients). Fourteen patients (54%) had the SE episode as the first manifestation of the tumor; in the remaining 12 (all patients with a HGG), the development of SE heralded tumor progression or reappearance. When TASE outcomes were compared with the ones observed in the general population of SE (SEGP), the response to treatment was not different between the two populations (refractory SE (RSE)/super-refractory SE (SRSE) 12% versus 13%, p = 0.75). In the short-term, group with TASE had a significantly lower global disability (modified Rankin scale (mRS) < 3 at discharge: 60% versus 32%, p < 0.001; at 30 days follow-up: 62% versus 30%, p < 0.001) and mortality (30 days mortality: 4% versus 27%, p = 0.008). Six months and 1 year mortality did not show any difference between the two groups (6 months: 46% and 45%, respectively, p = 0.9; 1 year: 68% and 52%, respectively, p = 0.22). The appearance of TASE often heralds tumor grow and progression. Even in this context, it appears to be as treatment-responsive as SEGP and the short-term disability and mortality related to SE episode are lower than those observed in the SEGP. Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures.


Assuntos
Neoplasias Encefálicas/mortalidade , Progressão da Doença , Glioma/mortalidade , Convulsões/mortalidade , Estado Epiléptico/mortalidade , Adulto , Idoso , Neoplasias Encefálicas/diagnóstico por imagem , Feminino , Glioma/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Convulsões/diagnóstico por imagem , Estado Epiléptico/diagnóstico por imagem , Resultado do Tratamento
2.
Brain Sci ; 13(2)2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36831869

RESUMO

Brain tumor-related epilepsy (BTRE) is a common comorbidity in patients with brain neoplasms and it may be either the first symptom or develop after the tumor diagnosis. Increasing evidence suggests that brain tumors and BTRE share common pathophysiological mechanisms. Glutamatergic mechanisms can play a central role in promoting both primary brain tumor growth and epileptogenesis. Perampanel (PER), which acts as a selective antagonist of glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, may play a role both in the reduction in tumor growth and the control of epileptiform activity. This systematic review aimed to summarize the pre-clinical and clinical evidence about the antitumor properties, antiseizure effects and tolerability of PER in BTRE. Eight pre-clinical and eight clinical studies were identified. The currently available evidence suggests that PER can be an effective and generally well-tolerated therapeutic option in patients with BTRE. In vitro studies demonstrated promising antitumor activity of PER, while no role in slowing tumor progression has been demonstrated in rat models; clinical data on the potential antitumor activity of PER are scarce. Additional studies are needed to explore further the effects of PER on tumor progression and fully characterize its potentialities in patients with BTRE.

3.
Case Rep Neurol ; 15(1): 24-30, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36762000

RESUMO

Hyper-/hypoglycemic states are rare but well-established causes of hyperkinetic movements, including chorea and ballismus, usually associated with brain lesions in the basal ganglia. We report a case of hemichorea-hemiballismus (HCHB) syndrome that developed after a severe hypoglycemic episode in a 71-year-old man with poorly controlled type 2 diabetes mellitus. Uncommonly, brain MRI showed contralateral cortical-subcortical T2 and T2-FLAIR-hyperintense frontoparietal lesions, with cingulate gyrus involved, while the basal ganglia were unaffected. In patients with hypoglycemic encephalopathy associated with cortical lesions, the long-term prognosis is usually poor. Nevertheless, in our patient, the dyskinesias and the cerebral lesions progressively regressed by achieving good glycemic control. After four and 12 months, the patient's neurological examination was normal. To our knowledge, this is the first evidence of hypoglycemic etiology of cortical HCHB syndrome, supporting recent theories that cortical circuitries may independently contribute to the pathogenesis of chorea and ballismus. This is also the first report of cingulate gyrus involvement in hypoglycemic encephalopathy. Finally, this case may indicate that a subset of patients with cortical lesions due to hypoglycemia could present a good clinical outcome, likely depending on the size of the lesions and the duration and severity of the hypoglycemic episode.

4.
J Psychosom Res ; 162: 111046, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36183575

RESUMO

OBJECTIVE: Psychogenic non-epileptic seizures (PNES) resemble epileptic seizures but are not due to underlying epileptic activity and in some cases coexist alongside epilepsy. We described the clinical characteristics of patients with PNES as reported in the literature from the outbreak of the COVID-19 pandemic. We evaluated differences between patients with a diagnosis made immediately before the pandemic (pPNES) and those newly diagnosed during it (nPNES). METHODS: A systematic search with individual patient analysis of PNES cases published since the COVID-19 pandemic outbreak was performed. Differences between pPNES and nPNES were analyzed using Chi-square or Fisher exact test. RESULTS: Eleven articles were included, with 133 patients (106 pPNES and 27 nPNES). In the pPNES group, PNES frequency increased during the pandemic in 20/106 patients, whereas in 78/106, the frequency remained stable or decreased. nPNES was associated with higher risks of SARS-CoV-2 infection and epilepsy diagnosis, whereas psychiatric comorbidities were less frequent. CONCLUSIONS: During the pandemic, most patients with pPNES remained stable or improved, whereas nPNES was associated with a lower burden of psychiatric comorbidities. These intriguing findings suggest that, at least in some patients, the COVID-19 pandemic may not necessarily lead to worsening in the frequency of PNES and quality of life.


Assuntos
COVID-19 , Epilepsia , COVID-19/epidemiologia , Eletroencefalografia , Epilepsia/diagnóstico , Epilepsia/epidemiologia , Humanos , Pandemias , Qualidade de Vida/psicologia , SARS-CoV-2 , Convulsões/diagnóstico
5.
Surgery ; 170(2): 558-562, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33714617

RESUMO

BACKGROUND: While elective surgery was shut down in most settings during the 2019 novel coronavirus pandemic, some referral centers were designated as surgery hubs. We sought to investigate how the pandemic scenario impacted the quality of a long-established enhanced recovery protocol colorectal surgery program in 2 referral centers, designated as colorectal surgery hubs, located in the epicentral Italian regions hardest hit by the pandemic. METHODS: We compared short-term outcomes of patients undergoing major colorectal surgery with a long-established enhanced recovery protocol during the coronavirus disease 2019 outbreak occurred in 2020 (group A) with the correspondent timeframe of 2019 (group B). Primary outcomes were morbidity and mortality, duration of stay, and readmission rate. RESULTS: One hundred and thirty-six patients underwent major colorectal surgery in group A and 173 in group B. Postoperative complications and readmission rate were comparable between the 2 groups. Oncologic case-log was predominant in group A compared with group B (73.5 vs 61%; P = .01). A significantly shorter overall duration of stay was found in group A (P < .001). Uncomplicated patients of group A had a shorter duration of stay when compared with uncomplicated patients of group B (P = .008). CONCLUSION: Under special precautionary measures, major colorectal surgery can be undertaken on elective basis even during coronavirus disease 2019 pandemic with reasonable results. A reduction of duration of stay within a long-established enhanced recovery protocol colorectal surgery program was observed during the coronavirus disease 2019 pandemic occurred in 2020 in comparison with the correspondent timeframe of the previous year without compromising short-term outcomes. The pandemic uncovered the positive impact of patients' commitment to reducing duration of stay as the empowered risk awareness likely promoted their compliance to the enhanced recovery protocol.


Assuntos
COVID-19 , Cirurgia Colorretal/estatística & dados numéricos , Recuperação Pós-Cirúrgica Melhorada , Tempo de Internação/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
6.
Updates Surg ; 73(2): 753-762, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33394354

RESUMO

The COVID-19 pandemic has raised concerns about the negative impact of the fear of contagion on people's willingness to seek medical care and the subsequent effects on patients' prognosis. To date, not much is known about the outcomes of acute surgical diseases in this scenario. The aim of this multicenter observational study is to explore the effects of COVID-19 outbreak on the outcomes of patients who underwent surgery for peritonitis. Patients undergoing surgery for secondary peritonitis during the first COVID-19 surge in Italy (March 23-May 4, 2020-COVID period group) were compared with patients who underwent surgery during the same time interval of year 2019 (no-COVID period group). The primary endpoint was the development of postoperative complications. Logistic regression analysis was conducted to identify predictors of complications. Of the 332 patients studied, 149 were in the COVID period group and 183 were in the no-COVID period group. Patients in the COVID period group had an increased frequency of late presentations to the emergency departments (43% vs. 31.1%; P = 0.026) and a higher rate of postoperative complications (35.6% vs. 18%; P < 0.001). The same results were found in the subset analysis of patients with severe peritonitis at surgical exploration. The ASA score, severity of peritonitis, qSOFA score, diagnosis other than appendicitis, and COVID period resulted independent predictors of complications. During the COVID-19 pandemic patients with peritonitis had a higher rate of complicated postoperative courses, weighing on hospital costs and assistance efforts already pressured by the ongoing sanitary crisis.


Assuntos
COVID-19/epidemiologia , Peritonite/cirurgia , Complicações Pós-Operatórias/epidemiologia , Adulto , Emergências , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Estudos Prospectivos , SARS-CoV-2
7.
Front Neurol ; 12: 622130, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33643200

RESUMO

Thrombotic complications are common in COVID-19 patients, but cerebral venous system involvement, timing after infection, optimal treatment, and long-term outcome are uncertain. We report a case of massive cerebral venous thrombosis and concomitant internal iliac vein thrombosis occurring in the late phase of paucisymptomatic COVID-19 infection. Mild respiratory symptoms, without fever, started 3 weeks before headache and acute neurological deficits. The patient had silent hypoxemia and typical COVID-19 associated interstitial pneumonia. Brain CT scan showed a left parietal hypodense lesion with associated sulcal subarachnoid hemorrhage. CT cerebral venography showed a massive cerebral venous thrombosis involving the right transverse sinus, the right jugular bulb, the superior sagittal sinus, the straight sinus, the vein of Galen, and both internal cerebral veins. Abdominal CT scan showed no malignancy but revealed an asymptomatic right internal iliac vein thrombosis. Both cerebral venous thrombosis and pelvic vein thrombosis were effectively treated with unfractionated heparin started on the day of admission, then shifted to low molecular weight heparin, with a favorable clinical course. Nasopharyngel swab, repeated twice, tested negative for SARS-CoV-2. Serological tests confirmed SARS-CoV-2 infection. Our case supports active surveillance and prevention of thrombotic complications associated with COVID-19, which may affect both peripheral and cerebral venous system. Early initiation of unfractionated heparin may lead to good neurologic outcome.

8.
J Hypertens ; 26(3): 486-93, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18300859

RESUMO

OBJECTIVE AND METHODS: Prednisone and its active metabolite prednisolone, both substrates for 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), may represent a pharmacological challenge for the enzyme. The aim of the present work was to define the possible role of abnormal cortisol/cortisone handling, as revealed by an urinary tetrahydrocortisol + allotetrahydrocortisol (THFs)/tetrahydrocortisone (THE) ratio between 1.5 and 3.0, by measuring urinary cortisol and cortisone metabolites in: normotensive individuals (n = 100) who received 7-8 mg/day of oral prednisone and were then followed for development of hypertension; essential hypertensive (EH) participants from primary care (n = 103); and EH hypertensive patients referred to the Hypertension Unit (n = 141). RESULTS: About one-third (14 out of 47, 30%) of glucorticoid-treated patients who developed hypertension showed a THFs/THE ratio >1.5, which was seen in 3% (n = 3) and 14% (n = 19) of primary and tertiary care hypertensive patients, respectively. A THFs/THE ratio >1.5 was associated with a 3.8-fold incremental risk of hypertension after glucocorticoid therapy, regardless of duration and intensity of prednisone therapy. CONCLUSIONS: A number of EH patients and glucocorticoid-treated participants shared a similar phenotype, characterized by both arterial hypertension and elevated urinary THFs/THE ratio. Such a phenotype is more common in severely, rather than in mildly, hypertensive patients.


Assuntos
Cortisona/urina , Glucocorticoides/efeitos adversos , Hidrocortisona/urina , Hipertensão/induzido quimicamente , Prednisona/efeitos adversos , Adulto , Idoso , Feminino , Humanos , Hidrocortisona/metabolismo , Hipertensão/urina , Masculino , Pessoa de Meia-Idade , Fenótipo , Fatores de Risco
9.
Clin Colorectal Cancer ; 17(2): e217-e228, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29352642

RESUMO

BACKGROUND: A noninvasive blood test for the early detection of colorectal cancer (CRC) is highly required. We evaluated a panel of 4 mRNAs as putative markers of CRC. MATERIALS AND METHODS: We tested LGALS4, CEACAM6, TSPAN8, and COL1A2, referred to as the CELTiC panel, using quantitative reverse transcription polymerase chain reaction, on subjects with positive fecal immunochemical test (FIT) results and undergoing colonoscopy. Using a nonparametric test and multinomial logistic model, FIT-positive subjects were compared with CRC patients and healthy individuals. RESULTS: All the genes of the CELTiC panel displayed statistically significant differences between the healthy subjects (n = 67), both low-risk (n = 36) and high-risk/CRC (n = 92) subjects, and those in the negative-colonoscopy, FIT-positive group (n = 36). The multinomial logistic model revealed LGALS4 was the most powerful marker discriminating the 4 groups. When assessing the diagnostic values by analysis of the areas under the receiver operating characteristic curves (AUCs), the CELTiC panel reached an AUC of 0.91 (sensitivity, 79%; specificity, 94%) comparing normal subjects to low-risk subjects, and 0.88 (sensitivity, 75%; specificity, 87%) comparing normal and high-risk/CRC subjects. The comparison between the normal subjects and the negative-colonoscopy, FIT-positive group revealed an AUC of 0.93 (sensitivity, 82%; specificity, 97%). CONCLUSION: The CELTiC panel could represent a useful tool for discriminating subjects with positive FIT findings and for the early detection of precancerous adenomatous lesions and CRC.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Idoso , Antígenos CD/sangue , Área Sob a Curva , Moléculas de Adesão Celular/sangue , Colágeno Tipo I/sangue , Fezes/química , Feminino , Proteínas Ligadas por GPI/sangue , Galectina 4/sangue , Humanos , Imuno-Histoquímica , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , RNA Mensageiro/sangue , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real/métodos , Sensibilidade e Especificidade , Tetraspaninas/sangue
10.
PLoS One ; 12(8): e0184118, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28859138

RESUMO

Inflammatory bowel diseases (IBD) profoundly affect quality of life and have been gradually increasing in incidence, prevalence and severity in many areas of the world, and in children in particular. Patients with suspected IBD require careful history and clinical examination, while definitive diagnosis relies on endoscopic and histological findings. The aim of the present study was to investigate whether the alveolar air of pediatric patients with IBD presents a specific volatile organic compounds' (VOCs) pattern when compared to controls. Patients 10-17 years of age, were divided into four groups: Crohn's disease (CD), ulcerative colitis (UC), controls with gastrointestinal symptomatology, and surgical controls with no evidence of gastrointestinal problems. Alveolar breath was analyzed by ion molecule reaction mass spectrometry. Four models were built starting from 81 molecules plus the age of subjects as independent variables, adopting a penalizing LASSO logistic regression approach: 1) IBDs vs. controls, finally based on 18 VOCs plus age (sensitivity = 95%, specificity = 69%, AUC = 0.925); 2) CD vs. UC, finally based on 13 VOCs plus age (sensitivity = 94%, specificity = 76%, AUC = 0.934); 3) IBDs vs. gastroenterological controls, finally based on 15 VOCs plus age (sensitivity = 94%, specificity = 65%, AUC = 0.918); 4) IBDs vs. controls, built starting from the 21 directly or indirectly calibrated molecules only, and finally based on 12 VOCs plus age (sensitivity = 94%, specificity = 71%, AUC = 0.888). The molecules identified by the models were carefully studied in relation to the concerned outcomes. This study, with the creation of models based on VOCs profiles, precise instrumentation and advanced statistical methods, can contribute to the development of new non-invasive, fast and relatively inexpensive diagnostic tools, with high sensitivity and specificity. It also represents a crucial step towards gaining further insights on the etiology of IBD through the analysis of specific molecules which are the expression of the particular metabolism that characterizes these patients.


Assuntos
Colite Ulcerativa/diagnóstico , Doença de Crohn/diagnóstico , Doenças Inflamatórias Intestinais/diagnóstico , Compostos Orgânicos Voláteis/isolamento & purificação , Adolescente , Testes Respiratórios , Criança , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Doença de Crohn/metabolismo , Doença de Crohn/patologia , Expiração , Feminino , Humanos , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/fisiopatologia , Masculino , Espectrometria de Massas , Compostos Orgânicos Voláteis/metabolismo
11.
Cancer Biol Med ; 12(4): 302-7, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26779367

RESUMO

OBJECTIVE: Cancer is one of the most common diagnoses in elderly patients. Of all types of abdominal cancer, colorectal cancer (CRC) is undoubtedly the most frequent. Median age at diagnosis is approximately 70 years old worldwide. Due to the multiple comorbidities affecting elderly people, frailty evaluation is very important in order to avoid over- or under-treatment. This pilot study was designed to investigate the variables capable of predicting the long-term risk of mortality and living situation after surgery for CRC. METHODS: Patients with 70 years old and older undergoing elective surgery for CRC were prospectively enrolled in the study. The patients were preoperatively screened using 11 internationally-validated-frailty-assessment tests. The endpoints of the study were long-term mortality and living situation. The data were analyzed using univariate Cox proportional-hazard regression analysis to verify the predictive value of score indices in order to identify possible risk factors. RESULTS: Forty-six patients were studied. The median follow-up time after surgery was 4.6 years (range, 2.9-5.7 years) and no patients were lost to follow-up. The overall mortality rate was 39%. Four of the patients who survived (4/28, 14%) lost their functional autonomy. The preoperative impaired Timed Up and Go (TUG), Eastern Cooperative Group Performance Status (ECOG PS), Instrumental Activities of Daily Living (IADLs), Vulnerable Elders Survey (VES-13) scoring systems were significantly associated with increased long term mortality risk. CONCLUSION: Simplified frailty-assessing tools should be routinely used in elderly cancer patients before treatment in order to stratify patient risk. The TUG, ECOG-PS, IADLs and VES-13 scoring systems are potentially able to predict long-term mortality and disability. Additional studies will be needed to confirm the preliminary data in order to improve management strategies for oncogeriatric surgical patients.

12.
J Chromatogr B Analyt Technol Biomed Life Sci ; 778(1-2): 199-210, 2002 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-12376127

RESUMO

A method for the determination of benzene, toluene, ethylbenzene and xylene in blood and urine of people not occupationally exposed to solvents is described. The headspace technique combined with gas chromatography with a mass spectrometer detector is used. The sensitivity of recent mass spectrometers is good enough to furnish reliable results also in biological samples collected from the general population. No treatment for concentrating solvents present in the blood or urine is necessary. The main features of the method are easy preparation of biological samples, small volumes (7 ml), good repeatability and linearity in the range of interest. The limits of detection in blood were 16, 43, 22 and 52 ng/l for benzene, toluene, ethylbenzene and m-xylene respectively. Slightly greater sensitivity was found for urine samples. The results obtained in biological samples from 25 woodworkers not occupationally exposed to BTEX (15 non-smokers and 10 smokers) are comparable to those obtained by other investigators.


Assuntos
Derivados de Benzeno/análise , Benzeno/análise , Tolueno/análise , Xilenos/análise , Derivados de Benzeno/sangue , Derivados de Benzeno/urina , Cromatografia Gasosa , Humanos , Controle de Qualidade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Tolueno/sangue , Tolueno/urina , Xilenos/sangue , Xilenos/urina
13.
Am J Hypertens ; 25(5): 597-603, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22278213

RESUMO

BACKGROUND: 11ß-hydroxysteroid dehydrogenase type 2 enzyme (11ß-HSD2) inactivates cortisol (F) to cortisone (E); its impairment is associated with hypertension. We reported that 15.7% of the Chilean essential hypertensives possessed a high F/E ratio suggesting a partial deficit in 11ß-HSD2 activity. It has been reported that the G534A(Glu178/Glu) polymorphism in the HSD11B2 gene is associated with hypertension. Investigate the frequency of the G534A polymorphism and its correlation with the glucocorticoid profile in Chilean essential hypertensive and normotensive subjects. METHODS: Essential hypertensive outpatients (n = 232) and normotensive subjects (n = 74) were recruited. A change in the AluI restriction enzyme digest pattern, caused by the presence of the G534A polymorphism, was utilized to screen DNA isolated from leukocytes within the cohort before confirmation by sequencing. Plasma renin activity (PRA), serum aldosterone, F, and E were measured by radioimmunoassay. Urinary tetrahydrocortisol (THF), 5α-tetrahydrocortisol (5α-THF), and tetrahydrocortisone (THE) were measured by gas chromatography-mass spectrometry. RESULTS: G534A polymorphism frequency was similar between hypertensive patients (19 of 232; 8.2%) and normotensive subjects (7 of 74; 9.5%). When categorized by presence or absence of the G534A polymorphism, no significant differences in the serum F/E ratio or other measured biochemical variables were detected. Despite a previous report that the G534A polymorphism is associated with a neighboring C468A (Thr156/Thr) polymorphism, analysis within our cohort showed that only one patient in each group presented with this double polymorphism. CONCLUSIONS: We report the frequency of the G534A polymorphism in the Spanish-Amerindian population. No correlation was detected between this polymorphism and the presence of hypertension and biochemical parameters in this Chilean cohort.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 2/genética , Genótipo , Hipertensão/etnologia , Hipertensão/genética , Polimorfismo Genético/genética , Aldosterona/sangue , Estudos de Casos e Controles , Chile , Estudos de Coortes , Cortisona/sangue , Feminino , Humanos , Hidrocortisona/sangue , Hipertensão/sangue , Masculino , Pessoa de Meia-Idade , Prevalência , Renina/sangue
14.
J Chromatogr B Analyt Technol Biomed Life Sci ; 878(27): 2515-9, 2010 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-20462811

RESUMO

N,N-dimethylacetamide (DMA) is used in the textile and plastics industry as a solvent alternative to more toxic N,N-dimethylformamide. Here we studied toxicokinetics of two major urinary metabolites of DMA, namely, S-(acetamidomethyl)mercapturic acid (AMMA) and N-methylacetamide (NMA). Urine samples were collected from workers exposed to DMA in a factory manufacturing acrylic fibers. AMMA and NMA were determined by HPLC/MS and GC/MS, respectively. The working scheme in the factory consisted of periods of three consecutive working shifts alternated regularly with two days off work. In the first stage of the study, NMA and AMMA were determined in urine samples collected before, in the middle, and at the end of one working shift. In the second stage, urine was collected five times during three consecutive days after a two-day rest: before and at the end of the first and second working shifts and before the third shift. It was found that the end-of-shift NMA levels were several folds higher than the pre-shift levels of the same day and dropped significantly until the next shift. On the other hand, there were no significant differences in AMMA levels before and at the end of the same shift but a continuous rise during the three-day working period was observed. Median values of NMA concentrations at the end of working shifts were between 10.1 and 17.3 mg/g creatinine, median AMMA concentrations in the second or third day of the working period varied between 12.4 and 38.1 mg/g creatinine. The approximate half-lives of NMA and AMMA (means) in the exposed workers were about 9 and 29 h, respectively. Thus, while NMA in the end-of-shift urine samples remains a preferential biomarker of DMA exposure during that shift, AMMA determined at the end of a work-week reflects cumulative exposure over the last few days. Further studies are needed to determine AMMA concentrations corresponding to the threshold limit value of DMA.


Assuntos
Acetamidas/toxicidade , Acetamidas/urina , Acetilcisteína/análogos & derivados , Biomarcadores/urina , Exposição Ocupacional , Acetilcisteína/urina , Cromatografia Gasosa/métodos , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Espectrometria de Massas/métodos , Reprodutibilidade dos Testes
15.
Endocrine ; 37(1): 106-14, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19882252

RESUMO

Cortisol availability is modulated by several enzymes: 11ß-HSD2, which transforms cortisol (F) to cortisone (E) and 11ß-HSD1 which predominantly converts inactive E to active F. Additionally, the A-ring reductases (5α- and 5ß-reductase) inactivate cortisol (together with 3α-HSD) to tetrahydrometabolites: 5αTHF, 5ßTHF, and THE. The aim was to assess 11ß-HSD2, 11ß-HSD1, and 5ß-reductase activity in hypertensive patients. Free urinary F, E, THF, and THE were measured by HPLC-MS/MS in 102 essential hypertensive patients and 18 normotensive controls. 11ß-HSD2 enzyme activity was estimated by the F/E ratio, the activity of 11ß-HSD1 in compare to 11ß-HSD2 was inferred by the (5αTHF + 5ßTHF)/THE ratio and 5ß-reductase activity assessed using the E/THE ratio. Activity was considered altered when respective ratios exceeded the maximum value observed in the normotensive controls. A 15.7% of patients presented high F/E ratio suggesting a deficit of 11ß-HSD2 activity. Of the remaining 86 hypertensive patients, two possessed high (5αTHF + 5ßTHF)/THE ratios and 12.8% had high E/THE ratios. We observed a high percentage of alterations in cortisol metabolism at pre-receptor level in hypertensive patients, previously misclassified as essential. 11ß-HSD2 and 5ß-reductase decreased activity and imbalance of 11ß-HSDs should be considered in the future management of hypertensive patients.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 2/metabolismo , 17-Hidroxicorticosteroides/urina , Hipertensão/enzimologia , Hipertensão/urina , Oxirredutases/metabolismo , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , 17-Hidroxicorticosteroides/química , 3-alfa-Hidroxiesteroide Desidrogenase (B-Específica)/metabolismo , Adulto , Algoritmos , Chile , Cromatografia Líquida de Alta Pressão , Cortisona/química , Cortisona/urina , Feminino , Humanos , Hidrocortisona/química , Hidrocortisona/urina , Hipertensão/classificação , Masculino , Pessoa de Meia-Idade , Síndrome de Excesso Aparente de Minerolocorticoides/diagnóstico , Síndrome de Excesso Aparente de Minerolocorticoides/enzimologia , Síndrome de Excesso Aparente de Minerolocorticoides/urina , Espectrometria de Massas em Tandem , Tetra-Hidrocortisol/química , Tetra-Hidrocortisol/urina , Tetra-Hidrocortisona/química , Tetra-Hidrocortisona/urina
16.
Int Arch Occup Environ Health ; 76(6): 461-6, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12687377

RESUMO

OBJECTIVES: To investigate and compare alveolar, blood, and urine concentrations of 1,3-butadiene, 2,5 dimethylfuran, and benzene, in non-occupational exposure to these products. METHODS: Benzene, 2,5-dimethylfuran and 1,3-butadiene were measured in the breath, blood, and urine samples of 61 subjects living in small mountain villages. All 61 were regularly employed as forestry workers. Sampling was done during the long winter-season non-working period. Samples were collected after overnight rest and analysed by headspace and GC-mass spectrometry methods. RESULTS: The median 1,3-butadiene level was 1.2 ng/l (range: <0.8-13.2 ng/l) in alveolar air, 2.2 ng/l (range: <0.5-50.2 ng/l) in blood, and 1.1 ng/l (range: <1-8.9 ng/l) in urine. The median benzene level was 5.7 ng/l (range: <1-24.9 ng/l) in alveolar air, 62.3 ng/l (range: 33.5-487.2 ng/l) in blood, and 63.4 ng/l (range: 25.8-1099.1 ng/l) in urine. The median 2,5-dimethylfuran level was 0.5 ng/l (range: <1-12.5 ng/l) in alveolar air, 2.5 ng/l (range: <5-372.9 ng/l) in blood, and 51.8 ng/l (range: <5-524.9 ng/l) in urine. In several cases, 2,5-dimethylfuran levels were below the detection limit in alveolar air and blood, especially in non-smokers. 1,3-Butadiene, 2,5-dimethylfuran and benzene levels were significantly higher in smokers than non-smokers in all biological media. CONCLUSIONS: 1,3-Butadiene and benzene, as ubiquitous pollutants, are detectable and quantifiable in human alveolar air, blood and urine. 2,5-Dimethylfuran, which is not a usual environmental pollutant, is almost always detectable in biological media, but only in smokers.


Assuntos
Benzeno/análise , Butadienos/análise , Exposição Ambiental/análise , Monitoramento Ambiental/métodos , Furanos/análise , Adulto , Biomarcadores/análise , Testes Respiratórios , Butadienos/sangue , Butadienos/urina , Agricultura Florestal , Furanos/sangue , Furanos/urina , Humanos , Masculino , Pessoa de Meia-Idade , População Rural , Fumar/sangue , Fumar/urina
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