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1.
Acta Microbiol Immunol Hung ; 70(1): 7-10, 2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-36753298

RESUMO

The high demand for COVID-19 diagnosis overwhelmed reference hospitals. Regional laboratories had to incorporate molecular technology to respond to the emergency. This work described the implementation of molecular diagnostic tools and the detection of SARS-CoV-2, in a regional hospital with no previous experience, from October 2020 to March 2022. The laboratory structure was significantly modified. The staff grew from 3 to 4 clinical microbiologists, and from 7 to 17 laboratory technicians to provide 24/7 coverage. A total of 144,442 samples were processed during the period of study. The highest peaks were reached in July 2021 with 25,285 samples processed, and between December 2021 and January 2022, with 32,245. COVID-19 pandemic has represented not only the challenge, but the opportunity to introduce Nucleic Acid Amplification Techniques (NAAT) in inexperienced laboratories. These secondary settings have shown an extraordinary ability to adapt and cannot be left behind in the progress of diagnostic techniques.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Laboratórios , Teste para COVID-19 , Espanha , Pandemias , Técnicas de Laboratório Clínico/métodos
2.
J Neurosci ; 40(47): 8976-8993, 2020 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-33055278

RESUMO

Mammalian Piezo2 channels are essential for transduction of innocuous mechanical forces by proprioceptors and cutaneous touch receptors. In contrast, mechanical responses of somatosensory nociceptor neurons evoking pain, remain intact or are only partially reduced in Piezo2-deficient mice. In the eye cornea, comparatively low mechanical forces are detected by polymodal and pure mechanosensory trigeminal ganglion neurons. Their activation always evokes ocular discomfort or pain and protective reflexes, thus being a unique model to study mechanotransduction mechanisms in this particular class of nociceptive neurons. Cultured male and female mouse mechano- and polymodal nociceptor corneal neurons display rapidly, intermediately and slowly adapting mechanically activated currents. Immunostaining of the somas and peripheral axons of corneal neurons responding only to mechanical force (pure mechano-nociceptor) or also exhibiting TRPV1 (transient receptor potential cation channel subfamily V member 1) immunoreactivity (polymodal nociceptor) revealed that they express Piezo2. In sensory-specific Piezo2-deficient mice, the distribution of corneal neurons displaying the three types of mechanically evoked currents is similar to the wild type; however, the proportions of rapidly adapting neurons, and of intermediately and slowly adapting neurons were significantly reduced. Recordings of mechano- and polymodal-nociceptor nerve terminals in the corneal surface of Piezo2 conditional knock-out mice revealed a reduced number of mechano-sensitive terminals and lower frequency of nerve terminal impulse discharges under mechanical stimulation. Eye blinks evoked by von Frey filaments applied on the cornea were lower in Piezo2-deficient mice compared with wild type. Together, our results provide direct evidence that Piezo2 channels support mechanically activated currents of different kinetics in corneal trigeminal neurons and contributes to transduction of mechanical forces by corneal nociceptors.SIGNIFICANCE STATEMENT The cornea is a richly innervated and highly sensitive tissue. Low-threshold mechanical forces activate corneal receptors evoking discomfort or pain. To examine the contribution of Piezo2, a low-threshold mechanically activated channel, to acute ocular pain, we characterized the mechanosensitivity of corneal sensory neurons. By using Piezo2 conditional knock-out mice, we show that Piezo2 channels, present in the cell body and terminals of corneal neurons, are directly involved in acute corneal mechano-nociception. Inhibition of Piezo2 for systemic pain treatment is hindered because of its essential role for mechano-transduction processes in multiple body organs. Still, topical modulation of Piezo2 in the cornea may be useful to selectively relief unpleasant sensations and pain associated with mechanical irritation accompanying many ocular surface disorders.


Assuntos
Doenças da Córnea/genética , Doenças da Córnea/fisiopatologia , Canais Iônicos/genética , Dor/genética , Dor/fisiopatologia , Animais , Piscadela , Células Cultivadas , Córnea/inervação , Mecanotransdução Celular , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neurônios , Nociceptores , Técnicas de Patch-Clamp , Estimulação Física , Terminações Pré-Sinápticas , Gânglio Trigeminal/fisiopatologia
3.
Future Oncol ; 17(19): 2529-2544, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33904318

RESUMO

Monoclonal antibodies are highly complex, large and biologic products with a substantial impact on the clinical management of a variety of diseases including cancer. The expiry of patents for essential monoclonal antibodies in cancer care such as bevacizumab, rituximab and trastuzumab, has prompted the global development of biosimilars to balance the biologics market. However, an understanding of the different approach of biosimilar development compared with its reference medicinal product, especially in the context of clinical trial design and end point selection may help oncologists integrating biosimilars into clinical practice. Herein, we reviewed the clinical development of biosimilars in oncology comparing the available clinical data of proposed biosimilars of bevacizumab, rituximab and trastuzumab.


Lay abstract In the last decades, patients with cancer have been treated with novel medicines as bevacizumab, rituximab and trastuzumab produced or derived by a biologic source. The expiry of patents for these biologic medicines brings the opportunity to develop similar biologic products, known as biosimilars. However, to be authorized and commercialized, biosimilars need to demonstrate their equivalence in quality, efficacy and safety to the reference medicinal product through a complete development process. An understanding of the different approach of biosimilar development compared with its reference medicinal product especially in the context of the clinical studies trials may help oncologists integrating biosimilars into clinical practice. Herein, we reviewed the clinical development of biosimilars in oncology comparing the available clinical data of proposed biosimilars of bevacizumab, rituximab and trastuzumab.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Medicamentos Biossimilares/uso terapêutico , Desenvolvimento de Medicamentos/tendências , Neoplasias/tratamento farmacológico , Antineoplásicos Imunológicos/farmacologia , Bevacizumab/farmacologia , Bevacizumab/uso terapêutico , Medicamentos Biossimilares/farmacologia , Desenvolvimento de Medicamentos/normas , Estudos de Equivalência como Asunto , Humanos , Oncologia/normas , Oncologia/tendências , Projetos de Pesquisa/normas , Projetos de Pesquisa/tendências , Rituximab/farmacologia , Rituximab/uso terapêutico , Trastuzumab/farmacologia , Trastuzumab/uso terapêutico
4.
J Bacteriol ; 201(16)2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31209076

RESUMO

Previous work from our group indicated an association between the gastrointestinal microbiota of infants with cystic fibrosis (CF) and airway disease in this population. Here we report that stool microbiota of infants with CF demonstrates an altered but largely unchanging within-individual bacterial diversity (alpha diversity) over the first year of life, in contrast to the infants without CF (control cohort), which showed the expected increase in alpha diversity over the first year. The beta diversity, or between-sample diversity, of these two cohorts was significantly different over the first year of life and was statistically significantly associated with airway exacerbations, confirming our earlier findings. Compared with control infants, infants with CF had reduced levels of Bacteroides, a bacterial genus associated with immune modulation, as early as 6 weeks of life, and this significant reduction of Bacteroides spp. in the cohort with CF persisted over the entire first year of life. Only two other genera were significantly different across the first year of life: Roseburia was significantly reduced and Veillonella was significantly increased. Other genera showed differences between the two cohorts but only at selected time points. In vitro studies demonstrated that exposure of the apical face of polarized intestinal cell lines to Bacteroides species supernatants significantly reduced production of interleukin 8 (IL-8), suggesting a mechanism whereby changes in the intestinal microbiota could impact inflammation in CF. This work further establishes an association between gastrointestinal microbiota, inflammation, and airway disease in infants with CF and presents a potential opportunity for therapeutic interventions beginning in early life.IMPORTANCE There is growing evidence for a link between gastrointestinal bacterial communities and airway disease progression in CF. We demonstrate that infants with CF ≤1 year of age show a distinct stool microbiota versus that of control infants of a comparable age. We detected associations between the gut microbiome and airway exacerbation events in the cohort of infants with CF, and in vitro studies provided one possible mechanism for this observation. These data clarify that current therapeutics do not establish in infants with CF a gastrointestinal microbiota like that in healthy infants, and we suggest that interventions that direct the gastrointestinal microbiota closer to a healthy state may provide systemic benefits to these patients during a critical window of immune programming that might have implications for lifelong health.


Assuntos
Bactérias/isolamento & purificação , Fibrose Cística/microbiologia , Fezes/microbiologia , Microbioma Gastrointestinal , Bactérias/classificação , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Bacteroides/genética , Bacteroides/crescimento & desenvolvimento , Bacteroides/isolamento & purificação , Estudos de Coortes , Fibrose Cística/imunologia , Feminino , Humanos , Lactente , Masculino , Sistema Respiratório/imunologia
5.
J Am Chem Soc ; 141(1): 33-37, 2019 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-30557011

RESUMO

The anaerobic gut microbial pathway that converts choline into trimethylamine (TMA) is broadly linked to human disease. Here, we describe the discovery that betaine aldehyde inhibits TMA production from choline by human gut bacterial isolates and a complex gut community. In vitro assays and a crystal structure suggest betaine aldehyde targets the gut microbial enzyme choline TMA-lyase (CutC). In our system, we do not observe activity for the previously reported CutC inhibitor 3,3-dimethylbutanol (DMB). The workflow we establish for identifying and characterizing betaine aldehyde provides a framework for developing additional inhibitors of gut microbial choline metabolism, including therapeutic candidates.


Assuntos
Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Colina/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia , Anaerobiose/efeitos dos fármacos , Domínio Catalítico , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/química , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Modelos Moleculares , Bibliotecas de Moléculas Pequenas/química
6.
J Perinat Med ; 47(6): 625-630, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31141492

RESUMO

Background Obesity in pregnancy is increasing worldwide, reaching epidemic proportions in many countries and frequently creating challenges for obstetricians. We conducted this study to assess the effects of maternal obesity on maternal and perinatal outcomes. Methods A historical cohort study was performed on 16,609 women who delivered singleton babies in a 5-year period (2013-2017). Data were retrieved from the Cruces Perinatal Database (CPD) and only women whose prepregnancy body mass index (BMI) was known were included. Women were categorized according to the World Health Organization (WHO) classification: normal weight (BMI 20-24.9 kg/m2) and obesity (BMI ≥ 30 kg/m2). Obstetric, perinatal and neonatal outcomes were compared, and adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) were calculated using the normal-weight group as the reference. Results Compared to women of normal weight (n = 9778), obese women (n = 2207) had a higher risk of preeclampsia (aOR 2.199, 95% CI: 1.46-3.29), rectovaginal group B streptococcus colonization (aOR 1.299, 95% CI: 1.14-1.47), induction of labor (aOR 1.593, 95% CI: 1.44-1.75), cesarean section (aOR 2.755, 95% CI: 2.46-3.08), cesarean section in women with a history of cesarean delivery (aOR 1.409, 95% CI: 1.03-1.92), fetal weight ≥4000 g (aOR 2.090, 95% CI: 1.803-2.422) and admission to the neonatal intensive care unit (NICU) (aOR 1.341, 95% CI: 1.12-1.59). No association was found with preterm birth (aOR 0.936, 95% CI: 0.77-1.13), stillbirth (aOR 0.921, 95% CI: 0.41-2.02) or neonatal mortality (aOR 2.205, 95% CI: 0.86-5.62). Conclusion Maternal obesity is associated with a higher risk of adverse pregnancy and perinatal outcomes. Pregnancy in this population of women should be considered and managed as high risk.


Assuntos
Cesárea/estatística & dados numéricos , Diabetes Gestacional/epidemiologia , Obesidade Materna , Pré-Eclâmpsia/epidemiologia , Complicações na Gravidez , Nascimento Prematuro/epidemiologia , Adulto , Índice de Massa Corporal , Feminino , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Idade Materna , Obesidade Materna/diagnóstico , Obesidade Materna/epidemiologia , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Gravidez de Alto Risco , Espanha/epidemiologia , Natimorto/epidemiologia
7.
J Vasc Surg ; 66(5): 1417-1426, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28823865

RESUMO

OBJECTIVE: The objective of this study was to determine risk factors for nosocomial infections (NIs) and predictors of mortality in patients with prosthetic vascular grafts (PVGs). METHODS: This was a prospective cohort study of all consecutive patients who underwent PVG of the abdominal aorta with or without iliac-femoral involvement and peripheral PVG from April 2008 to August 2009 at a university hospital. Patients younger than 15 years and those with severe immunodeficiency were excluded. The follow-up period was until 3 years after surgery or until death. RESULTS: There were 261 patients included; 230 (88.12%) were male, and the mean age was 67.57 (standard deviation, 10.82) years. The reason for operation was aortic aneurysm in 49 (18.77%) patients or lower limb arteriopathy in 212 (81.23%) patients. NIs occurred in 71 (27.20%) patients. Of these, 42 were surgical site infections (SSIs), of which 61.9% occurred in the lower extremities (14 superficial, 10 deep, and 2 PVG infections) and 38.1% in the abdomen (7 superficial, 7 deep, and 2 PVG infections); 15 were respiratory tract infections; and 15 were urinary tract infections. Active lower extremity skin and soft tissue infection (SSTI) at the time of surgery was a significant predictor of NI for both types of PVG (abdominal aortic PVG: adjusted odds ratio [OR], 12.6; 95% confidence interval [CI], 1.15-138.19; peripheral PVG: adjusted OR, 2.43; 95% CI, 1.08-5.47). Other independent predictors of NI were mechanical ventilation (adjusted OR, 55.96; 95% CI, 3.9-802.39) for abdominal aortic PVG and low hemoglobin levels on admission (adjusted OR, 0.84; 95% CI, 0.71-0.99) and emergent surgery (adjusted OR, 4.39; 95% CI, 1.51-12.74) for peripheral PVG. The in-hospital mortality rate was 1.92%. The probability of surviving the first month was 0.96, and significant predictors of mortality were active lower extremity SSTI (adjusted risk ratio [RR], 12.07; 95% CI, 1.04-154.75), high postsurgical glucose levels (adjusted RR, 1.02; 95% CI, 1.00-1.04), and noninfectious surgical complications (adjusted RR, 19.38; 95% CI, 2.25-167.29). The long-term mortality rate was 11.88%. The probability of surviving at 12, 24, and 36 months was 0.94, 0.92, and 0.87, respectively. Variables significantly associated with long-term death were older age (adjusted RR, 1.08; 95% CI, 1.01-1.15), high values of creatinine on discharge (adjusted RR, 1.91; 95% CI, 1.08-3.38), and an SSI with the highest adjusted RR (6.35; 95% CI, 1.87-21.53). CONCLUSIONS: SSI was the primary NI. The risk of NI depended primarily on the presence of a lower extremity SSTI at the time of surgery, whereas mortality was determined by age, surgical complications during the operation, and SSI. These findings suggest that in those cases in which surgery is reasonably delayed, surgery should be deferred until the lower extremity SSTIs are resolved.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/instrumentação , Prótese Vascular/efeitos adversos , Infecção Hospitalar/microbiologia , Doenças Vasculares Periféricas/cirurgia , Infecções Relacionadas à Prótese/microbiologia , Infecções Respiratórias/microbiologia , Infecção da Ferida Cirúrgica/microbiologia , Infecções Urinárias/microbiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Implante de Prótese Vascular/mortalidade , Distribuição de Qui-Quadrado , Creatinina/sangue , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/mortalidade , Infecção Hospitalar/terapia , Feminino , Mortalidade Hospitalar , Hospitais Universitários , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Modelos de Riscos Proporcionais , Estudos Prospectivos , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/mortalidade , Infecções Relacionadas à Prótese/terapia , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/mortalidade , Infecções Respiratórias/terapia , Fatores de Risco , Espanha , Infecção da Ferida Cirúrgica/diagnóstico , Infecção da Ferida Cirúrgica/mortalidade , Infecção da Ferida Cirúrgica/terapia , Fatores de Tempo , Resultado do Tratamento , Infecções Urinárias/diagnóstico , Infecções Urinárias/mortalidade , Infecções Urinárias/terapia
9.
Cancer Immunol Immunother ; 65(1): 47-59, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26611618

RESUMO

Reduced expression of HLA class I is an important immune escape mechanism from cytotoxic T cells described in various types of malignancy. It often correlates with poor prognosis and resistance to therapy. However, current knowledge about the frequency, underlying molecular mechanisms, and prognostic value of HLA class I and II alterations in prostate cancer (PC) is limited. Immunohistochemical analysis demonstrated that 88 % of the 42 studied cryopreserved prostate tumors have at least one type of HLA alteration as compared to adjacent normal prostate epithelium or benign hyperplasia. Total loss of HLA-I expression found in 50 % of tumors showed an association with increased incidence of tumor relapse, perineural invasion, and high D'Amico risk. The remaining HLA-I-positive tumors demonstrated locus and allelic losses detected in 26 and 12 % of samples, respectively. Loss of heterozygosity at chromosome 6 was detected in 32 % of the studied tumors. Molecular analysis revealed a reduced expression of B2M, TAP2, tapasin and NLRC5 mRNA in microdissected HLA-I-negative tumors. Analysis of twelve previously unreported cell lines derived from neoplastic and normal epithelium of cancerous prostate revealed different types of HLA-I aberration, ranging from locus and/or allelic downregulation to a total absence of HLA-I expression. The high incidence of HLA-I loss observed in PC, caused by both regulatory and structural defects, is associated with more aggressive disease development and may pose a real threat to patient health by increasing cancer progression and resistance to T-cell-based immunotherapy.


Assuntos
Antígenos de Histocompatibilidade Classe I/imunologia , Imunoterapia/métodos , Neoplasias da Próstata/imunologia , Microglobulina beta-2/imunologia , Humanos , Masculino , Recidiva Local de Neoplasia
10.
J Bacteriol ; 197(17): 2859-66, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26124240

RESUMO

UNLABELLED: Rhodobacter sphaeroides is a free-living alphaproteobacterium that contains two clusters of functional flagellar genes in its genome: one acquired by horizontal gene transfer (fla1) and one that is endogenous (fla2). We have shown that the Fla2 system is normally quiescent and under certain conditions produces polar flagella, while the Fla1 system is always active and produces a single flagellum at a nonpolar position. In this work we purified and characterized the structure and analyzed the composition of the Fla2 flagellum. The number of polar filaments per cell is 4.6 on average. By comparison with the Fla1 flagellum, the prominent features of the ultra structure of the Fla2 HBB are the absence of an H ring, thick and long hooks, and a smoother zone at the hook-filament junction. The Fla2 helical filaments have a pitch of 2.64 µm and a diameter of 1.4 µm, which are smaller than those of the Fla1 filaments. Fla2 filaments undergo polymorphic transitions in vitro and showed two polymorphs: curly (right-handed) and coiled. However, in vivo in free-swimming cells, we observed only a bundle of filaments, which should probably be left-handed. Together, our results indicate that Fla2 cell produces multiple right-handed polar flagella, which are not conventional but exceptional. IMPORTANCE: R. sphaeroides possesses two functional sets of flagellar genes. The fla1 genes are normally expressed in the laboratory and were acquired by horizontal transfer. The fla2 genes are endogenous and are expressed in a Fla1(-) mutant grown phototrophically and in the absence of organic acids. The Fla1 system produces a single lateral or subpolar flagellum, and the Fla2 system produces multiple polar flagella. The two kinds of flagella are never expressed simultaneously, and both are used for swimming in liquid media. The two sets of genes are certainly ready for responding to specific environmental conditions. The characterization of the Fla2 system will help us to understand its role in the physiology of this microorganism.


Assuntos
Proteínas de Bactérias/metabolismo , Flagelos/ultraestrutura , Flagelina/genética , Regulação Bacteriana da Expressão Gênica/fisiologia , Rhodobacter sphaeroides/ultraestrutura , Proteínas de Bactérias/genética , Flagelina/metabolismo , Polimorfismo Genético , Rhodobacter sphaeroides/genética , Rhodobacter sphaeroides/metabolismo
11.
Int J Cancer ; 134(1): 102-13, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-23784959

RESUMO

Cancer cells escape T-cell-mediated destruction by losing human leukocyte antigen (HLA) class I expression via various mechanisms, including loss of beta2-microglobulin (ß2m). Our study illustrates the immune escape of HLA class I-negative tumor cells and chronological sequence of appearance of tumor ß2m gene mutation in successive lesions obtained from a patient with metastatic melanoma. We observed a gradual decrease in HLA expression in consecutive lesions with few HLA-negative nodules in the primary tumor and the emergence of a totally negative lesion at later stages of the disease. We detected loss of ß2m in ß2m-negative nests of the primary tumor caused by a combination of two alterations: (i) a mutation (G to T substitution) in codon 67 in exon 2 of ß2m gene, producing a stop codon and (ii) loss of the second gene copy by loss of heterozygosity (LOH) in chromosome 15. The same ß2m mutation was found in a homogeneously ß2m-negative metastasis 10 months later and in a cell line established from a biopsy of a postvaccination lymph node. Microsatellite analysis revealed the presence of LOH in chromosomes 6 and 15 in tumor samples, showing an accumulation of chromosomal loss at specific short tandem repeats in successive metastases during disease progression. HLA loss correlated with decreased tumor CD8+ T-cell infiltration. Early incidence of ß2m defects can cause an immune selection and expansion of highly aggressive melanoma clones with irreversible genetic defects causing total loss of HLA class I expression and should be taken into consideration as a therapeutic target in the development of cancer immunotherapy protocols.


Assuntos
Antígenos de Histocompatibilidade Classe I/biossíntese , Melanoma/genética , Evasão Tumoral/genética , Microglobulina beta-2/genética , Idoso , Linhagem Celular Tumoral , Citometria de Fluxo , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Imuno-Histoquímica , Perda de Heterozigosidade , Melanoma/imunologia , Melanoma/patologia , Mutação , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Metástase Neoplásica , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Evasão Tumoral/imunologia , Microglobulina beta-2/imunologia
12.
J Neuropsychiatry Clin Neurosci ; 26(3): 262-70, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25093765

RESUMO

Serotonergic dysfunctions are implicated in conduct disorder, impulsivity, and aggression. Early adverse experiences increase the risk for these behaviors in adolescents. The authors investigated serotonergic activity in one adolescent male who experienced maternal abandonment and childhood abuse and exhibited severely aggressive sexual offenses. Platelet serotonin (5-HT) concentration, [14C]-5HT uptake kinetics, and plasma prolactin, cortisol response to D,L-fenfluramine (D,L-FEN) were measured. Results showed extremely low 5-HT concentration (2.9+/-0.7 ng/108 platelets), [14C]-5HT uptake rate (0.5+/-0.04 mM/min/107 platelets), undetectable Km and Vmax, and abnormally blunted prolactin, cortisol response to D,L-FEN. These abnormalities in this sexually aggressive adolescent may be a consequence of childhood abuse.


Assuntos
Agressão , Serotonina/sangue , Disfunções Sexuais Fisiológicas/sangue , Disfunções Sexuais Fisiológicas/metabolismo , Adolescente , Análise de Variância , Isótopos de Carbono/metabolismo , Fenfluramina/uso terapêutico , Humanos , Masculino , Prolactina/sangue , Radioimunoensaio , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Disfunções Sexuais Fisiológicas/tratamento farmacológico
13.
Otolaryngol Pol ; 78(2): 29-34, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38623858

RESUMO

<b><br>Introduction:</b> Although PET/CT is effective for staging HNSCC, its impact on patient management is somewhat controversial. For this reason, we considered it necessary to carry out a study in order to verify whether PET/CT helps to improve the prognosis and treatment in patients. This study was designed to address the impact of PET-FDG imaging when used alongside CT in the staging and therapeutic management of patients with HNSCC.</br> <b><br>Material and methods:</b> Data was collected from 169 patients diagnosed with HNSCC with both CT and PET/CT (performed within a maximum of 30 days of each other). It was evaluated whether discrepancies in the diagnosis of the two imaging tests had impacted the treatment.</br> <b><br>Results:</b> The combined use of CT and PET/CT led to a change in the treatment of 67 patients, who represented 39.7% of the sample. In 27.2% of cases, it entailed a change in the type of treatment which the patient received. In 3.0% of the cases, using both diagnostic tests led to modifications of the therapeutic intention of our patients.</br> <b><br>Conclusions:</b> Using PET/CT in addition to the conventional imaging method in staging resulted in more successful staging and more appropriate therapeutic decision-making.</br>.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/terapia , Fluordesoxiglucose F18 , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/terapia , Estadiamento de Neoplasias
14.
Acta Otolaryngol ; 142(7-8): 627-633, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36131532

RESUMO

INTRODUCTION: Squamous cell carcinoma (SCC) of the vocal cord in stages I or II can be treated with radiotherapy (RT) or transoral CO2 laser microsurgery (TLM), with good oncological results. OBJECTIVES: To study the survival of patients with SCC of the vocal cord in early stages, treated with RT or TLM, in a tertiary hospital. MATERIAL AND METHODS: Disease-free survival (DFS), specific survival (SS), and overall survival (OS) were studied in patients diagnosed with stage I and II SCC of the vocal cord, for a span of 10 years of follow-up, based on sociodemographic characteristics of the patient and the primary treatment (TLM or RT). RESULTS: Both treatments achieved good survival rates. However, long-term SS was greater in patients treated with TLM compared to those treated with RT (91.7% vs. 50%, respectively, p = .001). In addition, patients treated with TLM presented a higher OS in the short term than those treated with RT (99.0% vs. 89.1%, respectively. p = .004). CONCLUSIONS AND SIGNIFICANCE: Primary treatment with TLM obtained better results than RT in the survival of patients with SCC of the vocal cord in the early stages.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Laríngeas , Terapia a Laser , Dióxido de Carbono , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Intervalo Livre de Doença , Glote/patologia , Glote/cirurgia , Humanos , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/cirurgia , Terapia a Laser/métodos , Microcirurgia/métodos , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento
15.
Braz J Otorhinolaryngol ; 88 Suppl 4: S143-S151, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34933818

RESUMO

OBJECTIVE: The aim of this study is to find out if a single imaging test is enough to follow-up on an oncological post-treatment patient. In such a case, we would know which was more valuable after comparing the two, by CT or PET-CT. METHODS: Between January 2012 and July 2018, we collected data from all patients with previous medical history who were treated with a head and neck squamous cell carcinoma in our hospital, through surgery or by using an organ preservation protocol which we had done. Patients were required to have a CT and a PET-CT performed in a maximum period of 30 days between techniques. We compared the post post-treatment stage given to each case by using only the physical examination (only the CT and the PET-CT), with the ones given by the Tumor Board. After treatment, we analysed the similarity through Cramer's V statistic test. RESULTS: We performed a comparative analysis, obtaining a correlation of 0.426 between the stages given by the Tumor Board and the one assigned based on physical examination, without imaging techniques. By only using the computed tomography as an imaging method the correlation was 0.565, whereas with only the use of positron emission computed technology, it was estimated at 0.858. When we compared the statistical association between stages using exclusively one of the two imaging techniques, the correlation was 0.451. CONCLUSION: Independent of the modality, we have demonstrated that in patients who have received previous treatment, there was a higher correlation in the stages with respect to the diagnostic method conducted by the Tumor Board using PET-CT as the sole image. LEVEL OF EVIDENCE: Level 1.


Assuntos
Neoplasias de Cabeça e Pescoço , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/terapia , Tomografia Computadorizada por Raios X , Estadiamento de Neoplasias , Compostos Radiofarmacêuticos
16.
J Bacteriol ; 193(23): 6781-6, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21949068

RESUMO

Rhodobacter sphaeroides is able to assemble two different flagella, the subpolar flagellum (Fla1) and the polar flagella (Fla2). In this work, we report the swimming behavior of R. sphaeroides Fla2(+) cells lacking each of the proteins encoded by chemotactic operon 1. A model proposing how these proteins control Fla2 rotation is presented.


Assuntos
Proteínas de Bactérias/metabolismo , Quimiotaxia , Flagelos/fisiologia , Regulação Bacteriana da Expressão Gênica , Óperon , Rhodobacter sphaeroides/fisiologia , Proteínas de Bactérias/genética , Flagelos/genética , Rhodobacter sphaeroides/genética
18.
Braz J Otorhinolaryngol ; 87(1): 11-18, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-31337597

RESUMO

INTRODUCTION: Head and neck squamous cell carcinoma is the seventh most common malignant tumor. The advances in treatment have improved the global survival rates in the past years, although the prognosis is still grave. OBJECTIVE: The aim of the present study is to evaluate the correlation between positron emission computed tomography and computed tomography at the time of staging a previously untreated head and neck squamous cell carcinoma, and to determine which of the two imaging techniques gives us more information at the time of initial diagnosis. METHODS: Data from all patients diagnosed in our hospital of head and neck squamous cell carcinoma by a biopsy of any location or unknown primary tumor was collected, between January 2012 and July 2017. In all cases, computed tomography and positron emission computed tomography were performed with a maximum of 30 days difference between them and patients had not received any prior treatment to staging. The stage given to each case was compared based solely on the physical examination, only on the computed tomography/positron emission computed tomography, with respect to the stage given by the tumor board, observing the concordance obtained through Cramer's V statistical test. RESULTS: We performed a comparative analysis obtaining a correlation of 0.729 between the stage given by the tumor board and the one assigned based on the physical examination without imaging techniques. When only using computed tomography as an imaging method, the correlation was 0.848, whereas with only the use of positron emission computed tomography it was estimated at 0.957. When comparing the statistical association between staging using exclusively one of the two imaging techniques, correlation was 0.855. CONCLUSION: Positron emission computed tomography is useful for the diagnosis of head and neck squamous cell carcinoma, improving the patient's staging especially when detecting cervical and distant metastases. Therefore, we consider that the use of positron emission computed tomography for the staging of patients with head and neck squamous cell carcinoma is a diagnostic test to be considered.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Fluordesoxiglucose F18 , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Sensibilidade e Especificidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Tomografia Computadorizada por Raios X
19.
Neuron ; 106(5): 712-714, 2020 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-32497507

RESUMO

In this issue of Neuron, Paricio-Montesinos et al. (2020) unveil the essential cellular elements for warm temperature detection in mice. Surprisingly, the silencing of spontaneously firing, unmyelinated, polymodal sensory afferents harboring cold-activated TRPM8 channels is the key neural mechanism.


Assuntos
Canais de Cátion TRPM , Animais , Temperatura Baixa , Temperatura Alta , Camundongos , Neurônios , Temperatura
20.
Acta Otolaryngol ; 140(11): 954-958, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32677497

RESUMO

BACKGROUND: Glottic squamous cell carcinoma (SCC) in stages I or II can be treated by transoral CO2 laser microsurgery (TLM) or exclusive radiotherapy (RT). OBJECTIVES: To compare the oncological results of patients treated with TLM, to those treated with RT, in a tertiary hospital. MATERIAL AND METHODS: Data from patients diagnosed with glottic SCC in stages I and II between 2004 and 2018 were analyzed. Response to treatment was studied in terms of recurrence, local control and laryngeal preservation. RESULTS: Of 164 patients, 63.41% received treatment with TLM and 36.58% with RT. 26.21% presented a recurrence or progression of the tumor. Both treatments obtained good local control rates (84.15% in the case of TLM and 89.6% in the case of RT) and no significant association was found between tumor recurrence and type of treatment, nor with the involvement of the anterior commissure. However, treatment with RT obtained worse laryngeal preservation rate compared to TLM (81.6% and 100% respectively) (p < .001LR). Conclusions and significance: Both treatments obtained good oncological results. There were no significant differences regarding local control. However, TLM obtained a better laryngeal preservation rate. The involvement of the anterior commissure was not a poor prognosis factor for tumor recurrence.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Glote/cirurgia , Neoplasias Laríngeas/radioterapia , Neoplasias Laríngeas/cirurgia , Terapia a Laser , Microcirurgia , Feminino , Humanos , Masculino , Microcirurgia/métodos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Resultado do Tratamento
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