RESUMO
BACKGROUND: The impact of the distance from the root of splenic artery to tumor (DST) on the prognosis and optimal surgical procedures in the patients with pancreatic body/tail cancer has been unclear. METHODS: We retrospectively analyzed 94 patients who underwent distal pancreatectomy (DP) and 17 patients who underwent DP with celiac axis resection (DP-CAR) between 2008 and 2018. RESULTS: The 111 patients were assigned by DST length (in mm) as DST = 0: n = 14, 0Assuntos
Neoplasias Pancreáticas
, Artéria Esplênica
, Humanos
, Artéria Esplênica/cirurgia
, Prognóstico
, Estudos Retrospectivos
, Recidiva Local de Neoplasia/patologia
, Artéria Celíaca/cirurgia
, Artéria Celíaca/patologia
, Neoplasias Pancreáticas/patologia
, Pancreatectomia/métodos
RESUMO
Pulmonary neuroendocrine (NE) cells are rare airway epithelial cells. The balance between Achaete-scute complex homolog 1 (ASCL1) and hairy and enhancer of split 1, one of the target molecules of the Notch signaling pathway, is crucial for NE differentiation. Small cell lung cancer (SCLC) is a highly aggressive lung tumor, characterized by rapid cell proliferation, a high metastatic potential, and the acquisition of resistance to treatment. The subtypes of SCLC are defined by the expression status of NE cell-lineage transcription factors, such as ASCL1, which roles are supported by SRY-box 2, insulinoma-associated protein 1, NK2 homeobox 1, and wingless-related integration site signaling. This network reinforces NE differentiation and may induce the characteristic morphology and chemosensitivity of SCLC. Notch signaling mediates cell-fate decisions, resulting in an NE to non-NE fate switch. The suppression of NE differentiation may change the histological type of SCLC to a non-SCLC morphology. In SCLC with NE differentiation, Notch signaling is typically inactive and genetically or epigenetically regulated. However, Notch signaling may be activated after chemotherapy, and, in concert with Yes-associated protein signaling and RE1-silencing transcription factor, suppresses NE differentiation, producing intratumor heterogeneity and chemoresistance. Accumulated information on the molecular mechanisms of SCLC will contribute to further advances in the control of this recalcitrant cancer.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos , Diferenciação Celular , Neoplasias Pulmonares , Receptores Notch , Transdução de Sinais , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/metabolismo , Carcinoma de Pequenas Células do Pulmão/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Receptores Notch/metabolismo , Células Neuroendócrinas/patologia , Células Neuroendócrinas/metabolismoRESUMO
A 31-year-old primiparous woman underwent non-invasive prenatal testing. The result was trisomy 13 (T13) positive. The chromosome 13 t-statistics (Z-score) was significantly high. The result of amniocentesis was normal karyotype (46,XX). Detailed ultrasound showed no fetal structural abnormalities. We suspected T13 confined placental mosaicism (CPM) and observed the course naturally. From the late second trimester, severe fetal growth restriction manifested followed by proteinuria and hypertension, diagnosing her with preeclampsia (PE). At 35 + 5 weeks, emergent cesarean section was required, yielding a 1480 g female infant. We sampled five locations of chorionic villi in the placenta. T13 cells dominated cells with normal karyotypes in all parts and the rate of trisomic cells ranged from 57% to 96%, which were generally high rate. None developed PE in reported T13 CPM cases and this is the first case of PE. The dominancy of T13 cells can be associated with PE development.
RESUMO
Polymeric nanofibers generated via electrospinning offer a promising platform for drug delivery systems. This study examines the application of electrospun polyvinyl alcohol (PVA) nanofibers for controlled lysozyme (LZM) delivery. By using various PVA grades, such as the degree of polymerization/hydrolysis, this study investigates their influence on nanofiber morphology and drug-release characteristics. LZM-loaded PVA monolithic nanofibers having 50% drug content exhibit efficient entrapment, wherein rapid dissolution is achieved within 30 min. The initial burst of LZM from the nanofiber was reduced as the LZM content was lowered. The initial dissolution is greatly influenced by the choice of PVA grade used; fully hydrolyzed PVA nanofibers demonstrate controlled release due to the reduced water solubility of PVA. Furthermore, coaxial electrospinning, which creates core-shell nanofibers with polycaprolactone as a controlled release layer, enables sustained LZM release over an extended period. This study confirms a correlation between PVA characteristics and controlled drug release and provides valuable insights into tailoring nanofiber properties for pharmaceutical applications.
Assuntos
Nanofibras , Álcool de Polivinil , Preparações de Ação Retardada , Muramidase , Sistemas de Liberação de MedicamentosRESUMO
Phytochemicals isolated from essential oils are effective alternatives for inhibiting microbial pathogens. Bovine protothecal mastitis is the cause of a reduction in milk production and the secretion of thin, watery milk with white flakes. In the present study, we performed in vitro susceptibility testing of the phytochemicals carvacrol, citral, and thymol in Prototheca strains isolated from cases of protothecosis in small animals and cow feces. The susceptibility of the algae to carvacrol, citral, and thymol was assessed using the modified CLSI M27-A3 broth microdilution method. The ranges of the minimum inhibitory concentrations (MIC%) of the phytochemicals in all isolates were 0.03% to 0.125% for carvacrol, 0.03% to 0.25% for citral, and 0.06% to 0.25% for thymol. Based on these results, carvacrol, citral, and thymol appear effective against Prototheca species at the tested concentrations, and may thus be useful for environmental disinfection in barns.
Assuntos
Monoterpenos Acíclicos , Cimenos , Testes de Sensibilidade Microbiana , Óleos Voláteis , Compostos Fitoquímicos , Prototheca , Timol , Óleos Voláteis/farmacologia , Timol/farmacologia , Animais , Prototheca/efeitos dos fármacos , Cimenos/farmacologia , Compostos Fitoquímicos/farmacologia , Monoterpenos Acíclicos/farmacologia , Bovinos , Monoterpenos/farmacologia , Feminino , Mastite Bovina/microbiologia , Mastite Bovina/tratamento farmacológicoRESUMO
We present a unique case of transient global amnesia following intravenous administration of a non-ionic iodinated contrast agent for abdominal CT examination. Follow up MR imaging and MR angiography studies revealed hippocampal microinfarction and transient cerebral vasospasm. To our knowledge, this is the first reported case capturing arterial vasospasm following intravenous use of iodinated contrast. Medical professionals handling contrast agents should note the potential for these rare but serious adverse effects.
RESUMO
This study aimed to develop polyvinyl alcohol (PVA) nanofibers encapsulating 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)/siRNA complexes via electrospinning for the delivery of nucleic acid-based drugs. It also focused on the influence of the intrinsic properties of PVA on the efficacy of the system. PVA nanofibers, with diameters of 300-400 nm, were obtained, within which the siRNA remained intact and the DOTAP/siRNA complexes were uniformly dispersed. By incorporating DOTAP/siRNA complexes into the PVA nanofibers and assessing the impact of their RNA interference (RNAi) activity in A549-Luc cells, a stable inhibition of luciferase expression was observed. An examination of the nanofiber preparation process revealed that even when DOTAP or siRNA were added separately to the PVA solution without forming complexes, the RNAi effect was retained. The DOTAP/siRNA complexes released from the PVA nanofibers were internalized by the cells, with some PVA residues remaining on their surfaces. The significance of the degree of hydrolysis and polymerization of PVA on the performance of nanofibers was highlighted. Notably, PVA with a low degree of hydrolysis substantially enhanced RNAi effects, with luciferase expression inhibition reaching 91.5 ± 0.7%. Nanofibers made of PVA grades with anionic or cationic modifications were also evaluated, suggesting that they affect the efficacy of siRNA delivery. The insights obtained suggest avenues for future research to optimize drug delivery systems further.
RESUMO
Dry powder inhalers (DPIs) are the first choice for inhalation drug development. However, some conventional DPI formulation processes require heating, which may damage high molecular weight drugs such as proteins and nucleic acids. In this study, we propose a novel DPI preparation process that avoids the use of heat. Dry powders were prepared by cryomilling nanofiber mats composed of polyvinyl alcohol, D(-)-mannitol (Man), and α-chymotrypsin (α-Chy) as the model drug using the electrospinning method. The addition of Man conferred high dispersibility and excellent in vitro aerosol performance to the nanofiber mat powder in a very short milling time (less than 0.5 min) as assessed using the Andersen cascade impactor. Powders were classified according to the degree of friability, and among these, nanofiber mats containing 15 % Man and milled for 0.25 min exhibited the highest aerosol performance. Nanofiber mats containing Man milled for less than 0.5 min also exhibited greater α-Chy enzymatic activity than a nebulized α-Chy solution. Furthermore, single inhalation induced no significant lung tissue damage as evidenced by lactate dehydrogenase activity assays of mouse bronchoalveolar lavage fluid. This novel DPI formulation process may facilitate the safe and efficient inhalational delivery of therapeutic proteins.
Assuntos
Aerossóis , Quimotripsina , Manitol , Nanofibras , Nanofibras/química , Nanofibras/administração & dosagem , Animais , Administração por Inalação , Manitol/química , Quimotripsina/química , Camundongos , Inaladores de Pó Seco , Álcool de Polivinil/química , Pós , Sistemas de Liberação de Medicamentos , Pulmão/metabolismo , Líquido da Lavagem Broncoalveolar/química , MasculinoRESUMO
Purpose: The purpose of the study is to investigate the impact of large target offset distances on the dose distribution and gamma passing rate (GPR) in single-isocenter multiple-target stereotactic radiosurgery (SIMT SRS) using volumetric modulated arc therapy (VMAT) with a flattening filter-free (FFF) beam from a linear accelerator. Methods: Two targets with a diameter of 1 cm were offset by "±2, ±4, and ±6 cm from the isocenter in a verification phantom for head SRS (20 Gy/fr). The VMAT plans were created using collimator angles that ensured the two targets did not share a leaf pair from the multi-leaf collimator. To evaluate the low-dose spread intermediate dose spill (R50%), GPRs were measured with a criterion of 3%/2 mm using an electronic portal imaging device and evaluated using monitor unit (MU), modulation complexity score for VMAT (MCSv), and leaf travel (LT) parameters. Results: For offsets of 2, 4, and 6 cm, the respective parameters were: R50%, 4.75 ± 0.36, 5.13 ± 0.36, and 5.11 ± 0.33; GPR, 95.01%, 93.82%, and 90.67%; MU, 5893 ± 186, 5825 ± 286, and 5810 ± 396; MCSv, 0.24, 0.16, and 0.13; and LT, 189.21 ± 36.04, 327.69 ± 67.01, and 430.39 ± 114.34 mm. There was a spread in the low-dose region from offsets of ≥4 cm and the GPR negatively correlated with LT (r = -0.762). There was minimal correlation between GPR and MU or MCSv. Conclusions: In SIMT SRS VMAT plans with an FFF beam from a linear accelerator, target offsets of <4 cm from the isocenter can minimize the volume of the low-dose region receiving 10 Gy or more. During treatment planning, it is important to choose gantry, couch, and collimator angles that minimize LT and thereby improve the GPR.