RESUMO
Glioma is the most common neoplasm of the central nervous system, with the highest mortality rate. The present study was designed to examine the therapeutic effect of Iguratimod (IGU) encapsulated-poly (lactic-co-glycolic acid) PLGA nanoparticles (IGU-PLGA-NPs), which showed inhibition of glioma cells proliferation both in vitro and in vivo. IGU encapsulated in PLGA nanoparticles with an average size of 100-200 nm was prepared using modified double-emulsion (W1/O/W2) method. Cell Counting Kit-8 (CCK-8) analysis of Glioma cancer cells and glioma stem-like cells (GSCs) demonstrated significant inhibition of their growth treated with IGU-PLGA-NPs. IGU-PLGA-NPs inhibit migration in glioma cells as well as tumor sphere formation in GSCs. Treatment with IGU-PLGA-NPs showed a significant decrease in tumor growth through the apoptotic pathway in mice model without any visible organ toxicity and it can successfully cross the blood brain barrier (BBB). Most Importantly, IGU-PLGA-NPs significantly depleted growth of U251 Temozolomide-resistant (U251TMZ-R) cells.
Assuntos
Cromonas/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Glioma/tratamento farmacológico , Nanopartículas/química , Células-Tronco Neoplásicas/patologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Sulfonamidas/uso terapêutico , Temozolomida/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Autorrenovação Celular/efeitos dos fármacos , Cromonas/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Glioma/patologia , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Células-Tronco Neoplásicas/efeitos dos fármacos , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/patologia , Sulfonamidas/farmacologia , Temozolomida/farmacologia , Resultado do TratamentoRESUMO
Following an in vitro bioactivity-guided fractionation procedure, 14 compounds including eight flavonoids and six phenylpropanoids were isolated and identified from the AcOEt fraction of Clinopodium chinense (Benth.) O. Kuntze. All constituents were tested for α-glucosidase and high glucose-induced injury in human umbilical vein endothelial cells (HUVECs) inhibitory activities. All constituents exhibited varying degrees α-glucosidase inhibitory activity and protective activity on HUVECs. Among them, luteolin (2), eriodictyol (5), ethyl rosmarinate (13), and clinopodic acids B (14) were proved to be potent α-glucosidase inhibitors with IC50 value ranging from 0.6 to 2.0 µm. Additionally, luteolin (2), naringenin (4), eriodictyol (5), ethyl (2R)-3-(3, 4-dihydroxyphenyl)-2-hydroxypropanate (9), caffeic acid (11), ethyl rosmarinate (13), and clinopodic acids B (14) significantly ameliorate HUVECs injury induced by high glucose with an approximate EC50 value of 3 - 36 µm. These results suggest that the 14 bioactive constituents were responsible for hypoglycemic and protective vascular endothelium effect of C. chinense (Benth.) O. Kuntze and their structure-activity relationship was also analyzed briefly. Eriodictyol, luteolin, ethyl rosmarinate, and clinopodic acids B were the potential lead compounds of antidiabetic drugs.
Assuntos
Inibidores de Glicosídeo Hidrolases/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Lamiaceae/química , Fenóis/farmacologia , alfa-Glucosidases/metabolismo , Relação Dose-Resposta a Droga , Glucose/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Estrutura Molecular , Fenóis/química , Fenóis/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: The role of Ommaya reservoir implantation in children with tuberculous meningitis hydrocephalus (TBMH) has been seldomly reported. Therefore, we performed this study to determine the role of the Ommaya reservoir in the treatment of children with TBMH. METHODS: We retrospectively analyzed the effects of Ommaya reservoir implantation in 12 children with TBMH. Intracapsular puncture of the reservoir was performed for draining the cerebrospinal fluid and the TBM was treated by intraventricular injection of isoniazid. RESULTS: The ideal treatment outcome was observed in nine (75 %) of the 12 children; two (16.7 %) children developed serious disabilities and one of them (8.3 %) eventually died. The treatment method was effective for all six (100 %) children with Palur grade II TBM but showed no effect in three (50 %) children with grade III and IV TBM. The number of leukocytes in the cerebrospinal fluid decreased to 20 × 10(6)/L (75 %) within 2 weeks after implantation of the reservoirs. Finally, the Ommaya reservoirs in eight children were removed but were retained in four children. Four children had to undergo ventriculoperitoneal shunt. CONCLUSION: Ommaya reservoir implantation has been shown to be effective in treating children with TBMH. This method may be largely suitable for children with early grade II TBM or partly in children with grade III TBM who have mild or moderate hydrocephalus that can alleviate after short-term treatment. Thus, a good proportion of children who undergo Ommaya reservoir implantation can avoid ventriculoperitoneal shunt surgery.
Assuntos
Antituberculosos/administração & dosagem , Derivações do Líquido Cefalorraquidiano/instrumentação , Sistemas de Liberação de Medicamentos , Hidrocefalia/cirurgia , Tuberculose Meníngea/terapia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Hidrocefalia/etiologia , Lactente , Imageamento por Ressonância Magnética , Masculino , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Tuberculose Meníngea/complicaçõesRESUMO
OBJECTIVE: This study aims to evaluate effects and complications of the implantation of Ommaya reservoir in premature infants with posthemorrhagic hydrocephalus (PHH). METHODS: The effects and complications of the implantation of Ommaya reservoir in seven premature infants with PHH were retrospectively analyzed. Intracapsular puncture of the reservoir was performed for draining cerebrospinal fluid. RESULTS: Seven extremely low-weight premature infants with PHH (birthweight less than 1,000 g) were treated with the placement of an Ommaya reservoir. Ommaya reservoirs in five infants were removed, but were retained in two infants. Two premature infants had to undergo ventriculoperitoneal (VP) shunt. Postsurgical major complications (including skin dehiscence, cerebrospinal fluid (CSF) infection, ventricular hemorrhage, and CSF leak) occurred in 57% of all patients. Three infants of skin dehiscence and CSF leak occurred. Two infants of CSF infection occurred, as well as one clinically significant secondary hemorrhage. Six infants survived, and one died. CONCLUSION: The implantation of Ommaya reservoir is a cautious option of treating low-weight premature infants with PHH because of a relatively high complication rate. However, VP shunt surgery may be avoided in some infants.
Assuntos
Hemorragia Cerebral/complicações , Hidrocefalia/etiologia , Hidrocefalia/cirurgia , Lactente Extremamente Prematuro , Derivação Ventriculoperitoneal/efeitos adversos , Derivação Ventriculoperitoneal/instrumentação , Hemorragia Cerebral/líquido cefalorraquidiano , Feminino , Humanos , Hidrocefalia/líquido cefalorraquidiano , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Recém-Nascido , Masculino , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: Ventriculoperitoneal shunting is the current mainstay of treatment for children with tuberculous meningitis with hydrocephalus. However, ventriculoperitoneal shunting is highly associated with complications, and more importantly, long-term, indwelling shunt devices may adversely affect children's spirits and psychological health. Therefore, there is clearly a need to explore methods of CSF diversion to avoid ventriculoperitoneal shunting. METHODS: We studied 6 cases of children with tuberculous meningitis with hydrocephalus in whom external drainage from the ventricle to the subcutaneous abdomen was adopted. Outcomes were assessed over a 6- to 9-month follow-up period based on improvements in radiological features, such as ventricular morphology, as well as the need for ventriculoperitoneal shunting and any complications. RESULTS: The drainage tubes were removed in 4 cases 4-6 months after the modified external ventricular drainage surgery, and 2 patients went on to receive a ventriculoperitoneal shunt. All patients' CSF protein and cell counts returned to normal, and imaging showed improved ventricular morphology and no intracranial secondary infection. CONCLUSION: In our preliminary study, the modified ventricular drainage device can produce satisfactory outcomes and relatively safe effects and may help some patients to avoid ventriculoperitoneal shunt placement.
Assuntos
Drenagem/métodos , Hidrocefalia/cirurgia , Tuberculose Meníngea/cirurgia , Derivação Ventriculoperitoneal , Criança , Pré-Escolar , Drenagem/efeitos adversos , Feminino , Seguimentos , Humanos , Hidrocefalia/epidemiologia , Lactente , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Tuberculose Meníngea/epidemiologia , Derivação Ventriculoperitoneal/efeitos adversosRESUMO
Gelatin hydrogels are widely used materials that may require surfactants to adjust their solution's surface tension for cell attachment, surface adsorption enhancement, or foaming. However, gelatin is a highly surface-active polymer, and its concentrated solutions usually do not require surfactants to achieve low surface tension. However, anionic surfactants, such as sodium dodecyl sulfate (SDS), interact strongly with gelatin to form complexes that impact its hydrogels' rheological properties, influencing processability and functionality. Nevertheless, there is a lack of systematic research on the impact of these complexes on high gelatin content (i.e., high strength) hydrogels' rheological properties. In this work, the SDS/gelatin ratio-dependent viscoelastic properties (e.g., gel strength, gelation kinetics, and melting/gelling temperature) of high-strength gelatin hydrogels were investigated using rheology and correlated to surface tension, viscometry, FTIR, and UV-Vis spectrophotometry. SDS-gelatin ratio was proved to be an important factor in tailoring the rheological properties of gelatin hydrogels. The gel strength, gelation kinetics, and melting/gelling temperature of the gelatin hydrogels linearly increased with SDS incorporation up to a maximum value, from which they started to decline. The findings of this work have wide applicability in tailoring the properties of gelatin-SDS solutions and hydrogels during their processing.
RESUMO
BACKGROUND: Rhizoma dioscoreae nipponicae is a perennial herb and its roots have been widely used in Traditional Chinese Medicine (TCM). OBJECTIVE: To develop and optimize the extraction and hydrolysis technology of diosgenin from Rhizoma dioscoreae nipponicae. MATERIALS AND METHODS: 1-methyl-3-(3-sulfopropyl)-imidazolium hydrogen sulfate ([PSMIM]HSO4), as a kind of functional ionic liquid, replaced inorganic acid, and was used in a one-step ultrasonic extraction and hydrolysis for the preparation of diosgenin (the aglycone of dioscin and an important precursor chemical in the pharmaceutical industry) from Rhizoma dioscoreae nipponicae, for the first time. The effects of various factors were evaluated. The obtained product was studied using high performance liquid chromatography (HPLC). RESULTS: About 6.35 mg of diosgenin could be obtained from 2.0 g of raw material. Reusability and recycling of the ionic liquid were validated with fairly good results. The ionic liquid solution was reused four times, and the final extraction efficiency only decreased by 5%. CONCLUSION: In virtue of the obvious advantages of the green extraction and catalytic solvent, with further study, it is believed that this new one-step preparative method promises to replace the traditional methods.