RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The off-label nebulization of Shuang-Huang-Lian (SHL) injection is often utilized to treat respiratory tract infections in China. However, the pulmonary biopharmaceutics of SHL was generally unknown, limiting the rational selection of therapeutic dose and dose frequency. AIM OF THE STUDY: To characterize the size distribution of nebulized aerosols and to compare the pharmacokinetics and the lung distribution of three chemical makers of SHL, chlorogenic acid (CHA), forsythiaside A (FTA) and baicalin (BC), after intratracheal and intravenous administration of SHL to rats. MATERIALS AND METHODS: The droplet size distribution profiles over nebulization process were dynamically monitored using a laser diffraction method whereas the levels of CHA, FTA and BC in plasma, lung tissues and bronchoalveolar lavage fluids (BALF) were determined by a validated LC-MS/MS assay. The pulmonary anti-inflammatory efficacy was evaluated using a lipopolysaccharide (LPS) induced lung inflammation model as indicated by the level of tumor necrosis factor-α (TNF-α) in BALF. RESULTS: The nebulization of SHL showed good inhalability and allowed the aerosols to reach the upper or lower respiratory tract dependent on the performance of selected nebulizers. Following intratracheal administration of SHL at different doses, CHA, FTA and BC were absorbed into the bloodstream with the mean absorption time being 67.5, 63.5 and 114 min, respectively, rendering mean absolute bioavailabilities between 42.4% and 61.4% roughly independent of delivered dose. Relative to the intravenous injection, the intrapulmonary delivery increased the lung-to-plasma concentration ratios of CHA, FTA and BC by more than 100 folds and markedly improved the lung availability by 563-676 folds, leading to enhanced and prolonged lung retention. The production of TNF-α in BALF was decreased by ~50% at an intratracheal dose of 125 µL/kg SHL to LPS-treated mice. CONCLUSION: The nebulization delivery of SHL is a promising alternative to the intravenous injection for the treatment of respiratory tract infections.
Assuntos
Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/uso terapêutico , Ácido Clorogênico/metabolismo , Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/uso terapêutico , Flavonoides/metabolismo , Glicosídeos/metabolismo , Pneumonia/tratamento farmacológico , Administração por Inalação , Administração Intravenosa , Animais , Disponibilidade Biológica , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/imunologia , Ácido Clorogênico/sangue , Flavonoides/sangue , Glicosídeos/sangue , Lipopolissacarídeos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Nebulizadores e Vaporizadores , Pneumonia/induzido quimicamente , Pneumonia/imunologia , Ratos Wistar , Fator de Necrose Tumoral alfa/imunologiaRESUMO
Rice grain filling rate contributes largely to grain productivity and accumulation of nutrients. MicroRNAs (miRNAs) are key regulators of development and physiology in plants and become a novel key target for engineering grain size and crop yield. However, there is little studies, so far, showing the miRNA regulation of grain filling and rice yield, in consequence. Here, we show that suppressed expression of rice miR1432 (STTM1432) significantly improves grain weight by enhancing grain filling rate and leads to an increase in overall grain yield up to 17.14% in a field trial. Molecular analysis identified rice Acyl-CoA thioesterase (OsACOT), which is conserved with ACOT13 in other species, as a major target of miR1432 by cleavage. Moreover, overexpression of miR1432-resistant form of OsACOT (OXmACOT) resembled the STTM1432 plants, that is, a large margin of an increase in grain weight up to 46.69% through improving the grain filling rate. Further study indicated that OsACOT was involved in biosynthesis of medium-chain fatty acids. In addition, RNA-seq based transcriptomic analyses of transgenic plants with altered expression of miR1432 demonstrated that downstream genes of miR1432-regulated network are involved in fatty acid metabolism and phytohormones biosynthesis and also overlap with the enrichment analysis of co-expressed genes of OsACOT, which is consistent with the increased levels of auxin and abscisic acid in STTM1432 and OXmACOT plants. Overall, miR1432-OsACOT module plays an important role in grain filling in rice, illustrating its capacity for engineering yield improvement in crops.
Assuntos
Regulação da Expressão Gênica de Plantas/genética , MicroRNAs/genética , Oryza/genética , Reguladores de Crescimento de Plantas/metabolismo , Ácido Abscísico/metabolismo , Produtos Agrícolas , Grão Comestível/enzimologia , Grão Comestível/genética , Grão Comestível/crescimento & desenvolvimento , Perfilação da Expressão Gênica , Ácidos Indolacéticos/metabolismo , Especificidade de Órgãos , Oryza/enzimologia , Oryza/crescimento & desenvolvimento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , RNA de Plantas/genética , Sementes/enzimologia , Sementes/genética , Sementes/crescimento & desenvolvimento , Tioléster Hidrolases/genética , Tioléster Hidrolases/metabolismoRESUMO
PURPOSE: We evaluated the efficacy and tolerability of the ketogenic diet (KD) on generalised convulsions and status epilepticus (SE) in patients with Dravet syndrome (DS). METHODS: Patients with DS having ≥2 generalised convulsions/month despite drug treatment were included in this study and placed on a KD for 6 months. From 3 months before (baseline) to 6 months after KD initiation, caregivers recorded patients' seizure activity, antiepileptic drug use, and adverse events. The KD efficacy was determined by examining the frequency and duration of seizures at 3 and 6 months vs. baseline. Responders were defined as individuals whose generalised convulsions decreased in frequency by ≥50% vs. baseline. Seizures lasting ≥5â¯min and SE were specifically evaluated. Patients' cognition was also assessed at 3 and 6 months via questionnaire. RESULTS: Twenty patients continued the KD for at least 3 months. Of the 17 responders identified at month 3, seizures decreased by 50-89% and 90-99% in nine and two patients, respectively; six patients were seizure free. The KD was ineffective in three patients, who discontinued the diet. By month 6, seizures decreased by 50-89% and 90-99% in six and one patient(s), respectively; 10 patients were seizure free. The frequency of other seizure types also improved. During all 6 months, neither generalised convulsions lasting ≥5â¯min nor SE was detected in the 17 responders. The KD also improved patients' cognition. CONCLUSION: The KD is a good treatment option for medically intractable epilepsy.
Assuntos
Dieta Cetogênica , Epilepsia Resistente a Medicamentos/dietoterapia , Epilepsias Mioclônicas/dietoterapia , Convulsões/dietoterapia , Anticonvulsivantes/uso terapêutico , Cuidadores , Criança , Pré-Escolar , Dieta Cetogênica/efeitos adversos , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia Resistente a Medicamentos/fisiopatologia , Epilepsias Mioclônicas/tratamento farmacológico , Epilepsias Mioclônicas/fisiopatologia , Feminino , Seguimentos , Humanos , Lactente , Masculino , Estudos Prospectivos , Convulsões/tratamento farmacológico , Convulsões/fisiopatologia , Inquéritos e Questionários , Fatores de Tempo , Resultado do TratamentoRESUMO
PABCREATIC neuroendocrine tumours are uncommon neoplasms of the pancreas. They may cause a clinical syndrome due to hormone overproduction. Glucagonoma is a rare kind of pancreatic tumors. Here we report a case of glucagonoma. Hypercalcemia occurred when the patient underwent octreotide acetate long-acting release.
Assuntos
Antineoplásicos Hormonais/efeitos adversos , Glucagonoma/tratamento farmacológico , Hipercalcemia/induzido quimicamente , Octreotida/efeitos adversos , Neoplasias Pancreáticas/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The characteristic of oral submucous fibrosis (OSF) is related with the disturbance of synthesis and degradation of extracellular matrix. Arecoline, the areca nut (betel nut) component of betel quid, plays a major role in pathogenesis of OSF. But the exact mechanism how arecoline influences the collagen metabolism is unclear. METHODS: Oral keratinocytes and fibroblasts were cocultured and keratinocytes were pre-treated by arecoline. Fibroblasts alone, fibroblasts stimulated by arecoline, fibroblasts cocultured with keratinocytes and fibroblasts cocultured with keratinocyte pre-treated by arecoline were included as the four groups in the present study. The concentration of collagen, the content and activity of matrix metalloproteinase (MMP) and the concentration of tissue inhibitor of metalloproteinase (TIMP) were assessed. RESULTS: The collagen production of fibroblasts decreased when cocultured with keratinocytes; when cocultured with keratinocytes pre-treated by arecoline, fibroblasts produced more soluble collagen than non-pretreated coculture group. MMP-9 was produced only in coculture groups. There was no significant difference in the two coculture groups. The activation ratio of pro-MMP-2 in arecoline pre-treated keratinocytes-fibroblasts coculture group was significantly higher than that of non-coculture groups, but no significant difference existed in the two coculture groups. TIMP-1 produced by arecoline pre-treated keratinocytes-fibroblasts coculture group was significantly higher than those by the other three groups. CONCLUSION: TIMP-1 and the interaction of oral keratinocytes and fibroblasts play important role in pathogenesis of OSF.