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1.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(7): 995-1000, 2020 Jul 30.
Artigo em Chinês | MEDLINE | ID: mdl-32895151

RESUMO

OBJECTIVE: To study the plasma concentration and pharmacokinetics of 3, 29-Dibenzoyl Karounitriol (3, 29-DK) from sustained- release pellets and extracts of Trichosanthes at different time points in rats using high-performance liquid chromatography- tandem mass spectrometry (LC-MS/MS). METHODS: Healthy male SD rats were given a single gavage of Trichosanthes sustained-release pellets or Trichosanthes extract, and orbital blood samples were taken at different time points within 48 h after drug administration in the pellet group and within 5 h in Trichosanthes extract group for determination of the plasma concentrations of 3, 29-DK using LC-MS/MS. The standard curve of 3, 29-DK content was established, and the specificity, minimum detection limit, precision and accuracy, extraction recovery, stability and matrix effect of LC-MS/MS analysis were assessed. The mean plasms levels of 3, 29-DK at different time points after the drug administration were determined and its pharmacokinetic parameters were calculated using Das 2.0 software. RESULTS: LC-MS/MS analysis showed a good linearity of 3, 29-DK concentration within the range of 0.5-32 ng/mL, and the results of methodological validation confirmed the validity of this method for biological sample determination. Trichosanthes sustained-release pellets and Trichosanthes extract showed significant differences in their AUC(0-t), AUC(0-∞), MRT(0-t), MRT(0-∞), t1/2z and Tmax of 3, 29-DK after administration in rats (P < 0.05). CONCLUSIONS: Trichosanthes sustained-release pellets are capable of sustained-release of 3, 29-DK in rats, and thus provides a basis for the study of new dosage forms of Trichosanthes.


Assuntos
Trichosanthes , Animais , Cromatografia Líquida de Alta Pressão , Preparações de Ação Retardada , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem
2.
Nat Commun ; 11(1): 4450, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895379

RESUMO

Hollow multishelled structures (HoMSs), with relatively isolated cavities and hierarchal pores in the shells, are structurally similar to cells. Functionally inspired by the different transmission forms in living cells, we studied the mass transport process in HoMSs in detail. In the present work, after introducing the antibacterial agent methylisothiazolinone (MIT) as model molecules into HoMSs, we discover three sequential release stages, i.e., burst release, sustained release and stimulus-responsive release, in one system. The triple-shelled structure can provide a long sterility period in a bacteria-rich environment that is nearly 8 times longer than that of the pure antimicrobial agent under the same conditions. More importantly, the HoMS system provides a smart responsive release mechanism that can be triggered by environmental changes. All these advantages could be attributed to chemical diffusion- and physical barrier-driven temporally-spatially ordered drug release, providing a route for the design of intelligent nanomaterials.


Assuntos
Antibacterianos/administração & dosagem , Preparações de Ação Retardada/administração & dosagem , Portadores de Fármacos/química , Nanoestruturas/química , Antibacterianos/farmacocinética , Preparações de Ação Retardada/farmacocinética , Difusão , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Microesferas , Tiazóis/administração & dosagem , Tiazóis/farmacocinética
3.
Nat Commun ; 11(1): 4504, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32908131

RESUMO

The strategies concerning modification of the complex immune pathological inflammatory environment during acute spinal cord injury remain oversimplified and superficial. Inspired by the acidic microenvironment at acute injury sites, a functional pH-responsive immunoregulation-assisted neural regeneration strategy was constructed. With the capability of directly responding to the acidic microenvironment at focal areas followed by triggered release of the IL-4 plasmid-loaded liposomes within a few hours to suppress the release of inflammatory cytokines and promote neural differentiation of mesenchymal stem cells in vitro, the microenvironment-responsive immunoregulatory electrospun fibers were implanted into acute spinal cord injury rats. Together with sustained release of nerve growth factor (NGF) achieved by microsol core-shell structure, the immunological fiber scaffolds were revealed to bring significantly shifted immune cells subtype to down-regulate the acute inflammation response, reduce scar tissue formation, promote angiogenesis as well as neural differentiation at the injury site, and enhance functional recovery in vivo. Overall, this strategy provided a delivery system through microenvironment-responsive immunological regulation effect so as to break through the current dilemma from the contradiction between immune response and nerve regeneration, providing an alternative for the treatment of acute spinal cord injury.


Assuntos
Microambiente Celular/imunologia , Sistemas de Liberação de Medicamentos/instrumentação , Fator de Crescimento Neural/administração & dosagem , Regeneração Nervosa/efeitos dos fármacos , Traumatismos da Medula Espinal/terapia , Tecidos Suporte , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Preparações de Ação Retardada/administração & dosagem , Modelos Animais de Doenças , Liberação Controlada de Fármacos , Feminino , Humanos , Concentração de Íons de Hidrogênio , Interleucina-4/administração & dosagem , Lipossomos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/fisiologia , Fator de Crescimento Neural/farmacocinética , Regeneração Nervosa/imunologia , Ratos , Recuperação de Função Fisiológica/imunologia , Medula Espinal/citologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/imunologia , Traumatismos da Medula Espinal/imunologia
4.
Lancet Psychiatry ; 7(9): 749-761, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32828165

RESUMO

BACKGROUND: Most individuals with schizophrenia-spectrum disorders have relapses, which increase the risk of morbidity and mortality. Because non-adherence to antipsychotic maintenance treatment could affect more than half of individuals with schizophrenia-spectrum disorders, psychosis relapse can often be confounded by unnoticed treatment interruption. Research of relapse during confirmed antipsychotic exposure has basic clinical and neurobiological implications, but data are scarce. We aimed to generate reliable estimates of incidence and predictors of relapse during assured antipsychotic treatment. METHODS: We did a systematic review and individual participant data (IPD) meta-analysis of clinical trials of long-acting injectable antipsychotics (LAIs) for psychosis relapse-prevention, following IPD-PRISMA guidelines. Datasets were identified by searching relevant repositories from inception to Aug 1, 2019. Each LAI group was reanalysed as a separate cohort, further identifying subcohorts of individuals with and without prospectively determined symptom remission (PSR). Summary incidence rate of relapse, incidence rate ratios (IRRs) of relapse between individuals with and without PSR, hazard ratios (HRs) of covariates on risk of relapse, and standardised mean difference (SMDs) in changes in overall functioning associated with relapse were generated by pooling results from the harmonised reanalysis of each study. This study is registered with PROSPERO, number CRD42019137439. FINDINGS: 19 treatment cohorts consisting of 5130 individuals (2938 with PSR, 2192 without PSR), with 3959·53 observed participant-years, were meta-analysed. Pooled incidence of relapse was 22·97 per 100 participant-years (14·76 per 100 participant-years for the PSR subcohort, 31·51 per 100 participant-years for the non-PSR subcohort), with an IRR of 0·19 (95% CI 0·07 to 0·54). Relapse was associated with functional decline (overall SMD -0·76, 95% CI -1·14 to -0·37; PSR SMD -0·52, 95% CI -0·80 to -0·21; non-PSR SMD -0·72, 95% CI -1·18 to -0·26). The strongest predictor of relapse was tardive dyskinesia at treatment onset (HR 2·39, 95% CI 1·05 to 5·42). INTERPRETATION: Despite the established efficacy of antipsychotics in preventing relapse, these data indicate that these drugs might not prevent subsequent exacerbations for a proportion of individuals whose illness is stabilised on continuous antipsychotic treatment. Tardive dyskinesia in particular might have pathophysiological implications for relapse. FUNDING: Northwell Health.


Assuntos
Antipsicóticos/administração & dosagem , Transtornos Psicóticos/prevenção & controle , Esquizofrenia/tratamento farmacológico , Ensaios Clínicos como Assunto , Preparações de Ação Retardada , Humanos , Injeções , Esquizofrenia/prevenção & controle , Prevenção Secundária
5.
Nat Commun ; 11(1): 3859, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737298

RESUMO

Non-enzymatic proteins including antibodies function as biomarkers and are used as biopharmaceuticals in several diseases. Protein-responsive soft materials capable of the controlled release of drugs and proteins have potential for use in next-generation diagnosis and therapies. Here, we describe a supramolecular/agarose hydrogel composite that can release a protein in response to a non-enzymatic protein. A non-enzymatic protein-responsive system is developed by hybridization of an enzyme-sensitive supramolecular hydrogel with a protein-triggered enzyme activation set. In situ imaging shows that the supramolecular/agarose hydrogel composite consists of orthogonal domains of supramolecular fibers and agarose, which play distinct roles in protein entrapment and mechanical stiffness, respectively. Integrating the enzyme activation set with the composite allows for controlled release of the embedded RNase in response to an antibody. Such composite hydrogels would be promising as a matrix embedded in a body, which can autonomously release biopharmaceuticals by sensing biomarker proteins.


Assuntos
Anidrase Carbônica II/química , Preparações de Ação Retardada/síntese química , Hidrogéis/química , Ribonucleases/química , Sefarose/química , Animais , Anticorpos/química , Avidina/química , Biotina/química , Anidrase Carbônica II/antagonistas & inibidores , Inibidores da Anidrase Carbônica/química , Bovinos , Ativação Enzimática , Transição de Fase , Reologia , Ribonucleases/antagonistas & inibidores , Sulfonamidas/química
6.
Ecotoxicol Environ Saf ; 202: 110935, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32800218

RESUMO

This study investigated the ability of dual crosslinked interpenetrating polymer network (IPN) blend beads (DIN:SA/PVA-beads), composed of sodium alginate (SA) and poly (vinyl alcohol) (PVA), as a base-triggered carrier for the controlled release of dinotefuran (DIN) in Spodoptera litera midgut. The blend beads were characterized for morphology, encapsulation efficiency, swelling degree, and in vitro release of the blend beads were characterized. The results revealed that the double-crosslinked gel beads had a tightly interpenetrating network structure and exhibited a satisfactory embedding effect for DIN. The maximum of the DIN loading capacity was approximately 1.01%, with a high encapsulation efficiency of 83.19%. The triggered release of DIN from the blend beads was studied in deionized water (pH 3.0-11.0) via high-performance liquid chromatography (HPLC); it was found that the release rate was higher in alkaline pH conditions than in acidic and neutral conditions. An in vivo dynamics and degradation study also demonstrated that the excellent release characteristics of DIN:SA/PVA-beads in the midgut of S. litera. This study provides a promising controlled-release form of dinotefuran that is more effective and can be used for the targeted control of pests with alkaline midgut.


Assuntos
Guanidinas/metabolismo , Neonicotinoides/metabolismo , Nitrocompostos/metabolismo , Spodoptera/metabolismo , Alginatos/química , Animais , Preparações de Ação Retardada/química , Etanol , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Hidrogéis/química , Concentração de Íons de Hidrogênio , Polímeros , Álcool de Polivinil/química
7.
Crit Rev Ther Drug Carrier Syst ; 37(3): 271-303, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32749140

RESUMO

Nanotechnology has made great contributions in the development of materials with potential application in different areas, especially in the pharmaceutical sector, where nano-systems are being intensely studied for controlled drug release. These innovative systems are composed of structures such as nanoparticles, nanoemulsions, and cyclodextrins, with the aim of promoting enhanced bioavailability of bioactive molecules. Among these nanocarriers, vesicles such as liposomes and polymersomes are considered to be promising alternatives in delivering hydrophilic and lipophilic drugs. They have different classifications according to their composition, among which are hybrid vesicles, which unlike liposomes are composed of both lipids and polymers. These vesicular systems stand out for combining the advantages of both components, overcoming the limitations of traditional systems imposed by low stability and premature release of the encapsulated active substance. The polymers applied in hybrid vesicles can make up the membrane structure itself or be employed to coat preformed vesicles. Due to the relevance of these systems, this work covers their characteristics and summarizes recent articles about them in the literature.


Assuntos
Cosméticos/administração & dosagem , Lipídeos/administração & dosagem , Nanopartículas/administração & dosagem , Nanotecnologia/métodos , Polímeros/administração & dosagem , Nanomedicina Teranóstica/métodos , Animais , Cosméticos/química , Preparações de Ação Retardada , Sistemas de Liberação de Medicamentos/métodos , Humanos , Lipídeos/química , Lipossomos/administração & dosagem , Lipossomos/química , Nanopartículas/química , Polímeros/química
8.
Int J Nanomedicine ; 15: 5361-5376, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801694

RESUMO

Background and Aim: Polymeric nanoparticles (NPs) have received much attention as promising carrier systems in lung cancer and brain metastases. Methods: Here, for the first time, we investigated the feasibility of using inhaled cholesterol-PEG co-modified poly (n-butyl) cyanoacrylate NPs (CLS-PEG NPs) of docetaxel (DTX) for sustained pulmonary drug delivery in cancer metastasis. Results: Spray-dried or freeze-dried NPs yielded sustained drug release in vitro. In vitro inhalation evaluation data indicated that the inhalation formulation had better inhalability. Compared with intravenous (IV) administration, pharmacokinetic data suggested that the inhalation formulation prolonged plasma concentration of DTX for greater than 24 h and is more quickly and completely absorbed into the rat lung after intratracheal (IT) administration. Furthermore, freeze-dried powders were found to increase the t1/2 and area under curve (AUC) by 2.3 and 6.5 fold compared to the free drug after IT administration, and spray-dried powders were found to increase the t1/2 and AUC by 3.4 and 8.8 fold, respectively. After pulmonary administration of the inhalation formulation, DTX appeared to prolong the pulmonary absorption time. In addition, the inhalation formulation was distributed to the brain in a sustained release manner. Conclusion: These experimental results demonstrated that freeze- and spray-dried powders have the potential for pulmonary sustained release, and they also have the potential to be used as a novel treatment for the delivery of drugs that pass through the air-blood barrier and enter the brain and are efficient carriers for the treatment of brain metastasis.


Assuntos
Antineoplásicos/administração & dosagem , Docetaxel/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas/administração & dosagem , Células A549 , Administração por Inalação , Animais , Encéfalo/efeitos dos fármacos , Colesterol/química , Preparações de Ação Retardada , Docetaxel/farmacocinética , Portadores de Fármacos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Embucrilato/química , Feminino , Liofilização , Humanos , Pulmão/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Nanopartículas/química , Tamanho da Partícula , Polímeros/química , Pós/química , Ratos Wistar , Distribuição Tecidual
9.
Periodontol 2000 ; 84(1): 176-187, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32844422

RESUMO

Periodontal diseases are prevalent in humans. Conventional means of combating these diseases involve basic oral hygiene, mostly toothbrushing, use of mouthwashes, and flossing. Supplementary means of treatment, either clinical or pharmaceutical, are often necessary. The use of sustained-release delivery systems, applied locally to the periodontal pocket, seems to be one feasible approach: local sustained-release delivery of antibacterial agents to treat periodontal diseases is conceivable. The use of local (intrapocket) sustained-release delivery systems has numerous clinical, pharmacologic, and toxicologic advantages over conventional treatments for periodontal diseases. Sustained-release technology has been proven to be effective over the last few decades. Films, gels, and fibers are the three main classical intrapocket pharmaceutical delivery systems. Research today is more focused on improving drug delivery, and less on introducing new drugs. New approaches, eg, those making use of nanotechnology, are emerging for local drug-delivery systems. The local sustained-release delivery system concept is innovative and a few products are already commercially available.


Assuntos
Anti-Infecciosos/uso terapêutico , Doenças Periodontais/tratamento farmacológico , Preparações de Ação Retardada/uso terapêutico , Fantasia , Humanos , Bolsa Periodontal
10.
Cochrane Database Syst Rev ; 8: CD008227, 2020 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-32761612

RESUMO

BACKGROUND: Most people with cystic fibrosis (CF) (80% to 90%) need pancreatic enzyme replacement therapy (PERT) to prevent malnutrition. Enzyme preparations need to be taken whenever food is taken, and the dose needs to be adjusted according to the food consumed. A systematic review on the efficacy and safety of PERT is needed to guide clinical practice, as there is variability between centres with respect to assessment of pancreatic function, time of commencing treatment, dose and choice of supplements. This is an updated version of a published review. OBJECTIVES: To evaluate the efficacy and safety of PERT in children and adults with CF and to compare the efficacy and safety of different formulations of PERT and their appropriateness in different age groups. Also, to compare the effects of PERT in CF according to different diagnostic subgroups (e.g. different ages at introduction of therapy and different categories of pancreatic function). SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 07 November 2019. We also searched an ongoing trials website and the websites of the pharmaceutical companies who manufacture pancreatic enzyme replacements for any additional trials. Most recent search: 26 December 2019. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials in people of any age, with CF and receiving PERT, at any dosage and in any formulation, for a period of not less than four weeks, compared to placebo or other PERT preparations. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trials and extracted outcome data. They also assessed the risk of bias and quality of the evidence (GRADE) of the trials included in the review. MAIN RESULTS: 14 trials were included in the review (641 children and adults with CF), two of these were parallel trials and 12 were cross-over trials. Interventions included different enteric and non-enteric-coated preparations of varying formulations in comparison to each other. The number of participants in each trial varied between 14 and 129. 13 trials were for a duration of four weeks and one trial lasted seven weeks. The majority of the trials had an unclear risk of bias from the randomisation process as the details of this were not given; they also had a high risk of attrition bias and reporting bias. The quality of the evidence ranged from moderate to very low. We mostly could not combine data from the trials as they compared different formulations and the findings from individual trials provided insufficient evidence to determine the size and precision of the effects of different formulations. AUTHORS' CONCLUSIONS: There is limited evidence of benefit from enteric-coated microspheres when compared to non-enteric coated pancreatic enzyme preparations up to one month. In the only comparison where we could combine any data, the fact that these were cross-over trials is likely to underestimate the level of inconsistency between the results of the trials due to over-inflation of CIs from the individual trials.There is no evidence on the long-term effectiveness and risks associated with PERT. There is also no evidence on the relative dosages of enzymes needed for people with different levels of severity of pancreatic insufficiency, optimum time to start treatment and variations based on differences in meals and meal sizes. There is a need for a properly designed trial that can answer these questions.


Assuntos
Fibrose Cística/terapia , Terapia de Reposição de Enzimas/normas , Dor Abdominal/epidemiologia , Adulto , Fatores Etários , Cápsulas/administração & dosagem , Criança , Preparações de Ação Retardada , Terapia de Reposição de Enzimas/efeitos adversos , Fármacos Gastrointestinais/uso terapêutico , Humanos , Microesferas , Estado Nutricional , Pâncreas/enzimologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Ganho de Peso
11.
Cochrane Database Syst Rev ; 8: CD007372, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32852803

RESUMO

BACKGROUND: The setting in which induction of labour takes place (home or inpatient) is likely to have implications for safety, women's experiences and costs. Home induction may be started at home with the subsequent active phase of labour happening either at home or in a healthcare facility (hospital, birth centre, midwifery-led unit). More commonly, home induction starts in a healthcare facility, then the woman goes home to await the start of labour. Inpatient induction takes place in a healthcare facility where the woman stays while awaiting the start of labour. OBJECTIVES: To assess the effects on neonatal and maternal outcomes of third trimester home induction of labour compared with inpatient induction using the same method of induction. SEARCH METHODS: For this update, we searched the Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (31 January 2020)), and reference lists of retrieved studies. SELECTION CRITERIA: Published and unpublished randomised controlled trials (RCTs) in which home and inpatient settings for induction have been compared. We included conference abstracts but excluded quasi-randomised trials and cross-over studies. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study reports for inclusion. Two review authors carried out data extraction and assessment of risk of bias independently. GRADE assessments were checked by a third review author. MAIN RESULTS: We included seven RCTs, six of which provided data on 1610 women and their babies. Studies were undertaken between 1998 and 2015, and all were in high- or upper-middle income countries. Most women were induced for post dates. Three studies reported government funding, one reported no funding and three did not report on their funding source. Most GRADE assessments gave very low-certainty evidence, downgrading mostly for high risk of bias and serious imprecision. 1. Home compared to inpatient induction with vaginal prostaglandin E (PGE) (two RCTs, 1028 women and babies; 1022 providing data). Although women's satisfaction may be slightly better in home settings, the evidence is very uncertain (mean difference (MD) 0.16, 95% confidence interval (CI) -0.02 to 0.34, 1 study, 399 women), very low-certainty evidence. There may be little or no difference between home and inpatient induction for other primary outcomes, with all evidence being very low certainty: - spontaneous vaginal birth (average risk ratio (RR) [aRR] 0.91, 95% CI 0.69 to 1.21, 2 studies, 1022 women, random-effects method); - uterine hyperstimulation (RR 1.19, 95% CI 0.40 to 3.50, 1 study, 821 women); - caesarean birth (RR 1.01, 95% CI 0.81 to 1.28, 2 studies, 1022 women); - neonatal infection (RR 1.29, 95% CI 0.59 to 2.82, 1 study, 821 babies); - admission to neonatal intensive care unit (NICU) (RR 1.20, 95% CI 0.50 to 2.90, 2 studies, 1022 babies). Studies did not report serious neonatal morbidity or mortality. 2. Home compared to inpatient induction with controlled release PGE (one RCT, 299 women and babies providing data). There was no information on whether the questionnaire on women's satisfaction with care used a validated instrument, but the findings presented showed no overall difference in scores. We found little or no difference between the groups for other primary outcomes, all also being very low-certainty evidence: - spontaneous vaginal birth (RR 0.94, 95% CI 0.77 to 1.14, 1 study, 299 women); - uterine hyperstimulation (RR 1.01, 95% CI 0.51 to 1.98, 1 study, 299 women); - caesarean births (RR 0.95, 95% CI 0.64 to 1.42, 1 study, 299 women); - admission to NICU (RR 1.38, 0.57 to 3.34, 1 study, 299 babies). The study did not report on neonatal infection nor serious neonatal morbidity or mortality. 3. Home compared to inpatient induction with balloon or Foley catheter (four RCTs; three studies, 289 women and babies providing data). It was again unclear whether questionnaires reporting women's experiences/satisfaction with care were validated instruments, with one study (48 women, 69% response rate) finding women were similarly satisfied. Home inductions may reduce the number of caesarean births, but the data are also compatible with a slight increase and are of very low-certainty (RR 0.64, 95% CI 0.41 to 1.01, 2 studies, 159 women). There was little or no difference between the groups for other primary outcomes with all being very low-certainty evidence: - spontaneous vaginal birth (RR 1.04, 95% CI 0.54 to 1.98, 1 study, 48 women): - uterine hyperstimulation (RR 0.45, 95% CI 0.03 to 6.79, 1 study, 48 women); - admission to NICU (RR 0.37, 95% CI 0.07 to 1.86, 2 studies, 159 babies). There were no serious neonatal infections nor serious neonatal morbidity or mortality in the one study (involving 48 babies) assessing these outcomes. AUTHORS' CONCLUSIONS: Data on the effectiveness, safety and women's experiences of home versus inpatient induction of labour are limited and of very low-certainty. Given that serious adverse events are likely to be extremely rare, the safety data are more likely to come from very large observational cohort studies rather than relatively small RCTs.


Assuntos
Assistência Ambulatorial/métodos , Maturidade Cervical , Hospitalização , Trabalho de Parto Induzido/métodos , Cateterismo/métodos , Cesárea/estatística & dados numéricos , Preparações de Ação Retardada , Dinoprostona , Feminino , Humanos , Recém-Nascido , Tempo de Internação , Ocitócicos , Segurança do Paciente , Satisfação do Paciente , Gravidez , Resultado da Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Ying Yong Sheng Tai Xue Bao ; 31(7): 2422-2430, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-32715709

RESUMO

A field experiment with five treatments, control (CK, no fertilizer), conventional fertilization (U), double-effect inhibitor synergistic urea (DU), coated urea (CU) and slow/controlled release urea mixture (CDU), was conducted to investigate the effects of conventional fertilization (240 kg N·hm-2) and one-off application of different slow/controlled release fertilizers (180 kg N·hm-2) on the yield and quality of fresh maize, soil inorganic nitrogen (N), and ammonia (NH3) emissions. The results showed that the total amount of ammonia volatilization was the highest in treatment of conventional fertilization (U), with N topdressing being an important source of NH3 emission. Compared with U treatment, the NH3 volatilization in the DU, CU, and CDU treatments was reduced by 78%-81%. At harvest stage, the soil layer of 80-100 cm in the U treatment had the highest nitrate concentration (51.6 mg·kg-1), resulting in a high risk of N leaching. In contrast, the nitrate concentrations in the same soil layer in the slow/controlled release fertilizer treatments were much lower, reducing the risk of leaching. In comparison with U, three slow/controlled release fertilizer treatments with 25% lower N application did not decrease yield but increased seed Vc, soluble sugar and protein contents. The agronomic efficiency and economic benefit of DU treatment were the highest among three slow/controlled release fertilizers treatments. In conclusion, the application of new type of slow/controlled release fertilizer could improve the yield and quality of fresh maize, and significantly reduce the risk of ammonia loss and N leaching. Considering the higher cost of the polymer coated urea, the double-effect inhibitor urea has lower cost and is more convenient to make. It is therefore a better choice to fresh maize planting.


Assuntos
Amônia/análise , Fertilizantes/análise , Agricultura , Preparações de Ação Retardada , Nitrogênio , Solo , Zea mays
13.
AIDS Rev ; 22(2): 124-127, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32628223

RESUMO

Following the advent of penicillin as first widely used antibiotic during World War II, viruses have steadily replaced bacteria as major agents of infections, particularly for microorganisms that can spread globally. Good examples are pandemics caused by HIV, hepatitis B, hepatitis C, and nowadays severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the coronavirus of coronavirus disease (COVID)-19.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Betacoronavirus/imunologia , Preparações de Ação Retardada , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Humanos , Profilaxia Pré-Exposição , Vacinas
14.
Int J Nanomedicine ; 15: 4079-4090, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606665

RESUMO

Purpose: The aim of this study is to develop efficient localized therapy of sertaconazole nitrate for the treatment of vaginal candidiasis. Methods: Sertaconazole nitrate-loaded cationic liposomes were prepared by thin-film hydration method and coated with different concentrations of pectin (0.05%, 0.1% and 0.2%) to develop mucoadhesive liposomes. The formulated mucoadhesive vesicles were characterized in terms of morphology, entrapment efficiency, particle size, zeta value, mucoadhesive properties and drug release. The selected formula was incorporated into a gel base and further characterized by an ex vivo permeation study in comparison with conventional sertaconazole gel. Also, the in vivo study was performed to assess the efficacy of sertaconazole mucoadhesive liposomal gel in treating rats with vaginal candidiasis. Results: The mucoadhesive liposomes were spherical. Coating liposomes with pectin results in increased entrapment efficiency and particle size compared with uncoated vesicles. On the contrary, zeta values were reduced upon coating liposomes with pectin indicating efficient coating of liposomes with pectin. Mucoadhesive liposomes showed a more prolonged and sustained drug release compared with uncoated liposomes. Ex vivo study results showed that mucoadhesive liposomal gel increased sertaconazole tissue retention and reduced drug tissue penetration. In the invivo study, the mucoadhesive liposomal gel showed a significant reduction in the microbial count with a subsequent reduction in inflammatory responses with the lowest histopathological change compared with conventional gel. Conclusion: The study confirmed the potentiality of employing mucoadhesive liposomes as a successful carrier for the vaginal delivery of antifungal drugs.


Assuntos
Antifúngicos/uso terapêutico , Candidíase Vulvovaginal/tratamento farmacológico , Imidazóis/uso terapêutico , Muco/química , Tiofenos/uso terapêutico , Adesividade , Animais , Anti-Infecciosos/farmacologia , Biomarcadores/metabolismo , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Feminino , Géis , Humanos , Imidazóis/farmacologia , Imunoglobulina G/metabolismo , Imunoglobulina M/metabolismo , Mediadores da Inflamação/metabolismo , Lipossomos/ultraestrutura , Mucinas/metabolismo , Tamanho da Partícula , Ratos Sprague-Dawley , Ovinos , Eletricidade Estática , Tiofenos/farmacologia , Vagina/patologia , beta-Glucanas/metabolismo
15.
Int J Nanomedicine ; 15: 4363-4392, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606683

RESUMO

With continual rapid developments in the biomedical field and understanding of the important mechanisms and pharmacokinetics of biological molecules, controlled drug delivery systems (CDDSs) have been at the forefront over conventional drug delivery systems. Over the past several years, scientists have placed boundless energy and time into exploiting a wide variety of excipients, particularly diverse polymers, both natural and synthetic. More recently, the development of nano polymer blends has achieved noteworthy attention due to their amazing properties, such as biocompatibility, biodegradability and more importantly, their pivotal role in controlled and sustained drug release in vitro and in vivo. These compounds come with a number of effective benefits for improving problems of targeted or controlled drug and gene delivery systems; thus, they have been extensively used in medical and pharmaceutical applications. Additionally, they are quite attractive for wound dressings, textiles, tissue engineering, and biomedical prostheses. In this sense, some important and workable natural polymers (namely, chitosan (CS), starch and cellulose) and some applicable synthetic ones (such as poly-lactic-co-glycolic acid (PLGA), poly(lactic acid) (PLA) and poly-glycolic acid (PGA)) have played an indispensable role over the last two decades for their therapeutic effects owing to their appealing and renewable biological properties. According to our data, this is the first review article highlighting CDDSs composed of diverse natural and synthetic nano biopolymers, blended for biological purposes, mostly over the past five years; other reviews have just briefly mentioned the use of such blended polymers. We, additionally, try to make comparisons between various nano blending systems in terms of improved sustained and controlled drug release behavior.


Assuntos
Preparações de Ação Retardada/farmacologia , Nanopartículas/química , Polímeros/química , Sistemas de Liberação de Medicamentos , Hidrogéis/química
16.
Chemosphere ; 260: 127478, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32683022

RESUMO

Slow-releasing carbon source tablets were manufactured for an in-situ biological denitrification system. The average zero-order nitrate degradation rates seen, from highest to lowest, were in microcosms to which lactate, fumarate, propionate, and formate had been added. Fumarate was approximately 80% cheaper than lactate, and consequently was determined to be the most optimal slow-releasing carbon source in tablet form. The slow-releasing precipitating tablet (SRPT) and slow-releasing floating tablet (SRFT) were manufactured with hydroxypropyl methylcellulose (HPMC) as the agent of release control, microcrystalline cellulose pH 101 (MCC 101) as the binder, #8 sand as the precipitation agent, and calcium carbonate and citric acid as floating agents. Fourier transform infrared spectroscopy and powder X-ray diffraction indicated that the crystal arrangement in the SRPTs and SRFTs was maintained and ordered in a manner similar to raw excipients. SRFTs floated in water within 30 min and remained so for 5 d due to the buoyancy of carbon dioxide. The carbon source release rate was proportional to the quantity of HPMC added. The longevities of SRPT with 300 mg of HPMC and SRFT with 400 mg of HPMC were 25.4 d and 37.3 d, respectively. This study observed that SRPT and SRFT were manufactured effectively and are suitable for in-situ slow-releasing biological systems.


Assuntos
Desnitrificação , Água Subterrânea/química , Preparações de Ação Retardada , Excipientes/química , Derivados da Hipromelose , Nitratos , Pós , Solubilidade , Comprimidos , Água/química
17.
J Clin Psychiatry ; 81(4)2020 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-32609958

RESUMO

The goals of schizophrenia treatment are to control symptoms, prevent relapse, and improve functioning and quality of life. For many patients, these goals are not being met. This report highlights information provided by experts on the reasons for, impact of, and means to reduce relapse in patients with schizophrenia; on patient-centered and patient-reported assessment; on the benefits and risks of medication options, including long-acting injectable (LAI) antipsychotics; and on psychosocial interventions that may improve adherence and help prevent relapse in individuals living with schizophrenia. Modifiable risk factors for poor outcomes in patients with schizophrenia include longer duration of untreated illness, comorbid substance abuse, early nonresponse to an antipsychotic, and the number of relapses that are related to nonadherence. Recommendations include 1) adopting a patient-centered approach that incorporates the use of patient-reported outcome measures; 2) selecting medications based on a balanced risk-benefit assessment, including a focus on addressing symptoms for which the agents were superior to placebo and/or active controls; 3) considering LAIs as an alternative to oral medications, as they offer benefits such as reliable drug delivery, uncovering nonadherence and pseudo-resistance, and reduced relapse risk and mortality; and 4) implementing psychosocial interventions that have been proven to be effective in improving adherence and overall outcomes.


Assuntos
Antipsicóticos/uso terapêutico , Esquizofrenia/tratamento farmacológico , Antipsicóticos/administração & dosagem , Terapia Combinada/métodos , Preparações de Ação Retardada/uso terapêutico , Humanos , Injeções Intramusculares , Adesão à Medicação , Psicoterapia , Esquizofrenia/terapia , Prevenção Secundária
18.
Zh Nevrol Psikhiatr Im S S Korsakova ; 120(6. Vyp. 2): 61-67, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32729692

RESUMO

OBJECTIVE: A pharmacoeconomical analysis of the use of prolonged injectable antipsychotics in the treatment of patients with schizophrenia in Moscow over 2015-2019 in the context of the reform of the psychiatric service. MATERIAL AND METHODS: The authors studied the economic costs of treatment of psychiatric patients with prolonged injectable antipsychotics on the pharmaceutical market in Moscow for five years on the example of patients diagnosed with paranoid schizophrenia (ICD-10 F20.0) based on the dynamics of the registered contingent of patients with schizophrenic spectrum disorders over the past fifteen years including the period of active modernization of the psychiatric service. RESULTS AND CONCLUSION: A constant increase in public spending on treatment, including therapy with prolonged injectable neuroleptics (both first-generation drugs and atypical antipsychotics), was shown. At the same time, the increase in the use of atypical antipsychotics is ahead of schedule. The number of patients receiving treatment with prolonged injectable haloperidol and zupentixol increased approximately twice during this period, the number of patients receiving treatment with injectable risperidone and paliperidone palmitate increased by more than 3 and 13 times, respectively. There is a significant increase in public spending on the purchase and use of these drugs for the treatment of privileged categories of patients, most of this applies to injectable forms of paliperidone, the cost of using these drugs has increased more than 20 times over a five-year period. These trends indicate a shift in emphasis towards outpatient psychiatric care and improvement of approaches to treatment of patients with schizophrenia, which indicate a new stage in the development of out-of-hospital treatment and rehabilitation systems based on the latest achievements of psychopharmacology and the development of social support systems for patients with schizophrenia spectrum disorders.


Assuntos
Antipsicóticos/uso terapêutico , Preparações de Ação Retardada , Humanos , Moscou , Palmitato de Paliperidona , Risperidona , Mudança Social
19.
Zh Nevrol Psikhiatr Im S S Korsakova ; 120(6. Vyp. 2): 77-81, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32729694

RESUMO

OBJECTIVE: To determine the frequency of administration, efficacy and safety of long acting antipsychotics in day-to-day psychiatric practice in outpatient clinics. MATERIAL AND METHODS: The study included 90 patients with schizophrenia treated with haloperidol decanoate (n=18), rispolept consta (n=19), clopixol depot (n=25), paliperidone palmitate (n=25). Symptoms of schizophrenia were assessed with PANSS during 12 months. RESULTS AND CONCLUSION: The use of long acting antipsychotics has proven to be effective and safe to control all symptom clusters in patients regardless of the disease duration.


Assuntos
Antipsicóticos/uso terapêutico , Esquizofrenia/tratamento farmacológico , Assistência Ambulatorial , Preparações de Ação Retardada/uso terapêutico , Humanos , Palmitato de Paliperidona/uso terapêutico
20.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 40(7): 995-1000, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32701230

RESUMO

OBJECTIVE: To study the plasma concentration and pharmacokinetics of 3, 29-Dibenzoyl Karounitriol (3, 29-DK) from sustained- release pellets and extracts of Trichosanthes at different time points in rats using high-performance liquid chromatography- tandem mass spectrometry (LC-MS/MS). METHODS: Healthy male SD rats were given a single gavage of Trichosanthes sustained-release pellets or Trichosanthes extract, and orbital blood samples were taken at different time points within 48 h after drug administration in the pellet group and within 5 h in Trichosanthes extract group for determination of the plasma concentrations of 3, 29-DK using LC-MS/MS. The standard curve of 3, 29-DK content was established, and the specificity, minimum detection limit, precision and accuracy, extraction recovery, stability and matrix effect of LC-MS/MS analysis were assessed. The mean plasms levels of 3, 29-DK at different time points after the drug administration were determined and its pharmacokinetic parameters were calculated using Das 2.0 software. RESULTS: LC-MS/MS analysis showed a good linearity of 3, 29-DK concentration within the range of 0.5-32 ng/mL, and the results of methodological validation confirmed the validity of this method for biological sample determination. Trichosanthes sustained-release pellets and Trichosanthes extract showed significant differences in their AUC(0-t), AUC(0-∞), MRT(0-t), MRT(0-∞), t1/2z and Tmax of 3, 29-DK after administration in rats (P < 0.05). CONCLUSIONS: Trichosanthes sustained-release pellets are capable of sustained-release of 3, 29-DK in rats, and thus provides a basis for the study of new dosage forms of Trichosanthes.


Assuntos
Benzoatos/farmacocinética , Cromatografia Líquida , Espectrometria de Massas em Tandem , Trichosanthes , Animais , Área Sob a Curva , Preparações de Ação Retardada , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Trichosanthes/química
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