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1.
J Control Release ; 320: 484-494, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32027937

RESUMO

Defining the qualitative sameness of parenteral formulations comprised of poly(lactide-co-glycolide) (PLGA) requires assays of the relevant properties of polymer from each formulation. Gel-permeation chromatography with quaternary detection (GPC-4D) has been previously applied to other polymers, and the relevant mathematical parameters for their characterization are available; however, such parameters have not been described for branched PLGA polymers. Little information is available for the determination of glucose within glucose-PLGA (Glu-PLGA) branched polymers. This study describes the experimental methods of defining the mathematical parameters for characterization of branched PLGA polymers and the validation of these parameters using known branched-PLGA standards. The glucose, used as an initiator, was tracked through the synthesis of Glu-PLGA by both 13C NMR and enzymatic analysis. The analytical determination of the relevant parameters defining Glu-PLGA, such as the branching number, and the presence of glucose, requires the use of appropriate procedures experimentally validated in a systematic manner. The procedures described in this study were developed for characterization of Glu-PLGA with the lactide:glycolide (L:G) ratio of 55:45 used in Sandostatin® LAR. The procedures can also be used for characterization of Glu-PLGAs made of different L:G ratios.

2.
Phys Chem Chem Phys ; 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31984391

RESUMO

Dissociative adsorption of molecular hydrogen (H2) and migration of the adsorbed H adatom as a hydride or a proton on two of the most stable facets of the In2O3 catalyst in the cubic (c-In2O3) and hexagonal (h-In2O3) phases for CO2 hydrogenation to methanol were investigated by extensive density functional theory (DFT) calculations. Due to the relatively small variation in the oxygen vacancy (Ov) formation energy with respect to surface Ov coverage of these In2O3 surfaces, especially c-In2O3(110) and h-In2O3(012), no limit on the Ov coverage is expected to exist under the typical reaction conditions. Thus, we consider three scenarios for the dissociative adsorption of H2 and the migration of the H adsorbate, namely on the perfect (stoichiometric) In2O3 surfaces, on the partially reduced In2O3 surfaces with a single Ov site, and on the fully reduced In2O3 surfaces. Our DFT calculations show that the oppositely charged In and O pair sites on the perfect and partially reduced In2O3 surfaces facilitate the heterolytic dissociation of H2, leading to the formation of the anionic hydride at the In site crucial for CO2 hydrogenation to methanol. Our comparative studies on the four In2O3 surfaces suggest that the h-In2O3(104) surface is superior to the other three surfaces due to the facile formation of the Ov sites at low coverage and the favorable formation of the hydride adsorbate at the In site from H2 dissociation. These results indicate that this surface might be preferred for CO2 hydrogenation to methanol.

3.
J Control Release ; 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31935481

RESUMO

A spray drying technique was developed to prepare injectable and biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres encapsulating a model luteinizing hormone-releasing hormone agonist (LHRHa)-based peptide, leuprolide. Various spray drying parameters were evaluated to prepare 1-month controlled release formulations with a similar composition to the commercial Lupron Depot ® (LD). A single water-in-oil emulsion of aqueous leuprolide/gelatin solution in PLGA 75/25 acid capped (13 kD Mw) dissolved in methylene chloride (DCM) was spray-dried before washing the microspheres in cold ddH2O and freeze-drying. The spray drying microencapsulation was characterized by: particle sizes/distribution (span), morphology, drug/gelatin loading, encapsulation efficiency, and residual DCM and water content. Long-term release was tested over 9 weeks in PBS + Tween 80 + 0.02% sodium azide pH 7.4 (PBST) at 37 °C. Several physical-chemical parameters were monitored simultaneously for selected formulations, including: water uptake, mass loss, glass transition temperature (Tg) or hydrated Tg, to help understand the related long-term release profiles and explore the underlying controlled release mechanisms. Compared with the commercial LD microspheres, some of the in-house spray-dried microspheres presented highly similar or even improved long-term release profiles, providing viable long-acting release (LAR) alternatives to the LD. The in vitro release mechanism of the peptide was shown to be controlled either by kinetics of polymer mass loss or by a second process, hypothesized to involve peptide desorption from the polymer. These data indicate spray drying can be optimized to prepare commercially relevant PLGA microsphere formulations for delivery of peptides, including LHRHa-like leuprolide.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31967341

RESUMO

Visceral hypersensitivity (VH) is common in irritable bowel syndrome (IBS), and female patients are more likely to seek healthcare services for IBS-related abdominal pain. Oestrogen has been reported to mediate pain modulation via its receptor, and mast cells are known to participate in the development of visceral hypersensitivity. Our previous studies showed that the G-protein-coupled oestrogen receptor (GPER, also known as GPR30) was expressed by mast cells in human colonic tissues and was associated with IBS type and severity of visceral pain. However, whether GPER is involved in oestrogen-dependent visceral hypersensitivity via mast cell degranulation is still unknown. Rats were subjected to wrap partial restraint stress to induce visceral hypersensitivity and were ovariectomized (OVX) to eliminate the effects of oestrogen on visceral hypersensitivity. OVX rats were treated with oestrogen, an oestrogen receptor α and ß antagonist (ICI 182.780), a GPER antagonist (G15) or a GPER agonist (G1), to evaluate the effects of oestrogen via its receptor. The colorectal distention test was performed to assess visceral sensitivity. Immunofluorescence studies were performed to evaluate GPER and mast cell tryptase co-expression. Mast cell number with degranulation was detected by specific staining. Mast cell tryptase expression in rat colon was also investigated by Western blot and immunohistochemistry. Substance P and histamine expression were examined by ELISA. GPER was expressed by the majority of tryptase-positive mast cells in the colonic mucosa. Stressed rats showed increased visceral sensitivity, increased mast cell degranulation, mast cell tryptase expression, and increased colon histamine levels. Ovariectomy reduced stress-induced VH in female rats and decreased mast cell degranulation, mast cell tryptase expression, and histamine levels, whereas oestrogen replacement reversed these effects. In OVX rats, the GPER antagonist G15 counteracted the enhancing effects of oestrogen on stress-induced VH, mast cell degranulation, mast cell tryptase, and histamine expression, whereas VH was preserved after treatment with ICI 182.780. On the other hand, pretreatment with the selective GPER agonist G1 at doses between 1 and 20 µg/kg significantly increased VH, mast cell tryptase, and histamine expression in OVX-stressed rats, mimicking the effects of oestrogen. GPER plays a pivotal role in the regulation of mast cell degranulation, mast cell tryptase expression, and histamine levels and contributes to the development of colonic hypersensitivity in a female rat model of IBS.

5.
BMJ Open ; 9(11): e033161, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31784448

RESUMO

OBJECTIVES: The aim of this study was to investigate the efficacy, tolerability, safety, and impact on quality of life (QoL) and functional status of vortioxetine treatment for patients with generalised anxiety disorder (GAD) by performing a meta-analysis of randomised controlled trials (RCTs). DESIGN: Systematic review and meta-analysis. DATA SOURCES: Data mining was conducted in January 2019 across PubMed, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials Cochrane Library, Web of science and ClinicalTrials.gov. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: All published RCTs, which assessed the effect of vortioxetine treatment for patients with GAD when compared with a placebo group, were included. DATA EXTRACTION AND SYNTHESIS: Relevant data were extracted and synthesised narratively. Results were expressed as standardised mean differences or ORs with 95% CIs. RESULTS: Our meta-analysis showed that multiple doses (2.5, 5 and 10 mg/day) of vortioxetine did not significantly improve the response rates, compared with placebo (OR 1.16, 95% CI 0.84 to 1.60, p=0.38; OR 1.41, 95% CI 0.82 to 2.41, p=0.21; and OR 1.05, 95% CI 0.76 to 1.46, p=0.75). Moreover, there was no statistically significant difference regarding the remission rates, discontinuation for any reason rates, discontinuation due to adverse events rates, Short-Form 36 Health Survey scores or Sheehan Disability Scale scores between administration of multiple doses (2.5, 5 and 10 mg/day) of vortioxetine and placebo. CONCLUSIONS: Although our results suggest that vortioxetine did not improve the GAD symptoms, QoL and functional status impairment of patients with GAD, it was safe and well tolerated. Clinicians should interpret and translate our data with caution, as the meta-analysis was based on a limited number of RCTs.

6.
PLoS One ; 14(12): e0226542, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31869357

RESUMO

Understanding the relationship between exogenous melatonin and water deficit stress is crucial for achieving high yields and alleviating the effects of water deficit stress on soybean (Glycine max (L.) Merrill) plants in agriculture. This study investigated the effects of exogenous melatonin on soybean photosynthetic capacity under water deficit stress induced by polyethylene glycol (PEG) 6000. We conducted a potting experiment in 2018 using the soybean (Glycine max L. Merrill) cultivar Suinong 26. We identified the impacts of a concentration of PEG 6000 simulating drought (15%, w/v) and an appropriate melatonin concentration (100 µmol/L) on the growth of soybean seedlings and flowering stages in a preliminary test. We applied exogenous melatonin by foliar spraying and root application to determine the effects on leaf photosynthesis during water deficit stress. Our results indicated that 15% PEG 6000 had an obvious inhibitory effect on the growth of soybean seedlings and flowering stages, causing oxidative stress and damage due to reactive oxygen species (ROS) (H2O2 and O2·-) accumulation and potentially reducing air exchange parameters and photosystem II (PSII) efficiency. The application of exogenous melatonin significantly relieved the inhibitory effects of PEG 6000 stress on seedlings and flowering growth, and gas exchange parameters, potentially improved PSII efficiency, improved the leaf area index (LAI) and the accumulation of dry matter, slowed down oxidative stress and damage to leaves by increasing the activity of antioxidant enzymes (SOD, POD, and CAT), reduced the content of malondialdehyde (MDA), and ultimately improved soybean yield. Overall, the results of this study demonstrated that application of exogenous melatonin at the seedlings and flowering stages of soybean is effective in alleviating plant damage caused by water deficit stress and improving the drought resistance of soybean plants. In addition, the results showed that application of exogenous melatonin by root is superior to foliar spraying.

7.
BMC Gastroenterol ; 19(1): 221, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31856738

RESUMO

BACKGROUND: Nerve growth factor (NGF) and enteric glial cells (EGCs) are associated with visceral hypersensitivity and gastrointestinal motility disorder, which may represent the pathogenesis of functional dyspepsia (FD). This study aimed to investigate the expression of NGF, its high affinity receptor tropomyosin receptor kinase A (TrkA) and the EGC activation marker glial fibrillary acidic protein (GFAP) in the gastric mucosa of patients with FD and the association of these proteins with dyspeptic symptoms. METHODS: Gastric mucosal biopsies taken from 27 FD patients (9 epigastric pain syndrome (EPS) patients, 7 postprandial distress syndrome (PDS) patients and 11 EPS overlap PDS patients) and 26 control subjects were used for analysis. The expression of NGF, TrkA and GFAP was examined, and the association of these proteins with dyspeptic symptoms, including epigastric pain, postprandial fullness, early satiation and epigastric burning, was analysed. RESULTS: The expression levels of NGF, TrkA, and GFAP in the gastric mucosa were significantly higher in the EPS group, the PDS group, and the EPS overlap PDS group than in the healthy control group. There was no significant difference between the FD subgroups. TrkA colocalized with GFAP, which indicated that TrkA was localized to EGCs, and the expression of TrkA in EGCs was significantly higher in the FD group than in the control group. Changes in the expression of NGF, TrkA, and GFAP were positively correlated with epigastric pain, postprandial fullness and early satiation but had no significant relationship with epigastric burning. CONCLUSIONS: The increased expression of gastric NGF, TrkA and GFAP might be involved in FD pathophysiology and symptom perception.

8.
Neurol Sci ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31754876

RESUMO

As a noninvasive technique, transcranial sonography (TCS) of substantia nigra (SN) has gradually showed its effectiveness not only in diagnosis but also in understanding clinical features of Parkinson's Disease (PD). This study aimed to further evaluate TCS for clinical diagnosis of PD, and to explore the association between sonographic manifestations and visual hallucinations (VH). A total of 226 subjects including 141 PD patients and 85 controls were recruited. All participants received TCS. A series of rating scales to evaluate motor and non-motor symptoms were performed in PD patients. Results showed that 172 subjects were successfully assessed by TCS. The area of SN was greater in PD patients than that in controls (P < 0.001). As receiver-operating characteristic (ROC) curve analysis showed, the best cutoff value for the larger SN echogenicity size was 23.5 mm2 (sensitivity 70.3%, specificity 77.0%). Patients with VH had larger SN area (P = 0.019), as well as higher Non-Motor Symptoms Scale (NMSS) scores (P = 0.018). Moreover, binary logistic regression analysis indicated that SN hyperechogenicity (odds ratio = 4.227, P = 0.012) and NMSS scores (odds ratio = 0.027, P = 0.042) could be the independent predictors for VH. In conclusion, TCS can be used as an auxiliary diagnostic tool for Parkinson's disease. Increased SN echogenicity is correlated with VH in Parkinson's disease, possibly because the brain stem is involved in the mechanism in the onset of VH. Further studies are needed to confirm these findings.

9.
J Comput Assist Tomogr ; 43(5): 697-707, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31490889

RESUMO

OBJECTIVE: To explore the application value of postlabeling delay (PLD) in 3D pseudocontinuous arterial spin-labeled (3D-pcASL) perfusion imaging in normal children and to find the optimal PLD values for children at each age group. METHODS: Five groups of children, with 50 patients in each group, who underwent routine magnetic resonance imaging scans with normal results were included. The patients were stratified according to the following ages: younger than 1 month, more than 1 month to 6 months, more than 6 months to 12 months, more than 1 year to 3 years, more than 3 years to 6 years, and more than 6 years to 18 years. All patients received 3D-pcASL perfusion magnetic resonance scanning. The PLD values were set to 1025, 1525, or 2025 milliseconds. In subjective evaluations, the signal-to-noise ratio (SNR) and cerebral blood flow (CBF) of 3D-pcASL perfusion images under different PLD values were compared and analyzed. RESULTS: For patients in the <1-month group and >1-month to 6-month group, the images were mainly grade A when the PLD value was 1025 milliseconds, which equaled 43 and 46 cases, respectively. The brain CBF values and SNR values were higher than those of the images with PLD values of 1525 and 2025 milliseconds. For patients in the >6-month to 12-month group, >1-year to 3-year group, >3-year to 6-year group, and >6-year to 18-year group, the images were mainly grade A when the PLD value was 1525 milliseconds, which equaled 43, 45, 43, and 46 cases, respectively. The brain CBF values and SNR values were higher than those of the images with PLD values of 1025 and 2025 milliseconds. CONCLUSIONS: The optimal PLD values for 3D-pcASL perfusion imaging are different in children of different ages. The optimal PLD value for infants who are 6 months younger is 1025 milliseconds. The optimal PLD value for children older than 6 months to 18 years is 1525 milliseconds.


Assuntos
Encéfalo/irrigação sanguínea , Artérias Cerebrais/diagnóstico por imagem , Circulação Cerebrovascular/fisiologia , Imagem por Ressonância Magnética/métodos , Imagem de Perfusão/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Imagem Tridimensional , Lactente , Recém-Nascido , Masculino , Valores de Referência , Marcadores de Spin
10.
IEEE Trans Neural Syst Rehabil Eng ; 27(10): 1962-1972, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31514144

RESUMO

Epilepsy is a neurological illness caused by abnormal discharge of brain neurons, where epileptic seizure can lead to life-threatening emergencies. By analyzing the encephalogram (EEG) signals of patients with epilepsy, their conditions can be monitored and seizure can be detected and intervened in time. As the identification of effective features in EEG signals is important for accurate seizure detection, this paper proposes a multi-view deep feature extraction method in attempt to achieve this goal. The method first uses fast Fourier transform (FFT) and wavelet packet decomposition (WPD) to construct the initial multi-view features. Convolutional neural network (CNN) is then used to automatically learn deep features from the initial multi-view features, which reduces the dimensionality and obtain the features with better seizure identification ability. Furthermore, the multi-view Takagi-Sugeno-Kang fuzzy system (MV-TSK-FS), an interpretable rule-based classifier, is used to construct a classification model with strong generalizability based on the deep multi-view features obtained. Experimental studies show that the classification accuracy of the proposed multi-view deep feature extraction method is at least 1% higher than that of common feature extraction methods such as principal component analysis (PCA), FFT and WPD. The classification accuracy is also at least 4% higher than the average accuracy achieved with single-view deep features.

11.
Rev Sci Instrum ; 90(8): 086101, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31472668

RESUMO

The HUST-PTF (proton therapy facility in Huazhong University of Science and Technology) is now under construction based on an isochronous superconducting cyclotron at Huazhong University of Science and Technology. Because the energy extracted by the cyclotron is fixed, an energy degrader is necessary to modulate the beam energy after the cyclotron for clinical requirements. However, the multiple Coulomb scattering that occurs in the degrader increases the beam emittance. Therefore, collimators are designed after the degrader to decrease the beam emittance. Because of the severe beam losses in the aforementioned energy degradation and emittance restriction, the main design consideration is improving the beam transmission efficiency. In this note, a novel energy degrader made of B4C/graphite composite (BGC) is studied regarding its material fabrication, improved beam transmission efficiency, energy degradation, emittance growth, and secondary-neutron yield using the Geant4 Monte Carlo software. Moreover, the thermal properties of the BGC degrader are analyzed. Finally, for a degrader with 40% boron content, the emittance after the degrader decreases by 5.5% and the transmission efficiency after the final collimator increases by 15.9% at 70 MeV compared with a pure-graphite degrader.

12.
J Forensic Leg Med ; 67: 7-14, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31352160

RESUMO

INTRODUCTION: Effectiveness and safety assessment for kinetic energy (KE) bullets is of importance, considering numerous reports about excessive damage cases of KE bullets in recent years. Early study of KE impacting targets mainly focused on threshold penetration issue, but did not involve cavity evolution of target and energy transfer. The paper aimed at analyzing cavity evolution and energy transfer during rubber bullet impacting skin-fat-muscle model. METHOD: In the ballistic experiment, skin-fat-muscle model was built including cowhide, paraffin gel and gelatin, respectively simulating skin, fat and muscle. 16 mm spherical rubber bullets were fired at a range of velocities (71 m/s-134 m/s) to skin-fat-muscle model. There were totally 7 valid impacts. Cavity evolution and cowhide deformation were captured by a high-speed camera. RESULT AND DISCUSSION: Experiment result indicates that cavity shape evolution can be divided into 3 stages: parabola stage, arc stage, and bowl stage. The cavity shape evolution at different velocities follows a similar changing rule. Cavity depth firstly increases and then decreases with time. Cavity width gradually increases with time and the rate at which the cavity width grows decreases with time. The maximum cavity depth and cavity width at the same moment increase linearly with impacting velocity. When bullet impacts on the model, deformation occurs on the cowhide, paraffin gel and gelatin. Kinetic energy of bullet gradually transfers into kinetic energy of cowhide, strain energy of cowhide, absorbing energy of soft tissue (paraffin gel and gelatin). Energy transfer analysis result of 134 m/s demonstrates rubber bullet kinetic energy mainly transfers into cowhide strain energy and absorbing energy of paraffin gel and gelatin. Moreover, cowhide strain energy firstly increases and then decreases with time.


Assuntos
Transferência de Energia , Balística Forense , Modelos Biológicos , Borracha , Gelatina , Humanos , Cinética , Parafina , Pele
13.
PLoS One ; 14(7): e0219284, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31283776

RESUMO

BACKGROUND: Currently, there are many studies on the application of the 3D pseudocontinuous arterial spin-labeled (3D-pcASL) perfusion MRI technique for adult brain examinations, but few studies exist on the application of the technique for child brain examinations. PURPOSE: To explore the application of a 3D-pcASL perfusion MRI scan combined with postlabeling delay (PLD) for assessing neonatal hypoxic-ischemic encephalopathy (HIE). MATERIALS AND METHODS: Two-hundred neonates diagnosed with neonatal HIE were equally divided into five groups (40/group): 0- to <24-hour-old HIE group, 1- to <3-day-old HIE group, 3- to <7-day-old HIE group, 7- to <15-day-old HIE group and 15- to 28-day-old HIE group; 200 healthy neonates were equivalently divided. All 10 groups received a conventional and a 3D-pcASL perfusion MRI scan. For groups <3 days old, PLD values for the 3D-pcASL cerebral perfusion MRI scan were preset at 1025 ms; in all other groups, PLD values were preset at 1525 ms. CBF values for the 3D-pcASL cerebral perfusion MRI were compared between the HIE and corresponding control groups to determine the distinguishing characteristics of CBF values in HIE neonates. RESULTS: On the 3D-pcASL cerebral perfusion MRI scan, in the 1- to <3-day-old groups, HIE neonate CBF values were higher than those of controls in all brain regions (excluding the frontal lobe); in the 0- to <24-hour-old and 3- to <7-day-old groups, HIE neonate CBF values were lower than those of corresponding controls in all brain regions; in the 7- to <15-day-old and 15- to 28-day-old groups, there were no significant differences in the CBF values between groups in any brain regions. CONCLUSIONS: The 3D-pcASL perfusion MRI scan combined with a PLD can assist in the early diagnosis of neonatal HIE, as this method more comprehensively reflects the HIE pathological process.

14.
Appl Microbiol Biotechnol ; 103(15): 6119-6128, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31165224

RESUMO

Biocatalytic reduction catalyzed by aldo-keto reductases (AKRs) is a valuable approach for asymmetric synthesis of chiral alcohols. In this study, four novel aldo-keto reductases with significant activity and stereoselectivity toward a variety of α-keto esters and halogen-substituted acetophenones were identified by genome mining. Through analysis of the crystal structure and multiple-sequence alignment of the starting AKR YvgN from Bacillus subtilis, residues F25 and W113 were proposed as the key positions that might control the stereoselectivity of YvgN. F25S and F25S/W113F variants of YvgN were able to improve its activity and stereoselectivity toward some α-keto ester compounds and halogen-substituted acetophenone derivatives. In addition, similar enhancement of catalytic activity and stereoselectivity was also found in the other three AKRs with corresponding mutations of starting YvgN.


Assuntos
Acetofenonas/metabolismo , Aldo-Ceto Redutases/metabolismo , Bacillus subtilis/enzimologia , Ésteres/metabolismo , Aldo-Ceto Redutases/química , Aldo-Ceto Redutases/genética , Bacillus subtilis/genética , Sítios de Ligação , Biologia Computacional , Cristalografia por Raios X , Alinhamento de Sequência , Especificidade por Substrato
15.
Nat Genet ; 51(7): 1106-1112, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31182810

RESUMO

Head or ear blight, mainly caused by Fusarium species, can devastate almost all staple cereal crops (particularly wheat), resulting in great economic loss and imposing health threats on both human beings and livestock1-3. However, achievement in breeding for highly resistant cultivars is still not satisfactory. Here, we isolated the major-effect wheat quantitative trait locus, Qfhs.njau-3B, which confers head blight resistance, and showed that it is the same as the previously designated Fhb1. Fhb1 results from a rare deletion involving the 3' exon of the histidine-rich calcium-binding-protein gene on chromosome 3BS. Both wheat and Arabidopsis transformed with the Fhb1 sequence showed enhanced resistance to Fusarium graminearum spread. The translation products of this gene's homologs among plants are well conserved and might be essential for plant growth and development. Fhb1 could be useful not only for curbing Fusarium head blight in grain crops but also for improving other plants vulnerable to Fusarium species.


Assuntos
Cálcio/metabolismo , Resistência à Doença/genética , Fusarium/fisiologia , Histidina/química , Mutação , Doenças das Plantas/genética , Proteínas de Plantas/genética , Triticum/genética , Mapeamento Cromossômico , Cromossomos de Plantas , Doenças das Plantas/microbiologia , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/microbiologia , Triticum/microbiologia
16.
J Control Release ; 304: 75-89, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31054992

RESUMO

Poly(lactide-co-glycolide) (PLGA) has been used in many injectable, long-acting depot formulations. Despite frequent use of PLGA, however, its characterization has been limited to measuring its molecular weight, lactide:glycolide (L:G) ratio, and end-group. These conventional methods are not adequate for characterization of unique PLGA polymers, such as branched PLGA. Glucose-initiated PLGA (Glu-PLGA) has been used in Sandostatin® LAR Depot (octreotide acetate for injectable suspension) approved by the U.S. Food and Drug Administration (FDA) in 1998. Glu-PLGA is a branched (also known as star-shaped) polymer and determining its properties has been challenging. It is necessary to develop methods that can determine and characterize the branching parameters of Glu-PLGA. Such characterization is important not only for the quality control of formulations, but also for developing generic parenteral formulations that are required to have the same excipients in the same amount (qualitative/quantitative (Q1/Q2) sameness) as their Reference Listed Drug (RLD). In this study, an analytical technique was developed and validated using a series of branched-PLGA standards, and it was used to determine the branching parameters of Glu-PLGA extracted from Sandostatin LAR, as well as Glu-PLGAs obtained from three different manufacturers. The analytical technique was based on gel-permeation-chromatography with quadruple detection systems (GPC-4D). GPC-4D enabled characterization of Glu-PLGA in its concentration, absolute molecular weight, hydrodynamic radius and intrinsic viscosity. The plot of the branch units per molecule as a function of molar mass provides a unique profile of each branched PLGA. The Mark-Houwink plots were also used to distinguish different Glu-PLGAs. These ensemble identification methods indicate that the branch units of Glu-PLGAs extracted from Sandostatin LAR range from 2 (i.e., linear) at the lower end of the molecular weight to <4 for the majority (94%) of Glu-PLGA.

17.
AAPS J ; 21(3): 51, 2019 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-30972562

RESUMO

Existing dissolution chambers have relatively large volume compared to the size of the periodontal pocket. A small volume dissolution method that simulates the physiological release environment for periodontal drug delivery is needed. The objectives were to construct a small, more physiologically relevant, dissolution chamber and investigate the properties of the new dissolution chamber for the assessment of sustained drug release systems in periodontal delivery. Flow-through dissolution chambers were constructed using three-dimensional (3D) printing. Drug release experiments were performed using the dissolution chamber and a commercially available long-acting periodontal insert product, PerioChip®. Similar experiments were performed under more traditional larger volume bulk solution conditions for comparison. Computer simulations and experimental results showed that drug clearance from the dissolution chamber was fast compared to drug release from the periodontal product. Drug clearance from the flow-through dissolution chamber and drug release from the sustained release product in the chamber were related to the dissolution medium flow rate and chamber volume. Drug release in the flow-through chamber was slower than that observed in bulk solution, but approached it when the medium flow rate increased. The presence of trypsin in the dissolution medium enhanced drug release from the product. A flow-through dissolution system was constructed that could evaluate drug release from a sustained release product in a small dimension environment by modifying the flow rate and composition of the dissolution medium.

18.
Front Psychiatry ; 10: 68, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30837905

RESUMO

[This corrects the article DOI: 10.3389/fpsyt.2018.00278.].

19.
Drug Dev Ind Pharm ; 45(2): 314-322, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30372644

RESUMO

OBJECTIVE: The objective was to evaluate the influencing factors in the fabrication of gelatin matrix (gelatin chips) for drug delivery. The attributes affecting drug release characteristics of the gelatin products were examined. SIGNIFICANCE: Understanding the attributes that affect drug release from gelatin matrix could provide the knowledge base for the development, manufacturing, and performance evaluation of gelatin-based drug products for sustained drug delivery. METHODS: Chlorhexidine (CHX) was the model drug in the gelatin-product testing. The gelatin products were fabricated by two methods: a single-pot mixing of all the components and a two-step gelatin crosslinking followed by drug loading. Different gelatin types (Type A porcine and Type B bovine), glutaraldehyde (GTA) crosslinking conditions, glycerin concentration, and CHX concentration in drug loading and loading time were used to fabricate the products. The cumulative amounts of CHX release from the gelatin products were determined using in vitro release testing (IVRT). RESULTS: The attributes affecting CHX release from the gelatin products were gelatin type, GTA crosslinking, and CHX loading concentration. The fabrication methods (two-step method of gelatin crosslinking and drug loading by equilibration vs. direct mixing of the components) also affected CHX release. Other attributes such as glycerin and CHX loading time did not show significant effects on drug release under the conditions studied. In addition, the results in the two IVRT methods employed in this study were comparable. CONCLUSION: Gelatin products of qualitative (Q1) and quantitative (Q2) differences could lead to different drug release behaviors. Drug release was also affected by the ingredient mixing steps during gelatin chip fabrication.


Assuntos
Clorexidina/administração & dosagem , Clorexidina/química , Desinfetantes/administração & dosagem , Desinfetantes/química , Gelatina/química , Animais , Bovinos , Reagentes para Ligações Cruzadas , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Excipientes , Glutaral/química , Glicerol/química , Suínos
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