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1.
Eur J Pharm Biopharm ; 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33248266

RESUMO

Polymeric nanoparticles (NPs) are produced using bio-compatible and bio-degradable materials such as PLGA (Poly(lactic-co-glycolic acid)). This technology provides a valuable tool to deliver molecules to the subcellular level with a relatively low risk of cytotoxicity. However their use in the field of reproductive biotechnology is not yet scientifically substantiated. The aim of the present study was to test if PLGA NPs can be taken-up by cumulus-enclosed oocytes as a first step towards potential oocyte-targeted applications to enhance oocyte quality and fertility. We conducted a series of experiments using bovine in vitro oocyte maturation as a model to study FITC-conjugated PLGA internalization (using laser-scanning confocal microscopy) and the effect of some important physical (particle size) and chemical (conjugation with PEG) modifications. We show evidence that PLGA NPs can be taken-up by cumulus cells and to a less extent by the enclosed oocytes regardless of the NP size. The NP transfer to the oocyte appear to be transcellular (via cumulus cells and transzonal projections) and paracellular (via zona pellucida). The PLGA NPs were detected in the vicinity of the oocyte as quick as 2h post-exposure in a protein-free medium and did not compromise cumulus cell viability nor subsequent early embryo development or embryo quality. These results suggest that PLGA NPs may have promising applications as carriers for drug or molecule delivery targeting cumulus cells and oocytes.

2.
Eur J Pharm Biopharm ; 2020 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-33238191

RESUMO

The upper respiratory tract (URT) is the main entrance point for many viral and bacterial pathogens, and URT infections are among the most common infections in the world. Recent evidences by our own group and others imply the importance of lactobacilli as gatekeepers of a healthy URT. However, the benefits of putting health-promoting microbes or potential probiotics, such as these URT lactobacilli, in function of URT disease control and prevention is underestimated, among others because of the absence of adequate formulation modalities. Therefore, this study entails important aspects in probiotic nasal spray development with a novel URT-derived probiotic strain by spray drying. We report quantitative and qualitative analysis of several spray-dried formulations, i.e. powders for reconstitution, based on disaccharide or sugar alcohol combinations with a polymer, including their long-term stability. Four formulations with the highest survival of >109 (Colony Forming Units) CFU/g after 28 weeks were further examined upon reconstitution which confirmed sufficiency of one bottle/dosage form during 7 days and rheological properties of shear-thinning. Tests also demonstrated maintained viability and cell morphology overall upon spraying through a nasal spray bottle in all 4 formulations. Lastly, application suitability in terms of high adherence to Calu-3 cells and antimicrobial activity against common URT pathogens was demonstrated and was not impacted neither by powder production process nor by spraying of reconstituted powder through a nasal spray device.

3.
AAPS PharmSciTech ; 21(7): 275, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033847

RESUMO

In the published manuscript, co-author Sarah Hendrickx name was misspelled and co-author Guy Caljon's last and first names were inadvertently switched.

4.
Nanomedicine (Lond) ; 15(27): 2671-2688, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33112210

RESUMO

Aim: This research aims to identify important formulation parameters for the enhancement of nanoparticle (NP) uptake and decreasing the cytotoxicity in macrophages. Materials & methods: Fluorescent poly(lactic-co-glycolic acid) (PLGA) nanocarriers were characterized for size distributions, zeta potential and encapsulation efficiency. Incubation time, size class, PLGA derivative and chitosan derivative were assessed for uptake kinetics and cell viability. Results: The major determining factor for enhancing cellular uptake were chitosan coatings, combined with acid-terminated PLGA and small NP size. Moreover, cytotoxicity was more favorable for small, chitosan glutamate-coated, acid-terminated PLGA NPs compared with its plain chitosan-coated counterparts. Conclusion: Chitosan glutamate has been shown to be a valuable alternative coating material for acid-terminated PLGA NPs to efficiently and safely target macrophages.

5.
Sci Rep ; 10(1): 17268, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33057006

RESUMO

Dry eye syndrome (DES), a multifactorial disorder which leads to ocular discomfort, visual disturbance and tear film instability, has a rising prevalence and limited treatment options. In this study, a newly developed trypsin-like serine protease inhibitor (UAMC-00050) in a tear drop formulation was evaluated to treat ocular inflammation. A surgical animal model of dry eye was employed to investigate the potential of UAMC-00050 on dry eye pathology. Animals treated with UAMC-00050 displayed a significant reduction in ocular surface damage after evaluation with sodium fluorescein, compared to untreated, vehicle treated and cyclosporine-treated animals. The concentrations of IL-1α and TNF-α were also significantly reduced in tear fluid from UAMC-00050-treated rats. Additionally, inflammatory cell infiltration in the palpebral conjunctiva (CD3 and CD45), was substantially reduced. An accumulation of pro-MMP-9 and a decrease in active MMP-9 were found in tear fluid from animals treated with UAMC-00050, suggesting that trypsin-like serine proteases play a role in activating MMP-9 in ocular inflammation in this animal model. Comparative qRT-PCR analyses on ocular tissue indicated the upregulation of tryptase, urokinase plasminogen activator receptor (uPAR) and protease-activated receptor 2 (PAR2). The developed UAMC-00050 formulation was stable up to 6 months at room temperature in the absence of light, non-irritating and sterile with compatible pH and osmolarity. These results provide a proof-of-concept for the in vivo modifying potential of UAMC-00050 on dry eye pathology and suggest a central role of trypsin-like serine proteases and PAR2 in dry eye derived ocular inflammation.

6.
Pharmaceutics ; 12(9)2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32937773

RESUMO

BACKGROUND: Intestinal nematode infections are usually treated with benzimidazole drugs, but the emergence of resistance to these drugs has led to an increasing demand of new anthelmintic strategies. A new microemulsion formulation (ME) consisting of an Artemisia absinthium extract with proven nematocidal efficacy was previously developed. The aim of our study is to implement a D-optimal mixture design methodology to increase the amount of a silica material (loaded with this ME) in a tablet formulation, considering its tensile strength and disintegration time. METHODS: 16 experiments or combinations of the 6 tablet components (loaded silica, microcrystalline cellulose, polyvinylpyrrolidone, croscarmellose, Syloid® 244 FP and magnesium stearate) were assessed. Tensile strength and disintegration time models were developed, and an optimization process was carried out. RESULTS: Tensile strength was improved by increasing the polyvinylpyrrolidone content, while croscarmellose decreased the disintegration time. The optimized powder mixture contains 49.7% w/w of the loaded silica material. A compression force of 12 kN was applied to the powder mixture to form tablets with a tensile strength of 2.0 MPa and a disintegration time of 3.8 min. CONCLUSIONS: Our results show that D-optimal mixture designs provide a promising approach to formulate liquid-loaded silica materials.

7.
Int J Pharm ; 588: 119755, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32783980

RESUMO

The human body harbours a large variety of microbial communities. It is already well-known that these communities play an important role in human health. Therefore, microbial imbalances can be responsible for several health disorders by different mechanisms. In recent years, probiotic bacteria have been increasingly applied to restore imbalances and stimulate microbiome functions such as immune modulation. Tablets are the dosage form of choice for oral probiotics. Nevertheless, a probiotic tablet with a sufficient amount of viable cells remains a challenge due to the stress of the compression process. Recent research demonstrated that the applied pressure and tableting properties play an important role in the survival of Lacticaseibacillus rhamnosus GG during direct compression. This study focused on the importance of the cell surface molecules in the protection of this prototype probiotic strain during direct compression. Spray-dried powders of L. rhamnosus GG and its exopolysaccharide-deficient mutant and lipoteichoic acid mutant were blended with two different filler-binders and compacted at various compression pressures. Under each tableting condition, the survival rate and tableting properties were analysed. The results demonstrated that the cell surface molecules play an important role in the behaviour of L. rhamnosus GG during direct compression. Specifically, the long, galactose-rich exopolysaccharides of L. rhamnosus served a protective shield during tablet production, promoting the survival rate of this probiotic strain. The D-alanylation of the lipoteichoic acids plays also an important role. When the D-alanyl ester content was completely absent, the survival rate was less affected by the tableting properties. Moreover, this research revealed that the sensitivity to the tableting properties is species and strain dependent.

8.
AAPS PharmSciTech ; 21(5): 185, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32632542

RESUMO

The present study aimed to develop, characterize and evaluate the amphotericin B-loaded nanostructured lipid carriers (AmB-NLCs) for topical treatment of cutaneous leishmaniasis (CL) and vulvovaginal candidiasis (VVC). AmB-NLCs were characterized for particle size, zeta potential, encapsulation efficiency and surface morphology. Prepared NLCs were also characterized for in vitro drug release, ex vivo skin permeation and deposition before evaluating their in vitro and in vivo efficacy. Cytotoxicity of NLCs was assessed on MRC-5 cells, whereas skin irritation potential was evaluated in vivo using rats. Significant accumulation of drug in to the skin supported the topical application potential of drug-loaded NLCs. Encapsulation of AmB in NLCs resulted in enhanced in vitro potency against promastigotes and intracellular amastigotes of L. major JISH 118 (IC50 ± SEM = 0.02 ± 0.1 µM for both) compared with free drug (IC50 ± SEM = 0.15 ± 0.2 & 0.14 ± 0.0, respectively). Similar improved potency of AmB-NLCs was also observed for other Leishmania and fungal strains compared with drug solution. Topical application of AmB-NLCs on L. major-infected BALB/c mice caused a significant reduction in parasite burden per mg of lesion (65 × 108 ± 13) compared with the control group (> 167.8 × 108 ± 11). Topical AmB-NLCs gel demonstrated superior efficacy in the vaginal C. albicans rat model for VVC as compared with plain AmB gel. Moreover, results of in vitro cytotoxicity assay and in vivo skin irritation test confirmed AmB-NLCs to be non-toxic and safe for topical use. In conclusion, NLCs may have promising potential as carrier for topical treatment of various conditions of skin and mucosa.


Assuntos
Anfotericina B/administração & dosagem , Candidíase Vulvovaginal/tratamento farmacológico , Leishmaniose Cutânea/tratamento farmacológico , Nanoestruturas/administração & dosagem , Administração Tópica , Animais , Candidíase Vulvovaginal/metabolismo , Portadores de Fármacos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Feminino , Géis/metabolismo , Humanos , Lipídeos/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , Tamanho da Partícula , Ratos , Pele/metabolismo , Absorção Cutânea
9.
Sci Rep ; 10(1): 7976, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32409699

RESUMO

Vulvovaginal candidosis (VVC) is a common condition with severe symptoms and high recurrence rates. Probiotic lactobacilli are explored as alternatives to azole treatments. Although the vaginal microbiota is generally not depleted in lactobacilli during VVC, studies indicate that the functionality and antimicrobial activity of the lactobacilli is impaired. We selected three strains from the Lactobacillus genus complex (L. rhamnosus GG, L. pentosus KCA1 and L. plantarum WCFS1) based on in vitro evaluation and formulated them in a gel for vaginal application. This gel was evaluated in 20 patients suffering from acute VVC, who were followed for four weeks including a 10-day treatment period. The microbiome was assessed through 16S rRNA (bacteria) and internal transcribed spacer (ITS; fungi) amplicon sequencing, supplemented with quantitative PCR, culture and microscopy for Candida evaluation. 45% of women did not require rescue medication (3×200 mg fluconazole), implying an improvement of their symptoms. These women showed similar end concentrations of fungi as women treated with fluconazole. Moreover, fluconazole appeared to reduce numbers of endogenous lactobacilli. Our study points towards important aspects for future selection of lactobacilli for probiotic use in VVC and the need to investigate possible negative influences of azoles on the vaginal bacterial community.

10.
Eur J Clin Microbiol Infect Dis ; 39(8): 1551-1558, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32356027

RESUMO

In vitro studies suggest that certain probiotic bacterial strains have potential activity against opportunistic infections such as Candida. There are few in vivo trials using probiotics as a single treatment for acute Candida vulvovaginitis (CV). In this open-label, proof-of-concept study, selected Lactobacillus strains were tested in women with acute Candida vaginitis. Twenty women diagnosed with proven, symptomatic CV were instructed to administer a vaginal probiotic gel with L. plantarum YUN-V2.0, L. pentosus YUN-V1.0 and L. rhamnosus YUN-S1.0 for 10 consecutive days. Vaginal rinsing fluid, vaginal culture swab and vaginal smear for fresh wet-mount microscopy were collected before and 7, 14 and 28 days after start of treatment. On average, participating women were 39 years old and had an history of 5 vaginal infections of which 95% was CV. Nine women (45%) completed the study without the need of rescue medication. Women who needed rescue treatment experienced twice as much Candida infections in the past. A negative correlation was found between the clinical composite score and the time to use rescue medication (R2 = 0.127). Seventy-four per cent of participants found the study gel comfortable to use, and 42% of all women would use the tested gel again for this indication. Forty-five per cent of women were treated successfully for acute CV with a novel vaginal gel containing 3 selected Lactobacillus strains. Patients needing rescue treatment were suffering from more severe and long-standing disease. These results warrant for further testing of this new product, especially of its potential in cases with mild to moderate severity, as an adjuvant to antimycotics or as a preventive measure in women with recurrent vulvovaginal candidosis.

11.
Cell Rep ; 31(8): 107674, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32460009

RESUMO

Although an increasing number of beneficial microbiome members are characterized for the human gut and vagina, beneficial microbes are underexplored for the human upper respiratory tract (URT). In this study, we demonstrate that taxa from the beneficial Lactobacillus genus complex are more prevalent in the healthy URT than in patients with chronic rhinosinusitis (CRS). Several URT-specific isolates are cultured, characterized, and further explored for their genetic and functional properties related to adaptation to the URT. Catalase genes are found in the identified lactobacilli, which is a unique feature within this mostly facultative anaerobic genus. Moreover, one of our isolated strains, Lactobacillus casei AMBR2, contains fimbriae that enable strong adherence to URT epithelium, inhibit the growth and virulence of several URT pathogens, and successfully colonize nasal epithelium of healthy volunteers. This study thus demonstrates that specific lactobacilli are adapted to the URT and could have a beneficial keystone function in this habitat.

12.
Eur J Pharm Biopharm ; 145: 7-11, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31605741

RESUMO

The usefulness, the high production rate and the cost effectiveness make tablets the dosage form of choice for oral probiotics. Nevertheless, probiotic bacteria undergo a lot of mechanical stress during tableting which causes damage to their cell wall and membrane and other bio-active components. This can lead to an inactivation of the probiotic bacteria and therefore in a failure of the probiotic therapy. To obtain a tablet with a sufficient amount of viable cells, research on the influence of formulation and process parameters on bacterial survival is essential. This study aimed to decipher tableting properties of the probiotic powder blends that have a major impact on survival rates. The powder blends consisted of the prototype probiotic strain Lactobacillus rhamnosus GG, a filler-binder and a suitable amount of lubricant. They were manufactured by direct compression at different compression pressures and tableting speeds. The tableting properties were analysed in detail by a 3-D modelling technique, which characterized normalized time, pressure and displacement simultaneously. The results of the 3-D modelling demonstrated the significant effect of the pressure plasticity (e) and the angle of rotation (ω) on the viability of L. rhamnosus GG during direct compression.


Assuntos
Força Compressiva/efeitos dos fármacos , Probióticos/química , Comprimidos/química , Química Farmacêutica/métodos , Excipientes/química , Lactobacillus rhamnosus/química , Pós/química , Pressão
13.
Clin Microbiol Rev ; 32(4)2019 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-31270125

RESUMO

The microbiota of the upper respiratory tract (URT) protects the host from bacterial pathogenic colonization by competing for adherence to epithelial cells and by immune response regulation that includes the activation of antimicrobial and (anti-)inflammatory components. However, environmental or host factors can modify the microbiota to an unstable community that predisposes the host to infection or inflammation. One of the URT diseases most often encountered in children is otitis media (OM). The role of pathogenic bacteria like Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the pathogenesis of OM is well documented. Results from next-generation-sequencing (NGS) studies reveal other bacterial taxa involved in OM, such as Turicella and Alloiococcus Such studies can also identify bacterial taxa that are potentially protective against URT infections, whose beneficial action needs to be substantiated in relevant experimental models and clinical trials. Of note, lactic acid bacteria (LAB) are members of the URT microbiota and associated with a URT ecosystem that is deemed healthy, based on NGS and some experimental and clinical studies. These observations have formed the basis of this review, in which we describe the current knowledge of the molecular and clinical potential of LAB in the URT, which is currently underexplored in microbiome and probiotic research.


Assuntos
Microbiota , Otite Média/microbiologia , Otite Média/terapia , Probióticos/uso terapêutico , Humanos
14.
Eur J Pharm Biopharm ; 141: 172-179, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31150810

RESUMO

Mangiferin, a poorly water soluble compound, was processed via a dry amorphisation technique (ball milling) in combination with mesoporous silica to enhance the solubility of mangiferin. The amorphous samples were prepared by mixing 1:1 (w/w) Syloid® XDP 3050 silica-mangiferin mixtures using a planetary mono mill at different milling speeds and milling times according to a 32 full factorial experimental design. The prepared samples were characterized for dissolution profile, particle size distribution using laser diffraction particle size analyzer, thermal characteristics using DSC, crystalline characteristics using XRD and molecular interactions using FTIR and ss-NMR. The samples were tested for stability at stress conditions (40 °C/75%RH) for up to 6 months in open and closed containers. To improve stability of the samples, mixtures of 1:1:2 mangiferin-polymer (Soluplus or HPMC)-silica samples were also prepared and analyzed. Amorphisation of mangiferin is possible using dry amorphisation by ball milling with mesoporous silica in a short amount of time. The amorphisation rate of the samples improved with the energy input of the milling process. The samples prepared with high energy input resulted in amorphous samples and showed a better stability at the stress conditions for up to 3 months. Solubility of these samples increased from 0.32 to 0.50 mg/ml and the particle size decreased from 35.5 µm to around 7 µm. The spectral analysis suggest presence of interactions between the silica material and the compound. The amorphous stability was improved with addition of polymer, even though the solubility of the samples was lower.


Assuntos
Dióxido de Silício/química , Solubilidade/efeitos dos fármacos , Água/química , Xantonas/química , Varredura Diferencial de Calorimetria/métodos , Química Farmacêutica/métodos , Tamanho da Partícula , Polietilenoglicóis/química , Polímeros/química , Polivinil/química
15.
Microb Biotechnol ; 12(5): 849-855, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31225698

RESUMO

The preservation of the viability of microorganisms in probiotic formulations is the most important parameter ensuring the adequate concentration of live microorganisms at the time of administration. The formulation and processing techniques used to produce these probiotic formulations can influence the preservation of the microbial viability. However, it is also required that the bacteria maintain their key probiotic capacities during processing, formulation and shelf life. In this study, we investigated the impact of spray-drying on different cell wall properties of the model probiotic strain Lactobacillus rhamnosus GG, including its adherence to intestinal epithelial cells. The dltD gene knock-out mutant, L. rhamnosus GG CMPG5540, displaying modified cell wall lipoteichoic acids, showed significantly increased colony-forming units after spray-drying and subsequent storage under standard conditions compared to wild-type L. rhamnosus GG. In contrast, disruption of the biosynthesis of exopolysaccharides or pili expression did not impact survival. However, spray-drying did significantly affect the adherence capacity of L. rhamnosus GG. Scanning electron microscopy confirmed that the pili, key surface factors for adherence to intestinal cells and mucus, were sheared off during the spray-drying process. These data thus highlight that both the functionality and viability of probiotics should be assessed during the spray-drying process and subsequent storage.


Assuntos
Desidratação , Dessecação/métodos , Lactobacillus rhamnosus/fisiologia , Viabilidade Microbiana , Preservação Biológica/métodos , Aderência Bacteriana , Contagem de Colônia Microbiana , Células Epiteliais/microbiologia , Probióticos
16.
Water Sci Technol ; 79(4): 645-655, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30975931

RESUMO

In this study, the influence of the anaerobic mixed feeding rate on granule stability and reactor performance in a conventional sequencing batch reactor (C-SBR) was investigated while treating various industrial wastewaters. A laboratory-scale SBR fed with malting wastewater rich in phosphorus was operated for approximately 250 days, which was divided into two periods: (I) mixed pulse feed and (II) prolonged mixed feed. Initially, no bio-P activity was observed. However, by lowering the feeding rate biological P-removal was rapidly established and no effect on the aerobic granular sludge (AGS) characteristics was observed. Additionally, to investigate the effect of the mixed feeding rate when treating an industrial effluent with low phosphorus content, i.e. brewery wastewater, a laboratory-scale reactor was operated for approximately 400 days applying different mixed feeding rates. Morphological and molecular analysis indicated that a low substrate concentration promoted the enrichment of anaerobic carbon storing filaments when fed with brewery wastewater. Findings suggest that a prolonged mixed feeding regime can be used as a tool to easily establish bio-P removal in a C-SBR system for the treatment of phosphorus-rich wastewaters. It should however be considered that under P-limiting conditions, enrichment of poly-P storing filaments may occur, possibly due to their higher substrate affinity under anaerobic conditions.


Assuntos
Reatores Biológicos , Fósforo/análise , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/análise , Resíduos Industriais/análise , Esgotos , Águas Residuárias
17.
Sci Rep ; 9(1): 2028, 2019 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-30765714

RESUMO

Cecropia species are traditionally used in Latin American folk medicine and are available as food supplements with little information warranting their quality. The optimum conditions for the extraction of chlorogenic acid (CA), total flavonoids (TF) and flavonolignans (FL) from leaves of Cecropia species were determined using a fractional factorial design (FFD) and a central composite design (CCD). A reversed-phase high-performance liquid chromatographic method coupled to a diode array detector (HPLC-DAD) was validated for the quantification of CA, TF and FL, following the ICH guidelines. Quantitative and Principal Component Analysis (PCA) was also performed. The extraction-optimization methodology enabled us developing an appropriate extraction process with a time-efficient execution of experiments. The experimental values agreed with those predicted, thus indicating suitability of the proposed model. The validation parameters for all chemical markers of the quantification method were satisfactory. The results revealed that the method had excellent selectivity, linearity, precision (repeatability and intermediate precision were below than 2 and 5%, respectively) and accuracy (98-102%). The limits of detection and quantification were at nanogram per milliliter (ng/mL) level. In conclusion, the simultaneous quantification of chemical markers using the proposed method is an appropriate approach for species discrimination and quality evaluation of Cecropia sp.


Assuntos
Cecropia (Planta)/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Polifenóis/isolamento & purificação , Cromatografia de Fase Reversa/métodos , Flavonoides/química , Extratos Vegetais/química , Folhas de Planta/química , Polifenóis/análise , Ondas Ultrassônicas
18.
Bioresour Technol ; 280: 151-157, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30771569

RESUMO

Treatment of rapidly varying wastewaters in anaerobic/aerobic aerobic granular sludge (AGS) systems remains problematic. This study investigated AGS formation and the impact of varying COD and phosphorus concentrations on an enhanced biological phosphorus removal (EBPR) AGS SBR with a conductivity based anaerobic and OUR based aerobic dynamically controlled step. Phase 1 investigated the development of AGS. Phase 2 examined the flexibility of the dynamic control strategy and AGS efficiency while rapidly altering the influent composition. AGS was formed successfully in phase 1: the DV50 increased to 285 µm, and the SVI5 and SVI30 decreased to 51 and 40 ml/g respectively. In phase 2 the effluent COD and PO4-P concentration remained low at respectively 58 ±â€¯27 mg/L and 0.53 ±â€¯0.77 mg/L. With an anaerobic DOC uptake efficiency of 98.4 ±â€¯0.9%.


Assuntos
Fósforo/metabolismo , Esgotos , Reatores Biológicos
19.
Anal Bioanal Chem ; 411(19): 4383-4399, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30706073

RESUMO

Since the introduction of liquid chromatography tandem mass spectrometry in clinical laboratories, folate analysis has shifted from microbiological or protein-binding assays to chromatographic methods. Now, it is possible to sensitively and selectively determine several folate species in clinical samples where only a total folate content could be quantified using a microbiological or a binding assay. Although several chromatographic methods have been developed, validated, and published, interlaboratory variability limits the comparability of the results. In this review, we provide an overview of the latest strategies for sampling, sample treatment, and analysis and how these may influence the final analytical result. Among the variables covered are the effect of pH, temperature, and storage and the use of antioxidants and anticoagulants on analyte stability. In addition, we highlight the importance of correct assay calibration and the use of (labeled) certified reference materials in order to obtain correct and comparable results among different laboratories. Graphical abstract ᅟ.


Assuntos
Cromatografia Líquida/métodos , Ácido Fólico/sangue , Espectrometria de Massas em Tandem/métodos , Humanos , Concentração de Íons de Hidrogênio , Limite de Detecção , Temperatura
20.
Eur J Pharm Biopharm ; 135: 36-43, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30543948

RESUMO

Tablets are increasingly explored as dosage form for oral probiotics, especially for applications such as pharyngitis and dental health. In such tablets, the dry form increases the stability and the shelf life of the product. In addition, the probiotic cells are entrapped in the tablet matrix, which protects them against the environmental factors in the human body. However, the development of a probiotic tablet with an adequate number of viable cells remains a challenge due to the stress of the compression process. The adverse conditions during production can damage the cells, which leads to a loss of viability and a failure of the therapy. This study aimed to investigate the effect of the compression behavior of filler-binders on the survival of Lactobacillus rhamnosus GG during tablet production. The probiotic tablets were manufactured by direct compression of a freeze-dried mixture of the model L. rhamnosus GG, a filler-binder and a suitable amount of lubricant. The compression behavior was determined by analyzing Heckel and force-displacement plots. The results demonstrated that the elastic recovery of the filler-binder during decompression played a protective role in bacterial survival, reducing the compression stress during manufacturing. Consequently, the bacterial cells were less damaged, which resulted in a higher survival rate and a better stability during long-term storage. In conclusion, the elastic recovery of a filler-binder showed to be an important key in safeguarding probiotic cells during direct compression and storage.


Assuntos
Química Farmacêutica/métodos , Excipientes/química , Lactobacillus rhamnosus/fisiologia , Viabilidade Microbiana , Probióticos/administração & dosagem , Elasticidade , Liofilização , Pressão , Probióticos/química , Comprimidos , Fatores de Tempo
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