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1.
BMC Pharmacol Toxicol ; 23(1): 69, 2022 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-36100946

RESUMO

BACKGROUND: Hypolipidemic agents have been shown to be helpful in the primary and secondary prevention of cardiovascular disease. Most often, statins are prescribed to treat hyperlipidemia. There are a number of statins available in the market today, but atorvastatin is the most widely prescribed. It is essential that the drugs should have the appropriate amount of active pharmaceutical ingredient and meet the necessary physical properties. The main purpose of the study was to evaluate the quality of different marketed brands of atorvastatin calcium tablets available in Saudi Arabia. METHODS: In this study, innovator product coded as (AS-1) and five generics brands (coded as AS-2 to AS-6) of atorvastatin tablets 20 mg available in Saudi Arabia were evaluated for in vitro dissolution test, weight variations, friability and hardness tests. The analysis of drug was carried out by "high-performance liquid chromatography" (HPLC) method using C18 column (4.6 × 150 mm, 5 µm). The mobile phase was consisted of acetonitrile and HPLC water (pH 2.1, adjusted with orthophosphoric acid) in ratio of 52:48 v/v, the flow rate was 1.0 ml/min. Atorvastatin was detected at a wavelength of 254 nm. RESULTS: According to the results of the dissolution study, the investigated products released more than 90% of atorvastatin in 15 min. Within 60 min, the brands AS-1, AS-3, AS-5, and AS-6 depicted nearly 100% atorvastatin release, while the brand AS-2 displayed 91.69% drug release. According to our findings, the investigated atorvastatin innovator (AS-1) and generic brands such as AS-2 to AS-6 were of good pharmaceutical quality. CONCLUSIONS: All generic brands of atorvastatin tablets available in the Saudi Arabian market met the pharmacopoeia's consistency checks such as weight variation, friability, hardness and in vitro dissolution. Hence, focusing on their in vitro release properties, it was determined that these brands could be used interchangeably.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Atorvastatina , Medicamentos Genéricos , Glicolatos , Controle de Qualidade , Arábia Saudita , Comprimidos
2.
BMC Med Genomics ; 15(1): 195, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36114500

RESUMO

BACKGROUND: Formalin-fixed, paraffin-embedded (FFPE) tissues have many advantages for identification of risk biomarkers, including wide availability and potential for extended follow-up endpoints. However, RNA derived from archival FFPE samples has limited quality. Here we identified parameters that determine which FFPE samples have the potential for successful RNA extraction, library preparation, and generation of usable RNAseq data. METHODS: We optimized library preparation protocols designed for use with FFPE samples using seven FFPE and Fresh Frozen replicate pairs, and tested optimized protocols using a study set of 130 FFPE biopsies from women with benign breast disease. Metrics from RNA extraction and preparation procedures were collected and compared with bioinformatics sequencing summary statistics. Finally, a decision tree model was built to learn the relationship between pre-sequencing lab metrics and qc pass/fail status as determined by bioinformatics metrics. RESULTS: Samples that failed bioinformatics qc tended to have low median sample-wise correlation within the cohort (Spearman correlation < 0.75), low number of reads mapped to gene regions (< 25 million), or low number of detectable genes (11,400 # of detected genes with TPM > 4). The median RNA concentration and pre-capture library Qubit values for qc failed samples were 18.9 ng/ul and 2.08 ng/ul respectively, which were significantly lower than those of qc pass samples (40.8 ng/ul and 5.82 ng/ul). We built a decision tree model based on input RNA concentration, input library qubit values, and achieved an F score of 0.848 in predicting QC status (pass/fail) of FFPE samples. CONCLUSIONS: We provide a bioinformatics quality control recommendation for FFPE samples from breast tissue by evaluating bioinformatic and sample metrics. Our results suggest a minimum concentration of 25 ng/ul FFPE-extracted RNA for library preparation and 1.7 ng/ul pre-capture library output to achieve adequate RNA-seq data for downstream bioinformatics analysis.


Assuntos
Benchmarking , Biologia Computacional , Biomarcadores , Feminino , Formaldeído , Humanos , Inclusão em Parafina , Controle de Qualidade , RNA , Análise de Sequência de RNA/métodos , Fixação de Tecidos
4.
Cells ; 11(17)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36078137

RESUMO

Human umbilical cord-derived mesenchymal stem cell (UC-MSC) sheets have attracted much attention in cell therapy. However, the culture media and coating matrix used for the preparation of UC-MSC sheets have not been safe enough to comply with current clinical drug standards. Moreover, the UC-MSC sheet preservation systems developed before did not comply with Good Manufacturing Practice (GMP) regulations. In this study, the culture medium and coating matrix were developed for UC-MSC sheet production to comply with clinical drug standards. Additionally, the GMP-compliant preservation solution and method for the UC-MSC sheet were developed. Then, quality standards of the UC-MSC sheet were formulated according to national and international regulations for drugs. Finally, the production process of UC-MSC sheets on a large scale was standardized, and three batches of trial production were conducted and tested to meet the established quality standards. This research provides the possibility for clinical trials of UC-MSC sheet products in the development stage of new drugs and lays the foundation for industrial large-scale production after the new drug is launched.


Assuntos
Células-Tronco Mesenquimais , Cordão Umbilical , Meios de Cultura , Humanos , Controle de Qualidade
5.
Artigo em Inglês | MEDLINE | ID: mdl-36078495

RESUMO

The region of Puno, in Peru, is described as a region with some health conditions that may be associated with the water quality, such as a high index of anemia or cases of acute diarrhea in children. This study aimed at monitoring the drinking water quality of the city of Ilave, in Peru, and determining possible correlations between physical-chemical and microbiological parameters, and the water distribution conditions, such as the period of water availability. Physical-chemical parameters (turbidity, residual chlorine, temperature, conductivity, and pH), microbiological parameters (presence of coliforms), and heavy metals (Zn, Mn, Ni, Fe, and Cu) were determined. All the parameters quantified were within the maximum permissible limits according to Peruvian regulations, except for residual chlorine, which was, for all the treated water samples, below the recommended value of 0.5 mg/L. Coliforms that should be absent from drinking water were detected in all the household samples. These results demonstrate the need for the inclusion of additional steps of re-chlorination along the distribution system to guarantee the maintenance of residual levels of chlorine that assure the microbiological quality of water. The quality of the drinking water was not observed to correlate with the period of water availability.


Assuntos
Água Potável , Poluentes Químicos da Água , Criança , Cloro/análise , Humanos , Peru/epidemiologia , Controle de Qualidade , Microbiologia da Água , Poluentes Químicos da Água/análise , Qualidade da Água , Abastecimento de Água
6.
Annu Int Conf IEEE Eng Med Biol Soc ; 2022: 3870-3873, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36085718

RESUMO

Optical coherence tomography is widely used to provide high resolution images from retina. During data acquisition, several artifacts may be associated with OCT images which clearly remove information of retinal layers and degrade the quality of images. Manual assessment of the acquired OCT images is hard and time consuming. Therefore, an automatic quality control step is necessary to detect poor images for next decisions of eliminating them and even re-scanning. In this study, a novel automatic quality control methodology is proposed for early assessment of the OCT images quality by employing stochastic differential equations (SDE). In this method α-stable nature of OCT images is represented by applying a fractional Laplacian filter and parameters of the obtained α-stable are fed to an SVM to automatically detect high quality vs poor quality images. The simulation results on a large dataset of normal and abnormal OCT images show that proposed method has outstanding performance in detection of poor vs high quality images. The methodology is applicable to the image quality assessment of other OCT scanning devices as well. Clinical Relevance- Automatic quality control assessment of retinal OCT images provides reliable data for diagnosis of retinal and systematic diseases in clinical applications.


Assuntos
Retina , Tomografia de Coerência Óptica , Artefatos , Simulação por Computador , Controle de Qualidade , Retina/diagnóstico por imagem
7.
Annu Int Conf IEEE Eng Med Biol Soc ; 2022: 588-593, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36085930

RESUMO

Manual assessment of fragments during the pro-cessing of pathology specimens is critical to ensure that the material available for slide analysis matches that captured during grossing without losing valuable material during this process. However, this step is still performed manually, resulting in lost time and delays in making the complete case available for evaluation by the pathologist. To overcome this limitation, we developed an autonomous system that can detect and count the number of fragments contained on each slide. We applied and compared two different methods: conventional machine learning methods and deep convolutional network methods. For conventional machine learning methods, we tested a two-stage approach with a supervised classifier followed by unsupervised hierarchical clustering. In addition, Fast R-CNN and YOLOv5, two state-of-the-art deep learning models for detection, were used and compared. All experiments were performed on a dataset comprising 1276 images of colorec-tal biopsy and polypectomy specimens manually labeled for fragment/set detection. The best results were obtained with the YOLOv5 architecture with a map@0.5 of 0.977 for fragment/set detection.


Assuntos
Aprendizado de Máquina , Redes Neurais de Computação , Biópsia , Controle de Qualidade
8.
Annu Int Conf IEEE Eng Med Biol Soc ; 2022: 1049-1052, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36086027

RESUMO

The overwhelming need to improve the quality of complex data structures in healthcare is more important than ever. Although data quality has been the point of interest in many studies, none of them has focused on the development of quantitative and explainable methods for data imputation. In this work, we propose a "smart" imputation workflow to address missing data across complex data structures in the context of in silico clinical trials. AI algorithms were utilized to produce high-quality virtual patient profiles. A search algorithm was then developed to extract the best virtual patient profiles through the definition of a profile matching score (PMS). A case study was conducted, where the real dataset was randomly contaminated with multiple missing values (e.g., 10 to 50%). In total, 10000 virtual patient profiles with less than 0.02 Kullback-Leibler (KL) divergence were produced to estimate the PMS distribution. The best generator achieved the lowest average squared absolute difference (0.4) and average correlation difference (0.02) with the real dataset highlighting its increased effectiveness for data imputation across complex clinical data structures.


Assuntos
Algoritmos , Humanos , Controle de Qualidade
9.
Rinsho Ketsueki ; 63(8): 928-933, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-36058864

RESUMO

After a long-term hospitalization following a ski accident in college, I decided to choose a specialty in hematology and oncology. In graduate school, after learning the basics of biostatistics and the methodology of clinical trials, I had the opportunity to go through a series of clinical trial tasks, from launching to writing a clinical study report, which led to the study drug approval. This has greatly motivated me to be actively involved in this field. At the Dana-Farber Cancer Institute, I studied outcomes research under a supervisor, and at a time of difficulty, my good role model, Dr. Stephanie Lee, had urged me, saying, "That which does not kill you makes you stronger." Subsequently, I devoted myself to the establishment of a data center for a Japanese pediatric leukemia/lymphoma study group, currently a subcommittee of the Japan Children's Cancer Group, and to develop an academic research organization for conducting ICH-GCP-compliant international clinical trials, including the originally developed EDC system. I was struggling in balancing work and parenting. Fortunately, I was supported by my encounters with respectable people.


Assuntos
Hematologia , Oncologistas , Criança , Aprovação de Drogas , Humanos , Oncologia , Controle de Qualidade
10.
Zhongguo Zhong Yao Za Zhi ; 47(16): 4395-4402, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36046868

RESUMO

This study established the fingerprint and combined it with chemical pattern recognition to evaluate the quality of Atractylodes chinensis samples from different producing areas and then employed the quantitative analysis of multi-components by single marker(QAMS) method to verify the feasibility and applicability of the established method in the quality evaluation of A. chinensis. The fingerprints of A. chinensis samples were constructed via high performance liquid chromatography(HPLC) to evaluate the inter-batch consistency. With the quality control component atractylodin as the internal reference, the relative correction factors(RCFs) were established for atractylenolide Ⅰ, atractylenolide Ⅲ, and ß-eudesmol and the content of the four components was calculated. The external standard method was used to verify the accuracy of QAMS method. The quality of A. chinensis was further evaluated by similarity analysis, clustering analysis, and principal component analysis. The fingerprints of 13 batches of samples were calibrated with 21 common peaks, and 4 common peaks were identified with the similarities all above 0.9. The RCFs established with atractylodin as the internal reference represented good reproducibility under different experimental conditions. Specifically, the RCFs of atractylenolide Ⅰ, atractylenolide Ⅲ, and ß-eudesmol in A. chinensis were 2.091, 4.253, and 6.010, respectively. QAMS and ESM showed no significant difference in the results, indicating that the QAMS method established in this study was stable and reliable. Thus, HPLC fingerprint combined with QAMS can be used for the quality evaluation of A. chinensis, providing a basis for comprehensive and rapid quality evaluation of A. chinensis.


Assuntos
Atractylodes , Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Controle de Qualidade , Reprodutibilidade dos Testes
11.
Zhongguo Zhong Yao Za Zhi ; 47(16): 4536-4544, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36046883

RESUMO

As China is implementing the policy of "Announcement on Ending the Pilot Work of Chinese medicine formula gra-nules", the standard of Chinese medicine formula granules has gradually become the focus of industry development. Up to now, 196 national drug standards for Chinese medicine formula granules have been published by China, which guaranteed the production quality of Chinese medicine formula granules. However, there are still several challenges such as the rational application of national drug standards and the enrichment and improvement of varieties. The basic content of the issued national drug standards for Chinese medicine formula granules was analyzed and compared with the quality standard provisions of the corresponding decoction pieces in the Chinese Pharmacopoeia(2020 edition) in this paper. This paper discussed the main characteristics of paste-forming rate of each medicinal raw materials, "quantity-quality" transformation, equivalent ratio, and so on, and clarified the characteristics of the national standard for Chinese medicine formula granules. This paper provided references for achieving the unified quality control and meeting the overall quality requirements of Chinese medicine formula granules.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , China , Controle de Qualidade
12.
Zhongguo Zhong Yao Za Zhi ; 47(15): 3994-4006, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36046888

RESUMO

The detection method of characteristic spectrum for reference samples was established by preparing 15 batches of the reference samples of Huagan Decoction, and the peak attribution and the similarity range in the characteristic spectrum were clarified. The ranges of paste-forming rate, content, and transfer rate of the index components including geniposide, paeonol, and paeoniflorin were analyzed. The key quality attribute of the reference samples of Huagan Decoction was defined. The results showed that the 15 batches of the reference samples of Huagan Decoction had good similarities in the characteristic spectrum, which were all higher than 0.9. According to the information of characteristic peak, there were 18 characteristic peaks in the whole prescription, including seven common characteristic peaks from green tangerine peel and dried tangerine peel, four characteristic peaks from tree peony root bark(three of them were common characteristic peaks from tree peony root bark and red peony root), five characteristic peaks from cape jasmine fruit, one characteristic peak from paniculate bolbostemma, and one characteristic peak from oriental waterplantain rhizome.The paste-forming rate of the 15 batches of reference samples was 14.73%-18.83%. The content of geniposide was 1.68%-2.87%, with the average transfer rate of 70.05%±11.13%. The content of paeonol was 0.10%-0.16%, with the average transfer rate of 9.38%±1.78%. The content of paeoniflorin was 1.94%-2.74%, with the average transfer rate of 36.69%±4.63%. This study analyzed the quality value transfer of the reference samples of Huagan Decoction by the evaluation mode of combining the characteristic spectrum, the paste-forming rate, and the content of index components. The findings of this study initially established a stable and feasible standard decoction evaluation method and provided references for the quality control and the subsequent development of relevant preparations of Huagan Decoction.


Assuntos
Medicamentos de Ervas Chinesas , Paeonia , Cromatografia Líquida de Alta Pressão , Prescrições , Controle de Qualidade
13.
Zhongguo Zhong Yao Za Zhi ; 47(15): 4007-4014, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36046889

RESUMO

A comprehensive quality control method was established to provide references for quality control and evaluation of substance benchmarks of Danggui Sini Decoction(DSD). The HPLC separation was performed on a Kromasil 100 C-8 column(4.6 mm×250 mm, 5 µm) with acetonitrile(A)-0.05% phosphoric acid in water(B) as mobile phase in a gradient elution mode at the flow rate of 1 mL·min~(-1). The column temperature was 25 ℃ and the detection wavelength was set at 275 nm. Under these conditions, the content of seven components, including paeoniflorin, liquiritin, cinnamic acid, cinnamaldehyde, ammonium glycyrrhetate, ligustilide, and asarinin was simultaneously determined. Under the same chromatographic conditions, the HPLC fingerprint method for analysis of 15 batches of DSD was established. The content determination of aristolochic acid I, using the same test solution as the content determination item, was performed on an ACQUITY UPLC BEH C_(18) column(2.1 mm×50 mm, 1.7 µm) with methanol(A)-water(including 0.1% formic acid and 5 mmol·L~(-1) ammonium formate)(B) as the mobile phase in a gradient elution mode at the flow rate of 0.4 mL·min~(-1) and the column temperature of 40 ℃ by LC-MS/MS. The MS conditions included electrospray ionization(ESI) as an ion source, positive ion ionization, selective reaction monitoring(SRM), the parent ion of 359.3, and the daughter ion of 297.8. The results of the methodological investigation all met the requirements of content determination/fingerprint determination. As a result, the content ranges of paeoniflorin, liquiritin, cinnamic acid, cinnamaldehyde, ammonium glycyrrhetate, ligustilide, and asarinin were 5.419 8-11.267 3, 1.023-3.669 8, 0.145 6-0.444 1, 0.099 1-0.321 9, 3.159 1-7.731 9, 0.146 4-0.471 7, and 0.237 3-0.401 0 mg·g~(-1), respectively. Twenty-two common peaks were selected and 10 of them were identified by the comparison with the reference substances. The fingerprint similarity of 15 batches of DSD was in the range of 0.91-0.996 and the content of aristolochic acid I in DSD was 300.03-638.13 ng·g~(-1). The method established in this study is reliable and easy to operate and has great practical value, which can be used for overall quality control of substance benchmarks for DSD.


Assuntos
Compostos de Amônio , Medicamentos de Ervas Chinesas , Benchmarking , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida , Medicamentos de Ervas Chinesas/química , Controle de Qualidade , Espectrometria de Massas em Tandem/métodos , Água
14.
Zhongguo Zhong Yao Za Zhi ; 47(15): 4015-4024, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36046890

RESUMO

In this study, the critical quality attributes of Wuzhuyu Decoction reference sample were explored by using characteristic chromatogram, index component content and dry extract rate as indexes.The dissemination relationship of quantity value between medicinal materials-decoction pieces-reference sample was investigated to preliminarily formulate the quality standard of the reference sample.The characteristic chromatogram of 15 batches of Wuzhuyu Decoction was established by high performance liquid chromatography(HPLC) and the similarity analysis was conducted.Common peaks were demarcated and assigned to medicinal materials.Moreover, quantitative determination of limonin, evodiamine, rutaecarpine and ginsenoside Rb_1 of Wuzhuyu Decoction were performed.The dissemination of quantity value was explored combined with dry extract rate, similarity of characteristic chromatogram and transfer rate of index component content.A total of 18 common peaks were identified in the corresponding materials of Wuzhuyu Decoction reference sample, with the similarity of characteristic chromatogram greater than 0.9, and Fructus Evodiae, Radix Ginseng, Rhizoma Zingiberis Recens and Fructus Jujubae contributed 9, 5, 8 and 2 chromatographic peaks, respectively.The index component content of corresponding materials and the transfer rates of medicinal materials-decoction pieces and decoction pieces-reference sample of different batches of Wuzhuyu Decoction reference sample were as follows: the content of limonin was 0.16%-0.51%, and the transfer rates were 83.66%-115.60% and 38.54%-54.58%, respectively; the content of evodiamine was 0.01%-0.11%, the transfer rated were 80.80%-116.15% and 3.23%-12.93%, respectively; the content of rutaecarpine was 0.01%-0.05%, the transfer rates were 84.33%-134.53% and 5.72%-21.24%, respectively; the content of ginsenoside Rb_1 was 0.06%-0.11%, and the transfer rates were 90.00%-96.92% and 32.45%-67.24%, respectively.The dry extract rate of the whole prescription was 22.58%-29.89%.In this experiment, the dissemination of quantity value of Wuzhuyu Decoction reference sample was analyzed by the combination of characteristic chromatogram, index component content and dry extract rate.A scientific and stable quality evaluation method of the reference sample was preliminarily established, which provided basis for the subsequent development of Wuzhuyu Decoction and the quality control of related preparations.


Assuntos
Medicamentos de Ervas Chinesas , Ginsenosídeos , Limoninas , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Ginsenosídeos/análise , Limoninas/análise , Controle de Qualidade
15.
Zhongguo Zhong Yao Za Zhi ; 47(15): 4256-4260, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36046916

RESUMO

Traditional Chinese medicine(TCM) preparations in medical institutions are an important source of research and development(R&D) of TCM new drug. With years of usage in therapy, these preparations' safety and effectiveness have generally been validated in clinic. However, there are still a few disadvantages in TCM new medicine development, such as similar prescriptions, excessive prescription ingredients, too broad clinical orientation, lack of solid clinical data, issue in pharmaceutical quality control, and intellectual property disputes. Nowadays, the Three-Combined Evaluation System has strengthened policy support for the new TCM R&D. In order to improve the success rate of TCM R&D, due to the difficulties within, this paper proposes the process of transforming TCM preparations in medical institutions into new TCM and advocates the evaluation for druggability based on Human Use Experience(HUE). The potencial preparations ought to follow traditional Chinese Medical theory, sufficient HUE data in indication, syndrome type of TCM, target population, usage, dosage, and course of treatment are required. Particular attention should be paid to the source, evolution, and improvement process of prescription, and evaluate the dosage, ingredients, and herb resources of prescription. To assess the feasibility of mass production, it is necessary to determine whether the pharmaceutical process is mostly consistent with the new drug and whether the dosage form is reasonable. By summarizing the clinical application of the preparations, the whole picture of its clinical application would be reveal as much as possible. It is beneficial to evaluate its clinical value and R&D prospect. In consideration of the lack of clinical safety data of preparations, safety profile needs to be collected according to the prescription. The quality of clinical data needs to be evaluated by focusing on the integrity and accuracy of data to reduce bias and confusion. Significant care should be paid to intellectual property protection to avoid legal disputes.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Prescrições , Controle de Qualidade , Síndrome
16.
Clin Lab ; 68(9)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36125135

RESUMO

BACKGROUND: Quality control (QC) of analytical measurement is a stage used for the evaluation of whether the measurement method is appropriate to the standards required for patient care. QC encompasses internal (IQC) and external laboratory content (EQC). Measurement uncertainty (MU) is an important issue that expresses each analyte's measurement. Autoanalyzer's, calibrators, and control materials of analytes, reagents, measures contribute to MU. The aim of this study was to calculate the measurement uncertainty of nineteen immunoassay analytes in the biochemistry laboratory and to evaluate the compatibility of these measurements with the analytical quality targets derived from different biological variations. METHODS: In the study, Cobas 6000 Modular Analysis Series (Roche Diagnostics, USA) autoanalyzer was used. IQC data of the analytes between August 2017 and January 2018 were used together with the monthly EQC data of June 2017 to January 2018. NORDTEST guideline was used to calculate the MU. "Desirable" analytical quality goals of each analyte with Fraser's formula were calculated and evaluated the limits from EuBIVAS (The European Biological Variation Study) and Ricos's biological variation databases. RESULTS: MU of fT4 was seen to be higher than TEa (Total Allowable Analytical Error)Ricos in our study. MU of fT4 was seen to be lower than TEaEuBIVAS (MUfT4: 9.20%, TEaRicos: 8.00%; TEaEuBIVAS: 9.92%). CONCLUSIONS: The analytical quality performances of the analytes included in the study turned out to be sufficient in our laboratory.


Assuntos
Laboratórios , Humanos , Imunoensaio/métodos , Controle de Qualidade , Incerteza
17.
Sci Rep ; 12(1): 14862, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050356

RESUMO

The twin-arginine translocation (Tat) pathway involves an inbuilt quality control (QC) system that synchronizes the proofreading of substrate protein folding with lipid bilayer transport. However, the molecular details of this QC mechanism remain poorly understood. Here, we hypothesized that the conformational state of Tat substrates is directly sensed by the TatB component of the bacterial Tat translocase. In support of this hypothesis, several TatB variants were observed to form functional translocases in vivo that had compromised QC activity as evidenced by the uncharacteristic export of several misfolded protein substrates. These variants each possessed cytoplasmic membrane-extrinsic domains that were either truncated or mutated in the vicinity of a conserved, highly flexible α-helical domain. In vitro folding experiments revealed that the TatB membrane-extrinsic domain behaved like a general molecular chaperone, transiently binding to highly structured, partially unfolded intermediates of a model protein, citrate synthase, in a manner that prevented its irreversible aggregation and stabilized the active species. Collectively, these results suggest that the Tat translocase may use chaperone-like client recognition to monitor the conformational status of its substrates.


Assuntos
Proteínas de Escherichia coli , Arginina/metabolismo , Proteínas de Transporte/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Humanos , Proteínas de Membrana Transportadoras/metabolismo , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Dobramento de Proteína , Sinais Direcionadores de Proteínas , Transporte Proteico , Controle de Qualidade
18.
Biomed Pharmacother ; 153: 113470, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076496

RESUMO

Traditional Chinese medicine (TCM) fundamentally different from Western medicine, has been widely investigated using various approaches and made great contributions to the prevention and treatment of human diseases. In recent years, research about quality control, safety evaluations, and determination of mechanisms of TCMs focused on the single-cell and molecular levels and applied to a new type of analysis method imaging technology. Cellular-or molecular-based imaging can directly get spatial distribution information and relative content of biomolecules on the tissue and mainly contribute to the progress of our understanding of various diseases, diagnosis, and drug delivery, to assess noninvasively disease-specific in cellular and molecular levels of living models in vivo. Will provide new tools to treat patients with TCM, and accelerates new drug discovery from Chinese herbal medicine. Therefore, this article reviews the imaging technology and its application in the research of TCM against cerebrovascular and neurological diseases.


Assuntos
Medicamentos de Ervas Chinesas , Doenças do Sistema Nervoso , Descoberta de Drogas , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Medicina Tradicional Chinesa/métodos , Doenças do Sistema Nervoso/tratamento farmacológico , Controle de Qualidade
19.
J Pharm Biomed Anal ; 220: 115016, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36030753

RESUMO

Polysaccharides from natural medicines, being safe and effective natural mixtures, show great potential to be developed into botanical drugs. However, there is yet one polysaccharide-based case that has fulfilled the Botanical Guidance definition of a botanical drug product. One of the reasons is the analytical methods commonly used for qualitative and quantitative analysis of polysaccharides fall far behind the quality control criteria of botanical drugs. Here we systemically reviewed the recent advances in analytical methods. A critical evaluation of the strength and weaknesses of these methods was provided, together with possible solutions to the difficulties. Mass spectrometry with or without robust chromatographic separation was increasingly employed. And scientists have made significant progress in simplifying polysaccharide quantification by depolymerizing it into oligosaccharides. This oligosaccharides-based strategy is promising for qualitative and quantitative analysis of polysaccharides. And continuous efforts are still needed to develop a standardized quality control method that is specific, accurate, repeatable, and applicable for analyzing individual components in natural medicine formulas.


Assuntos
Medicamentos de Ervas Chinesas , Polissacarídeos , Medicamentos de Ervas Chinesas/química , Espectrometria de Massas/métodos , Oligossacarídeos , Polissacarídeos/química , Controle de Qualidade
20.
J Pharm Biomed Anal ; 220: 115018, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36030755

RESUMO

The early intervention is essential, and later development cannot compensate for this initial generation of an antibody drug. Especially for sequence variants (SVs), should cause concern during the early bioprocess development. The advancement of bioprocess development is paralleled by development of state-of-the-art analytical methods that will provide further information. In the present study, a mass spectrometry (MS)-based multi-attribute method (MAM) was used to simultaneously monitor the SVs and other quality attributes in the early bioprocess development of ofatumumab, and a sequence variant (SV) was detected by a subunit-based MAM. Subsequently, the variant was further identified by MS/MS and confirmed by adding a synthetic peptide. Furthermore, the content of the SV was detected via DNA sequencing. The levels of the variant (T175A mutant) in the light chain were demonstrate to be nearly consistent at the DNA and protein levels, suggesting that the mutation may have negligible effect on both the transcriptional and translational levels. Collectively, these results indicate that broad-spectrum, rapid, and accurate platform such as MS-based MAM should be implemented to quality control for the early development of therapeutic proteins, it will also be important to establish an effective and integrated MAM to control SVs during therapeutic proteins development.


Assuntos
Anticorpos Monoclonais , Espectrometria de Massas em Tandem , Anticorpos Monoclonais/química , DNA , Mutação , Controle de Qualidade
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