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1.
Sci Rep ; 14(1): 13974, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886360

RESUMO

The CNC (computerized numerically controlled) machines are widespread in use due to their high capability of precise manufacturing in industrial production. They have a wide range of designs depending on the working capacity in manufacturing. The associated form errors in large-capacity CNC machines during production shall be identified and corrected or eliminated. This study presents an investigation of one of the main form errors that may affect the manufacturing precision of these machines. This error type is a straightness error with both two kinds of horizontal and vertical errors. The study is carried out for a vertical turning center CNC machine type. The straightness errors are measured for the X axis at different latches in the Z direction and for the Z axis at three positions in the X direction with multi-displacement steps. Different algorithms are used in the determination of straightness errors. The X-axis has minimum horizontal straightness errors at latch Nr. 3 and minimum vertical straightness errors at latch Nr. 5. For the Z axis, the minimum values for horizontal and vertical straightness errors exist when the spindle is located 1200 mm away from the machining center to the right. The displacement steps have a significant impact on the determination of straightness errors.

2.
Sci Rep ; 13(1): 8117, 2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37208403

RESUMO

Removal of quartz from iron ore was accomplished industrially via an anionic reverse flotation technique. However, in that kind of flotation, the interaction of the flotation reagents with the components of the feed sample makes the flotation a complicated system. Thus, the selection and optimization of regent dosages at various temperatures were performed using a uniform experimental design to estimate the optimum separation efficiency. Besides, the produced data as well as the reagent system were mathematically modeled at different flotation temperatures, and the graphical user interface GUI of MATLAB was conducted. The advantage of this procedure is that the user interface displayed in real-time can be conducted by adjusting the temperature at different values to automatically control the reagent system, besides predicting the concentrate yield, total iron grade, and total iron recovery.

3.
Int J Biol Macromol ; 224: 667-675, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36280172

RESUMO

Recently, biopolymer-based structured oil has emerged to substitute saturated and trans-fats. Herein, the porous biopolymeric networks with the cellular structure were developed with cross-linked dialdehyde cellulose (DAC) and gelatin to prepare oleogels. The determination of aldehyde content in the DAC molecular chain revealed a high degree of oxidation of cellulose. The FTIR data showed the covalent cross-linking bond between the DAC and gelatin. The covalent cross-linking between DAC and gelatin promoted the composite aerogel (DG) to form a porous three-dimensional network structure with enhanced thermal stability, mechanical properties, and water stability. The DAC/gelatin composite aerogel with 5 wt% DAC (DG-5) exhibited the highest porosity (91.27 %) and lowest pore diameter (10.52 µm) with greater capillary force, resulting in a high oil absorption capacity of 11.24 g/g and oil holding capacity of 55.57 %. The DG oleogels containing 6 % thymol in the oil phase showed good antibacterial activities against Escherichia coli and Staphylococcus aureus for 24 h. This work provides a facile and promising strategy for developing oleogels by DAC/gelatin cross-linked conjugates as aerogel templates for oil structuring.


Assuntos
Gelatina , Bases de Schiff , Porosidade , Gelatina/química , Celulose/química
4.
Plants (Basel) ; 11(21)2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36365277

RESUMO

(1) Background: Hemp seeds are a source of plant-based protein, making them an appropriate supplement to a plant-based diet. The current work was focused on the preparation of the protein isolate from the hemp seeds with eco-friendly and cheap technology. Moreover, it evaluated the physicochemical and functional properties of hemp protein isolate for its potential application in food manufacturing. (2) Methods: The protein content of hemp seeds has been isolated through two main steps: (1) extraction of the protein content of an alkaline pH (10-12); (2) precipitation of the extracted protein on an acidic pH as an isoelectric point (pH = 4.5). (3) Results: The edastin protein is the most predominant protein in the protein profile with a molecular weight of 58.1 KDa beside albumin with a molecular weight of 31.5 KDa. The FTIR spectrum detected the absorption peaks of the amide I at 1750 and 1600 cm-1, which pointed to C=O stretching while N-H stretching at 1650-1580 cm-1. The peak at 3250 is found to be related to N-H stretching of the aliphatic primary amine (3400-3300 cm-1) and the N-H stretching for the secondary (II) amine appeared at 3350-3310 cm-1. The Hemp protein isolate (HPI) showed a high content of arginine (15.52 g/100 g), phenylalanine + tyrosine (9.63 g/100 g), methionine + cysteine (5.49 g/100 g), leucine + isoleucine (5.21 g/100 g), and valine (4.53 g/100 g). It contains a moderate level of threonine (3.29 g/100 g) and lysine (2.50 g/100 g) with tryptophan as the limiting amino acid (0.22 g/100 g). The HPI showed an appropriate water-and-oil holding capacity (4.5 ± 2.95 and 2.33 ± 1.88 mL/g, respectively). The foaming capacity of the HPI was increased with increasing the pH values to reach the maximum value at pH 11 (67.23 ± 3.20%). The highest emulsion ability index of the HPI was noted at pH 9 (91.3 ± 2.57 m2/g) with low stability (19.15 ± 2.03). (4) Conclusions: A strong positive correlation (r = 0.623) was shown between protein concentration and solubility. The current easy-to-use, cheap, and eco-friendly technology provides the industrial sector with a cheap protein isolate for manufacturing protein-rich diet and beverages. The HPI showed a good nutritional quality and functional properties that might be helpful in utilizing it in different food products such as beverages and bakery products.

5.
Antioxidants (Basel) ; 11(9)2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36139765

RESUMO

Plant by-products are safe, sustainable, and abundant natural antioxidant sources. Here we investigated the antioxidant activity of a mixture of lyophilized pomegranate, guava, and grape (PGG) leaves water extract (1:1:1) and examined its ability to retard the rancidity of soybean oil during accelerated storage at 65 °C for 30 days. To achieve this, we evaluated the oxidative stability of soybean oil enriched with PGG extract at 200, 400, and 800 ppm. We also compared the effect of PGG extract with butylated hydroxytoluene (BHT) (400/100 ppm) with that of only BHT (200 ppm). We observed that 8.19 and 1.78 µg/mL of the extract could scavenge 50% of DPPH• and ABTS•, respectively, indicating its enhanced antioxidant activity. Enriching soyabean oil with the extract at 800 ppm improved its oxidative stability by reducing the acid value to 1.71 mg/g and the total oxidation to 99.87 compared to 2.27 mg/g and 150.32 in the raw oil, respectively. Moreover, PGG-800 ppm inhibited oxidation by 46.07%. Similarly, PGG-400 ppm reinforced BHT (100 ppm) to provide oxidative stability as BHT (p > 0.05), with TOTOX values of 87.93 and 79.23, respectively. PGG-800 ppm and PGG/BHT mix potently inhibited the transformation of polyunsaturated fatty acids into saturated ones. Therefore, the PGG extract might be an efficient substitute for BHT (partially or totally) during industrial processes.

6.
Sci Rep ; 12(1): 11016, 2022 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-35773322

RESUMO

In the current study, a simple dry coating method was utilized to fabricate a super-hydrophobic super-magnetic powder (ZS@BIF) for oily water purification using zinc stearate (ZS) and banded iron formation (BIF). The produced composite was fully characterized as a magnetic sorbent for oily water treatment. The results of X-ray diffraction diffractometer (XRD), Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDS) and particle size analysis revealed the fabrication of homogenous hydrophobic-magnetic composite particles with core-shell structure. Contact angle and magnetic susceptibility results showed that 4 (BIF): 1 (Zs) was the ideal coverage ratio to render the core material superhydrophobic and preserve its ferromagnetic nature. The capability of the fabricated composite to sorb. n-butyl acetate, kerosene, and cyclohexane from oil-water system was evaluated. ZS@BIF composite showed a higher affinity to adsorb cyclohexane than n-butyl acetate and kerosene with a maximum adsorption capacity of about 22 g g-1 and 99.9% removal efficiency. Moreover, about 95% of the adsorbed oils could be successfully recovered (desorbed) by rotary evaporator and the regenerated ZS@BIF composite showed high recyclability over ten repeated cycles.


Assuntos
Ferro , Purificação da Água , Adsorção , Cicloexanos , Interações Hidrofóbicas e Hidrofílicas , Querosene , Fenômenos Magnéticos , Óleos , Purificação da Água/métodos
7.
Pharmaceuticals (Basel) ; 16(1)2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36678510

RESUMO

Alzheimer's disease (AD) is a devastating neurodegenerative disorder without a cure. Hence, developing an effective treatment or protective agent is crucial for public health. The present study aims to characterize orange peel extract (OPE) through in vitro and in silico studies. Furthermore, it examines the protective effect of OPE against experimentally-induced Alzheimer's disease in rats. The total phenolic and flavonoid content of OPE was 255.86 ± 1.77 and 52.06 ± 1.74 (mg/100 g), respectively. Gallic acid, the common polyphenol in OPE detected by HPLC was 3388.60 µg/100 g. OPE antioxidant IC50 was 67.90 ± 1.05, 60.48 ± 0.91, and 63.70 ± 0.30 by DPPH, ABTS and Hydroxyl radical scavenging activity methods, respectively. In vitro anti-acetylcholinesterase (AChE) IC50 was 0.87 ± 0.025 mg/mL for OPE and 2.45 ± 0.001 mg/mL for gallic acid. Molecular docking analysis for human AChE (4EY7) with donepezil, gallic acid, and acetylcholine showed binding energy ΔG values of -9.47, -3.72, and -5.69 Kcal/mol, respectively. Aluminum chloride injection (70 mg/Kg/day for 6 weeks) induced Alzheimer's-like disease in male rats. OPE (100 and 200 mg/kg/d) and gallic acid (50 mg/kg/d) were administered orally to experimental animals for 6 weeks in addition to aluminum chloride injection (as protective). OPE was found to protect against aluminum chloride-induced neuronal damage by decreasing both gene expression and activity of acetylcholinesterase (AChE) and a decrease in amyloid beta (Aß42) protein level, thiobarbituric acid-reactive substances (TBARS), and nitric oxide (NO), and increased reduced glutathione (GSH) level and activity of the antioxidant enzymes in the brain tissues. Additionally, gene expressions for amyloid precursor protein (APP) and beta secretase enzyme (BACE1) were downregulated, whereas those for presinilin-2 (PSEN2) and beta cell lymphoma-2 (BCL2) were upregulated. Furthermore, the reverse of mitochondrial alternation and restored brain ultrastructure might underlie neuronal dysfunction in AD. In conclusion, our exploration of the neuroprotective effect of OPE in vivo reveals that OPE may be helpful in ameliorating brain oxidative stress, hence protecting from Alzheimer's disease progression.

8.
J Pharm Investig ; 51(6): 735-757, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513113

RESUMO

Purpose: A novel coronavirus (COVID-19) that has not been previously identified in humans and has no specific treatment has recently spread. Treatment trials using antiviral and immune-modulating drugs such as hydroxychloroquine (HCQ) were used to control this viral outbreak however several side effects have emerged. Berberine (BER) is an alkaloid that has been reported to reveal some pharmacological properties including antioxidant and antimicrobial activities. Additionally, Zinc oxide nanoparticles (ZnO-NPs) possess potent antioxidant and anti-inflammatory properties. Therefore, this study was undertaken to estimate the efficiency of both BER and synthetic ZnO/BER complex as an anti-COVID-19 therapy. Methods: First, the ZnO/BER complex was prepared by the facile mixing method. Then in vitro studies on the two compounds were conducted including VeroE6 toxicity, anti-COVID-19 activity, determination of inhibitory activity towards papain-like proteinase (PL pro) and spike protein- and receptor- binding domain (RBD) as well as assessment of drug toxicity on RBCs. Results: The results showed that ZnO/BER complex acts as an anti-COVID-19 by inhibiting spike protein binding with angiotensin-converting enzyme II (ACE II), PL pro activity, spike protein and E protein levels, and expression of both E-gene and RNA dependent RNA polymerase (RdRp) at a concentration lower than that of BER or ZnO-NPs alone. Furthermore, ZnO/BER complex had antioxidant and antimicrobial properties where it prevents the auto oxidation of 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and the culture of lower respiratory system bacteria that affected Covid 19 patients. The ZnO/BER complex prevented as well the HCQ cytotoxic effect on both RBC and WBC (in vitro) and hepatotoxicity, nephrotoxicity and anemia that occurred after HCQ long administration in vivo. Conclusion: The ZnO/BER complex can be accounted as promising anti-COVID 19 candidate because it inhibited the virus entry, replication, and assembly. Furthermore, it could be used to treat a second bacterial infection that took place in hospitalized COVID 19 patients. Moreover, ZnO/BER complex was found to eliminate the toxicity of long-term administration of HCQ in vivo.

9.
ACS Omega ; 6(21): 13719-13727, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34095664

RESUMO

To develop a natural mineral-based electrochemical enzyme biosensor, natural molybdenite (MLN), tyrosinase (TYR), and acridine orange (AO) were coadsorbed onto a glassy carbon electrode (GCE). The developed TYR/AO/MLN-GCE-based amperometric TYR biosensor exhibited excellent performance for highly sensitive determination of catechol (linear range, 0.1-80 µM; sensitivity, 0.0315 µA/µM; LOD, 0.029 µM; response time, <4 s) with good reproducibility and good operational and storage stabilities. The electrochemical impedance spectroscopy (EIS) and quartz crystal microbalance with dissipation (QCM-D) revealed interesting roles of AO: (1) an efficient glue for enhancing the amount of the adsorbed TYR on the MLN-GCE, (2) an anchor for efficient orientation of the adsorbed TYR on the MLN-GCE, and (3) a stabilizer providing a suitable microenvironment for the adsorbed TYR on the MLN-GCE surface. This physical adsorption-based AO-coupled enzyme-modification strategy onto natural MLN would be a versatile strategy to develop cost-effective and environment-friendly natural mineral-based electrochemical biosensors and bioelectronic devices.

10.
J Pharm Investig ; 51(3): 281-296, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33688448

RESUMO

BACKGROUND: At the end of 2019, the new Coronavirus disease 2019 (COVID-19) strain causing severe acute respiratory syndrome swept the world. From November 2019 till February 2021, this virus infected nearly 104 million, with more than two million deaths and about 25 million active cases. This has prompted scientists to discover effective drugs to combat this pandemic. AREA COVERED: Drug repurposing is the magic bullet for treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). Therefore, several drugs have been investigated in silico, in vitro, as well as through human trials such as anti-SARS-CoV2 agents, or to prevent the complications resulting from the virus. In this review, the mechanisms of action of different therapeutic strategies are summarized. According to the WHO, different classes of drugs can be used, including anti-malarial, antiviral, anti-inflammatory, and anti-coagulant drugs, as well as angiotensin-converting enzyme inhibitors, antibiotics, vitamins, zinc, neutralizing antibodies, and convalescent plasma therapy. Recently, there are some vaccines which are approved against SARS-CoV2. EXPERT OPINION: A complete understanding of the structure and function of all viral proteins that play a fundamental role in viral infection, which contribute to the therapeutic intervention and the development of vaccine in order to reduce the mortality rate. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40005-021-00520-4.

11.
Arab J Sci Eng ; 46(9): 8261-8272, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33688457

RESUMO

Great efforts are now underway to control the coronavirus 2019 disease (COVID-19). Millions of people are medically examined, and their data keep piling up awaiting classification. The data are typically both incomplete and heterogeneous which hampers classical classification algorithms. Some researchers have recently modified the popular KNN algorithm as a solution, where they handle incompleteness by imputation and heterogeneity by converting categorical data into numbers. In this article, we introduce a novel KNN variant (KNNV) algorithm that provides better results as demonstrated by thorough experimental work. We employ rough set theoretic techniques to handle both incompleteness and heterogeneity, as well as to find an ideal value for K. The KNNV algorithm takes an incomplete, heterogeneous dataset, containing medical records of people, and identifies those cases with COVID-19. We use in the process two popular distance metrics, Euclidean and Mahalanobis, in an effort to widen the operational scope. The KNNV algorithm is implemented and tested on a real dataset from the Italian Society of Medical and Interventional Radiology. The experimental results show that it can efficiently and accurately classify COVID-19 cases. It is also compared to three KNN derivatives. The comparison results show that it greatly outperforms all its competitors in terms of four metrics: precision, recall, accuracy, and F-Score. The algorithm given in this article can be easily applied to classify other diseases. Moreover, its methodology can be further extended to do general classification tasks outside the medical field.

12.
Sci Rep ; 11(1): 6224, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33737634

RESUMO

In plants, Fruits and their wastes are the main sources of bioactive compounds. Currently, Annona fruits have attracted the attention of people interested in health-promoting foods due to their phytochemical content that their activities were not studied before. This study aimed to explore the potential antioxidant, antimicrobial, and in vitro anticancer activity of two cultivars Annona squamosa (Annona b. and Annona h.) seed, peel, and pulp. We also meausred phenolic, flavonoid, sulfated polysaccharide, tannins, and triterpenoids. Polyphenol identification was determined using RP-HPLC. Results of the antioxidant activity revealed that the highest activity was observed for Annona h. seed extract using DPPH and ABTS assays with IC50 6.07 ± 0.50 and 9.58 ± 0.53 µg/ml, respectively. The antimicrobial activity against various pathogenic strains revealed that the peel extracts of both Annona b. and Annona h. exhibited the best antimicrobial activity. We also assessed the IC50 values for anticancer activity in all six Annona b. and Annona h samples against four cancer cell lines colon (Caco-2), prostate (PC3), liver (HepG-2), and breast (MCF-7) using MTT assay. Annona b. and Annona h seed extracts had the lowest IC50 values for four cancer cell lines with 7.31 ± 0.03 and 15.99 ± 1.25 for PC-3 and MCF-7, respectively. Both seed extracts, Annona b. and Annona h., showed significantly down-regulated mRNA expression of Bcl-2 and up-regulated p53 in all treated cell lines. Apoptosis was evaluated using nuclear staining, flow cytometric analysis, and immunohistochemistry of the proliferation marker (Ki-67). Additional studies are required to characterize the bioactive compounds responsible for the observed activities of Annona seed and determine its mechanism as an anticancer drug.


Assuntos
Annona/química , Anti-Infecciosos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Flavonoides/farmacologia , Triterpenos/farmacologia , Anti-Infecciosos/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Antioxidantes/isolamento & purificação , Apoptose/efeitos dos fármacos , Apoptose/genética , Benzotiazóis/antagonistas & inibidores , Compostos de Bifenilo/antagonistas & inibidores , Células CACO-2 , Candida/efeitos dos fármacos , Candida/crescimento & desenvolvimento , Flavonoides/isolamento & purificação , Frutas/química , Expressão Gênica/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/crescimento & desenvolvimento , Células Hep G2 , Humanos , Concentração Inibidora 50 , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Células MCF-7 , Células PC-3 , Fenóis/isolamento & purificação , Fenóis/farmacologia , Picratos/antagonistas & inibidores , Extratos Vegetais/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Sementes/química , Ácidos Sulfônicos/antagonistas & inibidores , Taninos/isolamento & purificação , Taninos/farmacologia , Triterpenos/isolamento & purificação , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
13.
Behav Brain Res ; 372: 112004, 2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31163203

RESUMO

BACKGROUND: Alzheimer disease (AD) initially presents with cognitive decline that affects the affected individual's daily activities. Cognitive decline reversal represents an important medical need, where Phosphodiesterase-5 inhibitors (PDE-5Is) might play a role. AIM: This systematic review was performed to verify the efficacy of PDE-5Is in preventing cognitive impairment and to elucidate the underlying mechanism. METHODS: Preclinical animal studies assessing the efficacy of PDE-5Is in preventing cognitive impairment and pathological changes by measuring Aß-42 ß42 and p-Tau were included in the analysis. CAMARADES Checklist was used to assess study quality. Further, various signaling pathways in different studies were examined. RESULTS AND OUTCOMES: Data of behavioral tests were extracted and a meta-analysis was conducted. Fifteen animal trials met the inclusion criteria, and all reported the prevention of cognitive deficits by PDE-5Is in Alzheimer's disease. A significant effect of PDE-5Is in increasing the time spent in the target quadrant was reported in four of seven studies using the water maze. Four studies showed significant improvement in contextual fear memory freezing time, and three studies showed improvement in the 14 unit maze number of errors. CONCLUSIONS: Cognitive decline in preclinical AD finds tauopathy has a more impact than Aß-42. This systematic review showed that PDE-5 inhibitors might help prevent cognitive impairment in AD, and while its mechanism of action is non-related to Aß-42, it might include decrease p-Tau, increase CREB and BDNF or suppressing apoptosis and inflammation. However, the efficacy of PDE-5 inhibitors in preventing cognitive impairment remains unclear due to various limitations, such as the small number of included studies, the high risk of bias, the lack of an integrated study design, and low reporting quality.


Assuntos
Doença de Alzheimer/patologia , Disfunção Cognitiva/tratamento farmacológico , Inibidores da Fosfodiesterase 5/farmacologia , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Cognição/efeitos dos fármacos , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/metabolismo , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/prevenção & controle , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5/metabolismo , Modelos Animais de Doenças , Memória/efeitos dos fármacos , Inibidores da Fosfodiesterase 5/metabolismo , Proteínas tau/metabolismo
14.
Biomed Pharmacother ; 95: 1209-1218, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28931213

RESUMO

In metastatic breast cancer (MBC), the conventional doxorubicin (DOX) has various problems due to lack of selectivity with subsequent therapeutic failure and adverse effects. DOX- induced cardiotoxicity is a major problem that necessitates the presence of new forms to decrease the risk of associated morbidity. Nanoparticles (NPs) are considered an important approach to selectively increase drug accumulation inside tumor cells and thus decreasing the associated side effects. Tumor cells develop resistance to chemotherapeutic agents through multiple mechanisms, one of which is over expression of efflux transporters. Various NPs have been investigated to overcome efflux mediated resistance. To date, only liposomal doxorubicin (LD) and pegylated liposomal doxorubicin (PLD) have entered phase II and III clinical trials and FDA- approved for clinical use in MBC. This review addresses the effects of LD and PLD on the hematological and palmar-plantar erythrodysesthesia (PPE) in anthracycline naïve and pretreated MBC patients. For evidence, studies to be included in this review were identified through PubMed, Cochrane and Google scholar databases. The results derived from: four phase III clinical trials that compared LD with the conventional DOX in naïve MBC patients, and ten non-comparative clinical trials investigated LD and PLD as monotherapy or combination in pretreated MBC. This work confirmed the cardiac tolerability profile of LD and PLD versus DOX, while hematological and skin toxicities were more common. Other DOX-NPs in preclinical trials were discussed in a chronological order. Finally, the modern preclinical development framework for DOX includes exosomal DOX (exo-DOX). Exosomal NPs are non-toxic, non-immunogenic, and can be engineered to have high cargo loading capacity and targeting specificity. These NPs have not been investigated clinically. Our study shows that the full clinical potentiality of DOX-NPs remains to be addressed to move the field forward.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Terapia de Alvo Molecular , Nanopartículas/efeitos adversos , Animais , Doxorrubicina/farmacologia , Feminino , Humanos , Metástase Neoplásica , Resultado do Tratamento
15.
F1000Res ; 5: 223, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27583130

RESUMO

Recent improvements have been made in the treatment of hepatitis C virus (HCV) infection with the introduction of direct-acting antiviral agents (DAAs). However, despite successful viral clearance, many patients continue to have HCV-related disease progression. Therefore, new treatments must be developed to achieve viral clearance and prevent the risk of HCV-related diseases. In particular, the use of pitavastatin together with DAAs may improve the antiviral efficacy as well as decrease the progression of liver fibrosis and the incidence of HCV-related hepatocellular carcinoma. To investigate the management methods for HCV-related diseases using pitavastatin and DAAs, clinical trials should be undertaken. However, concerns have been raised about potential drug interactions between statins and DAAs. Therefore, pre-clinical trials using a replicon system, human hepatocyte-like cells, human neurons and human cardiomyocytes from human-induced pluripotent stem cells should be conducted. Based on these pre-clinical trials, an optimal direct-acting antiviral agent could be selected for combination with pitavastatin and DAAs. Following the pre-clinical trial, the combination of pitavastatin and the optimal direct-acting antiviral agent should be compared to other combinations of DAAs ( e.g., sofosbuvir and velpatasvir) according to the antiviral effect on HCV infection, HCV-related diseases and cost-effectiveness.

16.
J Crit Care ; 27(3): 315.e1-5, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21798708

RESUMO

PURPOSE: The objective of the study was to evaluate the accuracy of endoscopically directed middle meatal cultures in the diagnosis of bacterial sinusitis in intensive care unit (ICU) patients in comparison with computed tomographic (CT) scans. PATIENTS AND METHODS: The study was conducted at Alexandria University Hospitals on 51 ICU patients with occult fever and clinical signs suggestive of sinusitis. Sinus CT scans were done for all patients, and Calgi swabs were obtained from the middle meatus bilaterally under endoscopic vision using sterile endoscopes with avoidance of any contamination of the swabs. The results of middle meatal cultures were compared with the results of CT scans. RESULTS: Radiologic signs of sinusitis were bilateral in 10 patients (19.6%), unilateral in 31 patients (60.8%), and negative in 10 patients (19.6%). Middle meatal swabs yielded positive cultures on both sides in 13 patients (25.5%) and on one side in 27 patients (52.9%). On the other hand, the cultures were negative in 11 patients (21.6%). Middle meatal cultures had a sensitivity of 92.8%, a specificity of 80.0%, and an accuracy of 90.2% in comparison with CT scans. Polymicrobial colonization was more frequent than monomicrobial colonization. The organisms isolated most frequently were coagulase-negative staphylococci, Staphylococcus aureus, and Pseudomonas aeurginosa. Of 47 patients with actual or previous intubation, 38 (80.9%) had positive cultures. In addition, 92.3% of patients with unilateral positive cultures acquired sinusitis on the same side of previous intubation. CONCLUSIONS: The data of the present study indicated that endoscopically directed middle meatal cultures had high positive and negative predictive values and accurately diagnosed bacterial sinusitis and identified the causative bacteria with high sensitivity and specificity in comparison with the criterion standard CT scans. The procedure is simple, noninvasive, and can be easily performed at the bedside without discomfort or morbidity. Based on our data, the procedure can be considered as a trustworthy substitute to sinus CT scans in ICU patients especially when it is difficult to transport the patients for imaging. Computed tomographic scans can, therefore, be reserved for patients who do not respond to culture-specific antibiotherapy. A further advantage of this approach is avoidance of the cumulative effect of unnecessary radiation. The study also confirmed the role of nasogastric and nasotracheal intubation in the pathogenesis of ICU sinusitis.


Assuntos
Infecções Bacterianas/diagnóstico , Orelha Média/microbiologia , Endoscopia , Sinusite/diagnóstico , Tomografia Computadorizada por Raios X , Adulto , Idoso , Infecções Bacterianas/diagnóstico por imagem , Carga Bacteriana , Feminino , Febre de Causa Desconhecida/diagnóstico , Humanos , Unidades de Terapia Intensiva , Masculino , Sinusite Maxilar/diagnóstico , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Sinusite/diagnóstico por imagem , Manejo de Espécimes/métodos
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