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1.
J Nanobiotechnology ; 22(1): 140, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38556857

RESUMO

BACKGROUND: Herbal nanoparticles are made from natural herbs/medicinal plants, their extracts, or a combination with other nanoparticle carriers. Compared to traditional herbs, herbal nanoparticles lead to improved bioavailability, enhanced stability, and reduced toxicity. Previous research indicates that herbal medicine nanomaterials are rapidly advancing and making significant progress; however, bibliometric analysis and knowledge mapping for herbal nanoparticles are currently lacking. We performed a bibliometric analysis by retrieving publications related to herbal nanoparticles from the Web of Science Core Collection (WoSCC) database spanning from 2004 to 2023. Data processing was performed using the R package Bibliometrix, VOSviewers, and CiteSpace. RESULTS: In total, 1876 articles related to herbal nanoparticles were identified, originating from various countries, with China being the primary contributing country. The number of publications in this field increases annually. Beijing University of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, and Saveetha University in India are prominent research institutions in this domain. The Journal "International Journal of Nanomedicine" has the highest number of publications. The number of authors of these publications reached 8234, with Yan Zhao, Yue Zhang, and Huihua Qu being the most prolific authors and Yan Zhao being the most frequently cited author. "Traditional Chinese medicine," "drug delivery," and "green synthesis" are the main research focal points. Themes such as "green synthesis," "curcumin," "wound healing," "drug delivery," and "carbon dots" may represent emerging research areas. CONCLUSIONS: Our study findings assist in identifying the latest research frontiers and hot topics, providing valuable references for scholars investigating the role of nanotechnology in herbal medicine.


Assuntos
Nanopartículas , Plantas Medicinais , Humanos , China , Bibliometria , Extratos Vegetais
2.
J Environ Manage ; 357: 120725, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38554454

RESUMO

Since the electroplating industry is springing up, effective control of phosphate has attracted global concerns. In this study, a novel biosorbent (MIL-88@CS-HDG) was synthesized by loading a kind of Fe-based metal organic framework called MIL-88 into chitosan hydrogel beads and applied in deep treatment of phosphate removal in electroplating wastewater. The adsorption capacities of H2PO4- on MIL-88@CS-HDG could reach 1.1 mmol/g (corresponding to 34.1 mg P/g and 106.7 mg H2PO4-/g), which was 2.65% higher than that on single MOF powders and chitosan hydrogel beads. The H2PO4- adsorption was well described by the Freundlich isotherm model. Over 90% H2PO4- could be adsorbed at contact time of 3 h. It could keep high adsorption capacity in the pH range from 2 to 7, which had a wider pH range of application compared with pure MIL-88. Only NO3- and SO42- limited the adsorption with the reduction rate of 11.42% and 23.23%, proving it tolerated most common co-existing ions. More than 92% of phosphorus could be recovered using NaOH and NaNO3. Electrostatic attraction between Fe core and phosphorus in MIL-88@CS-HDG and ion exchange played the dominant role. The recovered MIL-88@CS-HDG remained stable and applicable in the treatment process of real electroplating wastewater even after six adsorption-regeneration cycles. Based on the removal properties and superb regenerability, MIL-88@CS-HDG is potentially applicable to practical production.


Assuntos
Quitosana , Poluentes Químicos da Água , Fosfatos , Hidrogéis , Quitosana/química , Águas Residuárias , Galvanoplastia , Fósforo , Adsorção , Poluentes Químicos da Água/química , Concentração de Íons de Hidrogênio , Cinética
3.
Int Wound J ; 21(2): e14791, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38361252

RESUMO

To assess the efficacy of moxibustion for diabetic foot, and compile the findings of randomised clinical trials. China National Knowledge Infrastructure Database, Medicine, WanFang Database, Embase, Chinese Scientific Journal Database and Web of Science were from the establishment to January, 2024 were searched. Randomised controlled trials, which evaluated the effects of moxibustion were included. A total of 12 randomised controlled trials involving 1196 patients were included. According to the pooled results of this meta-analysis, effective rate (relative risk 1.16, 95% confidence intervals, CI [1.11, 1.22]), healing time (mean difference [MD] -6.27, 95% CI [-8.68, -3.86]), wound area (MD 3.46, 95% CI [0.84, 6.09]), and ankle brachial index (MD 0.14, 95% CI [0.03, 0.24]) were statistically significant compared to the control group. This study suggests that moxibustion treatment has the potential for improving symptoms of diabetic foot. However, future in-depth research on the benefits and harms of moxibustion for the diabetic foot is needed before it can be accepted as an evidence-based treatment.


Assuntos
Pé Diabético , Moxibustão , Moxibustão/métodos , Humanos , Pé Diabético/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Cicatrização , Feminino , Pessoa de Meia-Idade , Masculino , Idoso , Adulto , Idoso de 80 Anos ou mais , China
4.
J Ethnopharmacol ; 321: 117481, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38007164

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Modified Da Chaihu decoction (MDCH) is a traditional Chinese herbal prescription that has been used in the clinic to treat type 2 diabetes (T2D). Previous studies have confirmed that MDCH improves glycemic and lipid metabolism, enhances pancreatic function, and alleviates insulin resistance in patients with T2D and diabetic rats. Evidence has demonstrated that MDCH protects pancreatic ß cells via regulating the gene expression of sirtuin 1 (SIRT1) and forkhead box protein O1 (FOXO1). However, the detailed mechanism remains unclear. AIM OF THE STUDY: Dedifferentiation of pancreatic ß cells mediated by FOXO1 has been recognized as the main pathogenesis of T2D. This study aims to investigate the therapeutic effects of MDCH on T2D in vitro and in vivo to elucidate the potential molecular mechanisms. MATERIALS AND METHODS: To predict the key targets of MDCH in treating T2D, network pharmacology methods were used. A T2D model was induced in diet-induced obese (DIO) C57BL/6 mice with a single intraperitoneal injection of streptozotocin. Glucose metabolism indicators (oral glucose tolerance test, insulin tolerance test), lipid metabolism indicators (total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol), inflammatory factors (C-reactive protein, interleukin 6, tumor necrosis factor alpha), oxidative stress indicators (total antioxidant capacity, superoxide dismutase, malondialdehyde), and hematoxylin and eosin staining were analyzed to evaluate the therapeutic effect of MDCH on T2D. Immunofluorescence staining and quantification of FOXO1, pancreatic and duodenal homeobox 1 (PDX1), NK6 homeobox 1 (NKX6.1), octamer-binding protein 4 (OCT4), neurogenin 3 (Ngn3), insulin, and SIRT1, and Western blot analysis of insulin, SIRT1, and FOXO1 were performed to investigate the mechanism by which MDCH inhibited pancreatic ß-cell dedifferentiation. RESULTS: The chemical ingredients identified in MDCH were predicted to be important for signaling pathways related to lipid metabolism and insulin resistance, including lipids in atherosclerosis, the advanced glycation end product receptor of the advanced glycation end product signaling pathway, and the FOXO signaling pathway. Experimental studies showed that MDCH improved glucose and lipid metabolism in T2D mice, alleviated inflammation and oxidative stress damage, and reduced pancreatic pathological damage. Furthermore, MDCH upregulated the expression levels of SIRT1, FOXO1, PDX1, and NKX6.1, while downregulating the expression levels of OCT4 and Ngn3, which indicated that MDCH inhibited pancreatic dedifferentiation of ß cells. CONCLUSIONS: MDCH has therapeutic effects on T2D, through regulating the SIRT1/FOXO1 signaling pathway to inhibit pancreatic ß-cell dedifferentiation, which has not been reported previously.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Células Secretoras de Insulina , Humanos , Ratos , Camundongos , Animais , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Experimental/metabolismo , Desdiferenciação Celular , Sirtuína 1/metabolismo , Farmacologia em Rede , Camundongos Endogâmicos C57BL , Insulina/metabolismo , Colesterol/metabolismo
5.
Bioresour Technol ; 390: 129842, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37820968

RESUMO

The effective control of total nitrogen (ETN) and total phosphorus (ETP) in effluent is challenging for wastewater treatment plants (WWTPs). In this work, automated machine learning (AutoML) (mean square error = 0.4200 âˆ¼ 3.8245, R2 = 0.5699 âˆ¼ 0.6219) and back propagation artificial neural network (BPANN) model (mean square error = 0.0012 âˆ¼ 6.9067, R2 = 0.4326 âˆ¼ 0.8908) were used to predict and analyze biological nutrients removal in full-scale WWTPs. Interestingly, BPANN model presented high prediction performance and general applicability for WWTPs with different biological treatment units. However, the AutoML candidate models were more interpretable, and the results showed that electricity carbon emission dominated the prediction. Meanwhile, increasing data volume and types of WWTP hardly affected the interpretable results, demonstrating its wide applicability. This study demonstrated the validity and the specific advantages of predicting ETN and ETP using H2O AutoML and BPANN model, which provided guidance on the prediction and improvement of biological nutrients removal in WWTPs.


Assuntos
Eliminação de Resíduos Líquidos , Purificação da Água , Eliminação de Resíduos Líquidos/métodos , Redes Neurais de Computação , Nitrogênio/análise , Nutrientes , Esgotos
6.
Artigo em Inglês | MEDLINE | ID: mdl-36248420

RESUMO

Introduction: IgA nephropathy (IgAN) is a common issue. In China, Abelmoschus manihot (AM) is widely used in the treatment of IgAN. However, their combined effectiveness and safety for this purpose have not yet been explored. AM is an effective medicine for treating IgAN. This meta-analysis aimed to evaluate the effectiveness of AM for IgAN. Materials and Methods: The Cochrane Library, PubMed, EMBASE, Allied and Complementary Medicine Database (AMED), Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure Database (CNKI), Chinese Science and Technique Journals Database (VIP), and the Wanfang Database were searched from their inceptions to June 2021. Random clinical trials (RCTs) comparing the effects of AM treatment in patients with IgAN were included. The study evaluated the efficacy or effectiveness of AM for IgAN and had clear outcome data, such as total effectiveness rate or proteinuria. Results: A total of 11 RCTs with 850 participants were included in this meta-analysis. The results of the meta-analysis showed that, compared with that of the conventional therapy alone, being combined with conventional treatment was significantly more effective for the total efficacy rate (OR = 4.33; 95% CI = 2.66, 7.04; P < 0.00001) and proteinuria (MD = -0.41 g/24 h; 95% CI = -0.44, -0.38; P < 0.00001) but had no effect on serum creatinine (Scr) (MD = -2.23 µmol/L; 95% CI = -5.90, 1.45; P=0.24), eGFR (MD = -0.45 mL/min·1.73 m2; 95% CI = -1.24, 2.13; P=0.60), Bun (MD = -0.22 mmol/L; 95% CI = -0.59, 0.14; P=0.23), systolic blood pressure (MD = -0.04 mmHg; 95% CI = -2.59, 2.51; P=0.98), diastolic blood pressure (MD = -0.34 mmHg, 95% CI = -1.65, 2.33; P=0.74), systolic blood pressure (MD = -0.04 mmHg, 95% CI = -2.59, 2.51; P=0.98), or serum albumin (MD = 1.70 g/L, 95% CI = -1.06, 4.45; P=0.23). Conclusions: AM provided additional benefits to proteinuria individuals with IgAN. However, due to the high clinical heterogeneity and small sample size of the included trials, future studies should conduct more rigorous RCTs on the clinical efficacy and safety of AM and RCTs with a larger sample size involving multicenters.

7.
Biomed Pharmacother ; 133: 111061, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33378964

RESUMO

QiDiTangShen granules (QDTS), a traditional Chinese herbal medicine, have been used in clinical practice for treating diabetic kidney disease for several years. In our previous study, we have demonstrated that QDTS displayed good efficacy on reducing proteinuria in mice with diabetic nephropathy (DN). However, the exact mechanism by which QDTS exerts its reno-protection remains largely unknown. To ascertain whether QDTS could target the gut microbiota-bile acid axis, the db/db mice were adopted as a mouse model of DN. After a 12-week of treatment, we found that QDTS significantly reduced urinary albumin excretion (UAE), and attenuated the pathological injuries of kidney in the db/db mice, while the body weight and blood glucose levels of those mice were not affected. In addition, we found that QDTS significantly altered the gut microbiota composition, and decreased serum levels of total bile acid (TBA) and BA profiles such as ß-muricholic acid (ß-MCA), taurocholic acid (TCA), tauro ß-muricholic acid (Tß-MCA) and deoxycholic acid (DCA). These BAs are associated with the activation of farnesoid X receptor (FXR), which is highly expressed in kidney. However, there was no significant difference between QDTS-treated and -untreated db/db mice regarding the renal expression of FXR, indicating that other mechanisms may be involved. Conclusively, our study revealed that QDTS significantly alleviated renal injuries in mice with DN. The gut microbiota-bile acid axis may be an important target for the reno-protection of QDTS in DN, but the specific mechanism merits further study.


Assuntos
Ácidos e Sais Biliares/sangue , Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Rim/efeitos dos fármacos , Animais , Biomarcadores/sangue , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/microbiologia , Nefropatias Diabéticas/patologia , Modelos Animais de Doenças , Disbiose , Fezes/microbiologia , Intestinos/microbiologia , Intestinos/patologia , Rim/metabolismo , Rim/ultraestrutura , Masculino , Proteinúria/sangue , Proteinúria/microbiologia , Proteinúria/prevenção & controle
8.
Front Pharmacol ; 11: 837, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32714182

RESUMO

Hyperlipidemia is common, and its renal toxicity has attracted a great deal of attention. Si-miao-yong-an (SMYA) is a famous ancient decoction of traditional Chinese medicine (TCM), which is still widely used in clinical treatment. In this study, we observed and explored its efficacy and mechanism in protecting renal function in an atherosclerosis model. The results showed that the serum, Cr urinal KIM-1, and NGAL were significantly decreased in SMYA group. Although SMYA failed to alleviate the lipid accumulation, decrease p-NFκB, or increase SOD in kidney tissue, the levels of ubiquitinated protein and P62 were decreased in SMYA group. What is more, a higher LC3 II level was observed in the SMYA group. In conclusion, these data indicated that SMYA decoction may protect renal function in hyperlipidemia via regulating the autophagy-mediated degradation of ubiquitinated protein.

9.
J Ren Nutr ; 30(2): 101-110, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31466888

RESUMO

OBJECTIVE: This study aimed to investigate the effect of antioxidant vitamins, including vitamins E and C, on patients with diabetes and albuminuria by conducting a meta-analysis of randomized controlled trials. DESIGN: The PubMed, Embase, CENTRAL (the Cochrane Central Register of Controlled Trials at the Cochrane Library), Web of Science, OVID, and www.clinicaltrials.gov (latest search: December 10, 2018) databases were searched. This study was limited to randomized controlled trials. Patients with diabetes and albuminuria were included regardless of diabetic type, and patients must have received treatment with vitamins C or E. RESULTS: Ten studies, representing 445 participants, were identified for analysis. Antioxidant vitamins had significant effects on serum creatinine levels (mean difference = -0.11 mg/dL, 95% confidence interval -0.19 to -0.03, P = .007) and systolic pressure (mean difference = -6.02 mm Hg, 95% confidence interval -9.65 to -2.40, P = .001) with low heterogeneity. Antioxidant vitamins had no effect on albuminuria or proteinuria, diastolic blood pressure, glucose, or lipid metabolism. CONCLUSION: This meta-analysis indicated that antioxidant vitamins can benefit kidney function and systolic blood pressure in patients with diabetes and albuminuria. Further studies with larger sample sizes and longer follow-up are needed to completely understand the effect of antioxidant vitamins in these patients.


Assuntos
Albuminúria/tratamento farmacológico , Antioxidantes/farmacologia , Diabetes Mellitus/tratamento farmacológico , Suplementos Nutricionais , Vitaminas/farmacologia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Biomed Pharmacother ; 121: 109599, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31707345

RESUMO

Diabetic nephropathy (DN) is a common but intractable diabetic microvascular complication. Tripterygium, a Chinses herb, has been proven to be effective for DN treatment. In this review, the efficacy and pharmacological mechanism of tripterygium and its extracts on DN is elucidated. Tripterygium and its extracts could effectively reduce urine protein and protect renal function. Its pharmacological mechanism involves anti-inflammation, anti-oxidation, anti-glomerulosclerosis and anti-fibrosis, which is achieved by balancing the Th1/Th2 cells, regulating macrophage infiltration, and regulating the following pathways: p38 MAPK, NF-κB, TGF-ß, Wnt/ß-catenin, Akt and Notch1. Although tripterygium and its extracts may result in some adverse effects, including liver-function damage, gastrointestinal reaction, menstrual disorders, and reproductive problems, they are considered good alternative medicines for DN if used with caution and in the proper manner.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Tripterygium , Animais , Ensaios Clínicos como Assunto/métodos , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/metabolismo , Humanos , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Resultado do Tratamento
11.
Environ Technol ; 39(2): 253-263, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28278102

RESUMO

The combined biological processes of branched water-adjustment, chemical precipitation, hydrolysis acidification, secondary sedimentation, Anoxic/Oxic and activated carbon treatment were used for chemical industrial wastewater treatment in the Taihu Lake Basin. Full-scale treatment resulted in effluent chemical oxygen demand, total nitrogen, NH3-N and total phosphorus of 35.1, 5.20, 3.10 and 0.15 mg/L, respectively, with a total removal efficiency of 91.1%, 67.1%, 70.5% and 89.3%, respectively. In this process, short-circuited organic carbon from brewery wastewater was beneficial for denitrification and second-sulfate reduction. The concentration of effluent fluoride was 6.22 mg/L, which also met the primary standard. Gas Chromatography-Mass Spectrometry analysis revealed that many types of refractory compounds were present in the inflow. Microbial community analysis performed in the summer by PCR-denaturing gradient gel electrophoresis and MiSeq demonstrated that certain special functional bacteria, such as denitrificans, phosphorus-accumulating bacteria, sulfate- and perhafnate-reducing bacteria, aromatic compound-degrading bacteria and organic fluoride-degrading bacteria, present in the bio-tanks were responsible for the acceptable specific biological pollutant reduction achieved.


Assuntos
Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/química , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Bactérias , Análise da Demanda Biológica de Oxigênio , Reatores Biológicos/microbiologia , Precipitação Química , Eletroforese em Gel de Gradiente Desnaturante , Desnitrificação , Nitrogênio , Fósforo , Esgotos/microbiologia
12.
Environ Sci Pollut Res Int ; 23(11): 10990-11001, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26903125

RESUMO

Constructed wetlands are ecosystems that use plants and microorganisms to remediate pollution in soil and water. In this study, two parallel pilot-scale vertical flow wetland and horizontal flow wetland (VF-HF) systems were implemented to investigate the treatment performance and microorganism community structure in the secondary effluent of an industrial park wastewater treatment plant (WWTP) with a loading rate of 100 mm/day near the Yangtze River in Suzhou City, East China. Removal efficiencies of 82.3, 69.8, 77.8, and 32.3 were achieved by the VF-HF systems for ammonium nitrogen (NH4 (+)-N), total nitrogen (TN), total phosphorus (TP), and chemical oxygen demand (COD), respectively. The VF system specialized in COD and NH4 (+)-N removal (73.6 and 79.2 %), whereas the HF system mainly contributed to TN removal (63.5 %). The effluents in all seasons are capable of achieving the "surface water environmental quality standard" (GB3838-2002) grade IV. In the VF system, the 16S gene and nirK gene were significantly correlated with depth, with the 16S gene showing significant correlations with the dissolved oxygen (DO) level (r = 0.954, p < 0.05), which was determined by real-time PCR and high-throughput sequencing. Many types of bacteria capable of biodegradation, including nitrifiers, denitrifiers, and polyaromatic hydrocarbon (PAH) degraders (improvement of the BOD5/COD ratio), were observed, and they contributed to approximately 90 % of the nitrogen removal in the VF-HF system.


Assuntos
Águas Residuárias , Purificação da Água/métodos , Áreas Alagadas , Biodegradação Ambiental , Análise da Demanda Biológica de Oxigênio , China , Cidades , Nitrogênio/análise , Fósforo/análise , Rios , Estações do Ano , Eliminação de Resíduos Líquidos , Águas Residuárias/análise , Microbiologia da Água , Qualidade da Água
13.
Toxicol Pathol ; 31(1): 14-21, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12597445

RESUMO

Recombinant staphylokinase (rSTAR) is a profibrinolytic agent of bacterial origin. The objective of this study was to assess the toxicity of rSTAR administered with bolus intravenous infusion in rhesus monkeys (2/sex/group) at the dosages of 0, 4, 14, and 49 mg/kg/day for 2 weeks. The clinical signs were thickening of the skin in all animals and mild hematoma formation in three dosage groups at the injection sites. There were no effects on body weight, absolute or relative organ weights, ophthalmology, or electrocardiogram. Urinalysis indicated that 2 monkeys in 14 or 49 mg/kg/day group developed proteinuria and mild hematuria. Increases in serum BUN levels (14 and 49 mg/kg/day), ALT activity, and bilirubin levels (49 mg/kg/day), and decreases in red blood cell counts, hemoglobin concentrations and Hct values (49 mg/kg/day) were observed at week 2. Significant prolongtion of APTT, PT, and TT (14 and 49 mg/kg/day), and decreases in circulating plasminogen levels (3 treatment groups) were noted. Dose-dependent increases in the titers of anti-rSTAR antibodies and neutralizing rSTAR activity were observed in the three treated groups. Increased neutralizing rSTAR activity diminished the phamacologic effects of rSTAR (ie, prolonged APTT, PT, and TT approaching baseline levels at week 2). Histopathological findings included hemorrhage, and perivascular inflammatory cell infiltration at the injection sites, heptocellular degeneration characterized as cytoplasmic eosinophilia, vacuolation and condensed nuclei (49 mg/kg/day), effusion of RBCs and plasma within some Bowman's capsules and hyaline casts within the lumen of some renal tubules in the kidneys (14 and 49 mg/day/kg), and mild to moderate megakaryocyte hypoplasia with varying levels of pyknotic nuclei at all dose levels. Immune deposits in glomeruli in the kidneys from the three treated groups were detected. These changes were reversible following a 4-week recovery period. In the present preclinical evaluation of toxicity in monkeys, rSTAR is well toleratte at doses up to 49 mg/kg/day. The toxic target organs are the liver, kidney, and bone marrow.


Assuntos
Dose Máxima Tolerável , Metaloendopeptidases/toxicidade , Ativadores de Plasminogênio/toxicidade , Proteínas Recombinantes/toxicidade , Alanina Transaminase/sangue , Animais , Formação de Anticorpos/imunologia , Contagem de Células Sanguíneas , Coagulação Sanguínea/efeitos dos fármacos , Nitrogênio da Ureia Sanguínea , Peso Corporal/efeitos dos fármacos , Medula Óssea/efeitos dos fármacos , Medula Óssea/patologia , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Eletrocardiografia , Escherichia coli/enzimologia , Olho/efeitos dos fármacos , Infusões Intravenosas , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Macaca mulatta , Tamanho do Órgão/efeitos dos fármacos , Pele/efeitos dos fármacos , Urinálise
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