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1.
Environ Monit Assess ; 194(2): 66, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34993647

RESUMO

Insecticides are effective against economic pests, but these pose serious threats to the environment and ecosystem components such as natural enemies. Resistance risk assessment forecasts insecticide resistance development in target pests and non-target biological control agents under special conditions. Field-collected Chrysoperla carnea was selected with two Insect Growth Regulators (IGRs) viz. cyromazine and methoxyfenozide for 15 generations to determine the resistance development potential of this natural enemy. Selection to cyromazine and methoxyfenozide induced 759.08-fold and 3531.67-fold resistance with realized heritability of 0.37 and 0.62 in C. carnea, respectively, suggesting higher additive genetic variations in first half of selection (h2 = 0.46 for cyromazine and h2 = 0.75 for methoxyfenozide) than in second half (h2 = 0.18 and 0.25, respectively). Estimates of projected rate of resistance development indicate C. carnea will take only 6 to 2 generations at h2 = 0.37, 8 to 2 at h2 = 0.27, and 5 to 2 at h2 = 0.27, at constant slope = 1.81 for a tenfold increase in cyromazine resistance. At h2 = 0.37, 3-1, and 10-8 generations would be needed for this increase in LC50 if slope = 0.82 and 2.82, respectively. Similarly, it may take 3 to 1 generations at h2 = 0.62 and 0.72, but 4 to 1 at h2 = 0.52, at constant slope = 1.62, for a tenfold increase in methoxyfenozide resistance. On the same h2 = 0.62, 1-0, and 5-1 generations would be required for increase if slope = 0.62 and 2.62, respectively. Selection and resistance to both insecticides induced an insignificant difference in the sex ratio of C. carnea. These results confirm that this natural enemy has tremendous potential for resistance development under selection pressure.


Assuntos
Resistência a Inseticidas , Inseticidas , Animais , Ecossistema , Monitoramento Ambiental , Hidrazinas , Resistência a Inseticidas/genética , Inseticidas/toxicidade , Hormônios Juvenis , Larva , Medição de Risco , Triazinas
2.
Spectrochim Acta A Mol Biomol Spectrosc ; 264: 120272, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34428636

RESUMO

Hydrazine, as a toxic substance, seriously endangers human health and the environment. Based on the excellent luminescent properties and low biological toxicity of pyrene derivatives, combing with chalcone derivatives easily attacked by nucleophilic group, a pyrene derivative PCA decorated by acryloyl terminal group as fluorescent probe for hydrazine was developed. The compound shows fluorescent peak red shift and intensity enhancement with increasing solvent polarity from hexane (459 nm) to methanol (561 nm). Based on strong fluorescence emission in methanol, methanol-HEPES mixed solution was used as the solvent in the spectral recognition experiments. The probe exhibits fluorescent change from yellow fluorescence (576 nm) to blue fluorescence (393 nm) with 800-fold ratiometric fluorescence enhancement (I393nm/I576nm) after the reaction with hydrazine. The probe can recognize hydrazine in fast response rate with kinetic constant calculated being 2.7 × 10-3 s-1 and 15 min as response time. The probe also can monitor hydrazine in real water samples and various soils.


Assuntos
Chalcona , Chalconas , Corantes Fluorescentes , Humanos , Hidrazinas , Pirenos , Espectrometria de Fluorescência
3.
Support Care Cancer ; 30(1): 497-509, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34331589

RESUMO

PURPOSE: Cancer-related fatigue (CRF) is the most frequent and debilitating symptom in patients with advanced cancer. There are limited effective treatments for CRF. The objective of this prospective longitudinal study was to evaluate the change in CRF at Day 43 after treatment with combination therapy of oral Anamorelin 100 mg daily with physical activity and nutrition counseling. METHODS: In this study, patients with CRF [≤ 34 Functional Assessment of Chronic Illness Therapy-Fatigue subscales(FACIT-F)] received Anamorelin 100 mg orally daily with standardized physical activity and nutrition counseling for 43 days. Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Anorexia Cachexia(FAACT-ACS), Multidimensional Fatigue Symptom Inventory-Short Form(MFSI-SF), Patient-Reported Outcomes Measurement Information System(PROMIS-Fatigue), body composition, and physical performance tests were assessed at baseline, Day 15, 29, and 43. Frequency and type of side effects were determined by NCI CTAE 4.0.(NCT03035409). RESULTS: 28/45 (62%) of patients dosed were evaluable at Day 43. The mean, SD for FACIT-F subscale improvement from baseline was 4.89 (± 13.07), P = .058, MFSI-SF (G) - 3.46 (± 6.86), P = 0.013, PROMIS-fatigue - 4.14 (± 7.88), P = 0.010, FAACT ACS 3.48 (± 8.13), P = 0.035. Godin Liesure-Time physical activity questionnaire 7.41 (± 16.50), P = 0.038. Weight (kg) 1.81 (± 2.63), P = 0.005, and Lean Body Mass 1.54 (± 1.85), P = 0.001, IGF-1 36.50 (± 48.76), P = 0.015. There was no significant improvement in physical performance outcomes. No adverse events > grade 3 related to the study drug were reported. CONCLUSION: The use of the combination therapy was associated with improvement of CRF (FACIT-F fatigue, PROMIS-fatigue, MFSI-SF-general), activity (Godin-leisure time), anorexia (FAACT), body composition, and IGF-1 levels. Further studies using combination therapy for CRF are justified.


Assuntos
Fadiga , Neoplasias , Aconselhamento , Exercício Físico , Fadiga/tratamento farmacológico , Fadiga/etiologia , Humanos , Hidrazinas , Estudos Longitudinais , Neoplasias/complicações , Oligopeptídeos , Estudos Prospectivos
4.
J Hazard Mater ; 422: 126891, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34416692

RESUMO

As a tremendously noxious and extensively utilized chemical reagent, hydrazine (N2H4) has become a serious threat to ecosystem and human health. Thus, it is desirable to exploit an efficient method for real-time tracking of hydrazine. Here, a novel ratiometric fluorescent probe PBQ-AB for hydrazine was rationally constructed from isolongifolanone. This probe displayed an extremely large Stokes shift of 230 nm and could selectively recognize hydrazine in the presence of other competitive species within an extremely short time ( 40 s). PBQ-AB also displayed some fascinating merits in the detection of hydrazine, including low detection limit (48 nM), wide pH range (5-12), excellent photostability (>240 min), and well-resolved emission wavelength shift (148 nm). Moreover, this probe was utilized to fabricate a ready-to-use electrospinning nanofibrous membrane for convenient detection of hydrazine vapor by virtue of smartphone. Furthermore, PBQ-AB was capable of determining hydrazine contaminant in environmental soil and water samples. Additionally, its favorable performance for detecting hydrazine was successfully demonstrated in live HeLa cells as well as in live Arabidopsis thaliana tissues, manifesting its promising application for labeling hydrazine in living systems. Therefore, we believed that this probe has great potential in environmental analysis and health supervision.


Assuntos
Ecossistema , Corantes Fluorescentes , Células HeLa , Humanos , Hidrazinas , Solo
5.
J Colloid Interface Sci ; 606(Pt 2): 1239-1248, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492462

RESUMO

Cuprous oxide (Cu2O) is a p-type semiconductor with excellent catalytic activity and stability that has gained much attention because it is non-toxic, abundant, and inexpensive. Porous carbon materials have large specific surface areas, which offer abundant electroactive sites, enhance the electrical conductivity of materials, and prevent the aggregation of Cu2O nanocubes. In this study, a composite with high electrocatalytic activity was prepared based on Cu2O nanocubes anchored onto three-dimensional macroporous carbon (MPC) by a simple, eco-friendly, and cheap method for hydrazine detection. Due to the synergistic effect of MPC and Cu2O, the sensor exhibited high electrocatalytic activity, sensitivity, better selectivity, and low limit of detection. The resulting sensor could be a sensitive and effective platform for detecting hydrazine and promising practical applications.


Assuntos
Carbono , Cobre , Hidrazinas
6.
J Hazard Mater ; 424(Pt A): 127303, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34601405

RESUMO

The development of convenient assays for the determination of hydrazine (N2H4) has drawn significant attention due to the high toxicity of this substance. Herein, we developed a concise, rapid and ultrasensitive surface-enhanced Raman scattering (SERS) sensor for N2H4 detection based on alpha-cyclodextrin-silver nanoparticles (α-CD-AgNPs) modified by 4-mercaptobenzaldehyde (4-MBA). The 4-MBA molecules can specifically capture the N2H4 molecules and undergo a Schiff base reaction. As a result, this induces the aggregation of nanoparticles and generates a new characteristic peak at 1529 cm-1 that is attributed to CN and CC vibrations. Compared with noble metal nanoparticles, 4-MBA not only formed AgS bonds but could also be fixed in the cavity of cyclodextrin to produce a more stable and stronger SERS signal. The SERS intensity at 1529 cm-1 and the logarithm of the concentration of N2H4 presented a good linear relationship from 10-9 to 10-7 M with an unprecedented limit of detection (LOD) of 38 pM. The proposed SERS sensor exhibited satisfactory selectivity and reproducibility and was applied to detect N2H4 in real and complex water samples. We expect this assay to be a promising alternative tool for the on-site detection of N2H4.


Assuntos
Nanopartículas Metálicas , Análise Espectral Raman , Hidrazinas , Reprodutibilidade dos Testes , Bases de Schiff , Prata
7.
Chem Biol Interact ; 352: 109779, 2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-34922904

RESUMO

Growing evidence shows that cancer progression links with both heterogeneity of the tumor microenvironment and dysregulated activity of immune cells. Cancer-secreted exosomes are being recognized as indispensable mediators of the exchange cargo between cancer and immune cells. The M2-phenotype tumor-associated macrophages have the function of promoting tumor progression and drug resistance. Diffuse large B-cell lymphoma(DLBCL) is a highly heterogeneous and very common malignant non-Hodgkin's lymphoma. Here, we demonstrate that different subtype DLBCL cell-derived exosomes are internalized by macrophages, which can affect macrophages polarization. The mechanism of DLBCL-derived exosomes on macrophage polarization remains unclear currently. This study showed that DLBCL-secreted exosomes could induce the transformation of macrophages to a protumor M2-like phenotype, and block the drug-induced apoptosis of DLBCL cells in an indirect co-culture system. Different DLBCL-derived exosomes could change the phenotype of macrophages through the STAT3 signaling, which upregulated the expression of oncogenic genes and classical markers of M2-like phenotype macrophages, such as IL-10, CD206, and CD163. The addition of DLBCL-derived exosomes resulted in the activation of the STAT3 signaling pathway of M0/M2 macrophages in an indirect co-culture system. GP130 was highly enriched in DLBCL-derived exosomes, which triggered the activation of STAT3 of macrophages and subsequently induced the downstream targets such as BCL2, SURVIVIN, and BAX. The parallel changes of STAT3 and GP130 in macrophages confirmed that GP130 of DLBCL-derived exosomes promoted macrophage polarization by activating STAT3 signaling. Furthermore, all of these effects could be reversed by the GP130 inhibitor SC144. The data indicated that DLBCL-derived exosomes could trigger macrophages polarization into a pro-survival M2-like phenotype, which was at least partially through the GP130/STAT3 signaling pathway. Collectively, this study showed that DLBCL-derived exosomes could promote macrophages transformation to protumor M2-like phenotype in the tumor microenvironment.


Assuntos
Receptor gp130 de Citocina/imunologia , Exossomos/imunologia , Exossomos/metabolismo , Linfoma Difuso de Grandes Células B/imunologia , Linfoma Difuso de Grandes Células B/metabolismo , Fator de Transcrição STAT3/metabolismo , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Linhagem Celular Tumoral , Receptor gp130 de Citocina/antagonistas & inibidores , Humanos , Hidrazinas/farmacologia , Imunofenotipagem , Modelos Biológicos , Fenótipo , Quinoxalinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Microambiente Tumoral/imunologia , Macrófagos Associados a Tumor/classificação
8.
Medicina (Kaunas) ; 57(12)2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34946271

RESUMO

The occurrence of chronic myeloid leukemia (CML), or other myeloproliferative diseases, after the development of idiopathic thrombocytopenic purpura (ITP) is very rare in the current medical literature. Considering the advances in ITP management, and the wide use of new drugs for ITP and CML, we report an unusual case with this association. Our case report focused on a 64-year-old man with long-standing ITP treated with eltrombopag, who developed hyperleukocytosis during follow-up; after specific laboratory exams, it was diagnosed as CML and he began treatment with imatinib. The treatment with eltrombopag was balanced with imatinib to stabilize his platelet count. Data on bcr-abl and JAK2 transcripts were collected and revealed an optimal response with the achievement of negativization of both molecular signatures. We could demonstrate that treatment with imatinib and eltrombopag was well tolerated and allowed complete molecular remission of CML to be achieved, as well as of ITP.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Púrpura Trombocitopênica Idiopática , Benzoatos , Humanos , Hidrazinas/uso terapêutico , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Pirazóis
9.
Analyst ; 146(23): 7294-7305, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34749386

RESUMO

A novel fluorescent probe 2-(4-(diethylamino)-2-hydroxybenzylidene)-N-(2,3,3-trimethylbicyclo[2.2.1]heptan-2-yl)hydrazinecarbothioamide (HT) was prepared in this study by a condensation reaction. HT has been confirmed to possess high specificity toward Ga3+ over other metal ions (including Al3+ and In3+) via a distinct fluorescence light-up response. Moreover, HT exhibited good detection performances for Ga3+ including high selectivity, excellent anti-interference ability, a wide working pH range, and good reversibility. The association constant and limit of detection (LOD) were calculated to be 5.34 × 103 M-1 and 1.18 × 10-6 M, respectively. The detection mechanism of HT toward Ga3+ was proposed and confirmed by 1H NMR analysis, HRMS analysis, and DFT calculations. A simple test strip-based portable detecting device and a molecular INHIBIT logic circuit were established for improving its practical applicability. Furthermore, the desirable sensing performance of HT for Ga3+ was successfully reconfirmed in MCF-7 cells and zebrafish.


Assuntos
Corantes Fluorescentes , Peixe-Zebra , Animais , Hidrazinas , Limite de Detecção , Espectrometria de Fluorescência , Tioamidas
10.
Nihon Yakurigaku Zasshi ; 156(6): 370-381, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34719572

RESUMO

Anamorelin hydrochloride (hereinafter referred to as anamorelin) is an orally active, small-molecule drug with a similar pharmacological action to ghrelin, an endogenous ligand of growth hormone secretagogue receptor type 1a (GHS-R1a). It was first approved in Japan for the treatment of cancer cachexia, characterized by weight loss and anorexia. Anamorelin stimulated the secretion of growth hormone (GH) from cultured rat pituitary cells and increased plasma GH levels by oral administration to rats, pigs and humans. When anamorelin was orally administered once daily for 6 days to rats, larger body weight gain associated with increased food consumption compared to the control group was observed from after the first dose. Anamorelin is a selective agonist for GHS-R1a and enhanced GHS-R1a-mediated pituitary GH secretion and increased food consumption, resulting in body weight gain. In the two Japanese phase II studies in patients with cancer cachexia associated with non-small cell lung cancer (NSCLC), improvement of lean body mass (LBM) and body weight losses and anorexia were demonstrated. The tumor types of target patients in the Japanese phase III study were colorectal, gastric, and pancreatic cancer. As a result, maintenance and increase of LBM and body weight as well as improvement of anorexia were observed, and the efficacy against cancer cachexia associated with colorectal, gastric, and pancreatic cancer was confirmed. There were no observed events considered to be significant safety risks. In conclusion, anamorelin is expected to provide a new therapeutic option for cancer cachexia for which no effective treatment has been available.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Caquexia/tratamento farmacológico , Grelina , Humanos , Hidrazinas , Japão , Oligopeptídeos , Ratos , Suínos , Comprimidos , Resultado do Tratamento
11.
Rinsho Ketsueki ; 62(10): 1499-1504, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34732623

RESUMO

A 67-year-old woman diagnosed with adult T-cell leukemia/lymphoma received an induction chemotherapy and showed a partial response. She then underwent allogeneic peripheral blood stem cell transplantation from an HLA-identical sibling donor. Although cyclosporine (CS) was stopped at 120 days after transplantation, chronic graft-versus-host disease (cGVHD) of the skin developed. She was treated with a topical steroid, without exacerbation of the GVHD. She was admitted to our hospital due to the sudden development of pancytopenia at 212 days after the transplantation. She had an EB virus-associated post-transplant lymphoproliferative disorder (PTLD) in the hilum of the lung. The cGVHD of the skin resolved after the administration of prednisolone and CS. However, pancytopenia and PTLD persisted. Treatment with four cycles of rituximab (4×375 mg/m2/week) led to the complete resolution of PTLD, but transfusion-dependent cytopenia did not improve. Secondary engraftment failure was diagnosed, and granulocyte colony-stimulating factor (G-CSF) and eltrombopag (100 mg/day) were administered, leading to gradual improvement of pancytopenia. It was observed that persistent pancytopenia was caused by secondary engraftment failure due to cGVHD in this case. This case suggested that the treatment with G-CSF and eltrombopag is effective for cGVHD-associated secondary engraftment failure.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma de Células T do Adulto , Linfoma , Transplante de Células-Tronco de Sangue Periférico , Idoso , Benzoatos , Transplante de Medula Óssea , Feminino , Doença Enxerto-Hospedeiro/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Hidrazinas , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Pirazóis , Transplante Homólogo
12.
Blood Adv ; 5(19): 3799-3806, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34605871

RESUMO

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with isolated thrombocytopenia and risk of hemorrhage. Treatment with eltrombopag increases and maintains hemostatic platelet counts; however, to date, long-term data are lacking on the outcome of children with ITP who are treated with eltrombopag. This prospective, observational, longitudinal cohort study evaluated the efficacy and safety of eltrombopag in pediatric patients with persistent or chronic ITP. For the 116 pediatric patients enrolled, duration of eltrombopag treatment was at least 3 months. Median effective dose was 25 mg/day, 50 mg/day, and 50 mg/day, respectively, for children age 5 years or younger, 6 to 11 years, or 12 years or older. In all, 89 patients (76.7%) achieved overall response, 53 (45.7%) achieved complete response, and 36 (31.0%) achieved response. Median platelet counts increased by week 1 and were sustained throughout the treatment period. During treatment with eltrombopag, the proportion of patients with grade 1 to 4 bleeding symptoms decreased from 83.61% at baseline to 9.88% at 6 months when only grade 1 was reported. Forty-three patients (37.1%) reported using concomitant medications at study entry, which was reduced to 1 patient (2.5%) who needed concomitant medications at 12 months. All adverse events were grade 1 or 2 according to Common Terminology Criteria for Adverse Events. No serious adverse events, cataracts, malignancies, or thromboses were reported during the study. Long-term treatment with eltrombopag was generally safe, well tolerated, and effective in maintaining platelet counts and reducing bleeding in most pediatric patients with persistent or chronic ITP. Combined with future studies, these findings will help establish how eltrombopag should best be used in the management of pediatric patients with East Asian ancestry.


Assuntos
Púrpura Trombocitopênica Idiopática , Trombocitopenia , Benzoatos/efeitos adversos , Criança , Pré-Escolar , China , Humanos , Hidrazinas , Estudos Longitudinais , Estudos Prospectivos , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Pirazóis , Resultado do Tratamento
13.
Analyst ; 146(22): 6840-6845, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34608469

RESUMO

The direct analysis of glycans by matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) presents limited sensitivity due to the lower ionization efficiency of glycans. Various chemical derivatization methods have been developed to improve the detection sensitivity of glycans, but most of them need tedious preparation and cleanup procedures. Herein, a reactive matrix, 4-hydrazinoquinazoline (4-HQ), was developed for the rapid and sensitive detection of both neutral and sialylated glycans by MALDI MS. With 4-HQ as the reactive matrix, the detection limits of maltoheptaose and A3 glycan decreased 100-fold and 20-fold, respectively, compared with the conventional matrix. Moreover, 4-HQ formed homogeneous crystals and therefore showed good shot-to-shot reproducibility. Finally, the reactive matrix was successfully applied for the analysis of glycans released from glycoproteins and human serum. Importantly, the application of 4-HQ is the same as that of a conventional matrix with the additional advantage of on-target reaction at room temperature. Thus, 4-HQ can be used for the routine analysis of glycans by MALDI MS due to its simple use, great reproducibility, and enhanced detection of both neutral and sialylated glycans.


Assuntos
Hidrazinas , Polissacarídeos , Humanos , Quinazolinonas , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
14.
Exp Appl Acarol ; 85(2-4): 161-172, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34693496

RESUMO

Several genetic variants of the cd1- and ef-helices of the Qo site of mitochondrial cytochrome b have been associated with bifenazate resistance in the spider mite Tetranychus urticae, an important crop pest around the world. Maternal inheritance of bifenazate resistance has provided strong evidence for the involvement of many of these mutations alone or in combination. A number of populations highly resistant to bifenazate were uncovered that carried the G126S substitution in combination with other target-site mutations. This G126S mutation has therefore been investigated in several studies in the context of resistance evolution and the development of diagnostic markers. However, experimental data that link bifenazate resistance with the presence of the G126S mutation without additional cd1- and ef-helices mutations, remain very limited. Here, we genotyped 38 T. urticae field populations for cytochrome b and uncovered nine field populations with a fixed or segregating G126S substitution without other target-site mutations in the conserved cd1- and ef-helices of the cytochrome b Qo pocket. Toxicity bioassays showed that all nine field populations were very susceptible to bifenazate, providing strong evidence that G126S alone does not confer bifenazate resistance. These findings also implicate that previous T. urticae populations with G126S found to be low to moderately resistant to bifenazate, evolved alternative mechanisms of resistance, and more importantly, that this mutation cannot be used as a molecular diagnostic for bifenazate resistance.


Assuntos
Tetranychidae , Animais , Carbamatos , Citocromos b/genética , Hidrazinas , Tetranychidae/genética
15.
Chem Commun (Camb) ; 57(80): 10415-10418, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34546227

RESUMO

Ultrafine ternary carbide Co6W6C@C nanoparticles (NPs) were successfully synthesized and these NPs exhibited high catalytic activities for the hydrazine oxidation reaction (HzOR) under alkaline conditions. In a practical O2-hydrazine fuel cell test, its peak power density reached 203 mW cm-2, a value superior to that of the state-of-the-art commercial Pt/C catalyst.


Assuntos
Fontes de Energia Elétrica , Hidrazinas/química , Nanopartículas Metálicas/química , Carbono/química , Catálise , Cobalto/química , Eletrodos , Oxirredução , Oxigênio/química , Compostos de Tungstênio/química
16.
Hematology ; 26(1): 697-708, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34547980

RESUMO

OBJECTIVE: To assess real-world treatment patterns in patients with immune thrombocytopenia (ITP) who received thrombopoietin receptor agonists (TPO-RAs) in Germany. METHODS: This was a longitudinal, retrospective study using anonymized patient-level data (IQVIA healthcare prescription database, covering 82% of German statutory prescriptions). Eligible patients (aged ≥18 years) had received ≥1 TPO-RA prescription (romiplostim/eltrombopag) from July 2016 to June 2019 (treatment duration ≥30 days). ITP medication use was assessed for 18 months prior to, during and for ≥6 months after TPO-RA treatment. RESULTS: A total of 3553 patients (median age 64 years) were included. Median persistence on TPO-RAs was 12 months (range 1-34). In the periods before, during and after TPO-RA treatment, oral corticosteroids were the most commonly used therapy (64.4%, 43.4% and 36.1% of patients, respectively); median cumulative doses across each period were 2521.9, 2000.0 and 2277.8 mg. The median total duration of corticosteroid use before, during and after TPO-RA therapy was 15, 18 and 32 weeks, respectively. The total median cumulative corticosteroid dose was 6799.7 mg. CONCLUSION: We identified a potential overuse of corticosteroids in patients with ITP in Germany. Earlier use of TPO-RA therapy after a short course of corticosteroids could avoid side effects associated with long-term use.


Assuntos
Benzoatos/administração & dosagem , Bases de Dados Factuais , Prescrições de Medicamentos , Hidrazinas/administração & dosagem , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Pirazóis/administração & dosagem , Receptores Fc/administração & dosagem , Receptores de Trombopoetina/agonistas , Proteínas Recombinantes de Fusão/administração & dosagem , Trombopoetina/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Alemanha/epidemiologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/epidemiologia , Estudos Retrospectivos
17.
FASEB J ; 35(10): e21925, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34569663

RESUMO

In mammalian testes, extensive remodeling of the microtubule (MT) and actin cytoskeletons takes place in Sertoli cells across the seminiferous epithelium to support spermatogenesis. However, the mechanism(s) involving regulatory and signaling proteins remains poorly understood. Herein, A-kinase anchoring protein 9 (AKAP9, a member of the AKAP multivalent scaffold protein family) was shown to be one of these crucial regulatory proteins in the rat testis. Earlier studies have shown that AKAP9 serves as a signaling platform by recruiting multiple signaling and regulatory proteins to create a large protein complex that binds to the Golgi and centrosome to facilitate the assembly of the MT-nucleating γ-tubulin ring complex to initiate MT polymerization. We further expanded our earlier studies based on a Sertoli cell-specific AKAP9 knockout mouse model to probe the function of AKAP9 by using the techniques of immunofluorescence analysis, RNA interference (RNAi), and biochemical assays on an in vitro primary Sertoli cell culture model, and an adjudin-based animal model. AKAP9 robustly expressed across the seminiferous epithelium in adult rat testes, colocalizing with MT-based tracks, and laid perpendicular across the seminiferous epithelium, and prominently expressed at the Sertoli-spermatid cell-cell anchoring junction (called apical ectoplasmic specialization [ES]) and at the Sertoli cell-cell interface (called basal ES, which together with tight junction [TJ] created the blood-testis barrier [BTB]) stage specifically. AKAP9 knockdown in Sertoli cells by RNAi was found to perturb the TJ-permeability barrier through disruptive changes in the distribution of BTB-associated proteins at the Sertoli cell cortical zone, mediated by a considerable loss of ability to induce both MT polymerization and actin filament bundling. A considerable decline in AKAP9 expression and a disruptive distribution of AKAP9 across the seminiferous tubules was also noted during adjudin-induced germ cell (GC) exfoliation in this animal model, illustrating AKAP9 is essential to maintain the homeostasis of cytoskeletons to maintain Sertoli and GC adhesion in the testis.


Assuntos
Proteínas de Ancoragem à Quinase A/metabolismo , Citoesqueleto de Actina/metabolismo , Proteínas do Citoesqueleto/metabolismo , Microtúbulos/metabolismo , Espermatogênese , Testículo/citologia , Testículo/metabolismo , Animais , Núcleo Celular/metabolismo , Hidrazinas/metabolismo , Indazóis/metabolismo , Masculino , Modelos Animais , Ratos , Células de Sertoli/citologia , Células de Sertoli/metabolismo , Testículo/química
18.
Blood Coagul Fibrinolysis ; 32(7): 519-521, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34520405

RESUMO

Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated thrombocytopenia (platelet count <100 × 109/l) in the absence of other causes or disorders associated. The incidence of ITP in pregnancy is one to two cases per 1000 gestations. ITP could be diagnosed before or during pregnancy; sometimes a relapse of a previously diagnosed ITP can occur. Intravenous immune globulins (IVIg) and corticosteroids are the standard frontline therapy because of their well known safety profile either for the mother or for the neonate. Treatments for refractory patients are limited by potential fetal risk. We report the case of a patient with ITP along pregnancy, refractory to corticosteroids and IVIg, successfully treated with, the thrombopoietin receptor agonist (TPO-RA) eltrombopag. Patient received this compound for almost the whole pregnancy and in particular for the whole first trimester, without any complication for the mother and the neonate. Although transient administration of TPO-RAs in pregnancy seems to be well tolerated, their use during the whole gestation is still controversial; this is the reason of the description of this case, which did not show any complications, and thus it could add useful information on this field.


Assuntos
Benzoatos/uso terapêutico , Hidrazinas/uso terapêutico , Complicações Hematológicas na Gravidez/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Pirazóis/uso terapêutico , Adolescente , Feminino , Humanos , Recém-Nascido , Contagem de Plaquetas , Gravidez , Receptores de Trombopoetina/agonistas
19.
Chem Commun (Camb) ; 57(80): 10351-10354, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34533141

RESUMO

We report here the synthesis of a novel family of N-CF3 hydrazines from a direct way involving the available and cheap Langlois reagent (CF3SO2Na). These derivatives have shown very high stability whatever the conditions used and are excellent precursors for building previously inaccessible N-CF3 functionalized compounds, such as substituted hydrazides, hydrazine-amino-acids, hydrazones, N-aziridines and pyrazoles.


Assuntos
Compostos Azo/química , Ésteres/química , Hidrazinas/síntese química , Hidrocarbonetos Fluorados/química , Indicadores e Reagentes/química , Mesilatos/química , Metilação , Estrutura Molecular
20.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(9): 944-950, 2021.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34535211

RESUMO

OBJECTIVES: To systematically assess the efficacy and safety of eltrombopag in the treatment of children with immune thrombocytopenia (ITP). METHODS: PubMed, Embase, Cochrane Library, Weipu Data, CNKI, and Wanfang Data were searched for studies on eltrombopag used for the treatment of children with ITP. RevMan 5.3 and R version 3.6 were used to perform a Meta analysis of included studies. RESULTS: A total of 11 studies were included, with 2 randomized controlled trials and 9 cohort studies. The Meta analysis of the 9 cohort studies showed that eltrombopag had a response rate of about 70% (95%CI: 65%-76%) in the treatment of children with ITP, with no serious adverse events. The Meta analysis of the randomized controlled trials showed that the eltrombopag group had a higher response rate than the placebo group (RR=2.64, 95%CI: 1.58-4.44, P<0.05), while there was no significant difference in the incidence rates of adverse events and serious adverse events between the two groups (P>0.05). CONCLUSIONS: Eltrombopag has good efficacy and safety as a second-line treatment regimen for children with ITP.


Assuntos
Púrpura Trombocitopênica Idiopática , Benzoatos , Criança , Humanos , Hidrazinas/efeitos adversos , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Pirazóis , Receptores Fc , Trombopoetina
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