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1.
Adv Pharmacol ; 87: 113-158, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32089231

RESUMO

TCM-based medications have been used for millennia in China and have always been "different" from current Western-based medicines in that they frequently are still mixtures of predominately plant products. From the early 20th Century, there has been a move to identify both the actual compounds in these mixes, and then over the past approximately 50years, to utilize early information for current diseases, with an example being artemisinin for treatment of malaria. Since that discovery, Western scientists, together with their Chinese counterparts, have begun to investigate how TCM compositions can be utilized to discover new agents, sometimes the actual TCM-based compound(s) but also by utilizing the pharmacophores from such preparations that have utility in human diseases. The examples in this review include artemisinin derivatives and their manifold bioactivities, indirubins and derivatives as antitumor agents, arsenicals predominately as treatment for leukemia, though extending into other cancer types. Finally, there are sections discussing the use of current computerized techniques that combine metabolomics, mass spectroscopy/HPLC, and network pharmacology with the aim of identifying the "active principles" in relevant TCM preparations and finally how high content screening can be utilized in conjunction with the other analytical techniques.


Assuntos
Medicina Tradicional Chinesa , Arsenicais/farmacologia , Arsenicais/uso terapêutico , Artemisininas/química , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Metabolômica , Estereoisomerismo
2.
J Ethnopharmacol ; 247: 112299, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31606537

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Hua-Feng-Dan (HFD) is a traditional Chinese medicine used for neurological disorders. HFD contains cinnabar (HgS) and realgar (As4S4). The ethnopharmacological basis of cinnabar and realgar in HFD is not known. AIM OF THE STUDY: To address the role of cinnabar and realgar in HFD-produced neuroprotection against neurodegenerative diseases and disturbance of gut microbiota. MATERIALS AND METHODS: Lipopolysaccharide (LPS) plus rotenone (ROT)-elicited rat dopaminergic (DA) neuronal damage loss was performed as a Parkinson's disease animal model. Rats were given a single injection of LPS. Four months later, rats were challenged with the threshold dose of ROT. The clinical dose of HFD was administered via feed, starting from ROT administration for 46 days. Behavioral dysfunction was detected by rotarod and Y-maze tests. DA neuron loss and microglial activation were assessed via immunohistochemical staining and western bolt analysis. The colon content was collected to extract bacterial DNA followed by real-time PCR analysis with 16S rRNA primers. RESULTS: LPS plus ROT induced neurotoxicity, as evidenced by DA neuron loss in substantia nigra, impaired behavioral functions and increased microglial activation. HFD-original (containing 10% cinnabar and 10% realgar) rescued loss of DA neurons, improved behavioral dysfunction and attenuated microglial activation. Compared with HFD-original, HFD-reduced (3% cinnabar and 3% realgar) was also effective, but to be a less extent, while HFD-removed (without cinnabar and realgar) was ineffective. In analysis of gut microbiome, the increased Verrucomicrobiaceae and Lactobacteriaceae, and the decreased Enterobacteeriaceae by LPS plus ROT were ameliorated by HFD-original, and to be the less extent by HFD-reduced. CONCLUSION: Cinnabar and realgar are active ingredients in HFD to exert beneficial effects in a neurodegenerative model and gut microbiota.


Assuntos
Arsenicais/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Compostos de Mercúrio/farmacologia , Fármacos Neuroprotetores/farmacologia , Síndromes Neurotóxicas/tratamento farmacológico , Sulfetos/farmacologia , Animais , Arsenicais/química , Arsenicais/uso terapêutico , DNA Bacteriano/isolamento & purificação , Modelos Animais de Doenças , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/patologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/genética , Enterobacteriaceae/isolamento & purificação , Etnofarmacologia , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/imunologia , Humanos , Mediadores da Inflamação/metabolismo , Lactobacillaceae/efeitos dos fármacos , Lactobacillaceae/genética , Lactobacillaceae/isolamento & purificação , Lipopolissacarídeos/toxicidade , Masculino , Compostos de Mercúrio/química , Compostos de Mercúrio/uso terapêutico , Microglia/efeitos dos fármacos , Microglia/imunologia , Microglia/patologia , Degeneração Neural , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/uso terapêutico , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/imunologia , Síndromes Neurotóxicas/patologia , RNA Ribossômico 16S/genética , Ratos , Rotenona/toxicidade , Sulfetos/química , Sulfetos/uso terapêutico , Verrucomicrobia/efeitos dos fármacos , Verrucomicrobia/genética , Verrucomicrobia/isolamento & purificação
3.
Arch Pharm Res ; 42(11): 962-976, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31701373

RESUMO

Arsenic is a potent chemotherapeutic drug that is applied as a treatment for cancer; it exerts its functions through multiple pathways, including angiogenesis inhibition. As angiogenesis is a critical component of the progression of many diseases, arsenic is a feasible treatment option for patients with other angiogenic diseases, including rheumatoid arthritis and psoriasis, among others. However, arsenic is also a well-known carcinogen, demonstrating a pro-angiogenesis effect. This review will focus on the dual effects of arsenic on neovascularization and the relevant mechanisms underlying these effects, aiming to provide a rational understanding of arsenic treatment. In particular, we expect to provide a comprehensive overview of the current knowledge of the mechanisms by which arsenic influences angiogenesis.


Assuntos
Arsenicais/farmacologia , Neoplasias/tratamento farmacológico , Neovascularização Patológica/induzido quimicamente , Neovascularização Fisiológica/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Arsenicais/uso terapêutico , Carcinógenos/farmacologia , Linhagem Celular Tumoral , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Esquema de Medicação , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Exposição Ambiental/efeitos adversos , Humanos , Infusões Intravenosas , Neoplasias/irrigação sanguínea , Neoplasias/patologia , PPAR gama/metabolismo , Receptores de Calcitriol/metabolismo , Transdução de Sinais/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/metabolismo , Vitamina D/administração & dosagem , Vitamina D/metabolismo
4.
Vet Parasitol ; 273: 11-16, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31442887

RESUMO

Heartworm infection (also known as dirofilariosis due to Dirofilaria immitis) in dogs causes chronic pulmonary disease that, if left untreated, can lead to right-side congestive heart failure. Currently, the only registered drug for adulticide therapy in dogs with heartworm disease (HWD) is melarsomine dihydrochloride. The recent targeting of the bacterial endosymbiont Wolbachia, through antibiotic therapy of the infected host, has offered an interesting alternative for the treatment of HWD. Recent reports of the adulticide activity of an ivermectin/doxycycline combination protocol has lead the American Heartworm Society (AHS) to include in its guidelines that, in cases where arsenical therapy is not possible or is contraindicated, a monthly heartworm preventive along with doxycycline for a 4-week period might be considered. In the present study, 20 dogs with confirmed natural D. immitis infection were included following owner consent. Fourteen dogs were treated with a topical formulation containing 10% w/v imidacloprid and 2.5% w/v moxidectin (Advocate®, Advantage Multi®, Bayer), monthly for nine months, associated to doxycycline (10 mg/kg/BID) for the first 30 days. Six dogs were treated with melarsomine (Immiticide®, Merial) (2.5 mg/kg) at enrollment, followed one month later by two injections 24 h apart. The presence of circulating antigens and the number of microfilariae (mf) were evaluated at the moment of enrollment and then at 1, 2, 3, 4, 5, 6, 7, 8, 12, 18, 24 months post enrollment. Echocardiogram and radiographs were performed at month 0, 6, 12, 18, 24. Monthly moxidectin combined with 30 days of doxycycline eliminated circulating microfilariae within one month, thus breaking the transmission cycle very quickly. Furthermore, dogs treated with the combination protocol started to become negative for circulating antigens at 4 months from the beginning of treatment and all except one were antigen negative at 9 months. All dogs treated with melarsomine were antigen negative by 5 months from the beginning of the treatment. No dogs showed worsening of pulmonary patterns or criteria indicative of pulmonary hypertension 12 to 24 months after. For the criteria mf concentration, antigen concentration, radiography and echocardiography at 12, 18 and 24 months the non-inferiority for the moxidectin group could be proven for a non-inferiority margin of 15% for the rate difference. Dogs treated with moxidectin and doxycycline became negative for microfilariae and antigens sooner when compared to melarsomine in the present study and to dogs treated with doxycycline combined with ivermectin in studies previously published.


Assuntos
Dirofilariose/tratamento farmacológico , Doxiciclina/uso terapêutico , Macrolídeos/uso terapêutico , Neonicotinoides/uso terapêutico , Nitrocompostos/uso terapêutico , Animais , Antígenos de Helmintos/sangue , Arsenicais/uso terapêutico , Dirofilaria immitis , Doenças do Cão/tratamento farmacológico , Cães , Quimioterapia Combinada , Feminino , Filaricidas/uso terapêutico , Masculino , Fatores de Tempo , Resultado do Tratamento , Triazinas/uso terapêutico
5.
J Pharmacol Sci ; 140(2): 162-170, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31285125

RESUMO

QTc prolongation has been observed during arsenic trioxide and realgar's clinical use, and become a huge obstacle for the application. Our lab has obtained the soluble arsenic from realgar named realgar transforming solution or RTS. In this study, we first evaluated the cytotoxicity on NB4 cell and found that RTS could remarkably inhibit proliferation of NB4 than arsenic trioxide. Then we figured out the QTc prolongation of RTS treatment contrasted with arsenic trioxide; results revealed that arsenic trioxide prolonged corrected QTc of mice by 20.1% and showed 1.9-fold higher cytotoxicity on H9c2 cell than RTS. On the contrary, there could not find any QTc prolongation of mice in RTS treatment. Also, arsenic trioxide elevated the intercellular calcium accumulation of H9c2 cell by 2.02-fold v.s control and RTS. HE staining and Masson's trichrome staining had shown that there was no injured section after RTS treatments. IK1 currents of rat ventricular cardiomyocytes were diminished by 45.0% after treating with arsenic trioxide while RTS showed no significance than the control group. The results above indicated that RTS could serve as an alternative arsenic agent on leukemia and had a lower risk of cardiotoxicity.


Assuntos
Arsenicais , Cardiotoxicidade/etiologia , Sulfetos/toxicidade , Animais , Arsenicais/efeitos adversos , Arsenicais/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Feminino , Humanos , Leucemia/tratamento farmacológico , Síndrome do QT Longo/induzido quimicamente , Masculino , Camundongos , Ratos Wistar , Risco , Soluções , Sulfetos/efeitos adversos , Sulfetos/uso terapêutico
6.
Chin J Integr Med ; 25(7): 497-501, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31278627

RESUMO

OBJECTIVE: To investigate the relation of blood arsenic concentration (BAC) with clinical effect and safety of arsenic-containing Qinghuang Powder (, QHP) in patients with myelodysplastic syndrome (MDS). METHODS: Totally 163 patients with MDS were orally treated with QHP for 2 courses of treatment, 3 months as 1 course. The BACs of patients were detected by atomic fluorescence spectrophotometry at 1, 3, and 6 months during the treatment, and the effective rate, hematological improvement and safety in patients after treatment with QHP were analyzed. RESULTS: After 2 courses of treatment, the total effective rate was 89.6% (146/163), with 31.3% (51/163) of hematological improvement and 58.3% (95/163) of stable disease. The hemoglobin increased from 73.48 ± 19.30 g/L to 80.39 ± 26.56 g/L (P<0.05), the absolute neutrophil count increased from 0.81 ± 0.48 × 109/L to 1.08 ± 0.62 × 109/L (P<0.05), and no significant changes were observed in platelet counts (P>0.05). Among 46 patients previously depended on blood transfusion, 28.3% (13/46) completely got rid of blood transfusion and 21.7% (10/46) reduced the volume of blood transfusion by more than 50% after treatment. The BACs were significantly increased in patients treated for 1 month with 32.17 ± 18.04 µ g/L (P<0.05), 3 months with 33.56 ± 15.28 µ g/L (P<0.05), and 6 months with 36.78 ± 11.92 µ g/L (P<0.05), respectively, as compared with those before treatment (4.08 ± 2.11 µ g/L). There were no significant differences of BACs among the patients treated for 1, 3 and 6 months (P>0.05). The adverse reactions of digestive tract during the treatment were mild abdominal pain and diarrhea in 14 cases (8.6%), and no patients discontinued the treatment. The BACs of patients with gastrointestinal adverse reactions were significantly lower than those without gastrointestinal adverse reactions (22.39 ± 10.38 vs. 37.89 ± 11.84, µ g/L, P<0.05). The BACs of patients with clinical effect were significantly higher than those failed to treatment (40.41 ± 11.69 vs. 23.84 ± 12.03, µ g/L, P<0.05). CONCLUSION: QHP was effective and safe in the treatment of patients with MDS and the effect was associated with BACs of patients.


Assuntos
Arsênico/sangue , Arsenicais/efeitos adversos , Arsenicais/uso terapêutico , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/tratamento farmacológico , Contagem de Células Sanguíneas , Transfusão de Sangue , Humanos , Cariótipo , Pós , Fatores de Risco
7.
Iran J Immunol ; 16(2): 170-181, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31182691

RESUMO

BACKGROUND: Realgar, an arsenic tetrasulfide compound, is a highly recognized traditional Chinese medicinal prescription that has been widely used to treat various diseases such as inflammatory diseases. However, there are still some problems in the clinical treatment of Realgar, such as large oral dose and high potential toxicity. OBJECTIVE: To evaluate effects of Realgar nanoparticles on lupus nephritis (LN) in vivo in MRL/lpr mice. METHODS: Ten-week mice were orally administered every day for eight consecutive weeks except the mice of normal model groups. The serum levels of anti-ds-DNA antibody IgG, IgM, IFN-γ, Creatinine (Cr), and blood urea nitrogen (BUN) were determined, and 24-hour urine protein was also measured. Renal inflammatory pathology analysis was assessed by hematoxylin-eosin (H&E) staining. The expression of phosphorylated signal transducer and activator of transcription 1 (p-STAT 1) and Janus Kinase 1 (JAK 1) in kidney tissue was determined by direct reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). RESULTS: The mice treated with Realgar nanoparticle in the high dose-treated (Realgar HD, 0.03 g/kg/d) group exhibited significantly reduced serum levels of anti-dsDNA (p<0.01), IgG (p<0.01), IgM (p<0.01), BUN (p<0.01), Cr (p<0.01), and inflammatory cytokine IFN-γ (p<0.01) as well as proteinuria (p<0.01) compared to the untreated model MRL/lpr mice. Additionally, high doses of Realgar nanoparticles significantly suppressed the phosphorylations of STAT 1(p<0.01) and the renal pathological changes. CONCLUSIONS: The study indicates that Realgar nanoparticles may be a potential agent to treat LN, and the down-regulated p-STAT1 expression suggests that it may be one of the LN treatment targets for Realgar nanoparticles.


Assuntos
Arsenicais/uso terapêutico , Rim/patologia , Nefrite Lúpica/terapia , Nanopartículas/uso terapêutico , Fator de Transcrição STAT1/metabolismo , Sulfetos/uso terapêutico , Animais , Arsenicais/química , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Janus Quinase 1/metabolismo , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos MRL lpr , Nanopartículas/química , Transdução de Sinais , Sulfetos/química
8.
J Vet Cardiol ; 23: 96-103, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31174734

RESUMO

Four dogs, referred for management of heartworm (HW) disease, were found to have HWs entangled in their tricuspid valve apparatus. None of the dogs were actively hemolyzing or showed signs of acute cardiovascular collapse that would have necessitated emergency transvenous HW extraction, and surgery was not performed at time of presentation. The dogs received pimobendan and sildenafil within 24 h of identifying HW in the tricuspid valve apparatus, and the HW moved to the pulmonary arteries within 2 days in most cases (median 2 days, range 1-14 days). All dogs survived to discharge from the original hospital admission and were subsequently treated with adulticide (melarsomine) without complication. All dogs were HW antigen negative 6 months after their last melarsomine injection. Four dogs appeared to respond positively to medical management aimed at decreasing pulmonary arterial pressure and improving the right ventricular function, but movement of HW out of the heart for other reasons cannot be excluded. This therapeutic option is not advised when dogs with HW disease are presented for acute collapse, ongoing hemolysis, and hypotension as surgical extraction is still considered the best option in these cases. It remains unknown if medical management is a safe option for all dogs with intracardiac HW without clinical signs of caval syndrome. Controlled prospective studies are required to determine the efficacy and safety of this treatment regimen in comparison with surgical extraction.


Assuntos
Dirofilariose/tratamento farmacológico , Doenças do Cão/tratamento farmacológico , Piridazinas/uso terapêutico , Citrato de Sildenafila/uso terapêutico , Animais , Antígenos de Helmintos/sangue , Arsenicais/uso terapêutico , Dirofilaria/imunologia , Cães , Feminino , Filaricidas/uso terapêutico , Masculino , Triazinas/uso terapêutico , Valva Tricúspide/parasitologia , Vasodilatadores/uso terapêutico
9.
Methods Mol Biol ; 1967: 295-304, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31069779

RESUMO

Conjugates of 4-(N-(S-glutathionylacetyl)amino)phenylarsonous acid (GSAO) with optical or radionuclide probes are able to image cell death in vivo. GSAO conjugates are retained in the cytosol of dying and dead cells via the formation of covalent bonds between the As(III) ion and the thiol groups of proximal cysteine residues. Here we describe the method for preparing a NODAGA-GSAO conjugate and its radiolabeling with gallium-68 (68Ga-NODAGA-GSAO) for positron-emission tomography (PET) imaging of cell death.


Assuntos
Morte Celular/genética , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/química , Tolueno/análogos & derivados , Acetatos/química , Acetatos/uso terapêutico , Animais , Arsenicais/química , Arsenicais/uso terapêutico , Radioisótopos de Gálio/química , Radioisótopos de Gálio/uso terapêutico , Glutationa/análogos & derivados , Glutationa/química , Glutationa/uso terapêutico , Compostos Heterocíclicos com 1 Anel/química , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Humanos , Radioisótopos/administração & dosagem , Radioisótopos/química , Compostos Radiofarmacêuticos/uso terapêutico , Tolueno/química
10.
Vet Parasitol ; 268: 87-97, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30981311

RESUMO

Dourine, caused by Trypanosoma equiperdum, is a life-threatening venereal disease in equidae. So far, there is no clear evidence on how and when stallions become infectious, nor which tissues are affected by the parasite in diseased animals. Post-infection, after a transient, temporary phase of parasitaemia, the parasite disperses to different tissues in an unknown distribution pattern. This study describes the distribution of the parasite after infection by artificial insemination (AI) or blood transfusion. Mares (N = 4) were artificially inseminated with T. equiperdum spiked semen whereas stallions (N = 4) were infected by blood transfusion. The course of the disease was monitored by parasitological (Woo) and molecular (PCR) tests and clinical signs and haematological parameters were recorded. At 120 days post infection, horses had a full necropsy, histopathology and PCR. A similar pattern of parasitaemia, disease progression and tissue distribution were seen in all horses. Ejaculated semen in the preclinical stage and epididymal semen in the chronic stage of the disease was positive on PCR and caused infection in mice. Cymelarsan® treatment in the chronic stage did not result in a clinico-haematological or histopathological improvement. At necropsy, lesions were observed in the nervous and reproductive system. Histopathological lesions were most severe in the peripheral nerves and associated ganglia, the testicles and genital mucosae with multifocal infiltration of lymphocytes, plasma cells and histocytes. The parasites disseminated to several tissues including the nervous system, testicles and semen. The results indicate that transmission of T. equiperdum is possible through semen even from symptomless stallions post-treatment.


Assuntos
Transfusão de Sangue , Doenças dos Cavalos/parasitologia , Doenças dos Cavalos/transmissão , Parasitemia/veterinária , Infecções do Sistema Genital/parasitologia , Animais , Arsenicais/uso terapêutico , Mal do Coito (Veterinária)/parasitologia , Doenças dos Cavalos/tratamento farmacológico , Cavalos/parasitologia , Masculino , Camundongos , Parasitemia/tratamento farmacológico , Nervos Periféricos/parasitologia , Nervos Periféricos/patologia , Reação em Cadeia da Polimerase , Infecções do Sistema Genital/patologia , Sêmen/parasitologia , Coluna Vertebral/parasitologia , Coluna Vertebral/patologia , Tripanossomicidas/uso terapêutico , Trypanosoma/genética
11.
Dermatol Ther ; 32(4): e12849, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30707471

RESUMO

Systemic lupus erythematosus (SLE) is an autoimmune disease of uncertain etiology that affects multiple tissues and organs. Tetra-arsenic tetra-sulfide (As4 S4 ), a traditional Chinese medicine, is effective on acute promyelocytic leukemia with mild side effects. In our previous study, BXSB lupus-prone mice treated with As4 S4 has showed improved monocytosis, decreased serum interleukin (IL)-6 and suppressed skin, liver and renal lesions with well-tolerance. In this study, we explored the effect and mechanism of As4 S4 on the MRL/lpr mice. MRL/lpr and wild MRL/MpJ mice were divided into control and As4 S4 treatment groups and dosed with As4 S4 or placebo for 8 weeks. We found that As4 S4 prevented the skin, renal and lung lesions of MRL/lpr mice. As4 S4 significantly decreased the double negative T (DN T) cells and reduced the serum levels of IL-17, IL-10, and antinuclear antibodies titer. Further results revealed that the FasL was decreased, and activated caspases elevated in DN T cells in As4 S4 treated MRL/lpr mice. Taken together, As4 S4 could selectively suppresses DN T cells by inducing apoptosis. It also reduced inflammatory cytokines IL-17, which may be produced by DN T cells. As4 S4 may represent a new therapy for SLE.


Assuntos
Arsenicais/uso terapêutico , Interleucina-17/antagonistas & inibidores , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Sulfetos/uso terapêutico , Linfócitos T/efeitos dos fármacos , Animais , Arsenicais/farmacologia , Feminino , Interleucina-10/fisiologia , Interleucina-17/fisiologia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/mortalidade , Camundongos , Camundongos Endogâmicos MRL lpr , Tamanho do Órgão/efeitos dos fármacos , Baço/efeitos dos fármacos , Baço/patologia , Sulfetos/farmacologia , Linfócitos T/imunologia
12.
Chin J Integr Med ; 25(6): 409-415, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29619748

RESUMO

OBJECTIVES: To investigate the relationship between gene mutations and response to Compound Qinghuang Powder (, CQHP) in patients with myelodysplastic syndrome (MDS). METHODS: Forty-three MDS patients were genotyped by ultra-deep targeted sequencing and the clinical data of patients were collected and the relationship between them was analyzed. RESULTS: Up to 41.86% of patients harbored genet mutations, in most cases with more than one mutation. The most common mutations were in SF3B1, U2AF1, ASXL1, and DNMT3A. After treatment with CQHP, about 88.00% of patients no longer required blood transfusion, or needed half of prior transfusions. CONCLUSIONS: CQHP is an effective treatment for patients with MDS, especially those with gene mutations in SF3B1, DNMT3A, U2AF1, and/or ASXL1.


Assuntos
Arsênico/uso terapêutico , Arsenicais/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Estudos de Associação Genética , Mutação/genética , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/genética , Adulto , Transfusão de Sangue , Feminino , Humanos , Cariótipo , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
13.
Chin J Integr Med ; 25(5): 354-359, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-29500545

RESUMO

OBJECTIVE: To explore the effect of Qinghuang Powder (QHP,()combined with Bupi Yishen Decoction (BPYS, ) on myelodysplastic syndromes (MDS) patients with refractory cytopenia with multilineage dysplasia (RCMD) and determine the change of DNA methylation in MDS-RCMD patients after the treatment of Chinese medicine formula. METHODS: All 308 MDS-RCMD patients were treated with QHP combined with BPYS for 2 months at least, absolute neutrophil count (ANC), hemoglobin (Hb), platelets (PLT), primitive bone marrow cells and chromosome karyotype were chosen as the main evaluation indexes to analyze the treatment effect according to criteria from the MDS International Working Group. Then 43 bone marrow samples from 15 MDS-RCMD patients and 28 healthy donors were obtained for the examination of DNA methylation. Gene Ontology (GO) and Pathway analysis were applied to analyze the methylation data. RESULTS: The overall MDS response rate to QHP was 61.68% (190/360) including hematologic improvement-neutrophil (HI-N) or hematologic improvement-erythroid (HI-E) or hematologic improvement-platelet (HI-P). Patients with anemia had a better response rate than patients with neutropenia or thrombocypenia (55.88% vs 31.54% or 55.88% vs. 36.9%). The DNA methylation microarray analysis disclosed that 4,257 hypermethylated genes were demethylated upon the treatment with QHP and BPYS. GO analysis and Pathway analysis showed that these demethylated genes were involved in a lot of tumor-related pathways and functions. CONCLUSIONS: QHP combined with BPYS could effectively treat MDS-RCMD patients through hematologic improvement (HI-N, HI-P or HI-E) and PLT and RBC transfusion independence due to the demethylation, thereby providing another choice for the treatment of patients with MDS-RCMD.


Assuntos
Arsenicais/uso terapêutico , Linhagem da Célula , Metilação de DNA/efeitos dos fármacos , Medicamentos de Ervas Chinesas/uso terapêutico , Transtornos Leucocíticos/tratamento farmacológico , Transtornos Leucocíticos/genética , Arsenicais/administração & dosagem , Arsenicais/farmacologia , Linhagem da Célula/efeitos dos fármacos , Desmetilação , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Ontologia Genética , Humanos , Masculino , Pessoa de Meia-Idade , Pós , Resultado do Tratamento
14.
Cancer Chemother Pharmacol ; 83(3): 519-530, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30542770

RESUMO

PURPOSE: This study aimed at investigating the anti-tumor effect of arsenic sulfide (As2S2) against liver cancer both in vivo and in vitro and to elucidate its underlying mechanisms. METHODS: Cell viability of the human hepatocellular carcinoma cell lines SMMC-7721, BEL-7402, HepG2 were measured by CCK-8 assay. The effects of As2S2 on cell proliferation and apoptosis of SMMC-7721 cells were investigated using Calcein-AM and PI staining, Hoechst 33258 staining, crystal violet staining, and JC-1 staining. Cell cycle and Annexin V/PI assay were analyzed via flow cytometry. The expression of apoptosis-related proteins, phosphorylation of PI3K and AKT were detected by Western blotting. H22-bearing mice model was established to evaluate the anti-tumor effect of As2S2 in vivo. HE staining, PCNA was observed via immunohistochemistry, and TUNEL assay was used to assess the anti-proliferation and pro-apoptotic effects of As2S2. RESULTS: As2S2 significantly inhibited the growth of human hepatoma cells SMMC-7721, BEL-7402 and HepG2. As2S2 inhibited cell proliferation effectively by inducing G0/G1 cell cycle arrest in SMMC-7721 cells. As2S2 could increase Bax/Bcl-2 ratio, decrease mitochondrial membrane potential, promote the release of cytochrome c, increase the levels of cleaved caspase-3 and PARP, indicating that As2S2 induced apoptosis in SMMC-7721 cells via mitochondrial-mediated apoptosis pathway. Further research showed that As2S2 inhibited the PI3K/AKT signaling pathway leading to apoptotic cell death. In addition, As2S2 significantly inhibited tumor growth in H22-bearing mice and induced apoptosis by deactivating PI3K/AKT pathway, which was consistent with the in vitro results. CONCLUSION: These findings suggested that As2S2 could induce apoptosis of liver cancer cells in vitro and in vivo, which was related to PI3K/AKT-mediated mitochondrial pathway and may provide a novel promising therapeutic agent for liver cancer treatment.


Assuntos
Apoptose/efeitos dos fármacos , Arsenicais/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Sulfetos/farmacologia , Animais , Arsenicais/uso terapêutico , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral/transplante , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Organismos Livres de Patógenos Específicos , Sulfetos/uso terapêutico
15.
Vet Parasitol ; 264: 47-51, 2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-30503091

RESUMO

The aim of this study was to evaluate the ability of melarsomine hydrochloride (Cymelarsan®) to cure horses suffering from a nervous form of dourine, a sexually-transmitted disease caused by Trypanosoma equiperdum. The recently described experimental model for assessing drug efficacy against horse trypanosomosis allowed us to obtain eight horses (Welsh pony mares) infected by T. equiperdum with parasites in their cerebrospinal fluid. The Cymelarsan® treatment evaluated consisted of the daily administration of 0.5 mg/kg of Cymelarsan® over 7 days. Two control horses remained untreated, three horses received the treatment 36 days p.i. and three horses received the treatment 16 days p.i. Following treatment, we observed parasite clearance in blood, stabilization of rectal temperature and a relative improvement in the mean packed cell volume levels for all treated horses. However, live parasites were later observed again in the CSF of all treated horses. Our results indicate the inability of Cymelarsan® to reach Trypanozoon located in the central nervous system of infected horses and thus discourage the use of Cymelarsan® to treat animals suffering from a nervous form of dourine.


Assuntos
Arsenicais/uso terapêutico , Líquido Cefalorraquidiano/parasitologia , Mal do Coito (Veterinária)/líquido cefalorraquidiano , Mal do Coito (Veterinária)/tratamento farmacológico , Doenças dos Cavalos/líquido cefalorraquidiano , Doenças dos Cavalos/tratamento farmacológico , Animais , Arsenicais/normas , Feminino , Doenças dos Cavalos/parasitologia , Cavalos/líquido cefalorraquidiano , Cavalos/parasitologia , Falha de Tratamento , Trypanosoma/fisiologia
16.
Int J Nanomedicine ; 13: 5937-5952, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30323584

RESUMO

Background: The Traditional Chinese Medicine, arsenic trioxide (ATO, As2O3) could inhibit growth and induce apoptosis in a variety of solid tumor cells, but it is severely limited in the treatment of glioma due to its poor BBB penetration and nonspecifcity distribution in vivo. Purpose: The objective of this study was encapsulating ATO in the modified PAMAM den-drimers to solve the problem that the poor antitumor effect of ATO to glioma, which provide a novel angle for the study of glioma treatment. Methods: The targeting drug carrier (RGDyC-mPEG-PAMAM) was synthesized based on Arg-Gly-Asp (RGDyC) and αvß3 integrin targeting ligand, and conjugated to PEGylated fifth generation polyamidoamine dendrimer (mPEG-PAMAM). It was characterized by nuclear magnetic resonance, fourier transform infrared spectra, Nano-particle size-zeta potential analyzer,etc. The in vitro release characteristics were studied by dialysis bag method. MTT assay was used to investigate the cytotoxicity of carriers and the antitumor effect of ATO formulation. In vitro blood-brain barrier (BBB) and C6 cell co-culture models were established to investigate the inhibitory effect of different ATO formulation after transporting across BBB. Pharmacokinetic and antitumor efficacy studies were investigated in an orthotopic murine model of C6 glioma. Results: The prepared RGDyC-mPEG-PAMAM was characterized for spherical dendrites, comparable size (21.60±6.81 nm), and zeta potential (5.36±0.22 mV). In vitro release showed that more ATO was released from RGDyC-mPEG-PAMAM/ATO (79.5%) at pH 5.5 than that of pH 7.4, during 48 hours. The cytotoxicity of PEG-modified carriers was lower than that of the naked PAMAM on both human brain microvascular endothelial cells and C6 cells. In in vitro BBB model, modification of RGDyC heightened the cytotoxicity of ATO loaded on PAMAM, due to an increased uptake by C6 cells. The results of cell cycle and apoptosis analysis revealed that RGDyC-mPEG-PAMAM/ATO arrested the cell cycle in G2-M and exhibited threefold increase in percentage of apoptosis to that in the PEG-PAMAM/ATO group. Compared with ATO-sol group, both RGDyC-mPEG-PAMAM/ATO and mPEG-PAMAM/ATO groups prolonged the half-life time, increased area under the curve, and improved antitumor effect, significantly. While the tumor volume inhibitory of RGDyC-mPEG-PAMAM/ATO was 61.46±12.26%, it was approximately fourfold higher than the ATO-sol group, and twofold to the mPEG-PAMAM/ATO group. Conclusion: In this report, RGDyC-mPEG-PAMAM could enhance the antitumor of ATO to glioma, it provides a desirable strategy for targeted therapy of glioma.


Assuntos
Arsenicais/uso terapêutico , Dendrímeros/química , Sistemas de Liberação de Medicamentos , Glioma/tratamento farmacológico , Oligopeptídeos/química , Óxidos/uso terapêutico , Polietilenoglicóis/química , Animais , Apoptose/efeitos dos fármacos , Trióxido de Arsênio , Arsenicais/administração & dosagem , Arsenicais/farmacocinética , Arsenicais/farmacologia , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Glioma/patologia , Humanos , Masculino , Camundongos , Óxidos/administração & dosagem , Óxidos/farmacocinética , Óxidos/farmacologia , Coelhos , Ratos , Eletricidade Estática , Resultado do Tratamento
17.
Jpn J Radiol ; 36(11): 686-690, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30251115

RESUMO

PURPOSE: In an Asian international multicenter phase II trial conducted in patients with peripheral T-cell lymphoma (PTCL), [F-18]FDG-PET/CT was used for evaluation of the therapeutic response. Standardization of the PET/CT scanners was necessary before patient enrollment. We therefore standardized the scanners by phantom tests based on the profile approved by the Quantitative Imaging Biomarkers Alliance (QIBA) of Radiological Society of North America (RSNA). MATERIALS AND METHODS: The tests were conducted on 12 scanners in 12 facilities in compliance with the QIBA Profile and used National Electrical Manufacturers Association (NEMA) International Electrotechnical Commission (IEC) body phantoms. We measured three parameters (standardized uptake value [SUV], resolution and noise) and adjusted the imaging parameter values. The indexes recommended in the Japanese Society of Nuclear Medicine (JSNM) guideline were also evaluated. RESULTS: In a total of 12 facilities, 6 facilities required no change in imaging conditions and 6 facilities required changes in imaging parameters. After revision, the three measurements (SUV, resolution and noise) met QIBA criteria at all sites, but 10 of the 12 scanners did not meet JSNM criteria. CONCLUSION: We standardized imaging conditions using phantoms as required in the RSNA-QIBA profile for response evaluation by [F-18]FDG PET/CT images in a multicenter study.


Assuntos
Arsenicais/uso terapêutico , Fluordesoxiglucose F18 , Glutationa/análogos & derivados , Linfoma de Células T Periférico/diagnóstico por imagem , Linfoma de Células T Periférico/tratamento farmacológico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Idoso , Ásia , Biomarcadores , Feminino , Glutationa/uso terapêutico , Humanos , Internacionalidade , Japão , Masculino , Pessoa de Meia-Idade , América do Norte , Imagens de Fantasmas , Radiologia , Padrões de Referência , Sociedades Médicas , Resultado do Tratamento
18.
J Am Anim Hosp Assoc ; 54(5): 246-256, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30040440

RESUMO

This descriptive study was designed to ascertain the current heartworm treatment strategies employed by veterinary graduates of a single college of veterinary medicine, to assess the frequency with which each of these treatment strategies is prescribed, and to report the motivation behind the use of these treatment strategies. A survey containing a combination of multiple-choice and open-ended questions was distributed via e-mail with an online link during 2013 to graduates of the University of Georgia College of Veterinary Medicine. Demographic data and opinions regarding treatment for cases of canine heartworm disease (HWD) were obtained, and motivation for recommending different treatment strategies was assessed. Nearly all 170 respondents (99%) indicated that they recommend melarsomine dihydrochloride for first-line treatment of canine HWD. Exercise restriction (80%) and monthly heartworm preventive (75%) were components of the treatment approach to HWD with no clinical signs. The majority of respondents (74%) indicated that when first-line treatment recommendations were declined, they endorsed long-term administration of ivermectin (i.e., "slow-kill" method) despite current American Heartworm Society guidelines that recommend against the use of long-term macrocyclic lactone administration for the monotherapy treatment of canine HWD. Respondents also indicated that owners' financial concerns frequently result in modification of HWD treatment. Routine inclusion of exercise restriction is commonly, but not universally, utilized and may represent an opportunity for improvement in the management of this disease. In addition, when first-line recommendations for heartworm disease treatment are declined, a two-dose melarsomine protocol instead of the slow-kill method should be considered.


Assuntos
Dirofilariose/terapia , Doenças do Cão/terapia , Faculdades de Medicina Veterinária , Médicos Veterinários , Corticosteroides , Animais , Anti-Helmínticos/uso terapêutico , Arsenicais/uso terapêutico , Resina de Colestiramina , Coleta de Dados , Cães , Doxiciclina , Ivermectina/uso terapêutico , Condicionamento Físico Animal , Triazinas/uso terapêutico
19.
Methods Appl Fluoresc ; 6(4): 045001, 2018 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-29938685

RESUMO

Visualization of viruses in the host cell during the course of infection by correlative light-electron microscopy (CLEM) requires a specific labelling of the viral structures in order to recognize the nanometric viral cores in the intracellular environment. For Human immunodeficiency virus type 1 (HIV-1), the labelling approaches developed for fluorescence microscopy are generally not suited for transmission electron microscopy (TEM), so that imaging of HIV-1 particles in infected cells by CLEM is not straightforward. Herein, we adapt the labeling approach with a tetracystein tag (TC) and a biarsenical resorufin-based label (ReAsH) for monitoring the HIV-1 particles during the early stages of HIV-1 infection by CLEM. In this approach, the ReAsH fluorophore triggers the photo-conversion of 3,3-diaminobenzidine tetrahydrochloride (DAB), generating a precipitate sensitive to osmium tetroxide staining that can be visualized by transmission electron microscopy. The TC tag is fused to the nucleocapsid protein NCp7, a nucleic acid chaperone that binds to the viral genome. HeLa cells, infected by ReAsH-labeled pseudoviruses containg NCp7-TC proteins exhibit strong fluorescent cytoplasmic spots that overlap with dark precipitates in the TEM sections. The DAB precipitates corresponding to single viral cores are observed all over the cytoplasm, and notably near microtubules and nuclear pores. This work describes for the first time a specific contrast given by HIV-1 viral proteins in TEM images and opens new perspectives for the use of CLEM to monitor the intracellular traffic of viral complexes.


Assuntos
Arsenicais/uso terapêutico , Infecções por HIV/virologia , HIV-1/patogenicidade , Microscopia Eletrônica/métodos , Microscopia de Fluorescência/métodos , Oxazinas/uso terapêutico , Arsenicais/farmacologia , Humanos , Oxazinas/farmacologia
20.
Medicine (Baltimore) ; 97(18): e0613, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29718867

RESUMO

BACKGROUND: Primary hepatic carcinoma (PHC) is the third commonest leading to cancer death around the world, and transarterial chemoembolization (TACE) has been proposed as the first-line therapeutic treatment for patients with unresectable PHC. This study aims to determine whether the combination of As2O3 and TACE is superior to alone TACE for achieving more clinical therapeutic efficacy, survival time, life quality and safety in patients with unresectable PHC. METHODS: A comprehensive literature search was conducted on the clinical controlled trials comparing therapeutic effects of As2O3 & TACE versus alone TACE for unresectable PHC through English databases (including PubMed, Embase, and the Cochrane Library) and Chinese databases (including China Knowledge Resource Integrated Database, Wanfang Database, Weipu Database, and Chinese Biomedical Database). The last search was in 30 August 2017. A recursive search was performed with bibliographies of relevant studies. There were no language restrictions. Primary outcomes, defined a priori, were therapeutic responses (clinical effective rate and clinical benefit rate), survival time, life quality, and adverse events of As2O3 & TACE compared with alone TACE expressed as relative risk (RR) with 95% confidence intervals (CI). RESULTS: 25 clinical controlled trials involving 1886 participants were included. We found that there were significant superiority associated with As2O3 & TACE compared with alone TACE in clinical benefit rate (RR: 1.24, 95% CI: 1.12-1.37), clinical effective rate (RR: 1.35, 95% CI: 1.17-1.55), 2-year survival rate (RR: 1.45, 95% CI: 1.20-1.75), and improving of KPS (RR: 1.31, 95% CI: 1.14-1.50). These associations were also observed in subgroups by intervened methods of As2O3 and pulmonary metastasis. Notably, the pooled relative risk of retention of sodium and water was obviously raised in patients with As2O3 & TACE therapy (RR: 16.616, 95% CI: 8.01 - 34.486). CONCLUSION: The superiority of adjuvant As2O3 therapy combined with TACE in PHC individuals will outweigh alone TACE therapy, especially in PHC populations with pulmonary metastasis.


Assuntos
Antineoplásicos/uso terapêutico , Arsenicais/uso terapêutico , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Óxidos/uso terapêutico , Antineoplásicos/efeitos adversos , Trióxido de Arsênio , Arsenicais/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/mortalidade , Terapia Combinada , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Óxidos/efeitos adversos , Qualidade de Vida , Taxa de Sobrevida , Resultado do Tratamento
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