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1.
Molecules ; 28(6)2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36985774

RESUMO

Silver nanoparticles (Ag-NPs) are most effective against pathogens and have widely been studied as antibacterial agents in commodity clothing, medical textile, and other hygiene products. However, prolonged utilization of silver and rapid mutation in bacterium stains has made them resistant to conventional silver agents. On the other hand, strict compliance against excessive utilization of toxic reagents and the current sustainability drive is forcing material synthesis toward green routes with extended functionality. In this study, we proposed an unprecedented chemical-free green synthesis of bioactive Ag-NPs without the incorporation of any chemicals. Cinnamon essential oil (ECO) was used as a bio-reducing agent with and without the mediation of lime extract. A rapid reaction completion with better shape and size control was observed in the vicinity of lime extract when incorporated into the reaction medium. The interaction of natural metabolites and citrus compounds with nanoparticles was established using Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy. The application of as-prepared nanoparticles on textiles encompasses extended bioactivity to treated fabric with infused easy-care performance. To the best of our knowledge, this is the first reported instance of utilizing bioactive silver nanoparticles as a functional finish, both as an antimicrobial and as for easy care in the absolute absence of toxic chemicals. The easy-care performance of fabric treated with lime-mediated nanoparticles was found to be 141O, which is around 26% better than bare cotton without any significant loss in fabric strength. Furthermore, to enlighten the sustainability of the process, the development traits were mapped with the United Nations Sustainable Development Goals (SDGs), which show significant influence on SDGs 3, 8, 9, and 14. With the effective suspension of microorganisms, added functionality, and eco-mapping with SDGs with the chemical-free synthesis of nanoparticles, widespread utilization can be found in various healthcare and hygiene products along with the fulfillment of sustainability needs.


Assuntos
Nanopartículas Metálicas , Nanosferas , Prata/farmacologia , Prata/química , Desenvolvimento Sustentável , Nanopartículas Metálicas/química , Antibacterianos/química , Vestuário , Espectroscopia de Infravermelho com Transformada de Fourier , Extratos Vegetais/farmacologia , Extratos Vegetais/química
2.
Viruses ; 13(12)2021 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-34960653

RESUMO

Fraxinus rhynchophylla, common name ash, belongs to the family Oleaceae and is found in China, Korea, North America, the Indian subcontinent, and eastern Russia. It has been used as a traditional herbal medicine in Korea and various parts of the world due to its chemical constituents. During a field survey in March 2019, mild vein thickening (almost negligible) was observed in a few ash trees. High-throughput sequencing of libraries of total DNA from ash trees, rolling-circle amplification (RCA), and polymerase chain reaction (PCR) allowed the identification of a Fraxinus symptomless virus. This virus has five confirmed open reading frames along with a possible sixth open reading frame that encodes the movement protein and is almost 2.7 kb in size, with a nonanucleotide and stem loop structure identical to begomoviruses. In terms of its size and structure, this virus strongly resembles begomoviruses, but does not show any significant sequence identity with them. To confirm movement of the virus within the trees, different parts of infected trees were examined, and viral movement was successfully observed. No satellite molecules or DNA B were identified. Two-step PCR confirmed the virion and complementary strands during replication in both freshly collected infected samples of ash tree and Nicotiana benthamiana samples agro-inoculated with infectious clones. This taxon is so distantly grouped from other known geminiviruses that it likely represents a new geminivirus genus.


Assuntos
Fraxinus/virologia , Geminiviridae/classificação , Geminiviridae/isolamento & purificação , Doenças das Plantas/virologia , Sequência de Bases , DNA Viral/genética , Geminiviridae/genética , Genoma Viral , Fases de Leitura Aberta , Filogenia , República da Coreia , Nicotiana/virologia
3.
Front Mol Neurosci ; 14: 643483, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220447

RESUMO

Riboflavin, also known as vitamin B2, isfound in foods and is used as a dietary supplement. Its deficiency (also called ariboflavinosis) results in some skin lesions and inflammations, such as stomatitis, cheilosis, oily scaly skin rashes, and itchy, watery eyes. Various therapeutic effects of riboflavin, such as anticancer, antioxidant, anti-inflammatory, and anti-nociceptive effects, are well known. Although some studies have identified the clinical effect of riboflavin on skin problems, including itch and inflammation, its underlying mechanism of action remains unknown. In this study, we investigated the molecular mechanism of the effects of riboflavin on histamine-dependent itch based on behavioral tests and electrophysiological experiments. Riboflavin significantly reduced histamine-induced scratching behaviors in mice and histamine-induced discharges in single-nerve fiber recordings, while it did not alter motor function in the rotarod test. In cultured dorsal root ganglion (DRG) neurons, riboflavin showed a dose-dependent inhibitory effect on the histamine- and capsaicin-induced inward current. Further tests wereconducted to determine whether two endogenous metabolites of riboflavin, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), have similar effects to those of riboflavin. Here, FMN, but not FAD, significantly inhibited capsaicin-induced currents and itching responses caused by histamine. In addition, in transient receptor potential vanilloid 1 (TRPV1)-transfected HEK293 cells, both riboflavin and FMN blocked capsaicin-induced currents, whereas FAD did not. These results revealed that riboflavin inhibits histamine-dependent itch by modulating TRPV1 activity. This study will be helpful in understanding how riboflavin exerts antipruritic effects and suggests that it might be a useful drug for the treatment of histamine-dependent itch.

4.
Theranostics ; 10(26): 12111-12126, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33204332

RESUMO

Rationale: Psoriasis is a chronic inflammatory disease caused by a complex interplay between the immune and nervous systems with recurrent scaly skin plaques, thickened stratum corneum, infiltration and activation of inflammatory cells, and itch. Despite an increasing availability of immune therapies, they often have adverse effects, high costs, and dissociated effects on inflammation and itch. Activation of sensory neurons innervating the skin and TRPV1 (transient receptor potential vanilloid 1) are emerging as critical components in the pathogenesis of psoriasis, but little is known about their endogenous inhibitors. Recent studies have demonstrated that resolvins, endogenous lipid mediators derived from omega-3 fatty acids, are potent inhibitors of TRP channels and may offer new therapies for psoriasis without known adverse effects. Methods: We used behavioral, electrophysiological and biochemical approaches to investigate the therapeutic effects of resolvin D3 (RvD3), a novel family member of resolvins, in a preclinical model of psoriasis consisting of repeated topical applications of imiquimod (IMQ) to murine skin, which provokes inflammatory lesions that resemble human psoriasis. Results: We report that RvD3 specifically reduced TRPV1-dependent acute pain and itch in mice. Mechanistically, RvD3 inhibited capsaicin-induced TRPV1 currents in dissociated dorsal root ganglion (DRG) neurons via the N-formyl peptide receptor 2 (i.e. ALX/FPR2), a G-protein coupled receptor. Single systemic administration of RvD3 (2.8 mg/kg) reversed itch after IMQ, and repeated administration largely prevented the development of both psoriasiform itch and skin inflammation with concomitant decreased in calcitonin gene-related peptide (CGRP) expression in DRG neurons. Accordingly, specific knockdown of CGRP in DRG was sufficient to prevent both psoriasiform itch and skin inflammation similar to the effects following RvD3 administration. Finally, we elevated the translational potential of this study by showing that RvD3 significantly inhibited capsaicin-induced TRPV1 activity and CGRP release in human DRG neurons. Conclusions: Our findings demonstrate a novel role for RvD3 in regulating TRPV1/CGRP in mouse and human DRG neurons and identify RvD3 and its neuronal pathways as novel therapeutic targets to treat psoriasis.


Assuntos
Ácidos Graxos Insaturados/farmacologia , Dor/tratamento farmacológico , Prurido/tratamento farmacológico , Psoríase/tratamento farmacológico , Canais de Cátion TRPV/antagonistas & inibidores , Animais , Biópsia , Peptídeo Relacionado com Gene de Calcitonina/genética , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Capsaicina/toxicidade , Células Cultivadas , Modelos Animais de Doenças , Ácidos Graxos Insaturados/uso terapêutico , Gânglios Espinais/citologia , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/imunologia , Técnicas de Silenciamento de Genes , Humanos , Masculino , Camundongos , Neuroimunomodulação/efeitos dos fármacos , Neuroimunomodulação/imunologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Dor/induzido quimicamente , Dor/imunologia , Dor/patologia , Técnicas de Patch-Clamp , Cultura Primária de Células , Prurido/induzido quimicamente , Prurido/imunologia , Prurido/patologia , Psoríase/complicações , Psoríase/imunologia , Psoríase/patologia , Pele/efeitos dos fármacos , Pele/imunologia , Pele/inervação , Canais de Cátion TRPV/metabolismo
5.
Bioorg Med Chem Lett ; 29(3): 400-405, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30594431

RESUMO

To increase the contents of medicinally effective ginsenosides, we used high-temperature and high-pressure thermal processing of ginseng by exposing it to microwave irradiation. To determine the anti-melanoma effect, the malignant melanoma SK-MEL-2 cell line was treated with an extract of microwave-irradiated ginseng. Microwave irradiation caused changes in the ginsenoside contents: the amounts of ginsenosides Rg1, Re, Rb1, Rb2, Rc, and Rd were disappeared, while those of less polar ginsenosides, such as Rg3, Rg5, and Rk1, were increased. In particular, the contents of Rk1 and Rg5 markedly increased. Melanoma cells treated with the microwave-irradiated ginseng extract showed markedly increased cell death. The results indicate that the microwave-irradiated ginseng extract induced melanoma cell death via the apoptotic pathway and that the cytotoxic effect of the microwave-irradiated ginseng extract is attributable to the increased contents of specific ginsenosides.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Ginsenosídeos/farmacologia , Melanoma/tratamento farmacológico , Micro-Ondas , Extratos Vegetais/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Ginsenosídeos/química , Ginsenosídeos/isolamento & purificação , Glicosilação , Humanos , Melanoma/patologia , Estrutura Molecular , Panax/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Relação Estrutura-Atividade
6.
Neuropharmacology ; 135: 572-580, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29634983

RESUMO

Unlike in the central nervous system (CNS), in the adult peripheral nervous system (PNS), activation of GABAA receptors (GABAAR) is excitatory because of the relatively high concentration of intracellular chloride in these neurons. Indeed, exogenous GABA and muscimol, a GABAAR agonist, exacerbate acute inflammatory hypersensitivity in rodents. However, it remains unclear whether peripheral GABAAR and the endogenous GABA play an important role in persistent inflammatory hypersensitivity. In this study, we thus investigated how peripheral GABAAR affects pain hypersensitivity by using the complete Freund's adjuvant (CFA)-induced persistent inflammatory pain mouse model. We found that intraplantar (i.pl.) administration of GABAAR antagonists, picrotoxin, and 1(S),9(R)-(-)-bicuculline methiodide significantly inhibited both spontaneous nociceptive (paw licking and flinching) behavior and mechanical hypersensitivity in CFA-injected mice at day 3 (D3), but not in naïve mice. Interestingly, CFA-induced mechanical hypersensitivity was significantly reversed by anti-GABA antibody (anti-GABA, i.pl.). In addition, RT-qPCR revealed that glutamate decarboxylase Gad1 (GAD 67) and Gad2 (GAD 65) mRNA expression was also upregulated in the ipsilateral hind paw of CFA-injected mice at D3. Finally, 5α-pregnan-3α-ol-20-one (3α,5α-THP), a selective positive allosteric modulator of GABAAR, produced mechanical hypersensitivity in naïve mice in a dose-dependent manner. Taken together, our results indicate that peripheral GABAAR and endogenous GABA, possibly produced by the inflamed tissue, potentiate CFA-induced persistent inflammatory hypersensitivity, suggesting that they can be used as a therapeutic target for alleviating inflammatory pain.


Assuntos
Hiperalgesia/metabolismo , Inflamação/metabolismo , Receptores de GABA-A/metabolismo , Animais , Anticorpos/farmacologia , Adjuvante de Freund , Agonistas de Receptores de GABA-A/farmacologia , Antagonistas de Receptores de GABA-A/farmacologia , Glutamato Descarboxilase/metabolismo , Hiperalgesia/tratamento farmacológico , Inflamação/tratamento farmacológico , Masculino , Camundongos Endogâmicos C57BL , Dor Nociceptiva/tratamento farmacológico , Dor Nociceptiva/metabolismo , RNA Mensageiro/metabolismo , Distribuição Aleatória , Tato , Ácido gama-Aminobutírico/imunologia , Ácido gama-Aminobutírico/metabolismo
7.
J Korean Med Sci ; 32(5): 757-763, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28378548

RESUMO

The kidney is one of the most radiosensitive organs in the abdominal cavity and is the dose-limiting structure in cancer patients receiving abdominal or total body irradiation. In the present study, the effect of coenzyme Q10 (CoQ10) on radiation nephropathy was evaluated in rats. A total of 72 rats were equally randomized into 4 groups: Control, CoQ10, irradiation with 10 Gy (RT) + placebo, or RT + CoQ10. The 2 RT groups received single 10 Gy of abdominal irradiation. The 2 CoQ10 groups were supplemented daily with 1 mL of soybean oil containing 10 mg/kg of CoQ10. The RT + placebo and control groups received same dose of soybean oil. After 24 weeks, laboratory and histopathologic findings were compared. The 2 RT groups showed significant increases in blood urea nitrogen (BUN) and creatinine levels and significant pathologic changes such as glomerulosclerosis and tubulointerstitial fibrosis. CoQ10 supplementation resulted in significant reductions of BUN and creatinine levels compared with the RT + placebo group (P < 0.001 and P = 0.038, respectively). CoQ10 treatment significantly attenuated glomerular and tubular changes of irradiated kidney in semiquantitative analysis (P < 0.001 for both). Administration of CoQ10 can alleviate the radiation-induced nephropathy.


Assuntos
Raios gama , Nefropatias/prevenção & controle , Rim/efeitos da radiação , Ubiquinona/análogos & derivados , Animais , Nitrogênio da Ureia Sanguínea , Peso Corporal/efeitos da radiação , Creatinina/sangue , Suplementos Nutricionais , Rim/patologia , Nefropatias/patologia , Masculino , Efeito Placebo , Ratos , Ratos Sprague-Dawley , Ubiquinona/uso terapêutico
8.
Cell ; 164(1-2): 183-196, 2016 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-26771491

RESUMO

Proper establishment of synapses is critical for constructing functional circuits. Interactions between presynaptic neurexins and postsynaptic neuroligins coordinate the formation of synaptic adhesions. An isoform code determines the direct interactions of neurexins and neuroligins across the synapse. However, whether extracellular linker proteins can expand such a code is unknown. Using a combination of in vitro and in vivo approaches, we found that hevin, an astrocyte-secreted synaptogenic protein, assembles glutamatergic synapses by bridging neurexin-1alpha and neuroligin-1B, two isoforms that do not interact with each other. Bridging of neurexin-1alpha and neuroligin-1B via hevin is critical for the formation and plasticity of thalamocortical connections in the developing visual cortex. These results show that astrocytes promote the formation of synapses by modulating neurexin/neuroligin adhesions through hevin secretion. Our findings also provide an important mechanistic insight into how mutations in these genes may lead to circuit dysfunction in diseases such as autism.


Assuntos
Astrócitos/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Moléculas de Adesão Celular Neuronais/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Moléculas de Adesão de Célula Nervosa/metabolismo , Tálamo/metabolismo , Animais , Células COS , Chlorocebus aethiops , Dominância Ocular , Humanos , Camundongos , Camundongos Knockout , Doenças do Sistema Nervoso/metabolismo , Neurônios/metabolismo , Isoformas de Proteínas/metabolismo , Transdução de Sinais , Sinapses/metabolismo
9.
Gut Liver ; 9(4): 486-93, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25287166

RESUMO

BACKGROUND/AIMS: The aims of this study were to investigate whether a broccoli sprout extract containing sulforaphane (BSES) inhibited the Helicobacter pylori infection density and exerted an antioxidative effect on gastric mucosal damage. METHODS: The enrolled subjects were randomized in a double-blinded manner into three groups. Finally, 33 H. pylori (+) BSES treatment subjects (group A), 28 H. pylori (+) placebo subjects (group B), and 28 H. pylori (-) BSES treatment subjects (group C) were studied. H. pylori infection density was indirectly quantified by a (13)C-urea breath test (UBT), and the ammonia concentration in gastric juice aspirates was measured through gastroscopic examination. Malondialdehyde (MDA), an oxidative damage biomarker, and reduced glutathione (GSH), an antioxidant biomarker, were measured in the gastric mucosa by an enzyme-linked immunosorbent assay. RESULTS: BSES treatment did not significantly affect the UBT values or ammonia concentration in group A (p=0.634 and p=0.505, respectively). BSES treatment did significantly reduce mucosal MDA concentrations in group A (p<0.05) and group C (p<0.001), whereas the gastric mucosal GSH concentrations did not differ before and after treatment in any of the groups. CONCLUSIONS: BSES did not inhibit the H. pylori infection density. However, BSES prevented lipid peroxidation in the gastric mucosa and may play a cytoprotective role in H. pylori-induced gastritis.


Assuntos
Antioxidantes/farmacologia , Brassica/química , Mucosa Gástrica/efeitos dos fármacos , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Isotiocianatos/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Adulto , Amônia/metabolismo , Biomarcadores/análise , Testes Respiratórios , Método Duplo-Cego , Ensaio de Imunoadsorção Enzimática , Feminino , Suco Gástrico/enzimologia , Mucosa Gástrica/metabolismo , Glutationa/análise , Humanos , Masculino , Malondialdeído/análise , Pessoa de Meia-Idade , Extratos Vegetais/química , Sulfóxidos , Ureia
10.
Artigo em Inglês | MEDLINE | ID: mdl-24062787

RESUMO

Acute lung injury (ALI) is an inflammatory disease with high mortality, but therapeutics against it is unavailable. Recently, we elaborated a formula, named Chung-pae (CP), that comprises four ethnic herbs commonly prescribed against various respiratory diseases in Asian traditional medicine. CP is being administered in aerosol to relieve various respiratory symptoms of patients in our clinic. Here, we sought to examine whether CP has a therapeutic effect on ALI and to uncover the mechanism behind it. Reporter assays show that CP suppressed the transcriptional activity of proinflammatory NF- κ B and activated that of anti-inflammatory Nrf2. Similarly, CP suppressed the expression of NF- κ B dependent, proinflammatory cytokines and induced that of Nrf2 dependent genes in RAW 264.7. An aerosol intratracheal administration of CP effectively reduced neutrophilic infiltration and the expression of pro-inflammatory cytokines, hallmarks of ALI, in the lungs of mice that received a prior intraperitoneal injection of lipopolysaccharide. The intratracheal CP administration concomitantly enhanced the expression of Nrf2 dependent genes in the lung. Therefore, our results evidenced a therapeutic effect of CP on ALI, in which differential regulation of the two key inflammatory factors, NF- κ B and Nrf2, was involved. We propose that CP can be a new therapeutic formula against ALI.

11.
Artigo em Inglês | MEDLINE | ID: mdl-23762139

RESUMO

Decursin (D), purified from Angelica gigas Nakai, has been proven to exert neuroprotective property. Previous study revealed that D reduced A ß 25 ‒ 35-induced cytotoxicity in PC12 cells. Our study explored the underlying mechanisms by which D mediates its therapeutic effects in vitro. Pretreatment of cells with D diminished intracellular generation of ROS in response to A ß 25 ‒ 35. Western blot revealed that D significantly increased the expression and activity of HO-1, which was correlated with its protection against A ß 25 ‒ 35-induced injury. Addition of ZnPP, an HO-1 competitive inhibitor, significantly attenuated its protective effect in A ß 25 ‒ 35-treated cells, indicating the vital role of HO-1 resistance to oxidative injury. Moreover, D induced Nrf2 nuclear translocation, the upstream of HO-1 expression. While investigating the signaling pathways responsible for HO-1 induction, D activated ERK and dephosphorylated p38 in PC12 cells. Addition of U0126, a selective inhibitor of ERK, blocked D-induced Nrf2 activation and HO-1 induction and meanwhile reversed the protection of D against A ß 25 ‒ 35-induced cell death. These findings suggest D augments cellular antioxidant defense capacity through both intrinsic free radical scavenging activity and activation of MAPK signal pathways that leads to Nrf2 activation, and subsequently HO-1 induction, thereby protecting the PC12 cells from A ß 25 ‒ 35-induced oxidative cytotoxicity.

12.
Exp Toxicol Pathol ; 65(1-2): 73-80, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21741806

RESUMO

The possible protective effects of Chlorella vulgaris extract (CVE) on carbon tetrachloride (CCl(4))-induced acute hepatic injury in mice and the mechanism underlying these effects was investigated. CCl(4) administration caused a marked increase in the levels of serum aminotransferases, lipid peroxidation and cytochrome P450-2E1 (CYP450) expression. Also, decreased glutathione (GSH) content and activities of cellular antioxidant defense enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase and glutathione-S-transferase (GST) were found after CCl(4) exposure. All of these phenotypes were markedly reversed by preadministration of the mice with CVE. In addition, CVE exhibited antioxidant effects on FeCl(2)-ascorbate induced lipid peroxidation in mouse liver homogenates, and on superoxide radical scavenging activity. Taken together, these results suggest that CVE produced a protective action on CCl(4)-induced acute hepatic injury in mice, presumably through blocking CYP-mediated CCl(4) bioactivation, inducing the GSH levels, antioxidant enzyme activities and free radical scavenging effect. Therefore, CVE may be an effective hepatoprotective agent and viable candidate for treating hepatic disorders and other oxidative stress-related diseases.


Assuntos
Tetracloreto de Carbono/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Chlorella vulgaris/química , Sequestradores de Radicais Livres/uso terapêutico , Extratos Vegetais/uso terapêutico , Animais , Antioxidantes/metabolismo , Western Blotting , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Citocromo P-450 CYP2E1/metabolismo , Sequestradores de Radicais Livres/isolamento & purificação , Sequestradores de Radicais Livres/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Testes de Função Hepática , Masculino , Camundongos , Camundongos Endogâmicos ICR , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Superóxidos/química
13.
Lancet ; 379(9813): 315-21, 2012 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-22226517

RESUMO

BACKGROUND: D2 gastrectomy is recommended in US and European guidelines, and is preferred in east Asia, for patients with resectable gastric cancer. Adjuvant chemotherapy improves patient outcomes after surgery, but the benefits after a D2 resection have not been extensively investigated in large-scale trials. We investigated the effect on disease-free survival of adjuvant chemotherapy with capecitabine plus oxaliplatin after D2 gastrectomy compared with D2 gastrectomy only in patients with stage II-IIIB gastric cancer. METHODS: The capecitabine and oxaliplatin adjuvant study in stomach cancer (CLASSIC) study was an open-label, parallel-group, phase 3, randomised controlled trial undertaken in 37 centres in South Korea, China, and Taiwan. Patients with stage II-IIIB gastric cancer who had had curative D2 gastrectomy were randomly assigned to receive adjuvant chemotherapy of eight 3-week cycles of oral capecitabine (1000 mg/m(2) twice daily on days 1 to 14 of each cycle) plus intravenous oxaliplatin (130 mg/m(2) on day 1 of each cycle) for 6 months or surgery only. Block randomisation was done by a central interactive computerised system, stratified by country and disease stage. Patients, and investigators giving interventions, assessing outcomes, and analysing data were not masked. The primary endpoint was 3 year disease-free survival, analysed by intention to treat. This study reports a prespecified interim efficacy analysis, after which the trial was stopped after a recommendation by the data monitoring committee. The trial is registered at ClinicalTrials.gov (NCT00411229). FINDINGS: 1035 patients were randomised (520 to receive chemotherapy and surgery, 515 surgery only). Median follow-up was 34·2 months (25·4-41·7) in the chemotherapy and surgery group and 34·3 months (25·6-41·9) in the surgery only group. 3 year disease-free survival was 74% (95% CI 69-79) in the chemotherapy and surgery group and 59% (53-64) in the surgery only group (hazard ratio 0·56, 95% CI 0·44-0·72; p<0·0001). Grade 3 or 4 adverse events were reported in 279 of 496 patients (56%) in the chemotherapy and surgery group and in 30 of 478 patients (6%) in the surgery only group. The most common adverse events in the intervention group were nausea (n=326), neutropenia (n=300), and decreased appetite (n=294). INTERPRETATION: Adjuvant capecitabine plus oxaliplatin treatment after curative D2 gastrectomy should be considered as a treatment option for patients with operable gastric cancer. FUNDING: F Hoffmann-La Roche and Sanofi-Aventis.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Gastrectomia , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/análogos & derivados , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida
14.
J Agric Food Chem ; 59(2): 584-91, 2011 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-21175184

RESUMO

Tocochromanols are potent lipid-soluble antioxidants and essential nutrients for human health. Genetic engineering techniques were used to develop soybeans with enhanced vitamin E levels, including tocotrienols, which are not found in soybean. The gene encoding rice homogentisate geranylgeranyl transferase (HGGT) was overexpressed in soybeans using seed-specific and constitutive promoters. The association between abundance of vitamin E isomers and antioxidant activity was investigated during seed germination. With the exception of ß-tocotrienol, all vitamin E isomers were detected in germinating seeds expressing OsHGGT. The antioxidant properties of germinating seed extracts were determined using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radicals and lipid peroxidation (TBARS). Compared with intact wild-type seeds, transgenic seeds showed increases in radical scavenging of 5.4-17 and 23.2-35.3% in the DPPH and ABTS assays, respectively. Furthermore, the lipid peroxidation levels were 2.0-4.5-fold lower in germinating seeds from transgenic lines than in wild-type seeds. Therefore, it appears that the antioxidant potential of transgenic oil-producing plants such as soybean, sunflower, and corn may be enhanced by overexpressing OsHGGT during seed germination.


Assuntos
Alquil e Aril Transferases/genética , Antioxidantes/análise , Glycine max/química , Peroxidação de Lipídeos/efeitos dos fármacos , Oryza/enzimologia , Extratos Vegetais/análise , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/química , Alquil e Aril Transferases/metabolismo , Antioxidantes/farmacologia , Expressão Gênica , Germinação , Extratos Vegetais/farmacologia , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas/metabolismo , Sementes/química , Sementes/genética , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Glycine max/genética , Glycine max/crescimento & desenvolvimento , Glycine max/metabolismo
15.
J Microbiol Biotechnol ; 20(9): 1331-8, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20890099

RESUMO

This study was designed to investigate the potentially protective effects of Curcuma longa Linn. extract (CLE) on carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. Male Sprague-Dawley rats were pretreated with 50 or 100mg/kg of CLE or 100mg/kg of butylated hydroxytoluene (BHT) for 14 days before CCl4 administration. In addition, the CLE control group was pretreated with 100mg/kg CLE for only 14 days. Three hours after the final treatment, a single dose of CCl4 (20mg/kg) was administrated intraperitoneally to each group. After the completion of this phase of the experiment, food and water were removed 12 h prior to the next step. The rats were then anesthetized by urethane and their blood and liver were collected. It was observed that the aspartate aminotransferase and alanine aminotransferase activities of the serum, and the hepatic malondialdehyde levels had significantly decreased in the CLE group when compared with the CCl4-treated group. The antioxidant activities, such as superoxide dismutase, catalase, and glutathione peroxidase activities, in addition to glutathione content, had increased considerably in the CLE group compared with the CCl4-treated group. Phase II detoxifying enzymes, such as glutathione S-transferase, were found to have significantly increased in the CLE group as opposed to the CCl4-treated group. The content of Nrf2 was determined by Western blot analysis. Pretreated CLE increased the level of nuclear translocated Nrf2, and the Nrf2 then increased the activity of the antioxidant and phase II detoxifying enzymes. These results indicate that CLE has protective effects against CCl4-induced hepatotoxicity in rats, via activities of antioxidant and phase II detoxifying enzymes, and through the activation of nuclear translocated Nrf2.


Assuntos
Tetracloreto de Carbono/toxicidade , Curcuma/química , Citoproteção , Fígado/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Extratos Vegetais/farmacologia , Animais , Injeções Intraperitoneais , Fígado/metabolismo , Fígado/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Regulação para Cima
16.
Hepatogastroenterology ; 51(55): 253-5, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15011878

RESUMO

We encountered a case of total parenteral nutrition-associated lactic acidosis that did not respond to sodium bicarbonate or other conventional emergency treatments. He was characterized by minimal food intake before surgery, delayed gastric emptying after pylorus-preserving pancreatoduodenectomy due to pancreas head cancer and long-term total parenteral nutrition without food intake and vitamin supplements after surgery. After thiamine administration, the patient very quickly recovered with dramatic reestablishment of the acid-base balance. We emphasize the need to supplement total parenteral nutrition with thiamine-containing vitamins for the patients whose food intake does not meet nutritional requirements and to intravenously replenish using high-dose thiamine simultaneously with the manifestation of signs and symptoms of severe lactic acidosis with unknown cause. In conclusion, thiamine deficiency should be included in the differential diagnosis of lactic acidosis for the patients who received total parenteral nutrition without food intake and vitamin supplements.


Assuntos
Acidose Láctica/etiologia , Nutrição Parenteral Total/efeitos adversos , Deficiência de Tiamina/etiologia , Acidose Láctica/terapia , Esvaziamento Gástrico , Humanos , Infusões Intravenosas , Masculino , Diálise Renal , Tiamina/administração & dosagem , Deficiência de Tiamina/diagnóstico , Deficiência de Tiamina/terapia
17.
J Korean Med Sci ; 18(5): 756-7, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14555834

RESUMO

With acupuncture treatment becoming an increasingly popular analgesic, there have been increasing reports on its associated complications. Although pneumothorax is the most frequently reported injury caused by acupuncture needles, infectious complications may not be uncommon. Most infectious complications show less serious clinical manifestations than pneumothorax, but retroperitoneal or intraabdominal abscess caused by acupuncture may be much more serious conditions. We experienced a 56-yr-old male diabetic patient presenting with serious retroperitoneal abscess after acupuncture treatments. Emergency operative drainage with adequate antibiotic therapy was performed. Bacterial culture of blood and closed pus specimens recovered Klebsiella pneumoniae. In addition to application of better knowledge on anatomy, appropriate antiseptic practice by practitioners will reduce many serious complications associated with acupuncture.


Assuntos
Terapia por Acupuntura/efeitos adversos , Acupuntura , Antibacterianos/uso terapêutico , Infecções por Klebsiella/diagnóstico , Klebsiella pneumoniae/metabolismo , Abscesso Abdominal/diagnóstico por imagem , Complicações do Diabetes , Humanos , Infecções por Klebsiella/terapia , Masculino , Pessoa de Meia-Idade , Sepse/diagnóstico , Tomografia Computadorizada por Raios X
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