ABSTRACT
Acute myeloid leukemia (AML) is an aggressive hematologic cancer in adults. Some patients exhibit restricted T cell infiltration and do not respond to routine treatments. This may be prevented by enhancing adaptive immunity by stimulating innate immune cells inside the tumor microenvironment (TME). To activate the adaptive immunological reaction against tumors, type I interferons (IFNs) can promote the presentation of tumor-specific cytotoxic T lymphocyte (CTL) cell recruitment. During the activation of innate immunity, cyclic di-nucleotides (CDNs) bind to and stimulate the stimulator of interferon genes (STING), a protein localized inside the endoplasmic reticulum (ER) membrane, resulting in the expression of type I IFNs. The efficacy of STING agonists as effective stimulators of the anti-tumor response in AML is being investigated in numerous clinical studies. Therefore, the purpose of this investigation was to thoroughly review existing knowledge in this field and provide perspective into the clinical potential of STING agonists in AML.
Subject(s)
Immunity, Innate , Leukemia, Myeloid, Acute , Humans , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Nucleotides, Cyclic , Adaptive Immunity , Interferons , Immunotherapy/methods , Tumor MicroenvironmentABSTRACT
Resumo Fundamento A dupla antiagregação plaquetária (DAP) é o tratamento fundamental do infarto agudo do miocárdio (IAM). Objetivo O presente estudo visou investigar a eficácia e a segurança da tripla antiagregação plaquetária (TAP) em pacientes femininas idosas com diabetes e infarto agudo do miocárdio com supradesnível do segmento ST (IAMCSST), que foram submetidas à intervenção coronária percutânea ICP. Métodos Trata-se se de um estudo randomizado e mono-cego. O grupo controle A (97 pacientes idosos do sexo masculino com diabetes e STEMI, cujos escores CRUSADE foram < 30) recebeu aspirina, ticagrelor e tirofibana. Um total de 162 pacientes femininas idosas com diabetes e IAMCSST foram divididas aleatoriamente em dois grupos de acordo com o escore CRUSADE. O grupo B (69 pacientes com escore CRUSADE > 31) recebeu aspirina e ticagrelor. O grupo C (93 pacientes com escore CRUSADE < 30) recebeu aspirina, ticagrelor e tirofibana. Valores de p < 0,05 foram considerados estatisticamente significativos. Resultados Após a PCI, o fluxo sanguíneo grau 3 Thrombolysis in Myocardial Infarction (TIMI) e a perfusão miocárdica TIMI grau 3 foram significativamente menos prevalentes no grupo B, em comparação com o grupo A (p < 0,05). Quando comparada aos grupos A e C, a incidência de complicações adversas maiores foi significativamente maior no grupo B (p < 0,05). Conclusão A TAP pode efetivamente reduzir a incidência de complicações maiores em pacientes idosas com diabetes e IAMCSST. No entanto, atenção cuidadosa deve ser dada à hemorragia em pacientes que recebem TAP. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)
Abstract Background Dual antiplatelet therapy (DAPT) is the cornerstone treatment of acute myocardial infarction (AMI). Objective The present study aimed to investigate the efficacy and safety of triple antiplatelet therapy (TAPT) in elderly female patients with diabetes and ST segment elevation myocardial infarction (STEMI), who had undergone percutaneous coronary intervention (PCI). Methods We designed a randomized, single-blind study. Control group A (97 elderly male patients with diabetes and STEMI, whose CRUSADE scores were < 30) received aspirin, ticagrelor, and tirofiban. A total of 162 elderly female patients with diabetes and STEMI were randomly divided into two groups according to CRUSADE score. Group B (69 patients with CRUSADE score > 31) received aspirin and ticagrelor. Group C (93 patients with CRUSADE score < 30) received aspirin, ticagrelor and tirofiban. P values < 0.05 were considered statistically significant. Results Compared to the findings in group A, post-PCI Thrombolysis in Myocardial Infarction (TIMI) grade 3 blood flow and TIMI myocardial perfusion grade 3 were significantly less prevalent in group B (p < 0.05). When compared to groups A and C, the incidence of major adverse complications was significantly higher in group B (p < 0.05). Conclusion TAPT could effectively reduce the incidence of major complications in elderly female patients with diabetes and STEMI. However, close attention should be paid to hemorrhage in patients receiving TAPT. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)
Subject(s)
Humans , Male , Female , Aged , Diabetes Mellitus/drug therapy , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Myocardial Infarction/drug therapy , Platelet Aggregation Inhibitors/therapeutic use , Single-Blind Method , Treatment OutcomeABSTRACT
BACKGROUND: Dual antiplatelet therapy (DAPT) is the cornerstone treatment of acute myocardial infarction (AMI). OBJECTIVE: The present study aimed to investigate the efficacy and safety of triple antiplatelet therapy (TAPT) in elderly female patients with diabetes and ST segment elevation myocardial infarction (STEMI), who had undergone percutaneous coronary intervention (PCI). METHODS: We designed a randomized, single-blind study. Control group A (97 elderly male patients with diabetes and STEMI, whose CRUSADE scores were < 30) received aspirin, ticagrelor, and tirofiban. A total of 162 elderly female patients with diabetes and STEMI were randomly divided into two groups according to CRUSADE score. Group B (69 patients with CRUSADE score > 31) received aspirin and ticagrelor. Group C (93 patients with CRUSADE score < 30) received aspirin, ticagrelor and tirofiban. P values < 0.05 were considered statistically significant. RESULTS: Compared to the findings in group A, post-PCI Thrombolysis in Myocardial Infarction (TIMI) grade 3 blood flow and TIMI myocardial perfusion grade 3 were significantly less prevalent in group B (p < 0.05). When compared to groups A and C, the incidence of major adverse complications was significantly higher in group B (p < 0.05). CONCLUSION: TAPT could effectively reduce the incidence of major complications in elderly female patients with diabetes and STEMI. However, close attention should be paid to hemorrhage in patients receiving TAPT. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0).
FUNDAMENTO: A dupla antiagregação plaquetária (DAP) é o tratamento fundamental do infarto agudo do miocárdio (IAM). OBJETIVO: O presente estudo visou investigar a eficácia e a segurança da tripla antiagregação plaquetária (TAP) em pacientes femininas idosas com diabetes e infarto agudo do miocárdio com supradesnível do segmento ST (IAMCSST), que foram submetidas à intervenção coronária percutânea ICP. MÉTODOS: Trata-se se de um estudo randomizado e mono-cego. O grupo controle A (97 pacientes idosos do sexo masculino com diabetes e STEMI, cujos escores CRUSADE foram < 30) recebeu aspirina, ticagrelor e tirofibana. Um total de 162 pacientes femininas idosas com diabetes e IAMCSST foram divididas aleatoriamente em dois grupos de acordo com o escore CRUSADE. O grupo B (69 pacientes com escore CRUSADE > 31) recebeu aspirina e ticagrelor. O grupo C (93 pacientes com escore CRUSADE < 30) recebeu aspirina, ticagrelor e tirofibana. Valores de p < 0,05 foram considerados estatisticamente significativos. RESULTADOS: Após a PCI, o fluxo sanguíneo grau 3 Thrombolysis in Myocardial Infarction (TIMI) e a perfusão miocárdica TIMI grau 3 foram significativamente menos prevalentes no grupo B, em comparação com o grupo A (p < 0,05). Quando comparada aos grupos A e C, a incidência de complicações adversas maiores foi significativamente maior no grupo B (p < 0,05). CONCLUSÃO: A TAP pode efetivamente reduzir a incidência de complicações maiores em pacientes idosas com diabetes e IAMCSST. No entanto, atenção cuidadosa deve ser dada à hemorragia em pacientes que recebem TAP. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0).
Subject(s)
Diabetes Mellitus , Myocardial Infarction , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Aged , Diabetes Mellitus/drug therapy , Female , Humans , Male , Myocardial Infarction/drug therapy , Platelet Aggregation Inhibitors/therapeutic use , Single-Blind Method , Treatment OutcomeABSTRACT
BACKGROUND: Snakebites remain a major life-threatening event worldwide. It is still difficult to make a positive identification of snake species by clinicians in both Western medicine and Chinese medicine. The main reason for this is a shortage of diagnostic biomarkers and lack of knowledge about pathways of venom-induced toxicity. In traditional Chinese medicine, snakebites are considered to be treated with wind, fire, and wind-fire toxin, but additional studies are required. METHODS: Cases of snakebite seen at the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine were grouped as follows: fire toxin - including four cases of bites by Agkistrodon acutus and three bites by Trimeresurus stejnegeri - and wind-fire toxin - four cases of bites by vipers and three bites by cobras. Serum protein quantification was performed using LC-MS/MS. Differential abundance proteins (DAPs) were identified from comparison of snakebites of each snake species and healthy controls. The protein interaction network was constructed using STITCH database. RESULTS: Principal component analysis and hierarchical clustering of 474 unique proteins exhibited protein expression profiles of wind-fire toxins that are distinct from that of fire toxins. Ninety-three DAPs were identified in each snakebite subgroup as compared with healthy control, of which 38 proteins were found to have significantly different expression levels and 55 proteins displayed no expression in one subgroup, by subgroup comparison. GO analysis revealed that the DAPs participated in bicarbonate/oxygen transport and hydrogen peroxide catabolic process, and affected carbon-oxygen lyase activity and heme binding. Thirty DAPs directly or indirectly acted on hydrogen peroxide in the interaction network of proteins and drug compounds. The network was clustered into four groups: lipid metabolism and transport; IGF-mediated growth; oxygen transport; and innate immunity. CONCLUSIONS: Our results show that the pathways of snake venom-induced toxicity may form a protein network of antioxidant defense by regulating oxidative stress through interaction with hydrogen peroxide.
ABSTRACT
Snakebites remain a major life-threatening event worldwide. It is still difficult to make a positive identification of snake species by clinicians in both Western medicine and Chinese medicine. The main reason for this is a shortage of diagnostic biomarkers and lack of knowledge about pathways of venom-induced toxicity. In traditional Chinese medicine, snakebites are considered to be treated with wind, fire, and wind-fire toxin, but additional studies are required. Methods: Cases of snakebite seen at the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine were grouped as follows: fire toxin - including four cases of bites by Agkistrodon acutus and three bites by Trimeresurus stejnegeri - and wind-fire toxin - four cases of bites by vipers and three bites by cobras. Serum protein quantification was performed using LC-MS/MS. Differential abundance proteins (DAPs) were identified from comparison of snakebites of each snake species and healthy controls. The protein interaction network was constructed using STITCH database. Results: Principal component analysis and hierarchical clustering of 474 unique proteins exhibited protein expression profiles of wind-fire toxins that are distinct from that of fire toxins. Ninety-three DAPs were identified in each snakebite subgroup as compared with healthy control, of which 38 proteins were found to have significantly different expression levels and 55 proteins displayed no expression in one subgroup, by subgroup comparison. GO analysis revealed that the DAPs participated in bicarbonate/oxygen transport and hydrogen peroxide catabolic process, and affected carbon-oxygen lyase activity and heme binding. Thirty DAPs directly or indirectly acted on hydrogen peroxide in the interaction network of proteins and drug compounds. The network was clustered into four groups: lipid metabolism and transport; IGF-mediated growth; oxygen transport; and innate immunity. Conclusions: Our results show that the pathways of snake venom-induced toxicity may form a protein network of antioxidant defense by regulating oxidative stress through interaction with hydrogen peroxide.(AU)
Subject(s)
Animals , Snake Venoms/analysis , Snake Venoms/toxicity , Oxidative Stress , Antioxidants/analysis , Hydrogen Peroxide/analysis , ProteomeABSTRACT
Snakebites remain a major life-threatening event worldwide. It is still difficult to make a positive identification of snake species by clinicians in both Western medicine and Chinese medicine. The main reason for this is a shortage of diagnostic biomarkers and lack of knowledge about pathways of venom-induced toxicity. In traditional Chinese medicine, snakebites are considered to be treated with wind, fire, and wind-fire toxin, but additional studies are required. Methods: Cases of snakebite seen at the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine were grouped as follows: fire toxin - including four cases of bites by Agkistrodon acutus and three bites by Trimeresurus stejnegeri - and wind-fire toxin - four cases of bites by vipers and three bites by cobras. Serum protein quantification was performed using LC-MS/MS. Differential abundance proteins (DAPs) were identified from comparison of snakebites of each snake species and healthy controls. The protein interaction network was constructed using STITCH database. Results: Principal component analysis and hierarchical clustering of 474 unique proteins exhibited protein expression profiles of wind-fire toxins that are distinct from that of fire toxins. Ninety-three DAPs were identified in each snakebite subgroup as compared with healthy control, of which 38 proteins were found to have significantly different expression levels and 55 proteins displayed no expression in one subgroup, by subgroup comparison. GO analysis revealed that the DAPs participated in bicarbonate/oxygen transport and hydrogen peroxide catabolic process, and affected carbon-oxygen lyase activity and heme binding. Thirty DAPs directly or indirectly acted on hydrogen peroxide in the interaction network of proteins and drug compounds. The network was clustered into four groups: lipid metabolism and transport; IGF-mediated growth; oxygen transport; and innate immunity. Conclusions: Our results show that the pathways of snake venom-induced toxicity may form a protein network of antioxidant defense by regulating oxidative stress through interaction with hydrogen peroxide.(AU)
Subject(s)
Animals , Snake Venoms , Biomarkers , Oxidative Stress , Hydrogen Peroxide , Antioxidants , Trimeresurus , Proteome/analysisABSTRACT
Two new coordination polymers [Zn (bdc)(bpybzimH2)](DMF)0.5 (1, H2bdc=1,4-dicarboxybenzene, bpybzimH2=6,6'-bis-(1H-benzoimidazol-2-yl)-2,2'-bipyridine, DMF=N,N-dimethylformamide) and [Co (bpybzimH2)(sbc)]H2O (2, H2sbc=4-mercaptobenzoic acid) have been successfully prepared under solvothermal conditions using the multi-N chelating organic ligand bpybzimH2 as the foundational building block. In addition, the Cell Counting Kit-8 assay was conducted to evaluate the anti-proliferation activity of compounds 1 and 2 against human spinal tumor cells OPM-2. The cell viability curves showed that the two compounds have anti-proliferation activity on spinal tumor cells, and the activity of compound 1 is higher than compound 2. The annexin V-FITC/PI assay and western blot were used to detect the apoptotic percentage of OPM-2 cells incubated with compounds 1 and 2. The YAP protein expression and its role in cell apoptosis were further studied with qRT-PCR, immunoblotting, and flow cytometer.
Subject(s)
Apoptosis/drug effects , Caspases/metabolism , Cell Proliferation/drug effects , Cell Survival/drug effects , Ligands , Polymers/chemistry , Spinal Neoplasms/enzymology , Cell Line, Tumor , Humans , Reverse Transcriptase Polymerase Chain Reaction , Spinal Neoplasms/pathology , TransfectionABSTRACT
Two new coordination polymers [Zn (bdc)(bpybzimH2)](DMF)0.5 (1, H2bdc=1,4-dicarboxybenzene, bpybzimH2=6,6′-bis-(1H-benzoimidazol-2-yl)-2,2′-bipyridine, DMF=N,N-dimethylformamide) and [Co (bpybzimH2)(sbc)]H2O (2, H2sbc=4-mercaptobenzoic acid) have been successfully prepared under solvothermal conditions using the multi-N chelating organic ligand bpybzimH2 as the foundational building block. In addition, the Cell Counting Kit-8 assay was conducted to evaluate the anti-proliferation activity of compounds 1 and 2 against human spinal tumor cells OPM-2. The cell viability curves showed that the two compounds have anti-proliferation activity on spinal tumor cells, and the activity of compound 1 is higher than compound 2. The annexin V-FITC/PI assay and western blot were used to detect the apoptotic percentage of OPM-2 cells incubated with compounds 1 and 2. The YAP protein expression and its role in cell apoptosis were further studied with qRT-PCR, immunoblotting, and flow cytometer.
Subject(s)
Humans , Polymers/chemistry , Cell Survival/drug effects , Apoptosis/drug effects , Caspases/metabolism , Cell Proliferation/drug effects , Ligands , Spinal Neoplasms/enzymology , Spinal Neoplasms/pathology , Transfection , Reverse Transcriptase Polymerase Chain Reaction , Cell Line, TumorABSTRACT
Abstract Introduction Currently, there is limited information about the relationship between manganese superoxide dismutase (sod2) c47t polymorphism and susceptibility to noise-induced hearing loss (NIHL). Objective The aim of this meta-analysis was to clarify the association between SOD2 C47T polymorphism and NIHL. Methods A search in PubMed and Web of Science was performed to collect data. All full-text, English-written studies containing sufficient and complete case-and-control data about the relationship between SOD2 C47T polymorphism and NIHL were included. Three eligible studies, comprising 1094 subjects, were identified. pooled odds ratios (ORs) and 95% confidence intervals (CI) were calculated to evaluate the strength of the association between SOD2 C47T polymorphism and NIHL. Results No significant association between C47T polymorphism and risk of NIHL was found with the following combinations: T vs. C (OR = 0.83; 95% CI = 0.63–1.09); TT vs. CC (OR = 0.49; 95% CI = 0.22–1.09); CT vs. CC (OR = 0.54; 95% CI = 0.25–1.17); TT vs. CC + CT (OR = 0.82; 95% CI = 0.50–1.32); CC vs. TT + TC (OR = 0.49; 95% CI = 0.23–1.04). However, in subgroup analysis, a significant association was found for TT vs. CC + CT (OR = 0.77; 95% CI = 0.42–1.41) in the Chinese population. Conclusion The present meta-analysis suggests that SOD2 C47T polymorphism is significantly associated with increased risk of NIHL in the Chinese population. Further large and well-designed studies are needed to confirm this association.
Resumo Introdução Atualmente, são limitadas as informações acerca da relação entre o polimorfismo C47T de superóxido dismutase 2 (SOD2) dependente de manganês e suscetibilidade à perda auditiva induzida pelo ruído (PAIR). Objetivo O objetivo desta metanálise foi esclarecer a associação entre o polimorfismo C47T de SOD2 e PAIR. Método Foram feitas buscas no PubMed e Web of Science para coleta de dados. Foram incluídos todos os estudos no idioma inglês, com dados suficientes e completos de casos e controles sobre a relação entre o polimorfismo C47T de SOD2 e PAIR. Foram identificados três estudos qualificados, que abrangeram 1.094 indivíduos. Foram calculadas as razões das chances (odds ratio, OR) acumuladas e intervalos de confiança (IC) de 95% para que fosse avaliada a potência da associação entre o polimorfismo C47T de SOD2 e PAIR. Resultados Não foi encontrada uma associação significativa entre o polimorfismo C47T de SOD2 e risco de PAIR com as seguintes combinações: T vs. C (OR = 0,83, IC 95% = 0,63-1,09); TT vs. CC (OR = 0,49, IC 95% = 0,22-1,09); CT vs. CC (OR = 0,54, IC 95% = 0,25-1,17); TT vs. CC + CT (OR = 0,82, IC 95% = 0,50-1,32); CC vs. TT + TC (OR = 0,49, IC 95% = 0,23-1,04). Contudo, na análise de subgrupo, foi encontrada uma associação significativa para TT vs. CC + CT (OR = 0,77, 95% CI = 0,42-1.41) na população chinesa. Conclusão A presente metanálise sugere que o polimorfismo C47T de SOD2 demonstra associação significativa com maior risco de PAIR na população chinesa. Há necessidade de novos estudos de grande porte bem concebidos, para confirmação dessa associação.
Subject(s)
Humans , Polymorphism, Genetic/genetics , Superoxide Dismutase/genetics , Genetic Predisposition to Disease/genetics , Hearing Loss, Noise-Induced/geneticsABSTRACT
INTRODUCTION: Currently, there is limited information about the relationship between manganese superoxide dismutase (sod2) c47t polymorphism and susceptibility to noise-induced hearing loss (NIHL). OBJECTIVE: The aim of this meta-analysis was to clarify the association between SOD2 C47T polymorphism and NIHL. METHODS: A search in PubMed and Web of Science was performed to collect data. All full-text, English-written studies containing sufficient and complete case-and-control data about the relationship between SOD2 C47T polymorphism and NIHL were included. Three eligible studies, comprising 1094 subjects, were identified. pooled odds ratios (ORs) and 95% confidence intervals (CI) were calculated to evaluate the strength of the association between SOD2 C47T polymorphism and NIHL. RESULTS: No significant association between C47T polymorphism and risk of NIHL was found with the following combinations: T vs. C (OR=0.83; 95% CI=0.63-1.09); TT vs. CC (OR=0.49; 95% CI=0.22-1.09); CT vs. CC (OR=0.54; 95% CI=0.25-1.17); TT vs. CC+CT (OR=0.82; 95% CI=0.50-1.32); CC vs. TT+TC (OR=0.49; 95% CI=0.23-1.04). However, in subgroup analysis, a significant association was found for TT vs. CC+CT (OR=0.77; 95% CI=0.42-1.41) in the Chinese population. CONCLUSION: The present meta-analysis suggests that SOD2 C47T polymorphism is significantly associated with increased risk of NIHL in the Chinese population. Further large and well-designed studies are needed to confirm this association.
Subject(s)
Genetic Predisposition to Disease/genetics , Hearing Loss, Noise-Induced/genetics , Polymorphism, Genetic/genetics , Superoxide Dismutase/genetics , HumansABSTRACT
A type 2 vaccine-derived poliovirus (VDPV), differing from the Sabin 2 strain at 8.6% (78/903) of VP1 nucleotide positions, was isolated from seawater collected from a seaport in São Paulo State, Brazil. The P1/capsid region is related to the Sabin 2 strain, but sequences within the 5'-untranslated region and downstream of the P1 region were derived from recombination with other members of Human Enterovirus Species C (HEV-C). The two known attenuating mutations had reverted to wild-type (A481G in the 5'-UTR and Ile143Thr in VP1). The VDPV isolate had lost the temperature sensitive phenotype and had accumulated amino acid substitutions in neutralizing antigenic (NAg) sites 3a and 3b. The date of the initiating OPV dose, estimated from the number of synonymous substitutions in the capsid region, was approximately 8.5 years before seawater sampling, a finding consistent with a long time of virus replication and possible transmission among several individuals. Although no closely related type 2 VDPVs were detected in Brazil or elsewhere, this VDPV was found in an area with a mobile population, where conditions may favor both viral infection and spread. Environmental surveillance serves as an important tool for sensitive and early detection of circulating poliovirus in the final stages of global polio eradication.
Subject(s)
Poliovirus/metabolism , Seawater/virology , 5' Untranslated Regions , Amino Acid Sequence , Amino Acid Substitution , Antibodies, Viral/immunology , Brazil , Capsid Proteins/genetics , Capsid Proteins/metabolism , Cell Line , Humans , Molecular Sequence Data , Phenotype , Phylogeny , Poliovirus/classification , Poliovirus/isolation & purification , Promoter Regions, Genetic , Real-Time Polymerase Chain Reaction , Recombination, Genetic , Sequence Alignment , TemperatureABSTRACT
CONTEXT: Herbal preparation of Pao pereira [Geissospermum vellosii Allem (Apocynaceae)] has long been used by oncologic patients and Integrative Medicine practitioners in South America. However, its anticancer activities have not been systematically studied. OBJECTIVE: To investigate the anticancer effects of ß-carboline alkaloids-enriched extract from Pao pereira (Pao), either alone or in combination with carboplatin, in preclinical ovarian cancer models. MATERIALS AND METHODS: Cytotoxicity of Pao (0-800 µg/ml) against different ovarian cancer cell lines and an immortalized epithelial cell line was detected by flow cytometry, MTT assay and colony formation in soft agar. Combination of Pao and carboplatin, a primary chemotherapeutic drug for ovarian cancer, was evaluated using Chou-Talalay's methods. Mice bearing intraperitoneally spread ovarian cancer were treated with 20 or 50 mg/kg/day Pao by i.p. injection. Carboplatin at 15 mg/kg/week i.p. was compared and combined to Pao treatments. RESULTS: Pao selectively inhibited ovarian cancer cell growth with IC50 values of 180-235 µg/ml, compared to 537 µg/ml in normal cells. Pao induced apoptosis dose- and time-dependently and completely inhibited colony formation of tumor cells in soft agar at 400 µg/ml. Pao greatly enhanced carboplatin cytotoxicity, with dose reduction (DRIs) for carboplatin at 1.2-10 fold. In vivo, Pao alone suppressed tumor growth by 79% and decreased volume of ascites by 55%. When Pao was combined with carboplatin, tumor inhibition reached 97% and ascites was completely eradicated. DISCUSSION AND CONCLUSION: Pao possess potent antitumor activity and could enhance carboplatin effect, and therefore holds therapeutic potential in the treatment of ovarian cancer.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Apocynaceae/chemistry , Ovarian Neoplasms/drug therapy , Plant Extracts/pharmacology , Animals , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Apoptosis/drug effects , Carboplatin/administration & dosage , Cell Line, Tumor , Dose-Response Relationship, Drug , Female , Flow Cytometry , Humans , Injections, Intraperitoneal , Medicine, Traditional , Mice , Mice, Nude , Ovarian Neoplasms/pathology , Plant Extracts/administration & dosage , Plant Extracts/isolation & purification , South America , Time FactorsABSTRACT
BACKGROUND: Ecuador, the smallest of the Andean countries, is located in the northwest portion of South America. The nation's 14.5 million people have a tremendous need for high quality primary care. AIMS: To describe the profound advances as well as the persistent needs in medical education in Ecuador that have occurred with globalization and with the modernization of the country. METHODS: Through an extensive search of the literature; medical school data; reports from the Ecuador Ministry of Public Health and Ministry of Education; and information from the National Secretary of Higher Education, Science, and Innovation (SENESCYT), the medical education system in Ecuador has been thoroughly examined. RESULTS: The National System of Higher Education in Ecuador has experienced significant growth over the last 20 years. As of 2009 the system boasts 19 medical schools, all of which offer the required education needed to obtain the title of Physician, but only 12 of which offer postgraduate clinical training. Of these 19 universities, nine are public, five are private and self-financed, and five are private and co-financed. Post-graduate options for medical students include: (1) Clinical specialization, (2) Higher diploma, (3) Course specialization, (4) Master's degree, and (5) PhD degree. CONCLUSION: The rapid growth of Ecuador's system of medical education has led to inevitable gaps that threaten its ability to sustain itself. Chief among these is the lack of well-trained faculty to supply its medical schools. To ensure an adequate supply of faculty exists, the creation of sufficient postgraduate, sub-specialization, and PhD training positions must be created and maintained.
Subject(s)
Education, Medical/organization & administration , Ecuador , Education, Medical/trends , Humans , Internationality , Needs AssessmentABSTRACT
The fine particles serving as cloud condensation nuclei in pristine Amazonian rainforest air consist mostly of secondary organic aerosol. Their origin is enigmatic, however, because new particle formation in the atmosphere is not observed. Here, we show that the growth of organic aerosol particles can be initiated by potassium-salt-rich particles emitted by biota in the rainforest. These particles act as seeds for the condensation of low- or semi-volatile organic compounds from the atmospheric gas phase or multiphase oxidation of isoprene and terpenes. Our findings suggest that the primary emission of biogenic salt particles directly influences the number concentration of cloud condensation nuclei and affects the microphysics of cloud formation and precipitation over the rainforest.