Telbivudine-Induced Myopathy: Clinical Features, Histopathological Characteristics, and Risk Factors

Background@#and Purpose Oral nucleos(t)ide analogs (NAs) are the mainstay treatment for chronic hepatitis B (CHB). Myotoxicity is an important extrahepatic effect related to NA treatment. Telbivudine is the NA for CHB that is frequently associated with muscle-related side effects. The risk factors for telbivudine-induced myopathy (TIM) are not yet clear. @*Methods@#This study characterized the clinical, magnetic resonance images (MRI), and pathological features of 12 TIM cases. A group of telbivudine-tolerant (TT) patients with CHB who received regular telbivudine treatment during the same period without the occurrence of myopathy was collected. Demographic and clinical factors were compared between the patients with TIM and the TT controls. Factors independently associated with TIM were identified using logistic regression analysis. @*Results@#The patients with TIM (males/females: 7/5, mean age: 57 years) developed myopathy after using telbivudine for a median period of 19.5 months. Muscle histopathology revealed abnormal proliferation, subsarcolemmal or sarcoplasmic accumulations, and ultrastructural defects of mitochondria. When compared with TT cases, patients with TIM had a lower estimated glomerular filtration rate and were more frequently positive for hepatitis B e antigen (HBeAg). @*Conclusions@#Mitochondrial abnormalities are characteristic histopathological features, and impaired renal function and HBeAg positivity are risk factors for TIM. Telbivudine-induced mitochondrial dysfunction and immune activation related to mitochondrial damage and HBeAg serostatus changes may underlie TIM. Constant clinical surveillance of myopathy during telbivudine treatment is needed due to the significant latency of its development. Dose adjustment for impaired renal function does not eliminate the risk of TIM occurrence.

Ameliorative effects of morel mushroom (Morchella esculenta) against Cadmium-induced reproductive toxicity in adult male rats / Efeitos benéficos do cogumelo morel (Morchella esculenta) contra a toxicidade reprodutiva induzida por cádmio em ratos machos adultos

Cadmium (Cd) is one of the major toxicants, which affects human health through occupational and environmental exposure. In the current study, we evaluated the protective effects of morel mushrooms against Cd-induced reproductive damages in rats. For this purpose, 30 male rats were divided into 6 groups (n=5/group), the first group served as the control group, second group was treated with an intraperitoneal (i.p) injection of 1 mg/kg/day of Cd. Third and fourth groups were co-treated with 1 mg/kg/day of Cd (i.p) and 10 and 20 mg/kg/day of morel mushroom extract (orally) respectively. The final 2 groups received oral gavage of 10 and 20 mg/kg/day of morel mushroom extract alone. After treatment for 17 days, the animals were euthanized, and testes and epididymis were dissected out. One testis and epididymis of each animal were processed for histology, while the other testis and epididymis were used for daily sperm production (DSP) and comet assay. Our results showed that Cd and morel mushrooms have no effect on animal weight, but Cd significantly decreases the DSP count and damages the heritable DNA which is reversed in co-treatment groups. Similarly, the histopathological results of testes and epididymis show that morel mushrooms control the damage to these tissues. Whereas the morel mushroom extract alone could enhance the production of testosterone. These results conclude that morel mushrooms not only control the damage done by Cd, but it could also be used as a protection mechanism for heritable DNA damage.

O cádmio (Cd) é um dos principais tóxicos, que afeta a saúde humana por meio da exposição ocupacional e ambiental. No presente estudo, avaliamos os efeitos protetores dos cogumelos morel contra os danos reprodutivos induzidos pelo Cd em ratos. Para tanto, 30 ratos machos foram divididos em 6 grupos (n = 5 / grupo); o primeiro grupo serviu de controle, o segundo grupo foi tratado com injeção intraperitoneal (i.p) de 1 mg / kg / dia de Cd. O terceiro e o quarto grupos foram cotratados com 1 mg / kg / dia de Cd (i.p) e 10 e 20 mg / kg / dia de extrato de cogumelo morel (por via oral), respectivamente. Os dois grupos finais receberam gavagem oral de 10 e 20 mg / kg / dia de extrato de cogumelo morel sozinho. Após o tratamento por 17 dias, os animais foram sacrificados e os testículos e o epidídimo foram dissecados. Um testículo e epidídimo de cada animal foram processados para histologia, enquanto o outro testículo e epidídimo foram usados para produção diária de esperma (DSP) e ensaio cometa. Nossos resultados mostraram que os cogumelos Cd e morel não têm efeito sobre o peso do animal, mas o Cd diminui significativamente a contagem de DSP e danifica o DNA hereditário, que é revertido em grupos de cotratamento. Da mesma forma, os resultados histopatológicos dos testículos e do epidídimo mostram que os cogumelos morel controlam os danos a esses tecidos. Considerando que o extrato de cogumelo morel sozinho pode aumentar a produção de testosterona. Esses resultados concluem que os cogumelos morel não apenas controlam os danos causados pelo Cd, mas também podem ser usados como um mecanismo de proteção para danos hereditários ao DNA.

Ameliorative effects of morel mushroom (Morchella esculenta) against Cadmium-induced reproductive toxicity in adult male rats

Abstract Cadmium (Cd) is one of the major toxicants, which affects human health through occupational and environmental exposure. In the current study, we evaluated the protective effects of morel mushrooms against Cd-induced reproductive damages in rats. For this purpose, 30 male rats were divided into 6 groups (n=5/group), the first group served as the control group, second group was treated with an intraperitoneal (i.p) injection of 1 mg/kg/day of Cd. Third and fourth groups were co-treated with 1 mg/kg/day of Cd (i.p) and 10 and 20 mg/kg/day of morel mushroom extract (orally) respectively. The final 2 groups received oral gavage of 10 and 20 mg/kg/day of morel mushroom extract alone. After treatment for 17 days, the animals were euthanized, and testes and epididymis were dissected out. One testis and epididymis of each animal were processed for histology, while the other testis and epididymis were used for daily sperm production (DSP) and comet assay. Our results showed that Cd and morel mushrooms have no effect on animal weight, but Cd significantly decreases the DSP count and damages the heritable DNA which is reversed in co-treatment groups. Similarly, the histopathological results of testes and epididymis show that morel mushrooms control the damage to these tissues. Whereas the morel mushroom extract alone could enhance the production of testosterone. These results conclude that morel mushrooms not only control the damage done by Cd, but it could also be used as a protection mechanism for heritable DNA damage.

Resumo O cádmio (Cd) é um dos principais tóxicos, que afeta a saúde humana por meio da exposição ocupacional e ambiental. No presente estudo, avaliamos os efeitos protetores dos cogumelos morel contra os danos reprodutivos induzidos pelo Cd em ratos. Para tanto, 30 ratos machos foram divididos em 6 grupos (n = 5 / grupo); o primeiro grupo serviu de controle, o segundo grupo foi tratado com injeção intraperitoneal (i.p) de 1 mg / kg / dia de Cd. O terceiro e o quarto grupos foram cotratados com 1 mg / kg / dia de Cd (i.p) e 10 e 20 mg / kg / dia de extrato de cogumelo morel (por via oral), respectivamente. Os dois grupos finais receberam gavagem oral de 10 e 20 mg / kg / dia de extrato de cogumelo morel sozinho. Após o tratamento por 17 dias, os animais foram sacrificados e os testículos e o epidídimo foram dissecados. Um testículo e epidídimo de cada animal foram processados para histologia, enquanto o outro testículo e epidídimo foram usados para produção diária de esperma (DSP) e ensaio cometa. Nossos resultados mostraram que os cogumelos Cd e morel não têm efeito sobre o peso do animal, mas o Cd diminui significativamente a contagem de DSP e danifica o DNA hereditário, que é revertido em grupos de cotratamento. Da mesma forma, os resultados histopatológicos dos testículos e do epidídimo mostram que os cogumelos morel controlam os danos a esses tecidos. Considerando que o extrato de cogumelo morel sozinho pode aumentar a produção de testosterona. Esses resultados concluem que os cogumelos morel não apenas controlam os danos causados pelo Cd, mas também podem ser usados como um mecanismo de proteção para danos hereditários ao DNA.

Ameliorative effects of morel mushroom (Morchella esculenta) against Cadmium-induced reproductive toxicity in adult male rats / Efeitos benéficos do cogumelo morel (Morchella esculenta) contra a toxicidade reprodutiva induzida por cádmio em ratos machos adultos

Cadmium (Cd) is one of the major toxicants, which affects human health through occupational and environmental exposure. In the current study, we evaluated the protective effects of morel mushrooms against Cd-induced reproductive damages in rats. For this purpose, 30 male rats were divided into 6 groups (n=5/group), the first group served as the control group, second group was treated with an intraperitoneal (i.p) injection of 1 mg/kg/day of Cd. Third and fourth groups were co-treated with 1 mg/kg/day of Cd (i.p) and 10 and 20 mg/kg/day of morel mushroom extract (orally) respectively. The final 2 groups received oral gavage of 10 and 20 mg/kg/day of morel mushroom extract alone. After treatment for 17 days, the animals were euthanized, and testes and epididymis were dissected out. One testis and epididymis of each animal were processed for histology, while the other testis and epididymis were used for daily sperm production (DSP) and comet assay. Our results showed that Cd and morel mushrooms have no effect on animal weight, but Cd significantly decreases the DSP count and damages the heritable DNA which is reversed in co-treatment groups. Similarly, the histopathological results of tests and epididymis show that morel mushrooms control the damage to these tissues. Whereas the morel mushroom extract alone could enhance the production of testosterone. These results conclude that morel mushrooms not only control the damage done by Cd, but it could also be used as a protection mechanism for heritable DNA damage.

O cádmio (Cd) é um dos principais tóxicos, que afeta a saúde humana por meio da exposição ocupacional e ambiental. No presente estudo, avaliamos os efeitos protetores dos cogumelos morel contra os danos reprodutivos induzidos pelo Cd em ratos. Para tanto, 30 ratos machos foram divididos em 6 grupos (n = 5 / grupo); o primeiro grupo serviu de controle, o segundo grupo foi tratado com injeção intraperitoneal (i.p) de 1 mg / kg / dia de Cd. O terceiro e o quarto grupos foram cotratados com 1 mg / kg / dia de Cd (i.p) e 10 e 20 mg / kg / dia de extrato de cogumelo morel (por via oral), respectivamente. Os dois grupos finais receberam gavagem oral de 10 e 20 mg / kg / dia de extrato de cogumelo morel sozinho. Após o tratamento por 17 dias, os animais foram sacrificados e os testículos e o epidídimo foram dissecados. Um testículo e epidídimo de cada animal foram processados para histologia, enquanto o outro testículo e epidídimo foram usados para produção diária de esperma (DSP) e ensaio cometa. Nossos resultados mostraram que os cogumelos Cd e morel não têm efeito sobre o peso do animal, mas o Cd diminui significativamente a contagem de DSP e danifica o DNA hereditário, que é revertido em grupos de cotratamento. Da mesma forma, os resultados histopatológicos dos testículos e do epidídimo mostram que os cogumelos morel controlam os danos a esses tecidos. Considerando que o extrato de cogumelo morel sozinho pode aumentar a produção de testosterona. Esses resultados concluem que os cogumelos morel não apenas controlam os danos causados pelo Cd, mas também podem ser usados como um mecanismo de proteção para danos hereditários ao DNA.

The Role of Procalcitonin in the Diagnosis and Prognosis of Severe Surgical Patients with Sepsis

Purpose:To investigate the clinical significance of serum procalcitonin (PCT) concentrations and related indicators of infection in the early diagnosis and prognosis of severe surgical patients with infection. Methods: This study included 77 critically ill patients taken from the Surgery Department to the Intensive Care unit between June 2015 and July 2017. Patients were divided into control, sepsis and septic shock groups, and their serum concentrations of PCT and related indicators of infection were compared. Results: PCT levels increased significantly from the control to the sepsis group and from the sepsis to the septic shock group (P<0.01 each). There were no significant differences in white blood cell (WBC) count, neutrophil percentage and body temperature among the groups (P>0.05). Receiver operating curve (ROC) analysis showed that the areas under the curve (AUC) for PCT, WBC count, neutrophil percentage and body temperature were 0.949, 0.657, 0.640 and 0.656, respectively. PCT, with 0.52 µg/L as the cut-off concentration, had the highest performance in the diagnosis of severe surgical sepsis, with a sensitivity of 96.1%, a specificity of 92.3% and a Youden index of 0.884. Conclusion: PCT concentration is diagnostic of infection in severe surgical patients, has high specificity in the early diagnosis of sepsis, and can reflect the severity of infection.

Mutagenicity and antimutagenicity of Salacia crassifolia (mart. Ex. Schult.) G. Don. evaluated by Ames test / Mutagenicitade e antimutagenicidade de Salacia crassifolia (mart. Ex. Schult.) G. Don. avaliadas pelo teste de Ames

Abstract Salacia crassifolia (Mart. Ex. Schult.) G. Don. is a bush which belongs to Celastraceae family and occurs specially in Brazilian Cerrado. Its leaves, stem, seeds and fruits are popularly used for several medicinal purposes, such as antitumoral, antirheumatic, anti-inflammatory and antimicrobial. In this study, the mutagenic and antimutagenic activities of S. crassifolia stem bark fractions (hexane, ethyl acetate and hydroalcoholic) were evaluated by the Ames mutagenicity assay in Salmonella typhimurium TA98 and TA100 strains. By the obtained results, all S. crassifolia fractions did not significantly increase the number of prototrophic revertants for histidine (His+) in both S. typhimurium strains tested (p > 0.05), suggesting absence of mutagenicity. Regarding antimutagenicity, the fractions ethyl acetate and hydroalcoholic significantly decreased the number of His+ revertants colonies induced by positive control for strain TA98 (p < 0.05), demonstrating protection against mutagenicity induced by 4-nitroquinolile1-oxide, whereas the hexane fraction did not show antimutagenic effect in this strain. In the TA100 strain, all fractions of S. crassifolia protected DNA against the harmful action of sodium azide, and the hexane fraction exhibited the greatest protection in this work. Thus, it's possible conclude that the fractions of S. crassifolia tested in this study could be used in chemoprevention.

Resumo Salacia crassifolia (Mart. Ex. Schult.) G. Don. é uma árvore que pertence à família Celastraceae e ocorre especialmente no Cerrado Brasileiro. Suas folhas, caule, sementes e frutos são popularmente utilizados para vários fins medicinais, tais como antitumoral, antirreumático, anti-inflamatório e antimicrobiano. Neste estudo, nós avaliamos as atividades mutagênica e antimutagênica de frações da casca do caule de S. crassifolia (hexânica, acetato de etila e hidroalcoólica) pelo ensaio de mutagenicidade de Ames em Salmonella typhimurium, cepas TA98 e TA100. Pelos resultados obtidos todas as frações de S. crassifolia não aumentaram significativamente o número de revertentes prototróficas para histidina (His+) em ambas as cepas de S. typhimurium testadas (p > 0.05), sugerindo ausência de mutagenicidade. Em relação à antimutagenicidade, as frações acetate de etila e hidroalcoólica reduziram significativamente o número de colônias revertentes His+ induzidas pelo controle positive para a cepa TA98 (p < 0.05), demonstrando sua ação protetora contra a mutagenicidade induzida por 4-nitroquinolile1-oxide, enquanto a fração hexânica não demonstrou efeito antimutagênico nesta cepa. Na cepa TA100, todas as frações de S. crassifolia protegeram o DNA contra a ação lesiva de azida sódica, e a fração hexânica exibiu a maior proteção desse trabalho. Assim, concluímos que as frações de S. crassifolia testadas neste estudo poderiam ser utilizadas em quimioprevenção.

Efficacy, acceptability, and tolerability of antidepressant treatments for patients with post-stroke depression: a network meta-analysis

The aim of this study was to investigate the efficacy, acceptability, and tolerability of antidepressants in treating post-stroke depression (PSD) by performing a network meta-analysis of randomized controlled trials of the current literature. Eligible studies were retrieved from online databases, and relevant data were extracted. The primary outcome was efficacy as measured by the mean change in overall depressive symptoms. Secondary outcomes included discontinued treatment for any reason and specifically due to adverse events. Fourteen trials were eligible, which included 949 participants and 9 antidepressant treatments. Few significant differences were found for all outcomes. For the primary outcome, doxepin, paroxetine, and nortriptyline were significantly more effective than a placebo [standardized mean differences: −1.93 (95%CI=−3.56 to −0.29), −1.39 (95%CI=−2.59 to −0.21), and −1.25 (95%CI=−2.46 to −0.04), respectively]. Insufficient evidence exists to select a preferred antidepressant for treating patients with post-stroke depression, and our study provides little evidence that paroxetine may be the potential choice when starting treatment for PSD. Future studies with paroxetine and larger sample sizes, multiple medical centers, and sufficient intervention durations is needed for improving the current evidence.

Mutagenicity and antimutagenicity of Salacia crassifolia (mart. Ex. Schult.) G. Don. evaluated by Ames test

Abstract Salacia crassifolia (Mart. Ex. Schult.) G. Don. is a bush which belongs to Celastraceae family and occurs specially in Brazilian Cerrado. Its leaves, stem, seeds and fruits are popularly used for several medicinal purposes, such as antitumoral, antirheumatic, anti-inflammatory and antimicrobial. In this study, the mutagenic and antimutagenic activities of S. crassifolia stem bark fractions (hexane, ethyl acetate and hydroalcoholic) were evaluated by the Ames mutagenicity assay in Salmonella typhimurium TA98 and TA100 strains. By the obtained results, all S. crassifolia fractions did not significantly increase the number of prototrophic revertants for histidine (His+) in both S. typhimurium strains tested (p > 0.05), suggesting absence of mutagenicity. Regarding antimutagenicity, the fractions ethyl acetate and hydroalcoholic significantly decreased the number of His+ revertants colonies induced by positive control for strain TA98 (p 0.05), demonstrating protection against mutagenicity induced by 4-nitroquinolile1-oxide, whereas the hexane fraction did not show antimutagenic effect in this strain. In the TA100 strain, all fractions of S. crassifolia protected DNA against the harmful action of sodium azide, and the hexane fraction exhibited the greatest protection in this work. Thus, its possible conclude that the fractions of S. crassifolia tested in this study could be used in chemoprevention.

Resumo Salacia crassifolia (Mart. Ex. Schult.) G. Don. é uma árvore que pertence à família Celastraceae e ocorre especialmente no Cerrado Brasileiro. Suas folhas, caule, sementes e frutos são popularmente utilizados para vários fins medicinais, tais como antitumoral, antirreumático, anti-inflamatório e antimicrobiano. Neste estudo, nós avaliamos as atividades mutagênica e antimutagênica de frações da casca do caule de S. crassifolia (hexânica, acetato de etila e hidroalcoólica) pelo ensaio de mutagenicidade de Ames em Salmonella typhimurium, cepas TA98 e TA100. Pelos resultados obtidos todas as frações de S. crassifolia não aumentaram significativamente o número de revertentes prototróficas para histidina (His+) em ambas as cepas de S. typhimurium testadas (p > 0.05), sugerindo ausência de mutagenicidade. Em relação à antimutagenicidade, as frações acetate de etila e hidroalcoólica reduziram significativamente o número de colônias revertentes His+ induzidas pelo controle positive para a cepa TA98 (p 0.05), demonstrando sua ação protetora contra a mutagenicidade induzida por 4-nitroquinolile1-oxide, enquanto a fração hexânica não demonstrou efeito antimutagênico nesta cepa. Na cepa TA100, todas as frações de S. crassifolia protegeram o DNA contra a ação lesiva de azida sódica, e a fração hexânica exibiu a maior proteção desse trabalho. Assim, concluímos que as frações de S. crassifolia testadas neste estudo poderiam ser utilizadas em quimioprevenção.

Vernonanthura polyanthes leaves aqueous extract enhances doxorubicin genotoxicity in somatic cells of Drosophila melanogaster and presents no antifungal activity against Candida spp / O extrato aquoso das folhas de Vernonanthura polyanthes potencializa a genotoxicidade da doxorrubicina em células somáticas de Drosophila melanogaster e não apresenta atividade antifúngica contra Candida spp

Abstract Vernonanthura polyanthes (Spreng.) A.J. Vega & Dematt. (Asteraceae), known as “assa-peixe”, has been used in ethnomedicine for the treatment of various diseases such as bronchitis, pneumonia, hemoptysis, persistent cough, internal abscesses, gastric and kidney stone pain. Moreover, some studies demonstrated that species of Genus Vernonia present antifungal activity. Due to the biological relevance of this species, the aim of this study was to investigate the toxic, genotoxic, antigenotoxic and antifungal potential of V. polyanthes leaves aqueous extract in somatic cells of Drosophila melanogaster or against Candida spp. The aqueous extract of the plant showed no toxic, genotoxic and antigenotoxic activity in the experimental conditions tested using the wing somatic mutation and recombination test (SMART/wing). However, when the extract was associated with doxorubicin, used in this work as a positive control, the mutagenic potential of doxorubicin was enhanced, increasing the number of mutations in D. melanogaster somatic cells. In the other hand, no inhibitory activity against Candida spp. was observed for V. polyanthes leaves aqueous extract using agar-well diffusion assay. More studies are necessary to reveal the components present in the V. polyanthes leaves aqueous extract that could contribute to potentiate the doxorubicin genotoxicity.

Resumo Vernonanthura polyanthes (Spreng.) A.J. Vega & Dematt. (Asteraceae), conhecida como “assa-peixe”, tem sido utilizada na medicina popular para o tratamento de várias doenças, como bronquite, pneumonia, hemoptise, tosse persistente, abcessos internos, afecções gástricas e cálculo renal. Além disso, alguns estudos já demonstraram que espécies do Gênero Vernonia apresentam atividade antifúngica. Devido à relevância biológica dessa espécie, o objetivo deste estudo foi investigar os efeitos citotóxico, genotóxico, antigenotóxico e antifúngico do extrato aquoso das folhas de V. polyanthes em células somáticas de Drosophila melanogaster ou contra Candida spp. O extrato aquoso da planta não apresentou atividade citotóxica, genotóxica e antigenotóxica nas condições experimentais testadas usando o teste de recombinação e mutação somática em asa (SMART-asa). No entanto, quando o extrato foi associado com a doxorrubicina, utilizada neste trabalho como controle positivo, o potencial mutagênico da doxorrubicina foi potencializado, aumentando o número de mutações em células somáticas de D. melanogaster. Por outro lado, nenhuma atividade inibitória contra Candida spp. foi observada utilizando o extrato aquoso das folhas de V. polyanthes por meio do método de difusão em ágar. Mais estudos são necessários para desvendar os componentes presentes no extrato aquoso das folhas de V. polyanthes que possam contribuir para potencializar a genotoxicidade da doxorrubicina.

Gene expression profiling analysis of lung adenocarcinoma

The present study screened potential genes related to lung adenocarcinoma, with the aim of further understanding disease pathogenesis. The GSE2514 dataset including 20 lung adenocarcinoma and 19 adjacent normal tissue samples from 10 patients with lung adenocarcinoma aged 45-73 years was downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) between the two groups were screened using the t-test. Potential gene functions were predicted using functional and pathway enrichment analysis, and protein-protein interaction (PPI) networks obtained from the STRING database were constructed with Cytoscape. Module analysis of PPI networks was performed through MCODE in Cytoscape. In total, 535 upregulated and 465 downregulated DEGs were identified. These included ATP5D, UQCRC2, UQCR11 and genes encoding nicotinamide adenine dinucleotide (NADH), which are mainly associated with mitochondrial ATP synthesis coupled electron transport, and which were enriched in the oxidative phosphorylation pathway. Other DEGs were associated with DNA replication (PRIM1, MCM3, and RNASEH2A), cell surface receptor-linked signal transduction and the enzyme-linked receptor protein signaling pathway (MAPK1, STAT3, RAF1, and JAK1), and regulation of the cytoskeleton and phosphatidylinositol signaling system (PIP5K1B, PIP5K1C, and PIP4K2B). Our findings suggest that DEGs encoding subunits of NADH, PRIM1, MCM3, MAPK1, STAT3, RAF1, and JAK1 might be associated with the development of lung adenocarcinoma.

Caffeic acid improves cell viability and protects against DNA damage: involvement of reactive oxygen species and extracellular signal-regulated kinase

Hormesis is an adaptive response to a variety of oxidative stresses that renders cells resistant to harmful doses of stressing agents. Caffeic acid (CaA) is an important antioxidant that has protective effects against DNA damage caused by reactive oxygen species (ROS). However, whether CaA-induced protection is a hormetic effect remains unknown, as is the molecular mechanism that is involved. We found that a low concentration (10 μM) of CaA increased human liver L-02 cell viability, attenuated hydrogen peroxide (H2O2)-mediated decreases in cell viability, and decreased the extent of H2O2-induced DNA double-strand breaks (DSBs). In L-02 cells exposed to H2O2, CaA treatment reduced ROS levels, which might have played a protective role. CaA also activated the extracellular signal-regulated kinase (ERK) signal pathway in a time-dependent manner. Inhibition of ERK by its inhibitor U0126 or by its specific small interfering RNA (siRNA) blocked the CaA-induced improvement in cell viability and the protective effects against H2O2-mediated DNA damage. This study adds to the understanding of the antioxidant effects of CaA by identifying a novel molecular mechanism of enhanced cell viability and protection against DNA damage.

Inhibitory effect of liposomal quercetin on acute hepatitis and hepatic fibrosis induced by concanavalin A

Immune response plays an important role in the development of hepatic fibrosis. In the present study, we investigated the effects of quercetin on hepatitis and hepatic fibrosis induced by immunological mechanism. In the acute hepatitis model, quercetin (2.5 mg/kg) was injected iv into mice 30 min after concanavalin A (Con A) challenge. Mice were sacrificed 4 or 24 h after Con A injection, and aminotransferase tests and histopathological sections were performed. Treatment with quercetin significantly decreased the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Consistent with this observation, treatment with quercetin markedly attenuated the pathologic changes in the liver. A hepatic fibrosis model was also generated in mice by Con A challenge once a week for 6 consecutive weeks. Mice in the experimental group were treated with daily iv injections of quercetin (0.5 mg/kg). Histopathological analyses revealed that treatment with quercetin markedly decreased collagen deposition, pseudolobuli development, and hepatic stellate cells activation. We also examined the effects of quercetin on the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transforming growth factor beta (TGF-β) pathways by immunohistochemistry and real-time reverse transcriptase-polymerase chain reaction (RT-PCR). NF-κB and TGF-β production was decreased after treatment with quercetin, indicating that the antifibrotic effect of quercetin is associated with its ability to modulate NF-κB and TGF-β production. These results suggest that quercetin may be an effective therapeutic strategy in the treatment of patients with liver damage and fibrosis.

Changes in cardiac aldosterone and its synthase in rats with chronic heart failure: an intervention study of long-term treatment with recombinant human brain natriuretic peptide

The physiological mechanisms involved in isoproterenol (ISO)-induced chronic heart failure (CHF) are not fully understood. In this study, we investigated local changes in cardiac aldosterone and its synthase in rats with ISO-induced CHF, and evaluated the effects of treatment with recombinant human brain natriuretic peptide (rhBNP). Sprague-Dawley rats were divided into 4 different groups. Fifty rats received subcutaneous ISO injections to induce CHF and the control group (n=10) received equal volumes of saline. After establishing the rat model, 9 CHF rats received no further treatment, rats in the low-dose group (n=8) received 22.5 μg/kg rhBNP and those in the high-dose group (n=8) received 45 μg/kg rhBNP daily for 1 month. Cardiac function was assessed by echocardiographic and hemodynamic analysis. Collagen volume fraction (CVF) was determined. Plasma and myocardial aldosterone concentrations were determined using radioimmunoassay. Myocardial aldosterone synthase (CYP11B2) was detected by quantitative real-time PCR. Cardiac function was significantly lower in the CHF group than in the control group (P<0.01), whereas CVF, plasma and myocardial aldosterone, and CYP11B2 transcription were significantly higher than in the control group (P<0.05). Low and high doses of rhBNP significantly improved hemodynamics (P<0.01) and cardiac function (P<0.05) and reduced CVF, plasma and myocardial aldosterone, and CYP11B2 transcription (P<0.05). There were no significant differences between the rhBNP dose groups (P>0.05). Elevated cardiac aldosterone and upregulation of aldosterone synthase expression were detected in rats with ISO-induced CHF. Administration of rhBNP improved hemodynamics and ventricular remodeling and reduced myocardial fibrosis, possibly by downregulating CYP11B2 transcription and reducing myocardial aldosterone synthesis.

Association of adult weight gain and nonalcoholic fatty liver in a cross-sectional study in Wan Song Community, China

Our objective was to examine associations of adult weight gain and nonalcoholic fatty liver disease (NAFLD). Cross-sectional interview data from 844 residents in Wan Song Community from October 2009 to April 2010 were analyzed in multivariate logistic regression models to examine odds ratios (OR) and 95% confidence intervals (CI) between NAFLD and weight change from age 20. Questionnaires, physical examinations, laboratory examinations, and ultrasonographic examination of the liver were carried out. Maximum rate of weight gain, body mass index, waist circumference, waist-to-hip ratio, systolic blood pressure, diastolic blood pressure, fasting blood glucose, cholesterol, triglycerides, uric acid, and alanine transaminase were higher in the NAFLD group than in the control group. HDL-C in the NAFLD group was lower than in the control group. As weight gain increased (measured as the difference between current weight and weight at age 20 years), the OR of NAFLD increased in multivariate models. NAFLD OR rose with increasing weight gain as follows: OR (95%CI) for NAFLD associated with weight gain of 20+ kg compared to stable weight (change <5 kg) was 4.23 (2.49-7.09). Significantly increased NAFLD OR were observed even for weight gains of 5-9.9 kg. For the “age 20 to highest lifetime weight” metric, the OR of NAFLD also increased as weight gain increased. For the “age 20 to highest lifetime weight” metric and the “age 20 to current weight” metric, insulin resistance index (HOMA-IR) increased as weight gain increased (P<0.001). In a stepwise multivariate regression analysis, significant association was observed between adult weight gain and NAFLD (OR=1.027, 95%CI=1.002-1.055, P=0.025). We conclude that adult weight gain is strongly associated with NAFLD.

X-cephalometric study of different parts of the upper airway space and changes in hyoid position following mandibular fractures / Estudio cefalométrico con rayos X de diferentes partes del espacio de las vías respiratorias superiores y cambios en la posición hioidea tras fracturas mandibulares

OBJECTIVE: This study analyses the different parts of the upper airway space and the changes in hyoid position. The results provide a clinical reference for developing timely and effective treatment programmes for patients with mandibular fractures caused by maxillofacial trauma. METHODS: Standard X-cephalometric measurements of the lateral skull of 210 subjects were taken. The subjects were divided into four fracture groups: condylar, mandibular angle, mandibular body, and parasymphyseal. RESULTS: The radiographs of the mandibular fracture groups were compared with the normal occlusion group to analyse the upper airway space and the changes in hyoid position. Different types of fractures have different effects on the upper airway space. Bilateral mandibular body fracture and the parasymphyseal fracture have a significant influence on the lower oropharyngeal and laryngopharyngeal airway spaces, with serious obstructions severely restricting the ventilatory function ofpatients. CONCLUSIONS: Fractures at different parts of the mandibular structure are closely related to the upper airway and hyoid position.

OBJETIVO: Este estudio analiza las diferentes partes del espacio de las vías respiratorias superiores y los cambios de posición hioidea. Los resultados proporcionan una referencia clínica para desarrollar programas de tratamiento oportuno y eficaz para los pacientes con fracturas de la mandíbula, causadas por trauma maxilofacial. MÉTODOS: Se hicieron mediciones X-cefalométricas estándares del cráneo lateral a 210 sujetos. Los sujetos fueron divididos en cuatro grupos de fractura: ángulo mandibular, condilar, cuerpo mandibular y parasinfisaria. RESULTADOS: Las radiografías de los grupos de fractura mandibular fueron comparadas con el grupo de oclusión normal para analizar el espacio de las vías respiratorias superiores y los cambios de posición hioidea. Diferentes tipos de fracturas tienen diferentes efectos sobre el espacio de las vías respiratorias superiores. La fractura de cuerpo mandibular bilateral y la fractura de parasinfisaria tienen una influencia significativa en los espacios de las vías respiratorias orofaríngea y laringofaríngea inferiores, con serios obstáculos restringiendo severamente la función respiratoria de los pacientes. CONCLUSIONES: Las fracturas en diferentes partes de la estructura mandibular se hallan estrechamente vinculadas a las vías respiratorias superiores y a la posición hioidea.

Assessment of mutagenicity and cytotoxicity of Solanum paniculatum L. extracts using in vivo micronucleus test in mice / Avaliação da mutagenicidade e citotoxicidade de extratos de Solanum paniculatum L. usando o teste do micronúcleo in vivo em camundongos

Solanum paniculatum L. is a plant species widespread throughout tropical America, especially in the Brazilian Savanna region. It is used in Brazil for culinary purposes and in folk medicine to treat liver and gastric dysfunctions, as well as hangovers. Because of the wide use of this plant as a therapeutic resource and food, the present study aimed at evaluating the mutagenic and cytotoxic effects of S. paniculatum ethanolic leaf and fruit extracts using the mouse bone marrow micronucleus test. Our results indicate that neither S. paniculatum ethanolic leaf extract nor its ethanolic fruit extract exhibited mutagenic effect in mice bone marrow; however, at higher doses, both extracts presented cytotoxic activity.

Solanum paniculatum L., popularmente conhecida como jurubeba, ocorre em toda a América tropical, especialmente no Cerrado. No Brasil, é utilizada para fins culinários e na medicina popular para o tratamento de distúrbios gástricos e hepáticos, além de ressacas. Devido à grande utilização desta planta pela população como recurso terapêutico e alimentício, o presente estudo teve como objetivo avaliar as atividades mutagênica e citotóxica dos extratos etanólico das folhas e frutos de S. paniculatum utilizando o teste do micronúcleo em medula óssea de camundongos. Os resultados indicam que os extratos etanólicos tanto das folhas quanto dos frutos de S. paniculatum não apresentaram ação mutagênica em medula óssea de camundongos, porém, em doses mais elevadas, ambos os extratos exibiram atividade citotóxica.

Angiogenic activity of Synadenium umbellatum Pax latex / Atividade angiogênica do látex de Synadenium umbellatum Pax

Synadenium umbellatum Pax, popularly known as "cola-nota", is a medicinal plant that grows in tropical regions. Latex of this plant is used to treat various diseases such as diabetes mellitus, Hansen´s disease, tripanosomiases, leukemia and several malignant tumors. In the present study, the angiogenic activity of S. umbellatum latex was evaluated using the chick embryo chorioallantoic membrane (CAM) assay. Results showed significant increase of the vascular net (p < 0.05) compared to the negative control (H2O). The histological analysis was in accordance with the results obtained. In conclusion, our data indicate that S. umbellatum latex, under the conditions of this research, presented angiogenic effect.

Synadenium umbellatum Pax, popularmente conhecida como "cola-nota", é uma planta medicinal que cresce em regiões tropicais. O látex desta planta tem sido utilizado no tratamento de várias doenças, como diabetes mellitus, hanseníase, tripanossomíases, leucemia e vários tumores malignos. No presente estudo, a atividade angiogênica do látex de S. umbellatum foi avaliada pelo ensaio da membrana corio-alantóide (MCA) de ovo embrionado de galinha. Os resultados mostraram aumento significativo da rede vascular (p < 0.05) em relação ao controle negativo (H2O). A análise histológica está em concordância com os resultados obtidos. Em conclusão, os dados indicaram que, nas condições experimentais deste estudo, o látex de S. umbellatum exibiu efeito angiogênico.

The application of C12 biochip in the diagnosis and monitoring of colorectal cancer: systematic evaluation and suggestion for improvement.

BACKGROUND: The 12 tumor markers' (TMs) biochip diagnostic (C12) system has been proven useful in some previous studies but its value for colorectal cancer (CRC) only was not systematically investigated. AIMS: To evaluate the value of C12 system for CRC. SETTINGS AND DESIGN: The associations between TMs and clinicopathological characteristics were evaluated. The most relevant TMs, the most useful combinations, and the correlations between TM levels were assessed. MATERIALS AND METHODS: The TMs detected by the C12 system in the sera of 170 pathologically confirmed CRC patients were analyzed. One or more TMs higher than or equal to reference value were defined as positive. STATISTICAL ANALYSIS: Chi-square test, Spearman rank correlation test and Receiver-operating characteristic (ROC) curves were used for the analysis. RESULTS: The overall positive rate was 41.76%, and was low in stage 0-I (12.90%). Carcinoembryonic cantigen (CEA) had the highest positive rate of 36.47%. The positive rates were significantly correlated to clinical stages and lymph node status, but not to age, sex, tumor location and pathological types. Any combinations of the five highest positive TMs did not have significantly improvements. The levels of three most related TMs (CEA, CA19-9, CA242) of CRC had positive correlation with each other. CA242 and beta-HCG levels were associated with lymph node metastasis. CONCLUSIONS: C12 system has some value in advanced CRC, but not in early CRC.

Assessment of the mutagenic, antimutagenic and cytotoxic activities of ethanolic extract of araticum (Annona crassiflora Mart. 1841) by micronucleus test in mice

A typical Brazilian plant, araticum (Annona crassiflora Mart.), is widely used in humans as therapeutic medicine to treat several diseases such as diarrhea, rheumatism and syphilis. It contains acetogenins which present cytotoxic, antitumogenic, and antiparasitic properties. In this study, mutagenic, antimutagenic and cytotoxic effects of araticum leaves ethanolic extract were evaluated by micronucleus test in mice. To evaluate the mutagenic activity, animals were treated with ethanolic extract of araticum (EEA) using 10, 20, 50, 100 and 160 mg.kg-1. For all doses, micronucleated polychromatic erythrocytes (MNPCE) frequency was evaluated at 24, 48 and 72 hours after treatment. To evaluate the antimutagenic activity, animals were treated with 10, 20, 50 and 100 mg.kg-1 of EEA and 4 mg.kg-1 of MMC simultaneously. The frequency of MNPCE was evaluated 36 hours after exposure. Cytotoxicity was evaluated by the polychromatic and normochromatic erythrocytes ratio (PCE/NCE). In the mutagenicity assessment, all doses of EEA resulted in no significant increase of MNPCE (P > 0.05), compared to solvent- control group. Regarding administration time, no significant difference among three evaluation periods was observed (P > 0.05). Such results indicate that EEA did not exert mutagenic activity. Cytotoxicity was evident in doses of 50, 100 and 160 mg.kg-1 at 24 and 48 hours after exposure. Concerning antimutagenicity, except the 10 mg.kg-1 co-administered with 4 mg/kg of MMC, all doses reduced significantly the frequency of MNPCE compared to the positive control group (P < 0.05). These results, therefore, indicate an antimutagenic activity of the EEA. Cytotoxicity was significantly increased (P < 0.01) at 100 mg.kg-1 EEA doses co-administered with 4 mg.kg-1 of MMC.

O araticum (Annona crassiflora Mart.) é uma planta tipicamente brasileira, largamente utilizada em humanos como remédio para o tratamento de diversas doenças como diarréia, reumatismo e sífilis. Esta planta contém acetogeninas que apresentam propriedades citotóxica, antitumorigênica e antiparasitária. Neste estudo, foram avaliados os possíveis efeitos mutagênico, antimutagênico e citotóxico do extrato etanólico de folhas de araticum, pelo teste de micronúcleos em camundongos. Para a investigação da atividade mutagênica, os animais foram tratados com o extrato etanólico de araticum (EEA) utilizando 10, 20, 50, 100 e 160 mg.kg-1. Para todas as doses, as freqüências de eritrócidos policromáticos micronucleados (MNPCE) foram avaliadas em 24, 48 e 72 horas após o tratamento. Para a investigação da atividade antimutagênica, os animais foram tratados com 10, 20, 50 e 100 mg.kg-1 de EEA simultaneamente com 4 mg.kg-1 de MMC. A freqüência de MNPCE foi avaliada após 36 horas de exposição. A citotoxicidade foi avaliada pela razão de eritrócitos policromáticos e normocromáticos (PCE/NCE). Na avaliação da mutagenicidade, todas as doses de EEA não aumentaram significativamente o número de MNPCE (P > 0,05), comparativamente as do grupo solvente-controle. Em relação ao tempo de administração, não foi constatada diferença significativa entre os 3 períodos avaliados (P > 0,05). Esses resultados indicam que o EEA não exerceu atividade mutagênica.A citotoxicidade foi evidente nas doses de 50, 100 e 160 mg.kg-1 em 24 e 48 horas depois da exposição. Em relação à antimutagenicidade, exceto para a dose de 10 mg.kg-1 co-administrada com 4 mg.kg-1 de MMC, todas reduziram significativamente a freqüência de MNPCE, comparativamente as do grupo controle positivo (P < 0,05). Esses resultados, portanto, indicam uma atividade antimutagênica do EEA. A citotoxicidade foi significativamente aumentada (P < 0,01) na dose de 100 mg.kg-1 de EEA co-administrada com 4 mg.kg-1 de MMC.

Absence of antimutagenicity of Cochlospermum regium (Mart. and Schr.) Pilger 1924 by micronucleus test in mice

Cochlospermum regium (Mart. and Schr.) Pilger, popularly known as "algodãozinho do campo", is a medicinal plant that grows in the Cerrado of Brazil. This plant has been used in traditional medicine against various diseases such as leucorrhoea, gastritis and ulcers. It has also been effective in treating skin problems like pimples, boils and blotches. In the present study, the in vivo antimutagenicity of aqueous extract of C. regium was evaluated. The Micronucleus Test was performed in polychromatic erythrocytes from Swiss male mice treated with one of the four doses of extract of the plant (19, 38, 76 and 114 mg.kg-1 body weight), administered by intraperitonial injection (i.p.) simultaneously with cyclophosphamide (24 mg.kg-1 b.w.) or mitomycin C (4 mg.kg-1 b.w.). The cytotoxicity was evaluated by polychromatic and normochromatic erythrocytes ratio (PCE/NCE). The results showed no significant reduction of the micronucleated polychromatic erythrocytes frequency (P > 0.05). In conclusion, the data indicate that C. regium roots aqueous extract, for the conditions used, did not exhibit the antimutagenic effect.

Cochlospermum regium (Mart. & Schr.) Pilger, conhecido popularmente como "algodãozinho-do-campo", é uma planta medicinal que cresce no Cerrado brasileiro. Esta planta tem sido utilizada na medicina tradicional contra várias doenças como leucorréia, gastrites e úlceras. Esta também tem se mostrado efetiva no tratamento de doenças de pele como espinhas, furúnculos e manchas. No presente estudo, foi avaliada a antimutagenicidade do extrato aquoso de C. regium pelo Teste do Micronúcleo in vivo. Este ensaio foi realizado em eritrócitos policromáticos de camundongos machos Swiss tratados com quatro concentrações diferentes do extrato da planta (19, 38, 76 e 114 mg.kg-1 por peso corpóreo), administrado por injeção intraperitonial (i.p.) simultaneamente com ciclofosfamida (24 mg.kg-1 p.c.) ou mitomicina C (4 mg.kg-1 p.c.). A citotoxicidade foi avaliada pela razão eritrócitos policromáticos e normocromáticos (PCE/NCE). Os resultados obtidos não mostraram redução significativa da freqüência de eritrócitos policromáticos micronucleados (P > 0,05). Em conclusão, os resultados indicam que o extrato aquoso de raiz de C. regium, para as condições utilizadas, não exibiu efeito antimutagênico.