RESUMO
Objective: To analyze the clinical feature,treatment and survival outcome of elderly patients older than 80 years with large diffuse B-cell lymphoma. Methods: A total of 46 patients aged over 80 years with large diffuse B-cell lymphoma who were treated in Third Hospital of Peking University during the period from 2002 to 2018 were retrospectively analyzed, and the clinical features, laboratory data, survival and prognostic factors were included in Kaplan-Meier and prognostic analysis. Results: Patients older than 80 years old accounted for 15.7% (46/293) in all elderly patients, and the median age was 83 years old. There were 78.3% (36/46)patients who belonged to stage â ¢ or â £, 63%(29/46) who had more than two extranodal organ involvement, and the higher proliferation index(Ki-67≥80%) was present in 53.7%(22/41) patients. Immunohistochemistry showed that 37% patients in 27 cases were double-expressed DLBCL. With a median follow-up of 25 months, the overall response rate (ORR) for the whole group was 63.0%, the complete response (CR) rate was 36.4%, the 2, 3-year progression-free survival (PFS) rate was 49.9% and 41.7%, the 2, 3-year overall survival (OS) rate was 54.6% and 43.6% respectively. The ORR for patients who received anthracycline-based therapies and non-anthracycline-based therapies were 81.8% and 55.0%, and the 3-year OS rate were 50.0% and 39.0%, respectively, but the difference was not statistically significant (P>0.05). 45.5% patients had hematologic toxicity of Grade â ¢ or above, and 56.8% patients experienced infections during the treatment. Among the patients who died, the treatment-related mortality rate in group with high score of Charlson comorbidity index(CCI) was higher (43.8% vs 16.7%, P=0.03) . The National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) score, nodal involvement area ≥3, 6 cycles of chemotherapy, CCI score, initial treatment outcome and refractory-relapsed were predictive of overall survival. Multivariate analysis indicated the CCI score (HR=6.463, P=0.008) and initial treatment outcome (HR=0.086, P=0.001) were independent prognostic risk factors. Conclusions: The clinical and pathological features of patients older than 80 years were highly aggressive with poor chemotherapy tolerance and high adverse reaction rate. Anthracycline-based therapies may be less important in the treatment of DLBCL patients aged over 80 years. Patients with high CCI score have higher treatment-related mortality and CCI can help identify elderly patients who are suitable for larger chemotherapy dose.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Difuso de Grandes Células B , Idoso de 80 Anos ou mais , Ciclofosfamida/uso terapêutico , Doxorrubicina , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Prednisona/uso terapêutico , Prognóstico , Estudos Retrospectivos , Rituximab/uso terapêutico , Resultado do TratamentoRESUMO
Liquor distiller's grains with solubles (LDGS) is high in yield and rich in crude fiber and crude protein, which suggests that LDGS might be developed and used as unconventional feedstuff for ducks. The aim of this study was to investigate the effects of sources and levels of LDGS on growth performance, carcass characteristics, serum parameters, and intestinal morphology of Cherry Valley ducks from 15 to 42 D of age. A total of 3,300 15-day-old male ducks were randomly assigned into a 1 plus 2 × 5 factorial design including 2 different sources of LDGS (unfermented LDGS [ULDGS] and fermented LDGS [FLDGS]) at 5 levels (4, 8, 12, 16, and 20%) for 4 wk. Each treatment group included 6 pens with 50 ducks per pen. Levels of dietary LDGS and the interaction between sources and levels of LDGS had no effect on final body weight, average daily feed intake (ADFI), average daily gain, or feed-to-gain ratio (F:G) of ducks from day 15 to 42 (P > 0.05). Compared with dietary ULDGS, dietary FLDGS increased final body weight (P < 0.05) and ADFI (P < 0.05) and decreased the F:G (P = 0.03). The levels of LDGS and interaction effect between levels and sources of LDGS had no effect on carcass characteristics (P > 0.05). Regardless of the inclusion level, ducks fed with diets containing FLDGS had a higher percentage of thigh muscle (P < 0.01) than birds fed with diets containing ULDGS. Sources of dietary LDGS, levels of dietary LDGS, and their interaction had no effect on serum biochemistry parameters (P > 0.05) and intestinal morphology, including villus height, crypt depth, and villus height-to-crypt depth ratio (P > 0.05). In conclusion, the inclusion of LDGS in the diet at levels up to 20% had no negative effect on the growth performance, carcass characteristics, serum parameters, and intestinal morphology of ducks. Compared with ULDGS, FLDGS increased final body weight, ADFI, and thigh muscle yield and decreased the F:G of ducks. Therefore, LDGS, especially with fermentation, could be developed as an unconventional feedstuff resource for ducks from 15 to 42 D of age.
Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Suplementos Nutricionais , Patos , Grão Comestível , Crescimento , Ração Animal/normas , Animais , Análise Química do Sangue , Dieta/veterinária , Patos/sangue , Patos/crescimento & desenvolvimento , Patos/metabolismo , Grão Comestível/metabolismo , MasculinoRESUMO
Mitochondrial function is critical for cell vitality in all eukaryotes including plants. Although plant mitochondria contain many proteins, few have been studied in the context of plant development and physiology. We used knock-down mutant RPS9M to study its important role in male gametogenesis and seed development in Arabidopsis thaliana. Knock-down of RPS9M in the rps9m-3 mutant led to abnormal pollen development and impaired pollen tube growth. In addition, both embryo and endosperm development were affected. Phenotype analysis revealed that the rps9m-3 mutant contained a lower amount of endosperm and nuclear proteins, and both embryo cell division and embryo pattern were affected, resulting in an abnormal and defective embryo. Lowering the level of RPS9M in rps9m-3 affects mitochondrial ribosome biogenesis, energy metabolism and production of ROS. Our data revealed that RPS9M plays important roles in normal gametophyte development and seed formation, possibly by sustaining mitochondrial function.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Gametogênese , Sementes , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Gametogênese/genética , Técnicas de Silenciamento de Genes , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Pólen/genética , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , Sementes/genética , Sementes/crescimento & desenvolvimentoRESUMO
Objective: To evaluate the risk factors of coloanal anastomotic stricture after laparoscopic intersphincteric resection (Lap-ISR) for patients with low rectal cancer. Methods: A retrospective case-control study was performed to collect clinicopathological data from a prospective database (registration number: ChiCTR-ONC-15007506) at the Department of Colorectal Surgery, the Characteristic Medical center of PLA Rocket Force. From June 2011 to August 2018, a total of 144 consecutive patients with low rectal cancer who underwent Lap-ISR were enrolled in the study. Inclusion criteria: (1) reconstruction of digestive tract by end-to-end hand-made coloanal anastomosis (HCAA); (2) distance from lower tumor margin to anorected sphincter ring < 1 cm and distance from lower tumor margin to intersphincteric groove ≥ 1 cm; (3) T1-3 stage tumor with expected negative circumferential resection margin evaluated by preoperative MRI or 3D endoanal ultrasound; (4) rectal cancer confirmed as well- or moderately-differentiated adenocarcinoma; (5) preoperative Wexner incontinence score >10 points. Exclusion criteria: (1) follow-up period less than 3 months; (2) multiple primary cancers; (3) undergoing colonic J-pouch, coloplasty or reconstruction of end-to-side coloanal anastomosis; (4) death within perioperative period (within 3 months after surgery). Coloanal anastomotic stricture was diagnosed if the index finger or 12 mm electronic colonoscope had obvious resistance through the anastomosis or new rectum, or could not pass, accompanied by clinical symptoms such as difficult defecation and anal incontinence. Degree of anastomotic stricture was divided into 3 grades: grade A required anal enlargement, laxative or enema to assist defecation without active surgical treatment; grade B required surgery or endoscopic intervention; grade C required definitive ostomy, including unreducible preventive ileostomy or permanent colostomy. Univariate and multivariate analysis were used to evaluate the effects of 28 variables, including baseline data (age, gender, body mass index, neoadjuvant therapy, etc.), tumor-related factors (distance between tumor low margin and anal edge, maximum diameter of tumor, TNM staging, etc.), surgery-related factors (operation time, intraoperative blood loss, ISR procedure, anastomotic height, etc.) and anastomotic leakage, on the postoperative coloanal anastomotic stricture. Univariate analysis used χ(2) test or Fisher's exact test, then factors with P<0.05 were further included in multivariate analysis using logistic regression. Results: A total of 144 patients were enrolled in the study, including 90 males and 54 females with a median age of 59 years and median BMI of 24.88 kg/m(2). R0 resection rate was 96.5% (139/144). Median tumor distal resection margin was 1.5 (0.5 to 3.0) cm. Median follow-up was 31.5 (4 to 86) months. Coloanal anastomotic stricture was observed in 19 patients (13.2%), including 3 cases (2.1%) of grade A, 9 cases (6.2%) of grade B, and 7 cases (4.9%) of grade C. The median interval from the initial surgery to diagnosis of anastomotic stricture was 7 (1 to 31) months. Univariate analysis showed that male (χ(2)=6.795, P=0.009), radiotherapy (χ(2)=13.330, P=0.001), operation type of ISR (χ(2)=7.996, P=0.013), and anastomotic leakage (χ(2)=10.198, P=0.004) were associated with the postoperative coloanal anastomotic stricture. Multivariate analysis further indicated that male (OR=5.975, 95% CI: 1.209-29.534, P=0.028), postoperative radiotherapy (OR=8.748, 95% CI: 2.397-31.929, P=0.001), and anastomotic leakage (OR=6.313, 95% CI: 1.834-21.734, P=0.003) were independent risk factor of postoperative coloanal anastomotic stricture. Conclusion: For male patients, or patients with postoperative radiotherapy or anastomotic leakage, close follow-up should be carried out to prevent postoperative coloanal anastomotic stricture following Lap-ISR.
Assuntos
Adenocarcinoma/cirurgia , Canal Anal/patologia , Anastomose Cirúrgica/efeitos adversos , Colo/patologia , Constrição Patológica/patologia , Neoplasias Retais/cirurgia , Adenocarcinoma/complicações , Adenocarcinoma/patologia , Canal Anal/cirurgia , Colo/cirurgia , Constrição Patológica/etiologia , Feminino , Humanos , Laparoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias Retais/complicações , Neoplasias Retais/patologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
Ticks can spread a variety of diseases and cause serious damage to animal husbandry. However, the existing insecticide and vaccine control methods have some disadvantages. In this paper, we review the research status of tick pesticides, including the chemical pesticides and non-chemical pesticides (Chinese herbal medicine, nanometer material, virus, fungus and bacterium pesticides), and analyze the disadvantages of the existing researches on pesticides against ticks, in order to provide a theoretical reference for establishing high-efficient and safety tick control methods.
Assuntos
Criação de Animais Domésticos , Praguicidas , Infestações por Carrapato , Criação de Animais Domésticos/tendências , Animais , Medicamentos de Ervas Chinesas/normas , Medicamentos de Ervas Chinesas/uso terapêutico , Praguicidas/normas , Infestações por Carrapato/tratamento farmacológico , CarrapatosRESUMO
MOTIVATION: The area under the receiver operating characteristic (ROC) curve (AUC), long regarded as a 'golden' measure for the predictiveness of a continuous score, has propelled the need to develop AUC-based predictors. However, the AUC-based ensemble methods are rather scant, largely due to the fact that the associated objective function is neither continuous nor concave. Indeed, there is no reliable numerical algorithm identifying optimal combination of a set of biomarkers to maximize the AUC, especially when the number of biomarkers is large. RESULTS: We have proposed a novel AUC-based statistical ensemble methods for combining multiple biomarkers to differentiate a binary response of interest. Specifically, we propose to replace the non-continuous and non-convex AUC objective function by a convex surrogate loss function, whose minimizer can be efficiently identified. With the established framework, the lasso and other regularization techniques enable feature selections. Extensive simulations have demonstrated the superiority of the new methods to the existing methods. The proposal has been applied to a gene expression dataset to construct gene expression scores to differentiate elderly women with low bone mineral density (BMD) and those with normal BMD. The AUCs of the resulting scores in the independent test dataset has been satisfactory. CONCLUSION: Aiming for directly maximizing AUC, the proposed AUC-based ensemble method provides an efficient means of generating a stable combination of multiple biomarkers, which is especially useful under the high-dimensional settings. CONTACT: lutian@stanford.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Assuntos
Densidade Óssea/genética , Idoso , Algoritmos , Área Sob a Curva , Biomarcadores/metabolismo , Feminino , Expressão Gênica , Humanos , Curva ROCRESUMO
In this study, we continued to investigate the hypoglycemic activity of Swertia punicea Helmsl., the hypoglycemic and hypolipidemic effects of methylswertianin and bellidifolin from the active ethyl acetate (EtOAc) fraction, and the potential mechanism(s) underlying the improvement of insulin resistance. Streptozotocin (STZ)-induced type 2 diabetic male BABL/c mice treated with methylswertianin and bellidifolin at different doses (orally, 200 and 100mg/kg body wt./day) for 4 weeks were analyzed in comparison to untreated mice. The results proved that methylswertianin and bellidifolin significantly reduced fasting blood glucose (FBG). The administration of both compounds also improved the oral glucose tolerance and lowered fasting serum insulin (FINS). Moreover, post-administration evaluation revealed lower serum total cholesterol (TC), low density lipoprotein cholesterol (LDL) and triglyceride (TG) levels and increased relative high density lipoprotein cholesterol (HDL) concentrations (HDL/TC). Methylswertianin and bellidifolin appeared to improve insulin resistance by enhancing insulin signaling. The expression levels of insulin-receptor alpha subunit (InsR-alpha), insulin-receptor substrate-1 (IRS-1), and phosphatidylinositol 3-kinase (PI3K) were also increased after administration. Meanwhile, methylswertianin and bellidifolin increased hepatic glycogen content, decreased glucokinase (GK) activities and increased glucose-6-phosphatase (G6Pase) activities. In conclusion, these result indicated that methylswertianin and bellidifolin could be useful for treating type-2 diabetes, likely via the improvement of insulin resistance (IR).
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Resistência à Insulina , Insulina/metabolismo , Extratos Vegetais/farmacologia , Swertia/química , Xantonas/farmacologia , Animais , Glicemia/metabolismo , Colesterol/sangue , Diabetes Mellitus Experimental/metabolismo , Glucoquinase/metabolismo , Intolerância à Glucose/tratamento farmacológico , Glucose-6-Fosfatase/metabolismo , Glicogênio/metabolismo , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/uso terapêutico , Insulina/sangue , Proteínas Substratos do Receptor de Insulina/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fosfatidilinositol 3-Quinases/metabolismo , Fitoterapia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Receptor de Insulina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Triglicerídeos/sangue , Xantonas/isolamento & purificação , Xantonas/uso terapêuticoRESUMO
A study was conducted to determine the effects of dietary phospholipid (PL) levels in cobia (Rachycentron canadum) larvae with regard to growth, survival, plasma lipids and enzymes of lipid metabolism. Fish with an average weight of 0.4 g were fed diets containing four levels of PL (0, 20, 40 and 80 g kg(-1)dry matter: purity 97%) for 42 days. Final body weight (FBW), weight gain (WG) and survival ratio were highest in the 8% PL diet group and mortality was highest in PL-free diet group. We examined the activities of lipoprotein lipase (LPL) and hepatic lipase (HL) in liver, lecithin-cholesterolacyltransferase (LCAT) in plasma as well as plasma lipids and lipoprotein. LCAT activity showed a decrease of more than two-fold in PL-supplemented diet groups compared with the PL-free diet group. HL activity was highest in the 8% PL diet group and the other three groups showed no difference. LPL activity was significantly higher in the PL-supplemented diet groups than in the PL-free diet group. The dietary intervention significantly increased plasma phospholipids and total cholesterol (TC) levels, and the higher free cholesterol (FC) level contributed to the TC level. However, the fish fed PL exhibited a significantly decreased plasma triglyceride (TG) level. The lipoprotein fractions were also affected significantly by the PL. The PL-supplemented diet groups had significantly higher high-density lipoprotein (HDL) compared with the PL-free diet group, but showed a marked decrease in very low-density lipoprotein (VLDL). The results suggested that PL could modify plasma lipoprotein metabolism and lipid profile, and that the optimal dietary PL level may well exceed 80 g kg(-1) for cobia larvae according to growth and survival.
Assuntos
Dieta/veterinária , Gorduras na Dieta/farmacologia , Enzimas/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Perciformes/fisiologia , Fosfolipídeos/farmacologia , Animais , Larva/efeitos dos fármacos , Larva/enzimologia , Larva/crescimento & desenvolvimento , Larva/metabolismo , Lipoproteínas/sangue , Fígado/efeitos dos fármacos , Fígado/enzimologia , Perciformes/crescimento & desenvolvimento , Perciformes/metabolismo , Fosfolipídeos/administração & dosagem , Plasma/efeitos dos fármacos , Plasma/enzimologia , Análise de SobrevidaRESUMO
AIM: To clarify the mechanism of the therapeutic action of icariin on erectile dysfunction (ED). METHODS: PDE5 was isolated from the human platelet and PDE4 from the rat liver tissue using the FPLC system (Pharmacia, Milton Keynes, UK) and the Mono Q column. The inhibitory effects of icariin on PDE5 and PDE4 activities were investigated by the two-step radioisotope procedure with [(3)H]-cGMP/[(3)H]-cAMP. Papaverine served as the control drug. RESULTS: Icariin and papaverine showed dose-dependent inhibitory effects on PDE5 and PDE4 activities. The IC(50) of Icariin and papaverine on PDE5 were 0.432 micromol/L and 0.680 micromol/L, respectively and those on PDE4, 73.50 micromol/L and 3.07 micromol/L, respectively. The potencies of selectivity of icariin and papaverine on PDE5 (PDE4/PDE5 of IC(50)) were 167.67 times and 4.54 times, respectively. CONCLUSION: Icariin is a cGMP-specific PDE5 inhibitor that may be developed into an oral effective agent for the treatment of ED.
Assuntos
3',5'-GMP Cíclico Fosfodiesterases/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Flavonoides/farmacologia , Ereção Peniana/efeitos dos fármacos , 3',5'-AMP Cíclico Fosfodiesterases/antagonistas & inibidores , 3',5'-AMP Cíclico Fosfodiesterases/metabolismo , 3',5'-GMP Cíclico Fosfodiesterases/antagonistas & inibidores , Animais , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4 , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5 , Relação Dose-Resposta a Droga , Humanos , Técnicas In Vitro , Masculino , Papaverina/farmacologia , Ereção Peniana/fisiologia , Inibidores de Fosfodiesterase/farmacologia , Ratos , TrítioRESUMO
Xanthophylls are oxygenated carotenoids that perform critical roles in plants. Beta-carotene hydroxylases (beta-hydroxylases) add hydroxyl groups to the beta-rings of carotenes and have been cloned from several bacteria and plants, including Arabidopsis. The lut1 mutation of Arabidopsis disrupts epsilon-ring hydroxylation and has been suggested to identify a related carotene hydroxylase that functions specifically on epsilon-ring structures. We have used library screening and genomics-based approaches to isolate a second beta-hydroxylase genomic clone and its corresponding cDNA from Arabidopsis. The encoded protein is 70% identical to the previously reported Arabidopsis beta-hydroxylase 1. Phylogenetic analysis indicates a common origin for the two proteins, however, their different chromosomal locations, intron positions and intron sizes suggest their duplication is not recent. Although both hydroxylases are expressed in all Arabidopsis tissues analyzed, beta-hydroxylase 1 mRNA is always present at higher levels. Both cDNAs encode proteins that efficiently hydroxylate the C-3 position of beta-ring containing carotenes and are only weakly active towards epsilon-ring containing carotenes. Neither beta-hydroxylase cDNA maps to the LUT1 locus, and the genomic region encompassing the LUT1 locus does not contain a third related hydroxylase. These data indicate that the LUT1 locus encodes a protein necessary for epsilon-ring hydroxylation but unrelated to beta-hydroxylases at the level of amino acid sequence.
Assuntos
Arabidopsis/genética , Oxigenases de Função Mista/genética , Proteínas de Plantas/genética , Sequência de Aminoácidos , Arabidopsis/enzimologia , Northern Blotting , Mapeamento Cromossômico , DNA Complementar/química , DNA Complementar/genética , DNA Complementar/isolamento & purificação , DNA de Plantas/química , DNA de Plantas/genética , Éxons , Regulação Enzimológica da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genes de Plantas/genética , Íntrons , Isoenzimas/genética , Isoenzimas/metabolismo , Oxigenases de Função Mista/metabolismo , Dados de Sequência Molecular , Filogenia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Especificidade por Substrato , Distribuição TecidualRESUMO
Marigold (Tagetes erecta L.) flower petals synthesize and accumulate carotenoids at levels greater than 20 times that in leaves and provide an excellent model system to investigate the molecular biology and biochemistry of carotenoid biosynthesis in plants. In addition, marigold cultivars exist with flower colors ranging from white to dark orange due to >100-fold differences in carotenoid levels, and presumably similar changes in carbon flux through the pathway. To examine the expression of carotenoid genes in marigold petals, we have cloned the majority of the genes in this pathway and used these to assess their steady-state mRNA levels in four marigold cultivars with extreme differences in carotenoid content. We have also cloned genes encoding early steps in the biosynthesis of isopentenyl pyrophosphate (IPP), the precursor of all isoprenoids, including carotenoids, as well as two genes required for plastid division. Differences among the marigold varieties in the expression of these genes suggest that differences in mRNA transcription or stability underlie the vast differences in carotenoid synthesis and accumulation in the different marigold varieties.
Assuntos
Carotenoides/biossíntese , Perfilação da Expressão Gênica , Plantas Medicinais/genética , Northern Blotting , Carotenoides/análise , Cromatografia Líquida de Alta Pressão , DNA Complementar/química , DNA Complementar/genética , Regulação da Expressão Gênica no Desenvolvimento , Regulação da Expressão Gênica de Plantas , Dados de Sequência Molecular , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Plantas Medicinais/crescimento & desenvolvimento , Plantas Medicinais/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Análise de Sequência de DNA , Especificidade da EspécieRESUMO
BACKGROUND: In learning and memory tasks, requiring visual spatial memory (VSM), males exhibit superior performance to females (a difference attributed to the hormonal influence of estrogen). This study examined the influence of phytoestrogens (estrogen-like plant compounds) on VSM, utilizing radial arm-maze methods to examine varying aspects of memory. Additionally, brain phytoestrogen, calbindin (CALB), and cyclooxygenase-2 (COX-2) levels were determined. RESULTS: Female rats receiving lifelong exposure to a high-phytoestrogen containing diet (Phyto-600) acquired the maze faster than females fed a phytoestrogen-free diet (Phyto-free); in males the opposite diet effect was identified. In a separate experiment, at 80 days-of-age, animals fed the Phyto-600 diet lifelong either remained on the Phyto-600 or were changed to the Phyto-free diet until 120 days-of-age. Following the diet change Phyto-600 females outperformed females switched to the Phyto-free diet, while in males the opposite diet effect was identified.Furthermore, males fed the Phyto-600 diet had significantly higher phytoestrogen concentrations in a number of brain regions (frontal cortex, amygdala & cerebellum); in frontal cortex, expression of CALB (a neuroprotective calcium-binding protein) decreased while COX-2 (an inducible inflammatory factor prevalent in Alzheimer's disease) increased. CONCLUSIONS: Results suggest that dietary phytoestrogens significantly sex-reversed the normal sexually dimorphic expression of VSM. Specifically, in tasks requiring the use of reference, but not working, memory, VSM was enhanced in females fed the Phyto-600 diet, whereas, in males VSM was inhibited by the same diet. These findings suggest that dietary soy derived phytoestrogens can influence learning and memory and alter the expression of proteins involved in neural protection and inflammation in rats.
Assuntos
Estrogênios não Esteroides/farmacologia , Alimentos Formulados , Glycine max , Isoflavonas , Aprendizagem em Labirinto/efeitos dos fármacos , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Química Encefálica/efeitos dos fármacos , Calbindinas , Sinais (Psicologia) , Ciclo-Oxigenase 2 , Feminino , Lobo Frontal/química , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/metabolismo , Hipocampo/química , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Isoenzimas/análise , Isoenzimas/metabolismo , Masculino , Memória/efeitos dos fármacos , Memória/fisiologia , Modelos Animais , Fatores de Crescimento Neural/farmacologia , Fármacos Neuroprotetores/farmacologia , Fitoestrógenos , Preparações de Plantas , Prostaglandina-Endoperóxido Sintases/análise , Prostaglandina-Endoperóxido Sintases/metabolismo , Ratos , Ratos Long-Evans , Proteína G de Ligação ao Cálcio S100/análise , Proteína G de Ligação ao Cálcio S100/metabolismo , Caracteres Sexuais , Fatores SexuaisRESUMO
Recent neuroanatomical studies have revealed a direct hypothalamocerebellar histaminergic pathway. However, the functional significance of the histaminergic fibers in the cerebellum is not yet clear. In this study, the effects of histamine on the firing of cerebellar Purkinje cells (PCs) were investigated in vitro. Histamine predominantly produced excitatory (106/111, 95.5%) and in a few cases inhibitory (5/111, 4.5%) responses in PCs. The histamine-induced excitation was not blocked by perfusing the slice with low Ca2+ high/Mg2+ medium (n = 8), supporting a direct postsynaptic action of histamine. The histamine H2 receptor antagonist ranitidine effectively blocked the excitatory response of PCs to histamine (n = 20), but triprolidine, an H1 receptor antagonist, could not significantly block the histamine-induced excitation, or only very slightly decreased the excitatory effect of histamine on the cells (n = 13). On the other hand, the highly selective H2 receptor agonist dimaprit mimicked the excitatory effect of histamine on PCs and this dimaprit-induced excitation was also blocked by ranitidine (n = 20), but not triprolidine (n = 8). However, the H1 receptor agonists betahistine and 2-thiazolylethylamine did not show any effect on the PCs (n = 9 and 14). These results reveal that histamine excites cerebellar PCs via H2 receptors and suggest that the hypothalamocerebellar histaminergic fibers may play an important role in functional activities of the cerebellum.
Assuntos
Histamina/farmacologia , Células de Purkinje/efeitos dos fármacos , Receptores Histamínicos H2/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Cerebelo/citologia , Cerebelo/efeitos dos fármacos , Cerebelo/fisiologia , Agonistas dos Receptores Histamínicos/farmacologia , Antagonistas dos Receptores Histamínicos H1/farmacologia , Antagonistas dos Receptores H2 da Histamina/farmacologia , Hipotálamo/fisiologia , Vias Neurais/efeitos dos fármacos , Vias Neurais/fisiologia , Células de Purkinje/fisiologia , Ratos , Ratos Sprague-Dawley , Receptores Histamínicos H2/fisiologiaRESUMO
Pharmacologic effects of propolis were investigated in this article. The results suggested that propolis has pharmacologic functions in many aspects. It is a new-type medicine derived from animal in pharmacology and food both. To small mouse, propolis showed the functions of anti-fatigue and endurance to lack of oxygen. To high-blood-lipid-model mouse, it prevented increase of blood-mucus and blood lipid(TC, TG, LDL-C) (P < 0.05-0.01), but there were insignificant changes to red-blood-cell proportion (HCT) and high-density lipoprotein chelesteral (HDC-C). To small immunosuppessive-model mouse, propolis could strengthen macrophagocyte phagocytosis in the abdominal-cavity (P < 0.05), and increase the thymus-index (P < 0.05), but there were insignificant changes to the spleen-index. The LD50 > 7500 mg/kg to small mouse.
Assuntos
Hiperlipidemias/sangue , Hipolipemiantes/farmacologia , Materia Medica/farmacologia , Própole/farmacologia , Adjuvantes Imunológicos/farmacologia , Animais , Viscosidade Sanguínea , Fadiga/tratamento farmacológico , Feminino , Lipídeos/sangue , Macrófagos Peritoneais/imunologia , Masculino , Camundongos , Fagocitose , Ratos , Ratos WistarRESUMO
We have investigated the effect of tamoxifen (TAM) on endogenous or ultraviolet radiation (UVR)-induced oxidative damage to macromolecules in vitro and in vivo. In a system containing calf thymus DNA exposed to a germicidal UV lamp, both TAM and 4-hydroxytamoxifen (4-OH-TAM) inhibited UVR-induced the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in DNA in a dose-dependent manner. At low concentrations, 4-OH-TAM quenched 8-OHdG more potently than TAM. However, the reduction of 8-OHdG by TAM and 4-OH-TAM became similar at a concentration of 10 microM. In contrast, ascorbic acid had the similar effect to TAM, whereas glutathione exhibited little effect on UVR-induced 8-OHdG. The order of quenching efficacy was: 4-OH-TAM > TAM approximately = ascorbic acid > glutathione. We have further determined the effect of TAM on endogenous 8-OHdG formation, lipid peroxidation, and protein oxidation in the skin of SENCAR mice. Topical application of 5 micromol TAM significantly reduced the level of 8-OHdG in mouse epidermis by approximately 27% (P < 0.05). Endogenous lipid peroxidation and protein oxidation, measured as malondialdehyde (MDA) and carbonyl groups, were also substantially reduced by topical TAM. Further study was conducted to evaluate the effect of TAM on UVR-induced 8-OHdG and MDA in skin of hairless mice. In mice subacutely exposed to low dose (3.4 kJ/m2 x six doses) and high dose (16.8 kJ/m2 x three doses) of UVB irradiation, TAM significantly blocked the formation of 8-OHdG in mouse epidermis by 57-81% and MDA by 37-65%, respectively. Our studies suggest that reduction of oxidative damages to biological macromolecules in vitro and in vivo may at least in part explain the anti-carcinogenic and chemopreventive actions of tamoxifen.
Assuntos
Dano ao DNA , DNA/efeitos da radiação , Estresse Oxidativo/efeitos dos fármacos , Tamoxifeno/farmacologia , 8-Hidroxi-2'-Desoxiguanosina , Animais , Bovinos , Desoxiguanosina/análogos & derivados , Desoxiguanosina/biossíntese , Feminino , Camundongos , Camundongos Pelados , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/efeitos da radiação , Tamoxifeno/metabolismo , Raios UltravioletaRESUMO
Thresholds for the detection of a tone added in-phase to the carrier of a fully modulated SAM tone were measured. In some conditions the signal was added to a single SAM tone, and in other conditions the signal was added to the sum of three or more SAM tones. Level equalization ensured that the addition of the tonal signal did not lead to increases in energy. When multiple SAM tone maskers were used, a small number of reproducible maskers were tested, each masker being composed of SAM tones with a variety of relative modulator phases. The maskers were either fixed across intervals and trials, roved across trials but fixed across intervals, or randomly chosen across both intervals and trials. The frequency separation between the signal-centered and off-frequency SAM tones was also varied. For small signal-centered/off-frequency SAM tone frequency separations, a separation ratio of 1.3, thresholds in the fixed condition depend on the relative modulator phases, and a simple mixture model reasonably predicted thresholds in the roving condition based on thresholds in the fixed condition for two of the three observers. For signal-centered/off-frequency SAM tone frequency separation factor of 1.68, effects of relative modulator phases were not obtained. Thresholds in the target-alone condition were generally superior to thresholds measured with the comodulated masker. Comodulated thresholds were better than target-alone thresholds only when level equalization was not used, and so the addition of the signal led to increases in level.
Assuntos
Estimulação Acústica , Mascaramento Perceptivo , Detecção de Sinal Psicológico , Adulto , Limiar Auditivo , HumanosRESUMO
From the ethanolic extracts of the aerial parts of Fagopyrum cymosum, eleven compounds were isolated, of which eight have been identified as benzoic acid(1), beta-sitosterol(2),5,5'-di-alpha-furaldehyde dimethyl ether(3), p-hydroxybenzoic acid(4), rutin(5), quercetin(6), daucosterol(7), succinic acid(8) by spectroscopic methods. Compound 3 is obtained from the genus for the first time.
Assuntos
Medicamentos de Ervas Chinesas/química , Furaldeído/análogos & derivados , Furaldeído/isolamento & purificação , Parabenos/isolamento & purificação , Plantas Medicinais/química , Polygonaceae/química , Furaldeído/química , Estrutura Molecular , Parabenos/química , Brotos de Planta/química , Ácido Succínico/química , Ácido Succínico/isolamento & purificaçãoRESUMO
128 children of mental retardation were diagnosed in accordance with the diagnostic standards proposed by WHO in 1985. The patients were treated compositely with acupuncture, auriculo-acupoint pellet pressure and herbal plasters on acupoints, bringing about improved mental developments in intelligence quotient (IQ) and social adaptation behaviour (SAB), as evidenced by recognized intelligence tests for children.