RESUMO
The study was aimed to analyze the seasonal pollen allergen spectrum of patients with allergic rhinitis (AR) in Nanchang city, and to provide evidence for improving the clinical diagnosis, treatment, prevention and epidemiology of seasonal AR. A retrospective analysis was conducted on the results of skin prick test (SPT) among 1 752 patients with AR in outpatient at Department of Otolaryngology, the First Affiliated Hospital of Nanchang University from September 2020 to August 2021 (a total of 1 069 males and 683 females, age ranged from 2 to 84 years old). SPSS 22.0 software was used to analyze the positive rates of main allergens and their differences in gender, age, and month of visit. Differences among groups were compared by student t test, Wilcox rank sum test, or χ2 test. The results showed that among 1 752 SPT-positive patients, the number of simple seasonal AR and the number of perennial combined seasonal AR were 102 (5.82%) and 281 (16.04%), respectively. There was no significant difference between male and female patients in positive seasonal pollen allergens (χ2=2.181, P>0.05), but the positive rate of indoor seasonal pollen allergens in males was higher than that in females (χ2=7.901, P<0.05). The seasonal pollen allergens ranking top 5 of the positive rates were willow (6.62%, 116/1 752), humulus scandens (5.71%, 100/1 752), rape (5.54%, 97/1 752), grey pigweed (4.62%, 81/1 752) and birch (3.60%, 63/1 752). The positive rates of indoor and seasonal pollen allergens increased first and then decreased in different age groups, and the highest positive rates of seasonal pollen allergens were in the age group of 31-40 years old, with statistical significance compared with other groups (χ2=61.269, P<0.05). The seasonal allergen positive rate showed two peaks in time: March to May and September to November. The positive rate of pollen in spring was 60.27% (132/219), which was significantly higher than that in autumn (39.73%,87/219) (χ2=9.247, P<0.05). The positive rate of pollen combination in spring and autumn was 68.29% (112/164), which was significantly higher than that in spring and autumn alone (18.9%,31/164) and (12.8%, 21/164) (χ2=14.731, P<0.05). In summary, pollen allergy in Nanchang City cannot be ignored, accounting for more than 20% of the total number of AR. The incidence of seasonal AR in Nanchang City showed two peaks (March to May and September to November). The common allergens for seasonal AR in Nanchang City were willow, humulus scandens, rape, grey chenopods and birch.
Assuntos
Rinite Alérgica , Humanos , Feminino , Masculino , Adulto , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Estações do Ano , Pólen , Hospitais , AlérgenosRESUMO
Objective: To evaluate the efficacy and safety of different antimicrobial regimens in patients with bloodstream infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). Methods: The clinical date of patients with CRKP bloodstream infections were retrospectively analyzed at the First Affiliated Hospital of Zhejiang University Medical College between January 2017 and January 2018. All subjects were separated into three groups based on antibiotics regimens over 72 hours, including meropenem 2.0 g every 8 hours, tigecycline 200 mg as initial dose and 100 mg every 12 hours, and polymyxin B 1.25 mg/kg every 12 hours as salvage treatment of tigecycline. Results: A total of 86 patients were finally recruited, including 14, 52 and 20 patients in groups of meropenem, tigecycline and polymyxin B salvage, respectively. All of the strains were resistant to meropenem and susceptible to tigecycline and polymyxin B initially, while 2 of them became resistant to tigecycline during treatment. The 28-day mortality was significantly higher in meropenem group (13/14) than that in tigecycline group and polymyxin B salvage group (61.5%, 32/52) and (12/20), respectively (P<0.01), while as no significant difference was seen in the last two groups (χ(2)=0.014, P>0.05). The incidences of hepatic impairment [3.8%(2/52) vs. 1/20] and renal dysfunction (0 vs. 1/20) between tigecycline group and polymyxin B salvage group were both comparable (P>0.05). Conclusion: The meropenem-based therapy is not recommended for CRKP-related bloodstream infections. Tigecycline-based therapy is still disappointing despite salvage use of polymyxin B after 72 hours. Hepatic and nephretic toxicities caused by additional polymyxin B are acceptable.
Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Meropeném/uso terapêutico , Polimixinas/uso terapêutico , Tigeciclina/uso terapêutico , Antibacterianos/administração & dosagem , Bacteriemia/mortalidade , China/epidemiologia , Farmacorresistência Bacteriana Múltipla , Humanos , Infecções por Klebsiella/diagnóstico , Klebsiella pneumoniae/isolamento & purificação , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Resultado do Tratamento , Resistência beta-LactâmicaRESUMO
Hypertension and its cardiovascular complications can produce many serious problems for the health of Chinese residents, therefore, affect quality of the population. About a century ago, the research and treatment of hypertension were still in primary stage. Despite the material and cultural resources were extremely limited, modern Chinese medical scientists performed blood pressure surveys of different populations in China. Besides, they carried out researches on epidemiology and mechanisms of hypertension, as well as clinical trials. At the same time, substantive pioneering work was done in medical education and the spread of popular science. A large number of textbooks on physiology or internal medicine were translated, and popular science books such as the Prevention and Treatment of Hypertension were published. These works opened the prelude to the research, prevention and treatment of hypertension in China.
Assuntos
Anti-Hipertensivos , Hipertensão , Anti-Hipertensivos/uso terapêutico , Livros , China , Humanos , Hipertensão/tratamento farmacológico , TaiwanRESUMO
OBJECTIVES: To perform a systematic review and meta-analysis on the effects of audiovisual distraction on reducing dental anxiety in children during dental treatment under local anesthesia. METHODS: The authors identified eligible reports published through August 2017 by searching PubMed, EMBASE, and Cochrane Central Register of Controlled Trials. Clinical trials that reported the effects of audiovisual distraction on children's physiological measures, self-reports, and behavior rating scales during dental treatment met the minimum inclusion requirements. The authors extracted data and performed a meta-analysis of appropriate articles. RESULTS: Nine eligible trials were included and qualitatively analyzed; some of these trials were also quantitatively analyzed. Among the physiological measures, heart rate or pulse rate was significantly lower (p = .01) in children subjected to audiovisual distraction during dental treatment under local anesthesia than in those who were not; a significant difference in oxygen saturation was not observed. The majority of the studies using self-reports and behavior rating scales suggested that audiovisual distraction was beneficial in reducing anxiety perception and improving children's cooperation during dental treatment. CONCLUSION: The audiovisual distraction approach effectively reduces dental anxiety among children. Therefore, we suggest the use of audiovisual distraction when children need dental treatment under local anesthesia.
Assuntos
Ansiedade/prevenção & controle , Odontopediatria/métodos , Estimulação Acústica , Adolescente , Anestesia Local , Ansiedade/fisiopatologia , Criança , Comportamento Infantil , Pré-Escolar , Ensaios Clínicos Controlados como Assunto , Comportamento Cooperativo , Frequência Cardíaca , Humanos , Oxigênio/sangue , Estimulação Luminosa , AutorrelatoRESUMO
BACKGROUND: Alzheimer's Disease (AD) patients homozygous for the APOE4 allele (APOE4/4) have a distinct clinical and biological phenotype with high levels of beta amyloid (Aß) pathology and toxic Aß oligomers. Tramiprosate, an oral agent that inhibits Aß monomer aggregation into toxic oligomers, was evaluated in two Phase 3 Mild to Moderate AD studies which did not show efficacy in the overall population. Re-analyses of these trials showed the most consistent clinical benefits in APOE4/4 patients. We analyzed efficacy in the APOE4/4 patients with Mild disease. OBJECTIVES: To determine the optimal stage of AD for future trials in APOE4/4 homozygotes. DESIGN: Two randomized, double-blind, placebo-controlled parallel-arm multi-center studies of 78-weeks duration. SETTING: Academic Alzheimer's disease centers, community-based memory clinics, and neuropsychiatric research sites. PARTICIPANTS: Participants included 2,025 AD patients with MMSE 16-26. Approximately 13-15% had APOE4/4 genotype (N= 147 and 110 per study), mean age 71.1 years, 56% females. Almost all were on stable symptomatic drugs. INTERVENTION: Randomized subjects received oral placebo, 100mg BID, or 150mg BID of tramiprosate. MEASUREMENTS: Co-primary outcomes were change from baseline in the ADAS-cog11 and CDR-SB. Disability assessment for dementia (DAD) was a secondary outcome. RESULTS: In APOE4/4 homozygotes receiving 150mg BID tramiprosate, efficacy in the traditional Mild AD patients (MMSE 20-26) was higher than the overall group (MMSE 16-26) and efficacy in the Mild patients (MMSE 22-26) was highest. Tramiprosate benefits compared to placebo on ADAS-cog, CDR-SB, and DAD were 125%, 81% and 71%, respectively (p<0.02). The Mild subgroup (MMSE 22-26) showed cognitive stabilization with no decline over 78 weeks, both ADAS-cog and DAD effects increased over time. Tramiprosate safety in APOE4/4 patients was favorable. Most common adverse events were nausea, vomiting, depression and decreased weight. CONCLUSIONS: The Mild subgroup of APOE4/4 AD patients (MMSE 22-26) showed larger benefits on the high dose of tramiprosate than the overall Mild and Moderate group. Consistent with its preclinical effects on Aß oligomers, tramiprosate seemed to stabilize cognitive performance, supporting its disease modification potential. Confirmatory studies using ALZ-801, an improved pro-drug formulation of tramiprosate, will target APOE4/4 patients with Mild AD.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Apolipoproteína E4/genética , Nootrópicos/uso terapêutico , Taurina/análogos & derivados , Idoso , Peptídeos beta-Amiloides/antagonistas & inibidores , Peptídeos beta-Amiloides/metabolismo , Cognição/efeitos dos fármacos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Homozigoto , Humanos , Masculino , Testes de Estado Mental e Demência , Nootrópicos/efeitos adversos , Agregação Patológica de Proteínas/tratamento farmacológico , Índice de Gravidade de Doença , Taurina/efeitos adversos , Taurina/uso terapêutico , Resultado do TratamentoRESUMO
Objective: To evaluate the effect of traditional Chinese medicine (TCM) treatment as maintenance therapy on regulating the serum concentration of soluble cytotoxic T lymphocyte associated antigen-4 (sCTLA-4) in patients with advanced non-small-cell lung cancer (NSCLC) and the relationship between sCTLA-4 and time to progression (TTP). Methods: This study was conducted as a prospective, randomized, controlled trial. 64 non-progressive patients who responded to initial therapy were randomized 1â¶1 to the TCM arm (treated with cinobufacini injection, herbal decoction and Chinese acupoint application, n=32) or to the chemotherapy arm (n=32). Each cycle was 21 days. Cycles were repeated until disease progression, unacceptable toxicity, or until the patient requested therapy discontinuation.The serum concentration of sCTLA-4 was detected by enzyme linked immunosorbent assay (ELISA) in the 64 patients with advanced NSCLC before and after two cycles of maintenance treatment. Cox regression was used to analyze the relative ratio for the risk of disease progression. Results: After 2 cycles of maintenance TCM treatment, the serum concentration of sCTLA-4 in patients with advanced NSCLC was (12.77±2.37 pg/ml), significantly lower than that before treatment (40.30±10.75)(P=0.013). After 2 cycles of maintenance chemotherapy, the serum concentration of sCTLA-4 was higher than that before treatment, but was not significantly different (44.48±10.12 vs. 46.64±11.21 pg/ml, P=0.612). After 2 cycles of maintenance treatment, TCM treatment can significantly bring down the serum concentration of sCTLA-4 compared to chemotherapy (12.77±2.37 vs. 46.64±11.21 pg/ml, P=0.004). The multivariate analysis indicated that sCTLA-4 levels and treatment regimen were independent prognostic factors for TTP (P<0.05 for both). Conclusions: Regulating the serum concentration of sCTLA-4 may be one of the mechanisms of TCM maintenance treatment of NSCLC. Trial registration Chinese Clinical Trial Register, ChiCTR-TRC-10001017.
Assuntos
Venenos de Anfíbios/uso terapêutico , Antígeno CTLA-4/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Quimioterapia de Manutenção/métodos , Medicina Tradicional Chinesa , Pontos de Acupuntura , Idoso , Antígenos de Neoplasias/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Terapia Combinada/métodos , Progressão da Doença , Medicamentos de Ervas Chinesas , Feminino , Humanos , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/sangue , Fitoterapia , Prognóstico , Estudos ProspectivosRESUMO
OBJECTIVE: Previous studies on consumption of caffeine and risk of multiple sclerosis (MS) have yielded inconclusive results. We aimed to investigate whether consumption of coffee is associated with risk of MS. METHODS: Using two population-representative case-control studies (a Swedish study comprising 1620 cases and 2788 controls, and a US study comprising 1159 cases and 1172 controls), participants with different habits of coffee consumption based on retrospective data collection were compared regarding risk of MS, by calculating ORs with 95% CIs. Logistic regression models were adjusted for a broad range of potential confounding factors. RESULTS: Compared with those who reported no coffee consumption, the risk of MS was substantially reduced among those who reported a high consumption of coffee exceeding 900 mL daily (OR 0.70 (95% CI 0.49 to 0.99) in the Swedish study, and OR 0.69 (95% CI 0.50 to 0.96) in the US study). Lower odds of MS with increasing consumption of coffee were observed, regardless of whether coffee consumption at disease onset or 5 or 10 years prior to disease onset was considered. CONCLUSIONS: In accordance with studies in animal models of MS, high consumption of coffee may decrease the risk of developing MS. Caffeine, one component of coffee, has neuroprotective properties, and has been shown to suppress the production of proinflammatory cytokines, which may be mechanisms underlying the observed association. However, further investigations are needed to determine whether exposure to caffeine underlies the observed association and, if so, to evaluate its mechanisms of action.
Assuntos
Café , Ingestão de Líquidos , Esclerose Múltipla/epidemiologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Fatores de Proteção , Estudos Retrospectivos , Suécia/epidemiologia , Estados Unidos/epidemiologia , Adulto JovemRESUMO
The primary aims of this study were to investigate mitochondrial metabolism during experimental allergic encephalomyelitis (EAE) animal model axonal injury and to determine the correlation among neurological function scores, pathological changes, and the activities of the BB isoenzyme of creatine kinase (CK-BB), catalase (CAT), and calpain in the brain tissues of EAE rats. Another goal was to preliminarily define the mechanism of mitochondrial metabolism resulting from the effect of beta 2 adrenergic agonists in the process of EAE animal model axonal damage. EAE was induced in specific pathogen free Wistar rats by guinea pig spinal cord homogenate, complete Freund's adjuvant, and pertussis vaccine. We recorded the behavioral change in EAE rats, detected pathological changes in central nervous tissue, and observed the changes of the CK-BB, CAT, and calpain in the EAE rat brain and spinal cord. The results indicated that the average neurologic function score increased in the EAE group compared to that of the controls (P < 0.01). In addition, CAT and CK-BB activities significantly decreased and the calpain activity significantly increased compared with those of the control group (P < 0.05). The decrease of the activity of central nervous CK-BB and CAT content, as well as the increase of calpain activity at the highest time point were considered to be the consequences of EAE. Furthermore, the results revealed that use of salbutamol could alleviate disease symptoms and reduce the recurrence of the EAE disease.
Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Axônios/efeitos dos fármacos , Encefalomielite Autoimune Experimental/tratamento farmacológico , Animais , Calpaína/metabolismo , Catalase/metabolismo , Encefalomielite Autoimune Experimental/metabolismo , Feminino , Cobaias , Ratos , Ratos WistarRESUMO
This study investigated functional changes in the ovaries of women who have had conservative laparoscopic endometrial cystectomy and the effects of traditional kidney-reinforcing and blood-activating Traditional Chinese Medicine (TCM) on ovarian function. Seventy female patients who underwent laparoscopic endometrial cystectomy were randomized into two groups: TCM group receiving kidney-reinforcing and blood-activating Chinese medicine (N = 35) and control group receiving only routine follow-up (N = 35). The serum levels of all study participants were measured for follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and inhibin B (INHB) prior to and after endometrial surgery. Postoperative menstruation conditions were also assessed. Compared to preoperative conditions, both LH and FSH levels during the postoperative 1st month increased in both groups, while E2 and INHB levels decreased (P < 0.05). In the TCM group, in contrast to the control group and the postoperative 1st month, we observed a decrease in LH and FSH levels during the postoperative 4th month, while E2 and INHB levels increased (P < 0.05). In this study, we found that certain TCM prescriptions lowered postoperative serum FSH and LH levels and increased the serum INHB and basal E2 levels, thereby improving the ovarian reserve.
Assuntos
Cistectomia , Endométrio/cirurgia , Rim/fisiopatologia , Laparoscopia , Medicina Tradicional Chinesa , Ovário/fisiopatologia , Adulto , Endométrio/fisiopatologia , Feminino , Hormônios/sangue , Humanos , Subunidades beta de Inibinas/sangue , Menstruação , Pessoa de Meia-Idade , Adulto JovemRESUMO
MiR-155 is known to participate in various cellular processes by targeting gene expression. We previously revealed a link between miR-155 and perturbation of trophoblast invasion and differentiation. This study aimed to investigate the target molecule(s) of miR-155 on the influence on the proliferation and migration of trophoblast cells. Bioinformatics analysis showed that, at the 3' untranslated region (UTR) of cyclin D1, six bases are complementary to the seed region of miR-155. Luciferase assays and cyclin D1 3'UTR transfection assays validated that cyclin D1 3'UTR was the target of miR-155 in HTR-8/SVneo cells. Overexpression of miR-155 in HTR-8/SVneo cells reduced the level of cyclin D1 protein, decreased cell proliferation and invasion, and increased cell number at the G1 stage. Furthermore, the increased expression of miR-155 also regulated the protein levels of kinase inhibitory protein p27 and phosphorylated cytoskeletal protein filamin A. In conclusion, we found that cyclin D1 may be a target of miR-155 in HTR-8/SVneo cells, and demonstrated a negative regulatory role of miR-155 involved in cyclin D1/p27 pathway in proliferation and migration of the cells.
Assuntos
Movimento Celular/efeitos dos fármacos , Ciclina D1/metabolismo , MicroRNAs/farmacologia , Trofoblastos/fisiologia , Regiões 3' não Traduzidas , Adulto , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proteínas Contráteis/metabolismo , Ciclina D1/genética , Regulação para Baixo , Complexo I de Transporte de Elétrons/biossíntese , Complexo III da Cadeia de Transporte de Elétrons/biossíntese , Complexo IV da Cadeia de Transporte de Elétrons/biossíntese , Feminino , Filaminas , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , MicroRNAs/antagonistas & inibidores , Proteínas dos Microfilamentos/metabolismo , Pré-Eclâmpsia/fisiopatologia , Gravidez , Trofoblastos/efeitos dos fármacos , Trofoblastos/metabolismoRESUMO
PURPOSE: To examine the effects of caffeinated coffee consumption on intraocular pressure (IOP), ocular perfusion pressure (OPP), and ocular pulse amplitude (OPA) in those with or at risk for primary open-angle glaucoma (POAG). METHODS: We conducted a prospective, double-masked, crossover, randomized controlled trial with 106 subjects: 22 with high tension POAG, 18 with normal tension POAG, 20 with ocular hypertension, 21 POAG suspects, and 25 healthy participants. Subjects ingested either 237 ml of caffeinated (182 mg caffeine) or decaffeinated (4 mg caffeine) coffee for the first visit and the alternate beverage for the second visit. Blood pressure (BP) and pascal dynamic contour tonometer measurements of IOP, OPA, and heart rate were measured before and at 60 and 90 min after coffee ingestion per visit. OPP was calculated from BP and IOP measurements. Results were analysed using paired t-tests. Multivariable models assessed determinants of IOP, OPP, and OPA changes. RESULTS: There were no significant differences in baseline IOP, OPP, and OPA between the caffeinated and decaffeinated visits. After caffeinated as compared with decaffeinated coffee ingestion, mean mm Hg changes (± SD) in IOP, OPP, and OPA were as follows: 0.99 (± 1.52, P<0.0001), 1.57 (± 6.40, P=0.0129), and 0.23 (± 0.52, P<0.0001) at 60 min, respectively; and 1.06 (± 1.67, P<0.0001), 1.26 (± 6.23, P=0.0398), and 0.18 (± 0.52, P=0.0006) at 90 min, respectively. Regression analyses revealed sporadic and inconsistent associations with IOP, OPP, and OPA changes. CONCLUSION: Consuming one cup of caffeinated coffee (182 mg caffeine) statistically increases, but likely does not clinically impact, IOP and OPP in those with or at risk for POAG.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Cafeína/efeitos adversos , Estimulantes do Sistema Nervoso Central/efeitos adversos , Café/efeitos adversos , Glaucoma de Ângulo Aberto/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Pressão Intraocular/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Bebidas , Estudos Cross-Over , Método Duplo-Cego , Feminino , Gonioscopia , Humanos , Masculino , Pessoa de Meia-Idade , Hipertensão Ocular/fisiopatologia , Estudos Prospectivos , Tonometria OcularRESUMO
6-[(124)I]iodo-2-(4'-N,N-dimethylamino)-phenylimidazo[1,2-a]pyridine ([(124)I]IMPY) was synthesized and characterized as a positron-emitting probe to identify Alzheimer's disease in transgenic mouse models. A significant reduction in radioactivity retention in the hippocampus and frontal cortex by co-incubation with nonradioactive IMPY was observed. Highly specific retention of radioactivity in beta-amyloid-rich regions of brain sections was also noted. This study demonstrated that [(124)I]IMPY was a promising probe for the mouse model and may be useful for positron emission tomography to image beta-amyloid plaques in the human brain.
Assuntos
Doença de Alzheimer/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Placa Amiloide/diagnóstico por imagem , Piridinas/síntese química , Piridinas/farmacocinética , Peptídeos beta-Amiloides/análise , Animais , Benzotiazóis , Modelos Animais de Doenças , Lobo Frontal/diagnóstico por imagem , Hipocampo/diagnóstico por imagem , Radioisótopos do Iodo/farmacocinética , Camundongos , Camundongos Transgênicos , Tomografia por Emissão de Pósitrons , Cintilografia/métodos , Tiazóis/química , Distribuição TecidualRESUMO
The effects of yeast culture and fibrolytic enzyme preparation (containing cellulase and xylanase) on in vitro fermentation characteristics of rice straw, wheat straw, maize stover, and maize stover silage were examined using an in vitro gas production technique. Four levels of yeast culture and fibrolytic enzyme supplements (0, 2.5, 5.0, and 7.5 g/kg of straw DM, respectively) were tested in a 4 x 4 factorial arrangement. Supplementation of yeast culture increased the cumulative gas production, theoretical maximum of gas production, rate of gas production, IVDMD, and in vitro OM disappearance (IVOMD), and decreased the lag time for each type of straw. Fibrolytic enzyme supplementation tended to increase cumulative gas production, theoretical maximum of gas production, and rate of gas production; prolonged lag time of gas production; and enhanced IVDMD and IVOMD for 4 types of cereal straws, with the significance of this effect being dependent on the level of supplemented enzymes. There were significant interactions between fibrolytic enzymes and yeast on all in vitro gas production parameters, IVDMD, and IVOMD of each type of straw. The outcome of this research indicated that the application of fibrolytic enzyme preparation and yeast culture could improve in vitro gas production fermentation of cereal straws.
Assuntos
Celulase/administração & dosagem , Grão Comestível/metabolismo , Grão Comestível/microbiologia , Endo-1,4-beta-Xilanases/administração & dosagem , Cabras/metabolismo , Rúmen , Leveduras/metabolismo , Ração Animal , Animais , Contagem de Colônia Microbiana/veterinária , Fibras na Dieta/metabolismo , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Fermentação , Rúmen/metabolismo , Rúmen/microbiologiaRESUMO
Analogues of glutamyl-gamma-boronate (1) were synthesized as mechanism-based inhibitors of bacterial Glu-tRNA(Gln) amidotransferase (Glu-AdT) and were designed to engage a putative catalytic serine nucleophile required for the glutaminase activity of the enzyme. Although 1 provides potent enzyme inhibition, structure-activity studies revealed a narrow range of tolerated chemical changes that maintained activity. Nonetheless, growth inhibition of organisms that require Glu-AdT by the most potent enzyme inhibitors appears to validate mechanism-based inhibitor design of Glu-AdT as an approach to antimicrobial development.
Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Ácidos Borônicos/química , Ácidos Borônicos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Transferases de Grupos Nitrogenados/antagonistas & inibidores , Avaliação Pré-Clínica de Medicamentos , Concentração Inibidora 50 , Testes de Sensibilidade Microbiana , Relação Estrutura-AtividadeRESUMO
Oxidized LDL (oxLDL) produced a rapid depletion of intracellular glutathione (GSH) followed by an adaptive increase in J774 A.1 macrophages. OxLDL also induced a transient increase in the levels of gamma-glutamylcysteine synthetase heavy subunit (gamma-GCS-HS), representing the catalytic subunit of the rate-limiting enzyme for de novo GSH synthesis. The induction took place within 3 h, with maximum levels observed by 10 h of treatment. Pretreatment of oxLDL with ebselen inhibited GSH depletion and attenuated the gamma-GCS-HS induction. OxLDL-associated lipid hydroperoxides and their decomposition product aldehydes are two major components thought to account for GSH depletion in macrophages. Ebselen pretreatment had only a minor effect on malondialdehyde levels, whereas peroxide content was essentially abolished, suggesting that oxLDL-associated hydroperoxides may mediate both GSH depletion and gamma-GCS-HS induction. Acetylated LDL (AcLDL) also caused a moderate induction of gamma-GCS-HS protein along with a 30% transient increase in GSH by 3;-6 h, suggesting a minor involvement of scavenger receptor-mediated signaling of GSH synthesis. However, the level of gamma-GCS induction by AcLDL was insufficient to cause a sustained increase in GSH. Macrophages with higher glutathione peroxidase (GPx) activity experienced a more rapid and extensive depletion of GSH when treated with oxLDL under similar conditions, along with greater resistance to oxLDL- or peroxide-induced cytotoxicity. We conclude that oxLDL-associated peroxides are primarily responsible for GSH depletion, creating an oxidizing environment required for gamma-GCS induction and compensatory GSH synthesis. This is facilitated in cells expressing high GPx activity through a rapid depletion of GSH in the face of a peroxide challenge.
Assuntos
Glutamato-Cisteína Ligase/metabolismo , Glutationa/metabolismo , Lipoproteínas LDL/farmacologia , Macrófagos/metabolismo , Estresse Oxidativo/fisiologia , Antioxidantes/farmacologia , Azóis/farmacologia , Linhagem Celular , Indução Enzimática , Glutamato-Cisteína Ligase/química , Glutamato-Cisteína Ligase/genética , Glutationa/biossíntese , Humanos , Immunoblotting , Isoindóis , Peróxidos Lipídicos/metabolismo , Lipoproteínas LDL/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/enzimologia , Compostos Organosselênicos/farmacologia , Subunidades Proteicas , Espécies Reativas de Oxigênio , Selênio/farmacologia , Fatores de TempoRESUMO
Apolipoprotein AIV (apo AIV) is a satiety protein secreted by the small intestine. We demonstrate for the first time that apo AIV protein and apo AIV mRNA are present in rat hypothalamus, a site intimately involved in the integration of signals for regulation of food intake and energy metabolism. We further characterized the regulation of hypothalamic apo AIV mRNA levels. Food-deprived animals showed a pronounced decrease in gene expression of apo AIV in the hypothalamus, with a concomitant decrease in the jejunum. Refeeding fasted rats with standard laboratory chow for 4 h evokes a significant increase of apo AIV mRNA in jejunum but not in hypothalamus. However, lipid refeeding to the fasted animals restored apo AIV mRNA levels both in hypothalamus and jejunum. Intracerebroventricular administration of apo AIV antiserum not only stimulated feeding, but also decreased apo AIV mRNA level in the hypothalamus. These data further confirm the central role of apo AIV in the regulation of food intake.
Assuntos
Apolipoproteínas A/genética , Regulação da Expressão Gênica/fisiologia , Hipotálamo/fisiologia , Resposta de Saciedade/fisiologia , Transcrição Gênica , Animais , Anticorpos/farmacologia , Apolipoproteínas A/biossíntese , Apolipoproteínas A/fisiologia , Ventrículos Cerebrais , Infusões Parenterais , Jejuno/fisiologia , Masculino , Regiões Promotoras Genéticas , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Análise de Regressão , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The adsorption of total petroleum hydrocarbons (TPHs) on suspended particles in the marine environment is an important process affecting the fate of oils spilled in the ocean. Adsorption kinetics and adsorption isotherms of the water-soluble fraction of Fuel Oil No. 6 were performed on pure and humic acid-modified montmorillonite, alumina and kaolinite. The rates of adsorption on all sorbents are very fast and a pseudo-equilibrium is reached within 0.5 h. Linear adsorption isotherms were obtained for TPH and individual aromatic hydrocarbons on all sorbents. Higher sorption coefficients (Kd) were obtained for the humic acid-coated clays compared to the pure clays. However, a great contribution of mineral surface to overall adsorption was found on humic acid-modified particles in this study. A linear relationship between the log K and log Kow was also found for individual compounds on both pure alumina (log Km) and humic acid-coated alumina (log Koc).
Assuntos
Óleos Combustíveis/análise , Água do Mar/análise , Poluentes Químicos da Água/análise , Adsorção , Óxido de Alumínio , Silicatos de Alumínio , Bentonita , Argila , Cromatografia Gasosa-Espectrometria de Massas , Substâncias Húmicas , Caulim , Cinética , Minerais , Solubilidade , Propriedades de SuperfícieRESUMO
Acupuncture and electroacupuncture (EA) have been used in traditional Chinese medicine to treat a wide range of diseases and conditions, including angina pectoris and myocardial infarction. In a feline model of reflex-induced reversible myocardial ischemia, electrical stimulation of the median nerves to mimic EA (Neiguan acupoint) significantly improved ischemic dysfunction, secondary to an inhibitory effect of EA on reflex pressor effects evoked by bradykinin (BK). The central mechanism of EA's inhibitory effect in this model is unknown. Accordingly, in alpha-chloralose-anesthetized cats, BK (10 micrograms/ml) was applied to the gallbladder to elicit a cardiovascular reflex response that significantly (P < 0.05) increased arterial blood pressure and heart rate; normalized systolic wall thickening (%WTh) of the left ventricle, measured by ultrasonic single-crystal sonomicrometer, increased by 31 +/- 11% (P < 0.05). After ligation of a side branch of the left anterior descending coronary artery, the reflex pressor response to BK resulted in a significant decrease of %WTh (-32 +/- 6%) in the ischemic region. When bilateral EA of the Neiguan acupoints was performed, the pressor response to BK was inhibited and regional myocardial function was significantly improved (+19 +/- 20%). The inhibitory effects of EA on blood pressure and %WTh were reversed by intravenous injection of naloxone (0.4 mg/kg; n = 9) or microinjection of naloxone (10 nM in 0.1 microliter/site; n = 14) into the rostral ventrolateral medulla (rVLM). Thus %WTh with intravenous naloxone was reduced to -13 +/- 29% (P<0.05) during stimulation of the gallbladder. Our results indicate that the inhibitory effect of EA on the BK-induced pressor response and the consequent improvement of ischemic dysfunction is dependent on the activation of opioid receptors, specifically receptors located in the rVLM.