RESUMO
1. Infectious injury caused by lipopolysaccharide (LPS), a metabolite of gram-negative bacteria, can induce stress responses in animals and is a significant cause of morbidity and mortality in young birds. The purpose of this study was to investigate the effects of dietary supplementation with oleanolic acid (OA) on acute liver injury in broiler chickens challenged with LPS.2. In total, 120 broiler chickens were randomly divided into six groups and fed a basal diet containing 0, 50, 100, or 200 mg/kg OA or 100 mg/kg aureomycin. On d 15, broiler chickens were injected with either LPS or an equivalent volume of normal saline. Six hours after LPS injection, two broiler chicks were randomly selected for sampling in each replicate.3. The results indicated that dietary aureomycin was ineffective in alleviating LSP-associated liver injury, but protected broiler chickens from LPS-induced liver damage. This promoted a significant reduction in the levels of malondialdehyde and an increase in the levels of superoxide dismutase in liver. In addition, OA was found to cause significant reductions in the relative expression of IL-1ß, IL-6, and TNF-α in broiler liver tissues, whereas the relative expression of IL-10 was significantly increased.4. In conclusion, oleanolic acid can alleviate oxidative stress and injury in the livers of broiler chickens induced by lipopolysaccharide. Consequently, oleanolic acid has potential utility as a novel anti-inflammatory and antioxidant feed additive.
Assuntos
Clortetraciclina , Ácido Oleanólico , Animais , Ração Animal/análise , Antioxidantes/metabolismo , Galinhas/fisiologia , Clortetraciclina/metabolismo , Dieta/veterinária , Suplementos Nutricionais/análise , Lipopolissacarídeos/toxicidade , Fígado/metabolismo , Ácido Oleanólico/farmacologia , Ácido Oleanólico/metabolismoRESUMO
PURPOSE: To investigate the effects of metabolic abnormalities, hyperandrogenemia and ovulation induction by clomiphene/acupuncture on liver function parameters among women with polycystic ovary syndrome (PCOS). METHODS: This is a secondary analysis of a randomized controlled trial. All 1000 subjects were diagnosed as PCOS by modified Rotterdam criteria. Liver function parameters, metabolic panel and hormone profile were measured at baseline and after treatment. The relationship between liver parameters with metabolic, hormonal parameters and ovulation induction was examined. RESULTS: PCOS women with metabolic syndrome had higher liver enzyme levels but lower bilirubin and bile acid levels than without. PCOS women with hyperandrogenemia had higher liver enzyme, bilirubin levels than without. Correlation analyses showed that worsening of metabolic parameters was associated with higher liver enzyme levels but lower bilirubin and bile acid levels, while increased androgen levels were associated with higher liver enzyme, bilirubin and bile acid levels. Ovulation induction with clomiphene citrate could decrease bilirubin and bile acid levels, while acupuncture had no obvious effect on liver function. CONCLUSIONS: Among PCOS women, metabolic abnormalities and hyperandrogenemia impaired different liver function parameters. Clomiphene could decrease the bilirubin and bile acid levels while acupuncture had no obvious effect on liver function.
Assuntos
Clomifeno/farmacologia , Hiperandrogenismo/complicações , Fígado/fisiopatologia , Síndrome Metabólica/complicações , Indução da Ovulação , Síndrome do Ovário Policístico/tratamento farmacológico , Terapia por Acupuntura , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , Bilirrubina/metabolismo , Biomarcadores/metabolismo , Estudos de Casos e Controles , Feminino , Fármacos para a Fertilidade Feminina/farmacologia , Seguimentos , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Testes de Função Hepática , Síndrome do Ovário Policístico/etiologia , Síndrome do Ovário Policístico/patologia , Prognóstico , Estudos ProspectivosRESUMO
Objective: To investigate the efficacy and drug related adverse reactions of sorafenib and sunitinib as first-line tyrosine-kinase inhibitors (TKIs) for patients with metastatic renal cell carcinoma (mRCC) and analyze the clinical prognostic factor for survival. Methods: The data of 271 patients with metastatic renal cell carcinoma who had complete clinicopathological data were retrospectively analyzed, including 174 cases in sorafenib group and 97 cases in sunitinib group, to access patients' overall survival (OS) and progression-free survival (PFS). Prognostic values of all characteristics were determined by using univariate and multivariate Cox regression models. Results: The objective response rates (ORR) of the sorafenib and sunitinib groups were 14.9% and 19.6%, respectively, and the disease control rates (DCR) were 85.1% and 88.6%, respectively. No significant difference was found between the sorafenib and sunitinib group in ORR (P=0.325) or DCR (P=0.408). The most common grade 3 to 4 adverse events in the sorafenib group were hand-foot syndrome (6.7%), diarrhea (2.3%), and rash (2.3%). The most common grade 3 to 4 adverse events in the sunitinib group were neutropenia (6.2%), hand-foot syndrome (6.2%), and thrombocytopenia (4.6%). During the follow-up, 97 cases death occurred and 81 cases disease progression occurred in sorafenib group. The median PFS was 12 months (95% CI: 9-15 months), and the median OS was 25 months (95% CI: 21-29 months) in sorafenib group. While 74 cases death occurred and 40 cases disease progression occurred in sunitinib group, the median PFS was 12 months (95% CI: 10-12 months) and the median OS was 23 months (95% CI: 20-32 months) in sunitinib group. No significant difference was found between the sorafenib and the sunitinib group in PFS (P=0.771) or OS (P=0.548). Multivariate analysis showed Fuhrman grades (HR=1.358, 95%CI: 1.004-1.835), number of metastatic sites (HR=1.550, 95%CI: 1.143-2.101) and MSKCC risk grade (Intermediate risk group: HR=1.621, 95%CI: 1.117-2.232; Poor risk group: HR=2.890, 95%CI: 1.942-4.298) were independent prognostic factors for PFS. Fuhrman grades (HR=2.135, 95%CI: 1.533-2.974), number of metastatic sites (HR=1.774, 95%CI: 1.279-2.461) and MSKCC risk grade (Intermediate risk group: HR=1.415, 95%CI: 1.002-1.998; Poor risk group: HR=3.161, 95%CI: 2.065-4.838) were independent prognostic factors for OS. Conclusions: The results of this study indicate that sorafenib and sunitinib are both effective as the first-line TKIs for mRCC patients and sorafenib has comparable efficacy to sunitinib. But they have differences in the incidence of adverse effects. Fuhrman grades, number of metastatic sites and MSKCC risk grade are independent prognostic factors for mRCC patients.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/secundário , Indóis/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Pirróis/uso terapêutico , Antineoplásicos/efeitos adversos , Carcinoma de Células Renais/mortalidade , Diarreia/induzido quimicamente , Progressão da Doença , Intervalo Livre de Doença , Síndrome Mão-Pé/etiologia , Humanos , Indóis/efeitos adversos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Análise Multivariada , Neutropenia/induzido quimicamente , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Prognóstico , Modelos de Riscos Proporcionais , Pirróis/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Sorafenibe , Sunitinibe , Trombocitopenia/induzido quimicamente , Resultado do TratamentoRESUMO
Phototherapy has been widely used in treating neonatal jaundice, but detailed metabonomic profiles of neonatal jaundice patients and response to phototherapy have not been characterized. Our aim was to depict the serum metabolic characteristics of neonatal jaundice patients relative to controls and changes in response to phototherapy. A (1) H nuclear magnetic resonance (NMR)-based metabonomic approach was employed to study the metabolic profiling of serum from healthy infants (n = 25) and from infants with neonatal jaundice (n = 30) pre- and postphototherapy. The acquired data were processed by multivariate principal component analysis (PCA) and orthogonal partial least-squares-discriminant analysis (OPLS-DA). The PLS-DA and OPLS-DA model identified nine metabolites capable of distinguishing patients from controls. In addition, 28 metabolites such as ß-glucose, α-glucose, valine, and pyruvate changed in response to phototherapy. This study offers useful information on metabolic disorders in neonatal jaundice patients and the effects of phototherapy on lipids, amino acid, and energy metabolism.
Assuntos
Icterícia Neonatal/metabolismo , Icterícia Neonatal/terapia , Metabolômica , Análise Discriminante , Feminino , Humanos , Recém-Nascido , Icterícia Neonatal/sangue , Análise dos Mínimos Quadrados , Espectroscopia de Ressonância Magnética , Masculino , Metaboloma , Fototerapia , Projetos Piloto , Análise de Componente PrincipalRESUMO
Pyrroloquinoline quinone (PQQ) is linked to fundamental biological processes such as mitochondrial biogenesis and lipid metabolism. PQQ may also function as an essential micronutrient during animal development. Recent studies have shown the therapeutic potential of PQQ for several age-related diseases due to its antioxidant capacity. However, whether PQQ can promote longevity is unknown. Here, we investigate the effects of PQQ on oxidative stress resistance as well as lifespan modulation in Caenorhabditis elegans. We find that PQQ enhances resistance to oxidative stress and extends the lifespan of C. elegans at optimal doses. The underlying molecular mechanism involves the increased activities of the primary lifespan extension transcriptional factors DAF-16/FOXO, the conserved oxidative stress-responsive transcription factor SKN-1/Nrf2, and upregulation of daf-16, skn-1 downstream targets including sod-3, hsp16.2, gst-1 and gst-10. Our findings uncover a novel role of PQQ in longevity, supporting PQQ as a possible dietary supplement for overall health improvement.
Assuntos
Envelhecimento/fisiologia , Caenorhabditis elegans/fisiologia , Longevidade/fisiologia , Estresse Oxidativo , Cofator PQQ/farmacologia , Animais , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Ligação a DNA/genética , Fatores de Transcrição Forkhead/genética , RNA Mensageiro/genética , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/genética , Fatores de Transcrição/genéticaRESUMO
Obstructive jaundice is a common surgical disease and a variety of end-stage severe liver injuries still lack effective treatments. Compared to traditional liver transplantation therapy, herbal treatment is noninvasive and has fewer side effects. Research results have shown that a modified major decoction of bupleurum can reduce the toxic reaction of obstructive jaundice, even though the mechanism is unclear. A period of chronic exercise training can significantly reduce TLR4 expression in mononuclear cells and the secretion of inflammatory cell factors. Our study administered a modified major decoction of bupleurum in combination with exercise in rats with obstructive jaundice and the results indicated that applying a major bupleurum decoction in combination with moderately intense aerobic exercise showed a beneficial effect on adjusting the expression of liver inflammatory cytokines, which thus improved immunity and finally reduced the liver injury of rats with obstructive jaundice.
Assuntos
Bupleurum/química , Icterícia Obstrutiva/terapia , Condicionamento Físico Animal/métodos , Receptor 4 Toll-Like/metabolismo , Animais , Terapia Combinada , Citocinas/metabolismo , Modelos Animais de Doenças , Inflamação/fisiopatologia , Inflamação/terapia , Icterícia Obstrutiva/fisiopatologia , Hepatopatias/fisiopatologia , Hepatopatias/terapia , Masculino , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Índice de Gravidade de Doença , Transdução de SinaisRESUMO
Rheumatoid arthritis (RA) is one of the inflammatory kinds of arthritis in the clinical situation, and cytosolic Ca2+ overload has been proposed as one of the primary factors for many inflammatory cells activation, which lead to relative enzymes and inflammatory factors release. It is therefore accepted that Ca2+ channel blockers can protect joint injury from inflammation. In the present study we investigated the possible molecular mechanism of the antinociceptive efficacy of HWTX-I, a spider peptide toxin blocking Ca2+ channels, on the rat rheumatoid arthritis model. Our study demonstrates that HWTX-I can relieve pain in the inflammatory joints and eliminate arthrocele to some degree. Moreover, HWTX-I can also decrease the concentration of tumour necrosis factor α (TNF-α) and increase the concentration of interleukin 4(IL-4) and interleukin 10(IL-10) in rat's serum. HWTX-I can also decrease the mRNA expression level of related factors of TNF-α, interleukin 1ß (IL-1ß) and interleukin 6(IL-6) in inflammatory pathways in rheumatoid arthritis. Therefore, the present results show that the epidural administration of HWTX-I is effective in antinociception in the rat model of rheumatoid arthritis, which may act through its inhibition on certain inflammatory pathways.
Assuntos
Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Proteínas de Répteis/farmacologia , Venenos de Aranha/farmacologia , Analgésicos/administração & dosagem , Analgésicos/farmacologia , Animais , Artrite Experimental/fisiopatologia , Artrite Reumatoide/fisiopatologia , Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio/administração & dosagem , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/efeitos dos fármacos , Citocinas/efeitos dos fármacos , Citocinas/metabolismo , Injeções Epidurais , Masculino , Neurotoxinas/administração & dosagem , Neurotoxinas/farmacologia , Dor/tratamento farmacológico , Dor/etiologia , Ratos , Ratos Sprague-Dawley , Proteínas de Répteis/administração & dosagem , Venenos de Aranha/administração & dosagemRESUMO
Transcriptional profiling was used to identify genes and pathways that responded to intracerebroventricular injection of melanocortin-4 receptor (MC4R) agonist [Nle(4), d-Phe(7)]-α-melanocyte stimulating hormone (NDP-MSH) in pigs homozygous for the missense mutation in the MC4R, D298 allele (n = 12), N298 allele (n = 12), or heterozygous (n = 12). Food intake (FI) was measured at 12 and 24 h after treatment. All pigs were killed at 24 h after treatment, and hypothalamus, liver, and back-fat tissue was collected. NDP-MSH suppressed (P < 0.004) FI at 12 and 24 h in all animals after treatment. In response to NDP-MSH, 278 genes in hypothalamus (q ≤ 0.07, P ≤ 0.001), 249 genes in liver (q ≤ 0.07, P ≤ 0.001), and 5,066 genes in fat (q ≤ 0.07, P ≤ 0.015) were differentially expressed. Pathway analysis of NDP-MSH-induced differentially expressed genes indicated that genes involved in cell communication, nucleotide metabolism, and signal transduction were prominently downregulated in the hypothalamus. In both liver and adipose tissue, energy-intensive biosynthetic and catabolic processes were downregulated in response to NDP-MSH. This included genes encoding for biosynthetic pathways such as steroid and lipid biosynthesis, fatty acid synthesis, and amino acid synthesis. Genes involved in direct energy-generating processes, such as oxidative phosphorylation, electron transport, and ATP synthesis, were upregulated, whereas TCA-associated genes were prominently downregulated in NDP-MSH-treated pigs. Our data also indicate a metabolic switch toward energy conservation since genes involved in energy-intensive biosynthetic and catabolic processes were downregulated in NDP-MSH-treated pigs.
Assuntos
Tecido Adiposo/metabolismo , Ingestão de Alimentos/genética , Regulação da Expressão Gênica , Hipotálamo/metabolismo , Fígado/metabolismo , Mutação/genética , Receptor Tipo 4 de Melanocortina/genética , Sus scrofa/genética , Tecido Adiposo/efeitos dos fármacos , Animais , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Genótipo , Homozigoto , Hipotálamo/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Receptor Tipo 4 de Melanocortina/agonistas , Reprodutibilidade dos Testes , alfa-MSH/análogos & derivados , alfa-MSH/farmacologiaRESUMO
Stroke is a long-term disability and one of the leading causes of death. However, no successful therapeutic intervention is available for the majority of stroke patients. In this study, we explored a traditional Chinese medicine Baifuzi (Typhonium giganteum Engl.). We show, at first, that the ethanol extract of Baifuzi exerts neuroprotective effects against brain damage induced by transient global or focal cerebral ischemia in rats and mice. Second, the extract activated large-conductance Ca(2+)-activated K(+) channel (BK(Ca)) channels, and BK(Ca) channel blockade suppressed the neuroprotection of the extract, suggesting that the BK(Ca) is the molecular target of Baifuzi. Third, Baifuzi cerebroside (Baifuzi-CB), purified from its ethanol extract, activated BK(Ca) channels in a manner similar to that of the extract. Fourth, the stress axis hormone-regulated exon (STREX) domain of the BK(Ca) channel directly interacted with Baifuzi-CB, and its deletion suppressed channel activation by Baifuzi-CB. These results indicate that Baifuzi-CB activated the BK(Ca) channel through its direct interaction with the STREX domain of the channel and suggests that Baifuzi-CB merits exploration as a potential therapeutic agent for treating brain ischemia.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Animais , Ácido Glutâmico/metabolismo , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/química , Masculino , Camundongos , Ligação Proteica , Estrutura Terciária de Proteína , Ratos , Ratos Sprague-DawleyRESUMO
Although concerns over the environmental impact of excess P in the excreta from pig production and governmental regulations have driven research toward reducing dietary supplementation of P to swine diets for over a decade, recent dramatic increases in feed costs have further motivated researchers to identify means to further reduce dietary P supplementation. We have demonstrated that genetic background impacts P utilization in young pigs and have identified genetic polymorphisms in several target genes related to mineral utilization. In this study, we examined the impact of a SNP in the calcitonin receptor gene (CALCR) on P utilization in growing pigs. In Exp. 1, 36 gilts representing the 3 genotypes identified by this CALCR SNP (11, 12, and 22) were fed a P-adequate (PA) or a marginally P-deficient (approximately 20% less available P; PD) diet for 14 wk. As expected, P deficiency reduced plasma P concentration, bone strength, and mineral content (P < 0.05). However, the dietary P deficiency was mild enough to not affect the growth performance of these pigs. A genotype x dietary P interaction (P < 0.05) was observed in measures of bone integrity and mineral content, with the greatest reduction in bone strength and mineral content due to dietary P deficiency being associated with the allele 1. In Exp. 2, 168 pigs from a control line and low residual feed intake (RFI) line were genotyped for the CALCR SNP and fed a PA diet. As expected, pigs from the low RFI line consumed less feed but also gained less BW when compared with the control line (P < 0.05). Although ADFI did not differ between genotypes, pigs having the 11 genotype gained less BW (P < 0.05) than pigs having the 12 or 22 genotypes. Pigs of the 11 and 12 genotypes had bones that tolerated greater load when compared with animals having the 22 genotype (P < 0.05). A similar trend was observed in bone modulus and ash % (P < 0.10). These data are supportive of the association of this CALCR SNP with bone integrity and its response to dietary P restriction. Although the allele 1 is associated with greater bone integrity and mineral content during adequate P nutrition, it is also associated with the greatest loss in bone integrity and mineral content in response to dietary P restriction. Understanding the underlying genetic mechanisms that regulate P utilization may lead to novel strategies to produce more environmentally friendly pigs.
Assuntos
Osso e Ossos/fisiologia , Fósforo/deficiência , Polimorfismo de Nucleotídeo Único/genética , Receptores da Calcitonina/genética , Suínos/genética , Fosfatase Alcalina/sangue , Animais , Peso Corporal/genética , Peso Corporal/fisiologia , Feminino , Genótipo , Fósforo/sangue , Polimorfismo de Nucleotídeo Único/fisiologia , Receptores da Calcitonina/fisiologia , Suínos/crescimento & desenvolvimento , Suínos/fisiologiaRESUMO
As an endangered endemic herb, Dendrobium fimbriatum, is under threat from numerous impacts. In order to analyse the genetic diversity and structure of this endangered species, we provide details of 10 microsatellite loci (out of 15 primer pairs designed) which showed polymorphic for D. fimbriatum. These loci were used to screen 25 individuals from across the species' geographical range. Ten loci were polymorphic with 2 to 19 alleles; three loci were monomorphic, while the rest produced no amplification fragments. These loci will be used to investigate population genetic structure, genetic diversity, conservation, and individual authentication in the endangered D. fimbriatum.
RESUMO
AIMS: The mismatch negativity (MMN) to frequency deviant tones has yielded conflicting results in patients with schizophrenia. This might be because Axis I schizophrenia overlaps with Axis II diagnoses such as paranoid or schizotypal personality disorders. This study was designed to address this issue. METHODS: We evaluated the auditory MMN to frequency deviance in 17 patients with paranoid, 15 schizotypal, and 16 antisocial personality disorders. These were compared to 25 healthy subjects. RESULTS: N1 to both deviant and standard tones was shorter in the paranoid group when compared to healthy controls. MMN latencies were shorter at Fz, Cz, and Pz in the paranoid group when compared to healthy controls, schizotypal, and antisocial groups. MMN amplitudes were higher at Fz and Cz in the schizotypal and antisocial groups when compared to healthy controls and the paranoid group. CONCLUSIONS: Patients with paranoid personality disorder had faster automatic detection of auditory stimuli and of their change, but normal inhibition of irrelevant stimuli. By contrast, patients with schizotypal and antisocial personality disorders had normal discrimination of the auditory stimuli, but might have a deficit in inhibition on irrelevant stimuli. Our results might help differentiate these personality types, and clarify some MMN findings in schizophrenia.
Assuntos
Transtorno da Personalidade Antissocial/psicologia , Eletroencefalografia , Potenciais Evocados Auditivos/fisiologia , Esquizofrenia Paranoide/psicologia , Transtorno da Personalidade Esquizotípica/psicologia , Estimulação Acústica , Adolescente , Adulto , Análise de Variância , Transtorno da Personalidade Antissocial/fisiopatologia , Feminino , Lobo Frontal/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Esquizofrenia Paranoide/fisiopatologia , Transtorno da Personalidade Esquizotípica/fisiopatologia , Caracteres Sexuais , Lobo Temporal/fisiopatologiaRESUMO
BACKGROUND: Lysozyme (LZ), a host-defense protein, contains an 18 amino-acid domain with high affinity binding for sugar-derived proteins or lipids, called advanced glycation endproducts (AGE), that are implicated in diabetes- and age-dependent complications (DC). MATERIALS AND METHODS: A) The effects of LZ on AGE- removal were tested in vivo. LZ was injected (200 ug/day, i.p., X2 weeks) in non-obese diabetic (NOD), db/db (+/+) mice, and non-diabetic, AGE-infused Sprague-Dawley rats. B) LZ: AGE interactions with macrophage-like T1B-183 cells (Mf) and mesangial cells (MC) were tested in vitro. RESULTS: A) In NOD mice, LZ reduced the elevated basal serum AGE (sAGE) (p < 0.05), enhanced urinary AGE (uAGE) excretion by approximately 2-fold (p < 0.01), while it reduced albuminuria (UA), p < 0.005. In db/db mice, LZ infusion also reduced the elevated sAGE (p < 0.05), doubled uAGE excretion (p < 0.05), and decreased UA (p < 0.01). In addition, LZ maintained normal sAGE in normal rats infused with AGE-BSA, as it doubled the urinary AGE (uAGE) clearance (p < 0.01). B) LZ stimulated the uptake and degradation of (125) I-labeled AGE-BSA and (25) I-human serum AGE by Mf, while suppressing AGE-induced TNFalpha and IGF-I production. In MC, LZ suppressed the AGE-promoted PDGF-B, alpha1 type IV collagen, and tenascin mRNA levels, and restored the AGE-suppressed expression and activity of MMP-9, but not MMP-2. CONCLUSION: LZ may act to: a) accelerate renal in-vivo AGE clearance, b) suppress macrophage and mesangial cell- specific gene activation in vitro, and c) improve albuminuria due to diabetes. These data suggest that LZ by sequestering AGEs may protect against diabetic renal damage.
Assuntos
Anti-Infecciosos/farmacologia , Nefropatias Diabéticas/metabolismo , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Produtos Finais de Glicação Avançada/metabolismo , Rim/metabolismo , Muramidase/farmacologia , Animais , Galinhas , Diabetes Mellitus Tipo 1/metabolismo , Feminino , Mesângio Glomerular/metabolismo , Mesângio Glomerular/patologia , Produtos Finais de Glicação Avançada/urina , Humanos , Técnicas In Vitro , Rim/patologia , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos NOD , Pessoa de Meia-Idade , RatosRESUMO
Aromatase catalyzes the conversion of androgen to estrogen. This enzyme has been primarily localized in the neurons of specific areas of limbic system and hypothalamus of the brain. Astrocytes may also express this enzyme. Studies show that the gene expression of aromatase is driven by multiple tissue-specific exons, and the effective concentration of brain estrogen depends on the expression of brain aromatase. The locally produced estrogen plays an important role in the regulation of synaptogenesis, density of dendritic spine and the expression of neurotrophic factors and/or their receptors. Estrogen can also protect brain cells from the damages of neurotoxins and can greatly improve the deficits of learning and memory resulted from neurodegenerative disorders such as Alzheimer's diseases.
Assuntos
Aromatase/metabolismo , Encéfalo/enzimologia , Animais , Aromatase/biossíntese , Aromatase/fisiologia , Encéfalo/metabolismo , Humanos , Hipotálamo/metabolismo , Sistema Límbico/metabolismo , Memória/fisiologiaRESUMO
BACKGROUND: Central-venous-line infections can be successfully treated with appropriate antibiotics, thus avoiding the need for catheter removal. Based on our experience, vancomycin, gentamicin, piperacillin, ceftazidime, and amphotericin, alone or in combination, are usually administered, pending sensitivity results. This empirical list, however, has never been verified against actual sensitivity results nor has it been tested for cost or efficacy. METHODS: Medical records of inpatients on hyperalimentation over 1 year were reviewed. Success rate, therapy duration, and drug acquisition cost and charge were assessed for central-venous-line infections. Antibiotics then were paired and evaluated in terms of charge and efficacy against all microorganisms as determined by sensitivity results. RESULTS: In 500 inpatients receiving hyperalimentation for 9,698 patient-days, 8.4 central-venous-line infections/1,000 patient-days occurred. Staphylococcus non-aureus, Candida species, Enterococcus faecium, and Staphylococcus aureus predominantly were isolated. Of the infections, 51 (67%) were sensitive to one or more of the initial antibiotics. A 2-week course of antibiotics successfully treated 50 (66%) catheter infections without line removal. Appropriate initial therapy on average reduced treatment duration by 8 to 10 days and drug charges by $400 to $700. CONCLUSIONS: Amikacin-vancomycin appears to be the most cost-effective selection for presumed central-venous-line infections, pending sensitivity results, followed by valid alternatives. Lower failure rates are well worth the extra cost in pharmaceutical charges.
Assuntos
Antibacterianos , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/etiologia , Cateterismo Venoso Central/efeitos adversos , Quimioterapia Combinada/uso terapêutico , Nutrição Parenteral Total , Adolescente , Adulto , Bactérias/isolamento & purificação , Infecções Bacterianas/economia , Criança , Pré-Escolar , Análise Custo-Benefício , Quimioterapia Combinada/economia , Feminino , Hospitalização , Humanos , Lactente , Recém-Nascido , Masculino , Prontuários Médicos , Testes de Sensibilidade Microbiana , Micoses/tratamento farmacológico , Micoses/economiaRESUMO
The detection technology of peroxidase isoenzyme pattern were adopted in the study of the effect of simulated microgravity on some plants. Biochemical analysis indicated that the microgravity samples displayed an increased activity of peroxidase.
Assuntos
Frutas/enzimologia , Panax/enzimologia , Peroxidases/análise , Plantas Medicinais , Solanum tuberosum/enzimologia , Simulação de Ausência de Peso , Isoenzimas/análise , Isoenzimas/metabolismo , Peroxidases/metabolismo , Plantas ComestíveisRESUMO
OBJECTIVE: To investigate the effect of elemene emulsion injection (EEI) in treating malignant brain tumor. METHODS: By conducting a retrospective study of 40 patients with brain tumor, 29 of malignant glioma and 11 metastatic tumor, who were treated with EEI from January 1994 to May 1998. EEI 0.4-1.2 g/d was given to each patient by intravenous dripping or/and intravenous infusion by pumps, and directly injected into carotid artery or infused through a carotid artery catheter with pumps. The total dosage of 6-12 g was given in 2-6 therapeutic courses with an interval of 1-1.5 months between courses. The effectiveness of treatment was accessed according to the changes of tumor size, Karnofsky Performance Status (KPS) and survival time of patients. The control group consisted of 29 cases of malignant brain tumor (22 of primary and 7 of metastatic) was treated with chemotherapy 2-3 therapeutic courses with an interval of 1-1.5 months between them. RESULTS: (1) In the EEI treated group the mean tumor size was changed from 6.70 cm3 (before treatment) to 2.67 cm3 (after treatment), t = 3.02, P < 0.01, it was reduced by 61%; (2) In the EEI treated group 4 cases was CR, 26 PR, the total effective rate being 75.0% (95% credibility interval +/- 13.4%), while in the control group, 2 of CR, 10 PR, and the total effective rate 41.4% (95% credibility interval +/- 17.9%), the difference between the two groups was significant, chi 2 = 3.867, P < 0.05; (3) KPS decreased in the EEI group from 94.7 scores (before treatment) to 88.2 scores (after treatment), the decrement was 6.5 scores (t = 3.5313, P < 0.01); (4) The survival time in the EEI treated group was 25.4 months, and that in the control group was 17.4 months (t = 3.74, P < 0.01). CONCLUSION: Elemene has significant effect on treatment of malignant brain tumor. It could prolong the high quality survival time of patients and is worthy of further investigation.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Astrocitoma/tratamento farmacológico , Neoplasias Encefálicas/tratamento farmacológico , Óleos Voláteis/uso terapêutico , Sesquiterpenos , Adulto , Idoso , Astrocitoma/cirurgia , Neoplasias Encefálicas/cirurgia , Artéria Carótida Primitiva , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Emulsões , Feminino , Glioblastoma/tratamento farmacológico , Humanos , Infusões Intra-Arteriais , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos RetrospectivosRESUMO
The purpose of this study was to evaluate a "suture" type electrode for direct bladder stimulation in an animal model of a lower motor neuron lesion. During an initial surgery, five male cats were instrumented under anesthesia using multistranded, 316 LVM, stainless-steel, wire electrodes implanted on the bladder wall serosa above the trigone area. Electrodes were constructed with a needle attached to the end that was removed after suturing the electrode in place. Additional instrumentation included urinary bladder catheters (tubes) for pressure recording and filling, and hook type electrodes for leg and pelvic floor electromyography recording. Chronic bladder filling and stimulation studies were conducted in tethered animals three to four weeks following surgery. To test these electrodes in a spinal cord injury model, a lower motor neuron lesion was performed including the sacral cord and complete nerve roots at L6 and below. These animals were evaluated during weeks 3 and 10 after injury. Direct bladder stimulation induced active contractions and voiding both before and after spinal cord injury. Effective stimulation parameters consisted of 40 pulses per s, 300 micros to 1 ms pulse duration, a stimulation period from 3 to 4 s, and a stimulation current from 10 to 40 mA. Fluoroscopy revealed an open membranous urethra during stimulation and following stimulation. A small diameter penile urethra was observed to limit flow. Postmortem evaluation of the suture electrode revealed no abnormalities such as corrosion, migration into the bladder lumen or displacement. These findings indicate that suture electrodes are suitable and effective for short-term implantation in the lower motor neuron animal model.
Assuntos
Terapia por Estimulação Elétrica , Traumatismos da Medula Espinal/terapia , Bexiga Urinaria Neurogênica/terapia , Animais , Gatos , Modelos Animais de Doenças , Estudos de Avaliação como Assunto , Masculino , Técnicas de Sutura , Bexiga Urinaria Neurogênica/etiologia , UrodinâmicaRESUMO
The arsenic compounds in traditional Chinese medicine have been recorded to have therapeutic effects on the treatment of psoriasis, syphilis, rheumatosis and a number of malignant tumours. Recent studies showed that arsenic trioxide can induce clinical remission in patients with acute promyelocytic leukemia, including those who have relapsed after retinoic acid treatment. however, the mechanism of how arsenic trioxide targets tumour cells is not clearly understood. We have examined the effects of arsenic trioxide on oesophageal carcinoma cell line EC8712. Our results demonstrated that the growth and survival of tumour cells were markedly inhibited by arsenic trioxide. The half dose effect (ED50) was at the concentration of 1 microM. Electron microscopic study demonstrated that EC8712 tumour cells treated with arsenic trioxide display a typical morphological appearance of apoptosis, including chromatin condensation and fragmentation of the nuclei. In contrast, no apoptotic features were observed in tumour cells without arsenic trioxide treatment. TUNEL assay also showed the biological features of apoptosis in cells treated with arsenic trioxide. Flow cytometry analyses showed that apoptotic peak was identified in arsenic trioxide treated cells but not in the control. Apoptotic cells in arsenic trioxide treated group account for 35% of total cell populations after three days treatment at a dose of 3 microM. In short, our results suggested that the anticancer effect of arsenic trioxide is due, at least in part, to the induction of apoptosis in cancer cells.
Assuntos
Apoptose/efeitos dos fármacos , Arsenicais/farmacologia , Neoplasias Esofágicas/tratamento farmacológico , Óxidos/farmacologia , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Trióxido de Arsênio , Arsenicais/administração & dosagem , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias Esofágicas/patologia , Citometria de Fluxo , Humanos , Microscopia Eletrônica , Óxidos/administração & dosagem , Células Tumorais CultivadasRESUMO
After treatment of the elicitor derived from digesting ginseng cell walls by cellulase, the starch grains were degraded, and a large number of spherosomes were produced in Ginseng cells. In the mean time, the activity of amylase in the cells was increased and the activities of esterases in the cells were reduced; in addition, the content of soluble sugar and the content of lipoid were increased. These indicate that the emergency reactions and the adjustment of metabolism of lipoid were taken placed in the cells elicited. Besides, after the treatment with certain concentrations of elicitor, the content of ginseng saponin and the activity of phenylalanine ammonia lyase (PAL) were increased in ginseng cells. On the contrary, the activities of peroxidase (POD) and polyphenoloxidase (PPO) were reduced.