RESUMO
Objective: To explore the influencing factors of health-related quality of life (HRQoL) in patients with knee osteoarthritis, and to analyze the non-surgical treatment of knee osteoarthritis. Methods: Demographic variables, treatment modalities, imaging data, and 12-item short form health survey (SF-12) scores of patients with knee osteoarthritis in orthopedic outpatient departments of five hospitals in Beijing from December 2017 to November 2018 were collected to analyze influencing factors of HRQoL and non-surgical treatment. Results: A total of 2 034 patients were included. There were 530 males (26.1%) and 1 504 females (73.9%), with a mean age of (59.17±10.22) years. In terms of physical quality of life, female patients with knee osteoarthritis had lower physical components summary (PCS) compared with male patients (ß=-0.521, P=0.036); patients aged ≥64 years had lower PCS than those aged<55 years (ß=-0.636, P=0.026). Patients with an education of more than 12 years had higher PCS than those with less than 10 years (ß=1.063, P<0.001). Compared to patients with mild clinical symptoms, the PCS of patients with moderate clinical symptoms was lower (ß=-0.860, P=0.002), while the PCS of those with severe clinical symptoms was much lower (ß=-1.126, P<0.001). Patients treated with combination therapy had higher PCS than untreated patients (ß=0.731, P=0.005). In terms of mental quality of life, compared to patients engaged in sedentary work, the mental components summary (MCS) of patients engaged in mild manual labor jobs was lower (ß=-0.712, P=0.015); Compared to patients with a Charson comorbidity index of 0, patients with a Charlson comorbidity index ≥ 2 had lower MCS (ß=-1.183, P=0.007). In the past 12 months, 648 (31.9%), 143 (7.0%), 406 (20.0%), 680 (33.4%), 343 (16.9%), 681 (33.5%), 170 (8.4%) patients had used non-steroid anti-inflammatory drugs (NSAIDs), acetaminophen, glucosamine/chondroitin formulations, physical therapy, articular cavity puncture injection, traditional Chinese medicine treatment and exercise therapy, respectively. Total of 451 patients (22.2%) received monotherapy and 889 patients (43.7%) received combination therapy. Conclusions: The major non-surgical treatment methods for patients with knee osteoarthritis in Beijing are NSAIDs, physiotherapy and traditional Chinese medicine. Combination therapy is used more frequently than monotherapy. Physical quality of life is related to gender, age, education, severity of symptoms and treatment, while mental quality of life is related to occupational labor and comorbidities.
Assuntos
Osteoartrite do Joelho , Acetaminofen , Idoso , Anti-Inflamatórios não Esteroides , Condroitina , Estudos Transversais , Feminino , Glucosamina , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/cirurgia , Qualidade de VidaRESUMO
The potential benefits of Aspergillus-fermented mung bean seed coats (FMSC) for weaned pigs remain unexplored. Both in vitro and in vivo experiments were employed to evaluate the potential of FMSC supplement on the growth, antioxidant and immune responses of weaned pigs. The total polyphenols and DPPH scavenging capability of ethanol extract of FMSC exhibited a greater (p < 0.01) increase than those of pre-fermentation. With the addition of the polyphenol of FMSC extract, an increase in phagocytosis by neutrophils and proliferation of peripheral blood mononuclear cells (PBMC) were found. However, these observations were significantly inhibited (p < 0.05) in those activated cells. Next, 96 weaned pigs were allotted with a randomized complete block design into four dietary treatments, including 0 (control), 600, 1200 or 1800 mg/kg FMSC in a corn-soya bean meal basal diet for a 35-day trial. The pigs were injected with swine enzootic pneumonia (SEP) vaccines at day 3 and day 21 respectively. The results showed that dietary treatment failed to affect growth performance or serum SEP titre. The diet supplemented with 600-1800 mg/kg FMSC decreased faecal lactoferrin on day 21 and increased plasma trolox equivalent antioxidant capacity (TEAC) and erythrocytes catalase activity, as well as decreased (p < 0.01) plasma malondialdehyde (MDA) concentration on day 35. Diet supplementation of 1800 mg/kg FMSC increased phagocytosis by neutrophils and PBMC proliferation induced by pokeweed mitogen (PWM). However, the polymorphonuclear leucocytes (PMN)-positive respiratory burst cells were decreased in the supplementation of 1200 or 1800 mg/kg FMSC respectively. In addition, the serum haptoglobin concentration was decreased in the supplementation with 1200 mg/kg FMSC. Taken together, FMSC enriches polyphenols with antioxidative and immune modulated properties. After feeding FMSC, an improvement in antioxidative capability and immunocompetence was found, implying that FMSC could provide as a feed additive at optimal level 1200 mg/kg for weaned pigs.
Assuntos
Antioxidantes/metabolismo , Aspergillus/metabolismo , Sementes/química , Suínos/metabolismo , Vigna/química , Animais , Anticorpos Antivirais/sangue , Vacinas Bacterianas/imunologia , Eritrócitos/enzimologia , Fezes/química , Fermentação , Manipulação de Alimentos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Lactoferrina/química , Lactoferrina/metabolismo , Fagocitose , Pneumonia Suína Micoplasmática/prevenção & controle , Superóxido Dismutase-1/metabolismo , Suínos/imunologiaRESUMO
1. The disposition of 3-[2-oxo-3-[3-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl) propyl]-imidazolidin-1-yl]-3(S)-(6-methoxy-pyridin-3-yl)propionic acid (compound A), a potent and selective alpha(v)beta(3) antagonist, was characterized in several animal species in support of its selection for preclinical safety studies and potential clinical development. 2. Compound A exhibited marked species differences in pharmacokinetics; the plasma clearances and bioavailabilities ranged from 33-47 ml min(-1) kg(-1) in rats and mice to 4-9 ml min(-1) kg(-1) in dogs and monkeys, and about 20% in rats to 70-80% in dogs and monkeys, respectively. Both the intravenous (i.v.) and oral kinetics of compound A were linear over the dose range studied in dogs (0.1-5 mg kg(-1) i.v. and 0.25-20 mg kg(-1) orally [p.o.]) and rats (1-30 mg kg(-1) i.v. and 4-160 mg kg(-1) p.o.). 3. Compound A was eliminated substantially by urinary excretion; the urinary recovery of the unchanged drug was 67% in rhesus, 48% in dogs and about 30% in rats. In these animal species, biotransformation was modest. 4. Following i.v. administration of [(14)C]-compound A to rats, the radioactivity rapidly distributed to all tissues investigated, with high levels of the radioactivity detected in liver, kidney and intestine soon after the drug administration. The radioactivity declined rapidly, with less than 1% of the i.v. dose remaining at 30-h post-dose. 5. Compound A was moderately bound to plasma proteins, with unbound fractions of 26, 20, 14 and 5% for rats, dogs, monkeys and humans, respectively. It was bound primarily to human alpha(1)-acid glycoprotein (about 85% binding at 0.1% concentration), as compared with human albumin (< 50% binding at 4% concentration). 6. Using simple allometry, compound A was predicted to exhibit relatively low clearance (1-3 ml min(-1) kg(-1)) and low volume of distribution (0.1-0.3 l kg(-1)) in humans. Based on the predicted values, compound A was projected to exhibit a favourable oral pharmacokinetic profile in humans, with good bioavailability (50-80%). These predicted values provided a basis for compound selection for further development.
Assuntos
Integrina alfaVbeta3/antagonistas & inibidores , Naftiridinas/farmacocinética , Succinimidas/farmacocinética , Administração Oral , Animais , Proteínas Sanguíneas/metabolismo , Radioisótopos de Carbono , Cães , Avaliação Pré-Clínica de Medicamentos , Feminino , Previsões , Humanos , Infusões Intravenosas , Integrina alfaVbeta3/metabolismo , Macaca mulatta , Masculino , Taxa de Depuração Metabólica , Camundongos , Naftiridinas/sangue , Naftiridinas/química , Naftiridinas/urina , Ligação Proteica , Ratos , Ratos Sprague-Dawley , Succinimidas/sangue , Succinimidas/química , Succinimidas/urinaRESUMO
Sustainability aims to harmonise life on Earth without compromising the essential natural resources that should be the birthright of future generations. 'Sustainable medicine' (SM) is just one component of the wide range of possible sustainable approaches to peaceful co-existence. Sustainable medicine envisions an uncomplicated system of maintaining the health of people and animals, both now and for many years to come. This type of medicine is based on ancient wisdom, knowledge and healing arts, combined with the advantages and technical achievements of modern science and other areas of medicine; it is an integrated approach to preventive, safe and affordable healing. The term sustainable medicine also implies that the main therapeutic materials used in the course of practising this type of medicine can be replaced or replenished with minimal environmental damage after harvesting. The aim of sustainable medicine is to maintain the balance of nature, allowing an estimated 7 to 100 million species of life forms to co-exist and reproduce, and to sustain the long-term future of this planet. The world is in the midst of an environmental crisis: anthropogenic environmental damage in the last century was greater than in any previous century. One of the major concerns is the misuse of medicines, and the resulting immune depletion in people and animals. Many traditional medical systems have taught that appropriate adaptation by, and of, an effective defence system is the key to health and survival. This is only possible if priority is given to a preventive rather than a curative approach to health care; the very same approach that is advocated by proponents of SM: an approach based on proper diagnosis and the use of personalised, tailor-made medicine. The authors propose SM (the combination of the advantages of modern, traditional and complementary medical systems) as the best approach to providing better health care services for people and animals. The article presents a brief history of traditional medicines and outlines strategies for developing SM. The authors highlight some important factors in the development of SM in animal health care and attempt to encourage veterinarians to adopt a sustainable approach to treating animals.
Assuntos
Conservação dos Recursos Naturais/métodos , Medicina Veterinária/tendências , Animais , Terapias Complementares , Conservação dos Recursos Naturais/tendências , Saúde Global , Humanos , Medicina TradicionalRESUMO
Repeat breeders cause great economic loss in dairy herds. This study determined the efficacy of simple aquapuncture therapy (acupuncture combined with injection) to treat repeat breeders in two dairy herds (one in Hsinchu County and the other in Tainan County). Both herds had used gonadotropin-releasing hormone (GnRH) beforehand to treat the symptom but the success rate was poor--about 30%. Therefore, cows that failed to respond to GnRH were given the aquapuncture treatment. A total of 18 animals (two heifers and 16 cows) that had failed to conceive to 3-9 services were treated by aquapuncture, in which 10 ml and 5 ml of 50% glucose solution were injected at Baihui (Hundred Meetings, the depression in the center of the lumbosacral space) and Shenpeng (Kidney Shelf, the depression in the space between the lumbar vertebral transverse processes 5-6) acupoints, respectively with a 21G, 1.5-inch hypodermic needle. Both acupoints belong to the traditional acupuncture points of bovine and equine systems. Most animals showed heat within 14 days after aquapuncture and were inseminated artificially. Serum progesterone concentrations and rectal palpation were used for pregnancy diagnosis. The pregnancy rate after the treatment was 14/18 (77.7%) and 12/18 (66.6%) based on progesterone concentration and rectal palpation respectively, suggesting acupuncture as a simple and effective method to treat repeat breeders in dairy herds. However, the final result obtained from actual delivery of fetus in the experimental animals was only 8/18 (44.4%).
Assuntos
Terapia por Acupuntura/veterinária , Doenças dos Bovinos/terapia , Bovinos/fisiologia , Infertilidade Feminina/veterinária , Inseminação Artificial/veterinária , Pontos de Acupuntura , Animais , Indústria de Laticínios , Feminino , Glucose/administração & dosagem , Glucose/uso terapêutico , Infertilidade Feminina/terapia , Injeções/veterinária , Inseminação Artificial/métodos , Gravidez , Taxa de GravidezRESUMO
The needles of ponderosa pine (Pinus ponderosa Laws.) were reported to induce abortions when fed to late-term pregnant beef cows in North America. An in vivo study of pregnant cows suggested that isocupressic acid (IA) was the main abortifacient isolated from needles and bark of the pine. However, the mechanism of abortifacient activity of IA is not clear yet. In a pregnant cow, the corpus luteum of the ovary helps the maintenance of pregnancy by its progesterone production. This study involved the IA extracted from the root of the Taiwan cypress (Juniperus formosana) and used a frozen-thawed bovine luteal cell culture system to investigate the action of IA on progesterone production. Thawed bovine luteal cells (1 x 10(5) cells/ml/well) in M199 medium were cultured in 24-well culture plates at 37 degrees C in a 5% CO2 incubator. Ten ml of tested drugs, IA at 1 to 1000 ng/ml and/or ovine luteinizing hormone (oLH) at 1 to 100 ng/microl or 8-bromo-cyclic adenosine monophosphate (8-Br-cAMP) with 0.1-10 mM, were added into each well. After 4 hours of incubation, the media were harvested and assayed for progesterone by an enzyme immunoassay. Progesterone production from cells was the indicator used to evaluate the action of IA. All tested doses of IA significantly inhibited progesterone production in both basal and oLH stimulating conditions. Also those dosages inhibited cyclic adenosine-3',5'- monophosphate (cAMP) stimulation, suggesting a post-cAMP mechanism is involved in the IA action. We concluded that IA can induce pregnant cows to abort partly through blocking luteal function and may be identified as a new abortifacient chemical.
Assuntos
Ácidos Carboxílicos/farmacologia , Diterpenos/farmacologia , Células Lúteas/metabolismo , Progesterona/biossíntese , Substâncias para o Controle da Reprodução/farmacologia , Tetra-Hidronaftalenos/farmacologia , 8-Bromo Monofosfato de Adenosina Cíclica/farmacologia , Animais , Bovinos , Células Cultivadas , Técnicas Citológicas , Feminino , Técnicas Imunoenzimáticas , Técnicas In Vitro , Células Lúteas/efeitos dos fármacosRESUMO
Since the International Society of Veterinary Acupuncture (IVAS) was founded in 1974, acupuncture (AP) has received greater acceptance by veterinary professionals throughout the world. This article introduces some important animal diseases that respond well to AP therapy. These include resuscitation of small animals, treatment of anoestrous gilts and sows, bovine reproductive disease, canine vertebral problems and equine backpain, etc. Conventional medicine considers these to be difficult cases to treat. Veterinarians have become more aware of the benefits of AP especially for those diseases, thanks to the efforts of experienced practitioners and scientists, and the many published reports on veterinary AP that have introduced some good indications for AP therapy in veterinary practice. Possible mechanisms behind the effectiveness of AP are discussed. This article aims to introduce veterinarians to good indications for AP to initiate their interest in the practice of AP. Although this is a rapidly expanding field, a long march must begin with one step. We wish this article to be the shoes for such a march. For more information on veterinary AP, contact IVAS
Assuntos
Acupuntura/métodos , Medicina Veterinária/métodos , Acupuntura/normas , Animais , Bovinos , Doenças dos Bovinos/cirurgia , Doenças do Cão/cirurgia , Cães , Feminino , Doenças dos Cavalos/cirurgia , Cavalos , Masculino , Suínos , Doenças dos Suínos/cirurgia , Medicina Veterinária/normasRESUMO
Kang-chih-ma is the dried roots and stems of Helicteres angustifolia (Sterculiaceae) and a commonly used folk herbal drug in Taiwan. It possesses antidotal, analgesic, anti-inflammatory and anti-bacterial effects and is also known as a kind of tumor inhibitory plant. To evaluate the quality of H. angustifolia, a simple, rapid and accurate high-performance liquid chromatographic (HPLC) method was developed for the assay of three lupane type triterpenes: 3beta-acetoxy-27-benzoyloxylup-20(29)-en-28-oic acid methyl ester (methyl helicterate), 3beta-acetoxy-27-benzoyloxylup-20(29)-en-28-oic acid, and 3beta-acetoxy-27-(p-hydroxyl) benzoyloxylup-20(29)-en-28-oic acid methyl ester. The present HPLC system used an Inertsil ODS-2 column by gradient elution with acetonitrile and water as the mobile phase and detected at UV 230 nm. Regression equations revealed good linear relationships (correlation coefficients: 0.9922-0.9997). The relative standard deviations of these three constituents ranged between 1.05-3.14% (intraday) and 2.12-4.38% (interday). The contents of these three constituents of the heartwood and the bark of the roots of H. angustifolia in five different samples have also been determined.
Assuntos
Malvaceae/química , Triterpenos/análise , Cromatografia Líquida de Alta Pressão , Indicadores e Reagentes , Espectrometria de Massas , Epiderme Vegetal/química , Raízes de Plantas/química , Caules de Planta/química , Plantas Medicinais/química , Padrões de Referência , Solventes , Taiwan , MadeiraRESUMO
Within the past year, additional papers have been published that focus on higher-throughput drug-interaction screening. Some papers have described enzyme assays that can be used to evaluate inhibition or induction of the human cytochrome P450s. At the same time, numerous investigators have developed computational (in silico) methods to predict interactions and have validated the approach using in vitro (assay-derived) data. These so called 'in silico--in vitro' correlations have great potential and may complement existing 'in vitro--in vivo' correlations.
Assuntos
Avaliação Pré-Clínica de Medicamentos , Interações Medicamentosas , Inibidores das Enzimas do Citocromo P-450 , Sistema Enzimático do Citocromo P-450/biossíntese , Indução EnzimáticaRESUMO
Recent results from human clinical trials have established the critical role of HIV protease inhibitors in the treatment of acquired immune-deficiency syndrome (AIDS). However, the emergence of viral resistance, demanding treatment protocols, and adverse side effects have exposed the urgent need for a second generation of HIV protease inhibitors. The continued exploration of our hydroxylaminepentanamide (HAPA) transition-state isostere series of HIV protease inhibitors, which initially resulted in the identification of Crixivan (indinavir sulfate, MK-639, L-735,524), has now yielded MK-944a (L-756,423). This compound is potent, is selective, and competitively inhibits HIV-1 PR with a K(i) value of 0.049 nM. It stops the spread of the HIV(IIIb)-infected MT4 lymphoid cells at 25.0-50.0 nM, even in the presence of alpha(1) acid glycoprotein, human serum albumin, normal human serum, or fetal bovine serum. MK-944a has a longer half-life in several animal models (rats, dogs, and monkeys) than indinavir sulfate and is currently in advanced human clinical trials.
Assuntos
Antivirais/síntese química , Inibidores da Protease de HIV/síntese química , HIV-1/efeitos dos fármacos , Indanos/síntese química , Piperazinas/síntese química , Animais , Antivirais/química , Antivirais/farmacocinética , Antivirais/farmacologia , Bovinos , Técnicas de Cultura de Células , Cães , Avaliação Pré-Clínica de Medicamentos , Resistência Microbiana a Medicamentos , Inibidores da Protease de HIV/química , Inibidores da Protease de HIV/farmacocinética , Inibidores da Protease de HIV/farmacologia , Haplorrinos , Humanos , Indanos/química , Indanos/farmacocinética , Indanos/farmacologia , Masculino , Piperazinas/química , Piperazinas/farmacocinética , Piperazinas/farmacologia , Ligação Proteica , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Cálculos Urinários/induzido quimicamente , Cálculos Urinários/urinaRESUMO
We investigated the inhibition of IkappaB kinase (IKK) activity in lipopolysaccharide (LPS)-activated murine macrophages (RAW 264.7 cell line) by various polyphenols including (-)-epigallocatechin-3-gallate, theaflavin, a mixture of theaflavin-3 gallate and theaflavin-3'-gallate, theaflavin-3,3'-digallate (TF-3), pyrocyanidin B-3, casuarinin, geraniin, and penta-O-galloyl-beta-D-glucose (5GG). TF-3 inhibited IKK activity in activated macrophages more strongly than did the other polyphenols. TF-3 strongly inhibited both IKK1 and IKK2 activity and prevented the degradation of IkappaBalpha and IkappaBbeta in activated macrophage cells. The results suggested that the inhibition of IKK activity by TF-3 could occur by a direct effect on IKKs or on upstream events in the signal transduction pathway. Furthermore, geraniin, 5GG, and TF-3 all blocked phosphorylation of IKB from the cytosolic fraction, inhibited nuclear factor-kappaB (NFkappaB) activity, and inhibited increases in inducible nitric oxide synthase levels in activated macrophages. These results suggest that TF-3 may exert its anti-inflammatory and cancer chemopreventive actions by suppressing the activation of NFkappaB through inhibition of IKK activity.
Assuntos
Biflavonoides , Flavonoides , Ácido Gálico/análogos & derivados , Taninos Hidrolisáveis , Macrófagos/efeitos dos fármacos , NF-kappa B/metabolismo , Fenóis/farmacologia , Polímeros/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Animais , Antioxidantes/farmacologia , Catequina , Células Cultivadas , Regulação para Baixo , Inibidores Enzimáticos/farmacologia , Ácido Gálico/farmacologia , Expressão Gênica/efeitos dos fármacos , Glucosídeos/farmacologia , Quinase I-kappa B , Lipopolissacarídeos/farmacologia , Macrófagos/enzimologia , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase/biossíntese , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo II , Fosforilação , Polifenóis , Proteínas Serina-Treonina Quinases/metabolismo , Taninos/farmacologia , Chá/químicaRESUMO
Our previous report first showed evidence that polysaccharides isolated from ginseng leaves obtained from Jilin, China possess luteotropic activities. In this study, we made further investigations on the root and flowers of Korean ginseng by means of the same bioassay system described briefly as follows. Frozen-thawed bovine luteal cells (1 x 10(5) cells/ml/well) in M199 were incubated in 24-well culture plates at 37 degrees C in a 5 % CO2 incubator. Ten microl of tested drugs with 1, 10 and 100 microg/ml were added into each well. After 4- and 24-hr incubation, the media were harvested and assayed for progesterone by an enzyme immunoassay. The production of progesterone from cells is the indicator for evaluating the action of tested drugs. Results showed that hot water extracts ofginseng flowers (GF-1) with 10 to 100 microg/ml significantly increased progesterone production, whereas those from ginseng root (GR-1) could not. Crude polysaccharides (GF-2) isolated from GF-1 is the active component and the small molecules (mw < 10,000 dalton) are excluded, indicating that the ginseng root has no luteotropic activities, but the polysaccharides of ginseng flowers have.
Assuntos
Corpo Lúteo/efeitos dos fármacos , Panax/metabolismo , Plantas Medicinais , Progesterona/biossíntese , Animais , Bovinos , Células Cultivadas , Corpo Lúteo/citologia , Corpo Lúteo/metabolismo , Feminino , Extratos VegetaisRESUMO
We have identified a novel human gene, kiap (kidney inhibitor of apoptosis protein) that encodes a single BIR domain and a RING zinc finger domain. kiap has been assigned to the q13.3 region of human chromosome 20 by fluorescent in situ hybridization analysis. Northern blot analysis indicates that KIAP is expressed mainly in placenta, lymph node and fetal kidney. In this report, we show that overexpression of KIAP blocks apoptosis induced by menadione or by overexpression of BAX. In addition, we show that overexpression of KIAP enhances apoptosis induced by etoposide, and, that KIAP fails to block apoptosis induced by overexpression of Fas. Thus, KIAP, a new member of the inhibitor of apoptosis protein (IAP) family, has pleiotropic effects on apoptosis induced by various stimuli.
Assuntos
Apoptose/fisiologia , Proteínas de Bactérias/genética , Proteínas de Insetos , Rim/fisiologia , Proteínas , Sequência de Aminoácidos , Proteínas de Bactérias/classificação , Proteínas de Bactérias/isolamento & purificação , Proteínas de Bactérias/metabolismo , Sequência de Bases , Mapeamento Cromossômico , Cromossomos Humanos Par 20 , Clonagem Molecular , DNA Complementar/análise , Bases de Dados Factuais , Humanos , Proteínas Inibidoras de Apoptose , Cariotipagem , Rim/citologia , Dados de Sequência Molecular , Filogenia , Estrutura Terciária de Proteína , RNA Mensageiro/metabolismo , Homologia de Sequência de Aminoácidos , Distribuição Tecidual , Proteínas Virais/química , Receptor fas/biossíntese , Receptor fas/fisiologiaRESUMO
The cytochrome P450s (CYPs) constitute a superfamily of isoforms that play an important role in the oxidative metabolism of drugs. Each CYP isoform possesses a characteristic broad spectrum of catalytic activities of substrates. Whenever 2 or more drugs are administered concurrently, the possibility of drug interactions exists. The ability of a single CYP to metabolise multiple substrates is responsible for a large number of documented drug interactions associated with CYP inhibition. In addition, drug interactions can also occur as a result of the induction of several human CYPs following long term drug treatment. The mechanisms of CYP inhibition can be divided into 3 categories: (a) reversible inhibition; (b) quasi-irreversible inhibition; and (c) irreversible inhibition. In mechanistic terms, reversible interactions arise as a result of competition at the CYP active site and probably involve only the first step of the CYP catalytic cycle. On the other hand, drugs that act during and subsequent to the oxygen transfer step are generally irreversible or quasi-irreversible inhibitors. Irreversible and quasi-irreversible inhibition require at least one cycle of the CYP catalytic process. Because human liver samples and recombinant human CYPs are now readily available, in vitro systems have been used as screening tools to predict the potential for in vivo drug interaction. Although it is easy to determine in vitro metabolic drug interactions, the proper interpretation and extrapolation of in vitro interaction data to in vivo situations require a good understanding of pharmacokinetic principles. From the viewpoint of drug therapy, to avoid potential drug-drug interactions, it is desirable to develop a new drug candidate that is not a potent CYP inhibitor or inducer and the metabolism of which is not readily inhibited by other drugs. In reality, drug interaction by mutual inhibition between drugs is almost inevitable, because CYP-mediated metabolism represents a major route of elimination of many drugs, which can compete for the same CYP enzyme. The clinical significance of a metabolic drug interaction depends on the magnitude of the change in the concentration of active species (parent drug and/or active metabolites) at the site of pharmacological action and the therapeutic index of the drug. The smaller the difference between toxic and effective concentration, the greater the likelihood that a drug interaction will have serious clinical consequences. Thus, careful evaluation of potential drug interactions of a new drug candidate during the early stage of drug development is essential.
Assuntos
Inibidores das Enzimas do Citocromo P-450 , Sistema Enzimático do Citocromo P-450/metabolismo , Fígado/metabolismo , Animais , Avaliação Pré-Clínica de Medicamentos , Interações Medicamentosas , Ativação Enzimática , Inibidores Enzimáticos/farmacologia , Humanos , Fígado/enzimologiaRESUMO
Histologically, acupuncture points show neuronal innervation. One hundred seventy-seven tissue samples of acupuncture points and control points from 4 dogs were collected. Concentrations of substance P, a neurotransmitter, in the skin, muscle and subcutis of acupuncture points and control points were measured by means of enzyme immunoassay. The determined tissue concentrations of substance P (mean +/- SEM) in acupuncture points and control points were 1.81 +/- 0.13 and 1.51 +/- 0.1 ng/g in the muscle, 3.33 +/- 0.29 and 2.63 +/- 0.28 ng/g in the skin and 1.59 +/- 0.22 and 1.32 +/- 0.16 ng/g in the subcutis, respectively. The results indicate that there is a difference in the neurochemical profile between acupuncture points and control points.
Assuntos
Pontos de Acupuntura , Substância P/metabolismo , Animais , Cães , Feminino , Masculino , Músculos/metabolismo , Pele/metabolismoRESUMO
Direct administration of lipopolysaccharide (LPS) into the organum vasculosum laminae terminalis (OVLT) increased the amount of nitric oxide (NO) release and inducible NO synthase expression. These increases paralleled the increase in deep body temperature in unanesthetized rabbits. Pretreatment with dexamethasone, a synthetic glucocorticoid, not only reduced the fever but also attenuated the NO release and the inducible NO synthase expression in the OVLT following an intra-OVLT dose of LPS. The data suggest that steroids such as dexamethasone exert their antipyresis by inhibiting the NO pathway in the OVLT of rabbit brain.
Assuntos
Analgésicos não Narcóticos , Temperatura Corporal/efeitos dos fármacos , Dexametasona/farmacologia , Hipotálamo/fisiologia , Óxido Nítrico Sintase/biossíntese , Óxido Nítrico/fisiologia , Animais , Dexametasona/administração & dosagem , Indução Enzimática/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Hipotálamo/enzimologia , Lipopolissacarídeos/toxicidade , Masculino , Microinjeções , CoelhosRESUMO
1. Fever was induced in rabbits by administration of Escherichia coli endotoxin (lipopolysaccharide; LPS; 0.001-10 micrograms) into the organum vasculosum laminae terminalis (OVLT). Deep body temperature was evaluated over a period of 7 h. 2. The LPS-induced febrile response was mimicked by intra-OVLT injection of the nitric oxide (NO) donors, S-nitroso-acetylpenicillamine (SNAP, 1-10 micrograms), sodium nitroprusside (SNP, 50 micrograms), or hydroxylamine (10 micrograms), the cyclic GMP analogue 8-bromo-cyclic GMP (8-Br-cyclic GMP, 10-100 micrograms), or prostaglandin E2 (PGE2, 0.2 micrograms). 3. Dexamethasone (Dex, a potent inhibitor of the transcription of inducible NO synthase, iNOS, 10 micrograms), anisomycin (a protein synthesis inhibitor, 100 micrograms), L-N5-(1-iminoethyl)ornithine (L-NIO; an irreversible NOS inhibitor, 10-200 micrograms), aminoguanidine (a specific iNOS inhibitor, 1000 micrograms), or NG-methyl-L-arginine acetate (L-NMMA, a NOS inhibitor, 100 micrograms) inhibited fever induced by LPS when injected into the OVLT 1 h before LPS injection. An intra-OVLT dose of 1000 micrograms of NG-nitro-L-arginine methyl ester (L-NAME, a potent inhibitor of constitutive NOS) did not exhibit antipyretic effects. 4. Methylene blue (an inhibitor of NOS and soluble guanylate cyclase, 1-10 micrograms), 6-(phenylamino)-5,8-quinolinedione (LY-83583; an inhibitor of soluble guanylate cyclase and NO release, 20 micrograms), or indomethacin (an inhibitor of cyclo-oxygenase, COX, 400 micrograms) inhibited fever induced by LPS when injected into the OVLT 1 h before LPS injection. Pretreatment with methylene blue or haemoglobin (a NO scavenger, 100 micrograms) attenuated the fever induced by intra-OVLT injection of SNAP. 5. The PGE2-induced fever was potentiated, rather then attenuated, by pretreatment with an intra-OVLT dose of animoguanidine (1000 micrograms), L-NMMA (100 micrograms) or L-NIO (200 micrograms). 6. These results suggest that iNOS-COX pathways in the OVLT represent an important mechanism for modulation of pyrogenic fever in rabbits.
Assuntos
Febre/induzido quimicamente , Febre/enzimologia , Hipotálamo/enzimologia , Óxido Nítrico Sintase/fisiologia , Óxido Nítrico/fisiologia , Prostaglandina-Endoperóxido Sintases/fisiologia , Animais , Regulação da Temperatura Corporal/efeitos dos fármacos , GMP Cíclico/antagonistas & inibidores , GMP Cíclico/metabolismo , Inibidores de Ciclo-Oxigenase/farmacologia , Dinoprostona/farmacologia , Inibidores Enzimáticos/farmacologia , Guanilato Ciclase/antagonistas & inibidores , Hipotálamo/fisiologia , Indometacina/farmacologia , Lipopolissacarídeos/toxicidade , Masculino , CoelhosRESUMO
Ginseng, a panacea in the Orient, has been widely investigated in the last two decades and found to possess a wide range of pharmacological activities including anti-fatigue properties, a transient regulatory action on metabolism and blood pressure, and an increase in the hypothalamo-pituitary-adrenocortical activities. However, a panoramic clinical chemistry study including adrenal and thyroid functions has never been done before. Two experiments with the same design but different concentrations of dexamethasone were performed in this study. The results obtained from the two experiments indicated that ginseng administration at this regime did not influence the blood chemistry profiles in normal rats, but significantly decreased AST and ALT levels from those in dexamethasone-treated ones. It implies that ginseng has a liver-protective effect. Meanwhile, ginseng therapy restores the adrenal and thyroid functions of rats inhibited by dexamethasone treatment.
Assuntos
Análise Química do Sangue , Dexametasona/farmacologia , Panax , Plantas Medicinais , Animais , Glicemia , Cálcio/sangue , Corticosterona/sangue , Masculino , Medicina Tradicional Chinesa , Fitoterapia , Ratos , Ratos Wistar , Glândula Tireoide/efeitos dos fármacosRESUMO
Veterinary acupuncture has been receiving greater acceptance in veterinary medicine communities throughout the world in recent years. The American Veterinary Medical Association, for example, is beginning to accept acupuncture as a form of veterinary treatment. Another branch of traditional Chinese veterinary practice, herbal medicine, deserves similar recognition throughout the veterinary world. While herbal medicine carries a strong reputation for healing potential in the Orient, this treatment system is new to Western veterinary practices. Chinese herbal medicine should be incorporated into wider veterinary practice only after close scientific examination of these techniques. The authors examine the reasons for investigating Chinese herbal medicine, including the historical background, strategies of development, research plans and prospects for the use of Chinese herbal medicine in veterinary sciences. Potentially, this could lead to a unique combination of traditional and modern medicines, and to links whereby veterinary findings might acquire applications in human medicine.