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排序方式: 共有8350条查询结果,搜索用时 15 毫秒
81.
Lucca R. Policastro Isabela Dolci Andre S. Godoy Jos V. J. Silva Júnior Uriel E. A. Ruiz Igor A. Santos Ana C. G. Jardim Kirandeep Samby Jeremy N. Burrows Timothy N. C. Wells Laura H. V. G. Gil Glaucius Oliva Rafaela S. Fernandes 《Viruses》2022,14(7)
Chikungunya virus (CHIKV) is the causative agent of chikungunya fever, a disabling disease that can cause long-term severe arthritis. Since the last large CHIKV outbreak in 2015, the reemergence of the virus represents a serious public health concern. The morbidity associated with viral infection emphasizes the need for the development of specific anti-CHIKV drugs. Herein, we describe the development and characterization of a CHIKV reporter replicon cell line and its use in replicon-based screenings. We tested 960 compounds from MMV/DNDi Open Box libraries and identified four candidates with interesting antiviral activities, which were confirmed in viral infection assays employing CHIKV-nanoluc and BHK-21 cells. The most noteworthy compound identified was itraconazole (ITZ), an orally available, safe, and cheap antifungal, that showed high selectivity indexes of >312 and >294 in both replicon-based and viral infection assays, respectively. The antiviral activity of this molecule has been described against positive-sense single stranded RNA viruses (+ssRNA) and was related to cholesterol metabolism that could affect the formation of the replication organelles. Although its precise mechanism of action against CHIKV still needs to be elucidated, our results demonstrate that ITZ is a potent inhibitor of the viral replication that could be repurposed as a broad-spectrum antiviral. 相似文献
82.
Félix Carvalho Eduarda Fernandes Fernando Remião Maria Lourdes Bastos 《Archives of toxicology》1999,73(2):83-89
The purpose of this study was to evaluate rat tissue antioxidant status after repeated administration of d-amphetamine. Three groups of four rats each were used: control, d-amphetamine sulphate dosed (s.c., 20 mg/kg per day), and pair-fed. After 14 days of d-amphetamine daily administration, superoxide dismutase (CuZnSOD and MnSOD), catalase, glutathione peroxidase (GPx), glutathione
reductase (GRed), glutathione-S-transferase (GST), glutathione (GSH), cysteine and thiobarbituric acid reactive substances
(TBARS) were measured in liver, kidney, and heart. Various serum and urine parameters were also analysed. d-Amphetamine treatment induced an increase of liver GSH, as well as a decrease of cysteine and MnSOD levels in this organ.
A small increase in serum transaminases was also observed in comparison to the pair-fed group. Hepatic levels of TBARS, GPx,
GRed and CuZnSOD were found to be similar among the three groups of rats. d-Amphetamine treatment induced an increase of kidney GST, GRed and catalase levels, and an elevation of N-acetyl-β-d-glucosaminidase efflux to the urine, accompanied by a decrease in urinary creatinine, compared to the pair-fed group. In
d-amphetamine treated animals, heart cysteine levels were significantly depleted when compared to the pair-fed group, but all
three groups of rats were found to have similar heart antioxidant enzyme levels. These results indicate that repeated administration
of d-amphetamine caused a certain degree of stress in liver and kidney, which was followed by adaptations of antioxidant defences.
The mechanisms involved in d-amphetamine-induced toxicity may explain the different adaptations observed for the studied organs.
Received: 19 October 1998 / Accepted: 11 January 1999 相似文献
83.
P. Soares-da-Silva M. Helena Fernandes 《Naunyn-Schmiedeberg's archives of pharmacology》1990,342(4):415-421
Summary The effect of pinacidil on the release of endogenous noradrenaline and dopamine from the sympathetic innervation of the rat vas deferens was examined. Amine release was evoked by electrical stimulation (1, 2, 5 and 10 Hz) or by depolarization with high potassium (75 mmol/l) in the medium. Dopamine and noradrenaline were measured by means of high pressure liquid chromatography with electrochemical detection.Pinacidil (1, 5, 10 and 50 mol/l) produced a concentration-dependent inhibition of the electrically stimulated (2 Hz) overflow of noradrenaline and dopamine. Only pinacidil 50 mol/l increased the spontaneous loss of dopamine and noradrenaline. The inhibitory effects of pinacidil (5 mol/l) on amine overflow were also observed at other frequencies of stimulation (1, 5 and 10 Hz). The magnitude of the inhibitory effect on noradrenaline release was approximately the same at all frequencies (63% to 56% reduction); for dopamine, the higher the frequency of stimulation, the greater the inhibitory effect of pinacidil (up to 73% reduction). When the preparations were continuously stimulated for 70 min at 2 Hz, pinacidil (5 mol/l) reduced the overflow of dopamine and noradrenaline during the first 40 or 30 min of stimulation only. The addition of phentolamine (1 mol/l) to the perifusion medium slightly reduced the inhibitory effect of pinacidil on amine overflow, but the inhibition by pinacidil remained statistically significant. Tetraethylammonium (10 mmol/l) completely abolished the inhibitory effect of pinacidil (10 mol/l). Pinacidil (5 mol/l) did not reduce the potassium-evoked release of the amines.The results demonstrate that pinacidil impairs transmitter release from the sympathetic innervation of the rat vas deferens, probably as a consequence of the opening of potassium channels.
Send offprint request to P. Soares-da-Silva at the above adress 相似文献
84.
M. Fernandes 《Naunyn-Schmiedeberg's archives of pharmacology》1970,267(1):41-48
Summary The effect of perazine and the flavines FAD, FMN and riboflavine on the NAD-kinase of rat brain and the NAD-kinase of rat liver was studied.The flavine derivatives inhibited both enzymes. The inhibition mechanism was found to be non-competitive with rat liver NAD-kinase.Perazine, added simultaneously, restored the enzyme activity. The mechanism of interaction was elucidated by the use of the pA¯x-method and found to be competitive with rat liver NAD-kinase. The antagonism described occured with the rat brain enzyme too, but with the method used the mechanisms of inhibition and interaction could not be investigated. 相似文献
85.
André São Pedro Renan Fernandes Cristiane Flora Villarreal Rosana Fialho Elaine Cabral Albuquerque 《Journal of microencapsulation》2016,33(1):18-29
Context Opioids have been used as the reference treatment on chronic pain. However, they are related to serious adverse effects which affect the patient compliance to treatment, as well as, his quality of life. Particulate formulations have been investigated as an alternative to improve opioid efficacy and safety. Objective Summarise the available studies concerning micro and nanoencapsulated opioid formulations discussing their biopharmaceutical characteristics, such as composition, size, in vitro release, pharmacokinetic and antinociceptive profile. Methods Papers available in 1995–2015 at Medline, Science Direct and Web of Science databases were collected and assessed. Searches were performed using varied combinations of the keywords of this work. Results Opioid-loaded particles showed prolonged drug release with maintenance of serum therapeutic concentrations and extended analgesia when compared with the free drugs. The side effects incidences were reduced or maintained the same. Conclusion Particulate formulations can significantly increase both potency and safety profiles of opioids. 相似文献
86.
Although hydrogel extended-wear contact lenses (EWCLs) have been used extensively in the correction of aphakia in neonates, little is known about the effects of these lenses on infant corneas. Recent studies have demonstrated that long-term contact lenses can induce endothelial morphometric changes, including an increased coefficient of variation (CV) of mean endothelial cell area. Using wide-field specular microscopy, the authors studied 11 eyes of 10 patients, 1 to 3 years of age who, after lensectomy for congenital cataracts, wore EWCLs for the correction of aphakia. Except for two corneas in which increased pachometric readings and CV developed after repeated episodes of lens loss and inflammation, the EWCL were well tolerated and associated with few complications in this study. 相似文献
87.
Jorge MP Madjarof C Gois Ruiz AL Fernandes AT Ferreira Rodrigues RA de Oliveira Sousa IM Foglio MA de Carvalho JE 《Journal of ethnopharmacology》2008,118(3):361-366
ETHNOPHARMACOLOGICAL RELEVANCE: Arrabidaea chica Verlot. (Bignoniaceae), popularly known as Crajiru, has been traditionally used as wound healing agent. AIM OF THE STUDY: Investigate in vitro and in vivo healing properties of Arrabidaea chica leaves extract (AC). MATERIALS AND METHODS: AC was evaluated in vitro in fibroblast growth stimulation (0.25-250 microg/mL) and collagen production stimulation (250 microg/mL) assays. Allantoin (0.25-250 microg/mL) and vitamin C (25 microg/mL) were used as controls respectively. DPPH and Folin-Ciocalteau assays were used for antioxidant evaluation, using trolox (0.25-250 microg/mL) as reference antioxidant. To study wound healing properties in rats, AC (100mg/mL, 200 microL/wound/day) was topically administered during 10 days and wound area was evaluated every day. Allantoin (100mg/mL, 200 microL/wound/day) was used as standard drug. After treatment, wound sites were removed for histopathological analysis and total collagen determination. RESULTS: AC stimulated fibroblast growth in a concentration dependent way (EC50=30 microg/mL), increased in vitro collagen production and demonstrated moderate antioxidant capacity. In vivo, AC reduced wound size in 96%, whereas saline group showed only 36% wound healing. CONCLUSION: AC efficiency seems to involve fibroblast growing stimulus and collagen synthesis both in vitro and in vivo, beyond moderate scavenging activity, corroborating Crajiru folk use. 相似文献
88.
Delmanto A Nahas-Neto J Nahas EA de Oliveira ML Fernandes CE Traiman P 《European journal of obstetrics, gynecology, and reproductive biology》2008,139(2):187-192
OBJECTIVE: The objective was to analyze the effect of raloxifene on the vaginal epithelium of postmenopausal women. STUDY DESIGN: In this non-randomized clinical trial, 80 women (mean age = 60.6 years) were prospectively studied. Forty patients received 60 mg/day of raloxifene (RG), and 40 women constituted a non-treated control group (CG), paired by age and time since menopause. The treated group consisted of patients with osteoporosis of the lumbar spine. Those with a diagnosis of infection in the lower genital tract and using hormone therapy (HT) up to 6 months prior to the study were excluded. Vaginal smears were collected at baseline and after 6 months of intervention. The vaginal maturation value (VMV) was determined, and counts of superficial, intermediate and parabasal cells were performed. Smears were analyzed by only one cytopathologist who was blinded to patient data. The t-test, Wilcoxon test, and Chi-Squared test were used in the statistical analysis. RESULTS: The study groups were homogeneous regarding age, time since menopause, parity, HT use, smoking, and body mass index. No statistically significant differences were observed in VMV median values (RG, 39.7 and 35.7; CG, 50.0 and 50.0, respectively) or in the percentage of superficial, intermediate and parabasal cells between the groups at baseline and after 6 months (p>0.05). There was no significant correlation between VMV and age, time since menopause, previous HT use, or body mass index, in either of the groups. CONCLUSION: Treatment with raloxifene for 6 months has no effect on the maturation of the vaginal epithelium in postmenopausal women with osteoporosis. 相似文献
89.
Dusse LM Carvalho Md Bragança WF Paiva SG Godoi LC Guimarães DA Fernandes AP 《European journal of obstetrics, gynecology, and reproductive biology》2007,134(1):20-23
OBJECTIVE: The aim of the present study was to compare the distribution of G1691A, G20210A and C677T mutations in pre-eclamptic Brazilian women and in matched control women with an uncomplicated normal pregnancy. STUDY DESIGN: these mutations were investigated by PCR-RFLP in 83 normal pregnancies (control group) and in 30 pre-eclamptic pregnant women (severe form). RESULTS: G1691A mutation was detected neither in the control group nor in pre-eclamsia women. G20210A mutation was detected in heterozygosis in 3 (3.61%) control subjects, but not in pre-eclampsia group. C677T mutation was detected in homozygosis in 6 (7.23%) control subjects and 2 (6.67%) pre-eclamptic women and in heterozygosis in 31 (37.3%) control subjects and 12 (40%) pre-eclamptic women. Differences in the mutation frequencies detected in the two groups were not statistically significant. CONCLUSION: No correlation was observed between pre-eclampsia and presence of G1691A, G20210A and C677T mutations in Brazilian women. 相似文献
90.