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51.
D G Rodrigues 《Journal of investigative medicine》2007,55(5):223-229
Two decades ago, clinical trials were carried out only in developed countries. Drug development and the need to speed up clinical trials lead the conduction of clinical trials to other countries. Among the regions of interest, Latin America (LA) has played its role successfully. LA has a large number of naive patients, qualified investigators, established regulatory systems and reasonable costs. Furthermore, LA might be also considered as a new option for any company looking for international patterns on drug research and development. The region has good professionals with scientific qualifications, well-established multinational pharmaceutical bases and an expansive pharmaceutical regional market. This work summarizes the recent advances that have occurred in drug research and development in the region and the expansion of the clinical trial market in the last couple of years. 相似文献
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54.
Effect of excimer laser on microbiological organisms 总被引:2,自引:0,他引:2
The effect of radiation emitted from an excimer laser filled with argon fluoride gas at 193 nm on Serratia marcescens, Pseudomonas aeruginosa, Staphylococcus aureus, streptococcus faecalis, Hemophilus influenzae, Candida albicans, and Aspergillus niger (collectively labeled "the microorganisms") was examined. Colonies were subjected to a variable number of radiation pulses from the excimer laser applied after a 36-hour period of incubation at 37 degrees C, at which time the colonies were fully grown and showed no viability. The lack of viability was confirmed with a subculture from each area that received radiation; all subcultures were negative. The characteristics of the radiation paralleled those used by Serdavic, Darrell, Krueger, et al in 1985.(1) This radiation treatment is believed to be within a therapeutic range, which suggests that the excimer laser, pending further investigation, may be useful in the treatment of corneal infections. 相似文献
55.
Kaster MP Rosa AO Rosso MM Goulart EC Santos AR Rodrigues AL 《Neuroscience letters》2004,355(1-2):21-24
This study investigated the effect of adenosine in the forced swimming test (FST) and the tail suspension test (TST) in mice, and the contribution of adenosine A1 and A2A receptors to adenosine's antidepressant-like effect. The immobility time in the FST was reduced by adenosine given either by i.p. (5-10 mg/kg) or i.c.v. (0.01-10 microg/site) route. Adenosine (1-10 mg/kg, i.p.) also produced an antidepressant-like effect in the TST. No treatment affected locomotion in an open-field. The anti-immobility effect of adenosine (10 mg/kg, i.p.) in the FST was prevented by i.p. pretreatment of mice with caffeine (3 mg/kg), DPCPX (2 mg/kg) and ZM241385 (1 mg/kg). CHA (0.05 mg/kg, i.p.) and DPMA (1-5 mg/kg, i.p.) also produced an antidepressant-like effect in the FST. This is the first report of an antidepressant-like effect of adenosine in mice, apparently mediated through an interaction with A1 and A2A receptors. 相似文献
56.
Thomazi AP Godinho GF Rodrigues JM Schwalm FD Frizzo ME Moriguchi E Souza DO Wofchuk ST 《Mechanisms of ageing and development》2004,125(7):475-481
The excitotoxicity of the neurotransmitter glutamate has been shown to be connected with many acute and chronic diseases of the CNS. High affinity sodium-dependent glutamate transporters play a key role in maintaining adequate levels of extracellular glutamate. In the present study, we used slices of striatum, hippocampus and cortex from rat brain to describe the in vitro profile of glutamate uptake during development and ageing, and its sensitivity to guanosine. In all structures, glutamate uptake was higher in immature animals. There was a maximum decrease in glutamate uptake in striatum and hippocampus in 15-month-old rats, which later increased, while in cortex there was a significant decrease in rats aged 60 days old. The effect of guanosine seems to be age and structure dependent since the increase in basal glutamate uptake was only seen in slices of cortex from 10-day-old animals. 相似文献
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58.
Badauê-Passos D Ventura RR Silva LF Olivares EL Ramalho MJ Antunes Rodrigues J Reis LC 《Experimental physiology》2001,86(5):621-628
The involvement of angiotensin AT1 receptors in sodium appetite was studied in hypothyroid rats treated with the angiotensin II antagonist losartan. Losartan was administered chronically by the oral route or acutely by the subcutaneous route after water and sodium depletion or water, sodium and food deprivation. Three days after addition of losartan to the food at the dose of 1.0 mg x g(-1), the rats significantly reduced (P < 0.02) their spontaneous intake of 1.8% NaCl. Increasing the dose of losartan to 2.0 and 4.0 mg x g(-1) did not reduce NaCl intake; in contrast, the intensity of the sodium appetite gradually returned to previous levels. The simultaneous administration of captopril, an angiotensin converting enzyme inhibitor, and losartan significantly increased (P < 0.05) NaCl intake and after captopril removal NaCl intake returned to the levels observed with losartan treatment alone. The administration of losartan 4 days after the beginning of captopril treatment significantly reduced (P < 0.0001) NaCl intake. Following acute administration of losartan, water- and sodium-depleted rats significantly reduced their NaCl and water intake (P < 0.001). The administration of losartan also induced a significant reduction in NaCl and water intake in water, NaCl and food-deprived rats (P < 0.0001 and P < 0.001, respectively). The present results show that chronic treatment with oral losartan inhibited spontaneous sodium appetite in hypothyroid rats. Continuation of treatment rendered rats resistant to the blockade of AT1 receptors. Water and sodium depletion and water, NaCl and food deprivation induced sodium appetite, which in the short term depends on cerebral angiotensinergic activity mediated by the activation of AT1 receptors. 相似文献
59.
Taborda CP Nakaie CR Cilli EM Rodrigues EG Silva LS Franco MF Travassos LR 《Scandinavian journal of immunology》2004,59(1):58-65
The 43 kDa glycoprotein (gp43) of Paracoccidioides brasiliensis is the major diagnostic antigen of paracoccidioidomycosis (PCM), a prevalent fungal infection in South America. A 15-mer sequence from gp43, denominated P10, induced T-CD4+ T helper 1 cellular immune responses in mice of three different haplotypes and protected against intratracheal challenge by a virulent isolate of P. brasiliensis. In an attempt to improve delivery of P10, a promiscuous antigen also presented by human leucocyte antigen-DR alleles, aiming at immunotherapy, we synthesized a multiple antigen peptide with the protective T-cell epitope expressed in a tetravalent 13-mer analog of P10 (M10). M10 induced specific lymph node cell proliferation in mice preimmunized with peptides in complete Freund's adjuvant (CFA). In addition, M10 immunization without CFA significantly protected intratracheally infected mice. We conclude that M10 is a candidate for an anti-PCM vaccine. In this report we describe: (1) the synthesis of M10; (2) the induction of M10-elicited T-cell response and (3) in vivo protection of mice immunized with M10 and challenged by a virulent strain of P. brasiliensis. 相似文献
60.
Lethal encephalitis in myeloid differentiation factor 88-deficient mice infected with herpes simplex virus 1
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Mansur DS Kroon EG Nogueira ML Arantes RM Rodrigues SC Akira S Gazzinelli RT Campos MA 《The American journal of pathology》2005,166(5):1419-1426
Herpes simplex virus 1 (HSV-1), a large DNA virus from the Herpesviridae family, is the major cause of sporadic lethal encephalitis and blindness in humans. Recent studies have shown the importance of Toll-like receptors (TLRs) in the immune response to HSV-1 infection. Myeloid differentiation factor 88 (MyD88) is a critical adaptor protein that is downstream to mediated TLR activation and is essential for the production of inflammatory cytokines. Here, we studied the relationship between MyD88 and HSV-1 using a purified HSV-1 isolated from a natural oral recurrent human infection. We observed the activation of TLR-2 by HSV-1 in vitro using Chinese hamster ovary cells stably transfected with a reporter gene. Interestingly, we found that only peritoneal macrophages from MyD88-/- mice, but not macrophages from TRL2-/- or from wild-type mice, were unable to produce tumor necrosis factor-alpha in response to HSV-1 exposure. Additionally, although TLR2-/- mice showed no enhanced susceptibility to intranasal infection with HSV-1, MyD88-/- mice were highly susceptible to infection and displayed viral migration to the brain, severe neuropathological signs of encephalitis, and 100% mortality by day 10 after infection. Together, our results suggest that innate resistance to HSV-1 is mediated by MyD88 and may rely on activation of multiple TLRs. 相似文献