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41.
Patricio López-Jaramillo Director Marcelo Narváez Professor rés Calle Professor José Rivera Consultant Patricio Jácome Registrar César Ruano Professor Eduardo Nava Consultant 《BJOG : an international journal of obstetrics and gynaecology》1996,103(1):33-38
Objective To elucidate the role of the L-arginine: nitric oxide pathway in pregnancy and pre-eclampsia.
Participants Pregnant women (nulliparous, age < 25 years). Normotensive pregnancy ( n = 22 ) was defined when blood pressure remained at levels of < 120/80 mmHg and there was no proteinuria. Women with pre-eclampsia ( n = 22 ) had blood pressure measurements of > 140/90 mmHg and proteinuria of > 300 mg/l. Nonpregnant normotensive women ( n = 22 ) were studied as controls.
Study Design Blood samples were taken for measurements of ionised calcium, atrial natriuretic factor, cyclic guanosine 3'5'monophophate (GMP), arginine and asymmetric dimethylarginine. Urine samples were collected for determination of cyclic GMP excretion. Cyclic GMP concentrations were also determined in 12 women with severe pre-eclampsia before and after treatment with hydralazine.
Results L-arginine, asymmetric dimethylarginine and atrial natriuretic factor were not different in any group. Cyclic GMP concentrations in plasma [0.94 (SD 0.23) nM] as well as in urine [50.1 (SD15.7)μM] were increased significantly ( P < 0.05 ) in normal pregnancy compared to nonpregnant controls [plasma mean 0.46 (SD 0.12) nM and urine mean 18.4 (SD 10.3) μM], but not in the pre-eclampsia group [plasma mean 0.48 (SD 0.10) nM and urine mean 24.1 (SD 14.5) μM]. Concentrations of cyclic GMP in plasma and urine increased significantly ( P < 0.05 ) in women treated with hydralazine.
Conclusions The differences in cyclic GMP concentrations may reflect differences in nitric oxide production. Hydralazine increases cyclic GMP concentrations in severely pre-eclamptic women. This action could explain the antihypertensive effect of hydralazine. 相似文献
Participants Pregnant women (nulliparous, age < 25 years). Normotensive pregnancy ( n = 22 ) was defined when blood pressure remained at levels of < 120/80 mmHg and there was no proteinuria. Women with pre-eclampsia ( n = 22 ) had blood pressure measurements of > 140/90 mmHg and proteinuria of > 300 mg/l. Nonpregnant normotensive women ( n = 22 ) were studied as controls.
Study Design Blood samples were taken for measurements of ionised calcium, atrial natriuretic factor, cyclic guanosine 3'5'monophophate (GMP), arginine and asymmetric dimethylarginine. Urine samples were collected for determination of cyclic GMP excretion. Cyclic GMP concentrations were also determined in 12 women with severe pre-eclampsia before and after treatment with hydralazine.
Results L-arginine, asymmetric dimethylarginine and atrial natriuretic factor were not different in any group. Cyclic GMP concentrations in plasma [0.94 (SD 0.23) nM] as well as in urine [50.1 (SD15.7)μM] were increased significantly ( P < 0.05 ) in normal pregnancy compared to nonpregnant controls [plasma mean 0.46 (SD 0.12) nM and urine mean 18.4 (SD 10.3) μM], but not in the pre-eclampsia group [plasma mean 0.48 (SD 0.10) nM and urine mean 24.1 (SD 14.5) μM]. Concentrations of cyclic GMP in plasma and urine increased significantly ( P < 0.05 ) in women treated with hydralazine.
Conclusions The differences in cyclic GMP concentrations may reflect differences in nitric oxide production. Hydralazine increases cyclic GMP concentrations in severely pre-eclamptic women. This action could explain the antihypertensive effect of hydralazine. 相似文献
42.
Brett Claire M. Washington Carla B. Ott Ronda J. Gutierrez Marcelo M. Giacomini Kathleen M. 《Pharmaceutical research》1993,10(3):423-426
The therapeutic efficacy of nucleosides and nucleoside analogues as antitumor, antiviral, antiparasitic, and antiarrhythmic agents has been well documented. Pharmacokinetic studies suggest that many of these compounds are actively transported in the kidney. The goal of this study was to determine if therapeutically relevant nucleosides or analogues interact with the recently characterized Na+-driven nucleoside transport system of the brush border membrane of the human kidney. Brush border membrane vesicles (BBMV) were prepared from human kidney by divalent cation precipitation and differential centrifugation. The initial Na+-driven 3H-uridine uptake into vesicles was determined by rapid filtration. The effect of several naturally occurring nucleosides (cytidine, thymidine, adenosine), a pyrimidine base (uracil), a nucleotide (UMP), and several synthetic nucleoside analogues [zidovudine (AZT), cytarabine (Ara-C), and dideoxycytidine (ddC)] on Na+–uridine transport was determined. At a concentration of 100 µM the naturally occurring nucleosides, uracil, and UMP significantly inhibited Na+-uridine transport, whereas the three synthetic nucleoside analogues did not. Adenosine competitively inhibited Na+-uridine uptake with a K
i of 26.4 µM (determined by constructing a Dixon plot). These data suggest that naturally occurring nucleosides are substrates of the Na+–nucleoside transport system in the renal brush border membrane, whereas synthetic nucleoside analogues with modifications on the ribose ring are not. The K
i of adenosine is higher than clinically observed concentrations and suggests that the system may play a physiologic role in the disposition of this nucleoside. 相似文献
43.
An ideal vaccine has certain biological and physical characteristics. Technological advances have provided new strategies that may help the design of such a vaccine. 相似文献
44.
Stevenson HL Labruna MB Montenieri JA Kosoy MY Gage KL Walker DH 《Journal of medical entomology》2005,42(2):163-167
The flea and rodent samples studied in this project were collected from field study sites in New Mexico from winter 1998 to spring 2001. During this period, 155 small rodents (14 different species) were live-trapped and combed for the presence of fleas. A total of 253 fleas were collected, comprising 21 species. Two of the 253 fleas collected were polymerase chain reaction (PCR) positive for the Rickettsia 17-kDa protein gene. These two fleas were both Anomiopsyllus nudata Baker, each collected from an individual Neotoma albigula Hartley, on two occasions. Individual fleas positive for the Rickettsia 17-kDa protein gene were then tested with primers targeting the rickettsial genes for citrate synthase (gltA) and two major outer membrane proteins (ompA and ompB). The nucleotide sequences of the PCR products of these two fleas were identical to each other and were 100% (394/394), 100% (1150/1150), 99.8% (469/470), and 99.3% (818/824) similar to the corresponding sequences of the 17-kDa, gltA, ompA, and ompB genes of Rickettsia felis, respectively. Flea homogenates of individual PCR-positive fleas were inoculated into shell vials seeded with Vero cells, and the Gimenez stain technique was used to demonstrate the presence of Rickettsia-like organisms in detached cells found in aspirated medium 19 d after inoculation. These cells were harvested and tested by PCR, targeting portions of the 17-kDa and gltA genes, resulting in products 100% identical to R. felis. This work comprises the first report of R. felis detection in a flea species (A. nudata) endemic to the New World. 相似文献
45.
46.
Development and comparison of enzyme immunoassays for diagnosis of Chagas' disease using fixed forms of Trypanosoma cruzi (Epimastigotes, Amastigotes, and Trypomastigotes) and assessment of antigen stability for the three assays
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Berrizbietia M Ndao M Gottschalk M Aché A Vásquez F Lacouture S Medina M Ward BJ 《Journal of clinical microbiology》2004,42(4):1766-1769
Three enzyme immunoassays (EIAs) for diagnosis of Chagas' disease were developed with fixed forms of Trypanosoma cruzi using a panel of 435 sera from the following groups: Venezuelan subjects positive by immunofluorescence (n = 70), Venezuelan healthy controls (n = 85), healthy Canadians (n = 166), and subjects with other parasitic diseases (n = 114). All assays achieved 100% sensitivity and reasonable specificity for amastigotes (97.6%), epimastigotes (98.3%), and trypomastigotes (99.3%). The fixed-trypomastigote assay was stable over 4 months at 4 degrees C and room temperature. These data suggest that a fixed-trypomastigote EIA may be a suitable candidate for blood bank screening. 相似文献
47.
Morphologic Study of the Participation of the Complement System in Hyperacute Rejection of Renal Xenotransplants
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Jaime E. Mej¯a-Laguna Adolfo Mart¯nez-Palomo Carlos E. Biro Bibiana Ch¬vez Fernando LÌpez-Soriano Marcelo Garc¯a-Cornejo 《The American journal of pathology》1972,69(1):71-78
The role of polymorphonuclear leukocyte (PMN) and platelet infiltration in the hyperacute rejection of renal xenotransplants was studied. In a first group, a dog kidney was grafted to rabbit recipients with intact immune adherence and chemotaxis. A second group included recipients depleted of PMN's with nitrogen mustard, and in a third group, immune adherence and chemotaxis were modified by depleting the third component of complement by means of cobra venom factor. Serial kidney biopsies were studied with light and electron microscopic technics. A semiquantitative evaluation of PMN and platelet glomerular infiltration indicated that a reduction in the number of PMN's or platelets is associated with an increased survival time of the transplanted kidney. 相似文献
48.
Soluble factors released by Toxoplasma gondii-infected astrocytes down-modulate nitric oxide production by gamma interferon-activated microglia and prevent neuronal degeneration
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Rozenfeld C Martinez R Figueiredo RT Bozza MT Lima FR Pires AL Silva PM Bonomo A Lannes-Vieira J De Souza W Moura-Neto V 《Infection and immunity》2003,71(4):2047-2057
The maintenance of a benign chronic Toxoplasma gondii infection is mainly dependent on the persistent presence of gamma interferon (IFN-gamma) in the central nervous system (CNS). However, IFN-gamma-activated microglia are paradoxically involved in parasitism control and in tissue damage during a broad range of CNS pathologies. In this way, nitric oxide (NO), the main toxic metabolite produced by IFN-gamma-activated microglia, may cause neuronal injury during T. gondii infection. Despite the potential NO toxicity, neurodegeneration is not a common finding during chronic T. gondii infection. In this work, we describe a significant down-modulation of NO production by IFN-gamma-activated microglia in the presence of conditioned medium of T. gondii-infected astrocytes (CMi). The inhibition of NO production was paralleled with recovery of neurite outgrowth when neurons were cocultured with IFN-gamma-activated microglia in the presence of CMi. Moreover, the modulation of NO secretion and the neuroprotective effect were shown to be dependent on prostaglandin E(2) (PGE(2)) production by T. gondii-infected astrocytes and autocrine secretion of interleukin-10 (IL-10) by microglia. These events were partially eliminated when infected astrocytes were treated with aspirin and cocultures were treated with anti-IL-10 neutralizing antibodies and RP-8-Br cyclic AMP (cAMP), a protein kinase A inhibitor. Further, the modulatory effects of CMi were mimicked by the presence of exogenous PGE(2) and by forskolin, an adenylate cyclase activator. Altogether, these data point to a T. gondii-triggered regulatory mechanism involving PGE(2) secretion by astrocytes and cAMP-dependent IL-10 secretion by microglia. This may reduce host tissue inflammation, thus avoiding neuron damage during an established Th1 protective immune response. 相似文献
49.
50.
Toxoplasma gondii prevents neuron degeneration by interferon-gamma-activated microglia in a mechanism involving inhibition of inducible nitric oxide synthase and transforming growth factor-beta1 production by infected microglia 总被引:2,自引:0,他引:2
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Rozenfeld C Martinez R Seabra S Sant'anna C Gonçalves JG Bozza M Moura-Neto V De Souza W 《The American journal of pathology》2005,167(4):1021-1031
Interferon (IFN)-gamma, the main cytokine responsible for immunological defense against Toxoplasma gondii, is essential in all infected tissues, including the central nervous system. However, IFN-gamma-activated microglia may cause tissue injury through production of toxic metabolites such as nitric oxide (NO), a potent inducer of central nervous system pathologies related to inflammatory neuronal disturbances. Despite potential NO toxicity, neurodegeneration is not commonly found during chronic T. gondii infection. In this study, we describe decreased NO production by IFN-gamma-activated microglial cells infected by T. gondii. This effect involved strong inhibition of iNOS expression in IFN-gamma-activated, infected microglia but not in uninfected neighboring cells. The inhibition of NO production and iNOS expression were parallel with recovery of neurite outgrowth when neurons were co-cultured with T. gondii-infected, IFN-gamma-activated microglia. In the presence of transforming growth factor (TGF)-beta1-neutralizing antibodies, the beneficial effect of the parasite on neurons was abrogated, and NO production reverted to levels similar to IFN-gamma-activated uninfected co-cultures. In addition, we observed Smad-2 nuclear translocation, a hallmark of TGF-beta1 downstream signaling, in infected microglial cultures, emphasizing an autocrine effect restricted to infected cells. Together, these data may explain a neuropreservation pattern observed during immunocompetent host infection that is dependent on T. gondii-triggered TGF-beta1 secretion by infected microglia. 相似文献