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21.
Jonathan D Jones Irene Shyu Marianna M Newkirk William FC Rigby 《Arthritis research & therapy》2013,15(1):R20
Introduction
Rituximab (RTX) therapy of rheumatoid arthritis (RA) exhibits enhanced effectiveness in seropositive patients. Using patient sera, we tested if this improved efficacy was associated with enhanced RTX mediated complement-dependent cytotoxicity (RTX-CDC).Methods
We developed an in vitro assay for RTX-CDC using patient sera and the Daudi human B cell line. Using propidium iodide uptake and flow cytometry, we compared RTX-CDC with rheumatoid factor (RF)+ sera relative to normal volunteer, non-RA and RF- sera. Additional studies examined mixing studies of RF+ and RF- sera, as well as the effect of monoclonal IgA or IgM RF. Finally, the effect of RF on RTX mediated trogocytosis of normal B cells was evaluated.Results
Using human sera, addition of RTX resulted in rapid and profound (> 50%) Daudi cell death that was complement dependent. Surprisingly, RF+ patient sera exhibited reduced RTX-CDC relative to RF- sera, with an inverse relationship of RTX-CDC and RF titer. Mixing studies indicated the presence of an inhibitor of RTX-CDC in RF+ sera. The addition of monoclonal IgM or IgA RF to RF- sera markedly inhibited RTX-CDC. This effect was specific for RF binding to the Fc portion of RTX as it was not apparent with the F(ab)'' domains of RTX engineered onto IgG3 heavy chain. RF also modestly inhibited RTX mediated trogocytosis.Conclusions
Contrary to expectations, RF+ sera exhibits reduced RTX-CDC due to the presence of RF. The enhanced efficacy of RTX in seropositive RA patients cannot be attributed to improved B cell depletion through CDC. This result indicates that high RF levels may potentially modulate the efficacy of any therapeutic monoclonal antibody dependent on Fc effector function. 相似文献22.
Lebrão Cynthia Rosa Lana Mignone Viana Paim Fernanda P. Nassar Pedro M. El Bizri Hani R. Silva Felipe Ennes 《International journal of primatology》2021,42(4):523-527
International Journal of Primatology - Community-based tourism is a participatory approach implemented to support the economic and social development of local communities. Here, we present the... 相似文献
23.
Bagatini PB Saur L Rodrigues MF Bernardino GC Paim MF Coelho GP Silva DV de Oliveira RM Schirmer H Souto AA Vianna MR Xavier LL 《Invertebrate neuroscience : IN》2011,11(1):43-51
Studies have suggested that neuronal loss in Parkinson's disease (PD) could be related to the pacemaker activity of the substantia nigra pars compacta generated by L-type Ca(v) 1.3 calcium channels, which progressively substitute voltage-dependent sodium channels in this region during aging. Besides this mechanism, which leads to increases in intracellular calcium, other factors are also known to play a role in dopaminergic cell death due to overproduction of reactive oxygen species. Thus, dihydropyridines, a class of calcium channel blockers, and resveratrol, a polyphenol that presents antioxidant properties, may represent therapeutic alternatives for the prevention of PD. In the present study, we tested the effects of the dihydropyridines, isradipine, nifedipine, and nimodipine and of resveratrol upon locomotor behavior in Drosophila melanogaster. As previously described, paraquat induced parkinsonian-like motor deficits. Moreover, none of the drugs tested were able to prevent the motor deficits produced by paraquat. Additionally, isradipine, nifedipine, resveratrol, and ethanol (vehicle), when used in isolation, induced motor deficits in flies. This study is the first demonstration that dyhidropyridines and resveratrol are unable to reverse the locomotor impairments induced by paraquat in Drosophila melanogaster. 相似文献
24.
Rafaela M.M. Paim Marcos H. Pereira Ricardo N. Araújo Nelder F. Gontijo Alessandra A. Guarneri 《Insect biochemistry and molecular biology》2013,43(3):229-236
The parasite Trypanosoma rangeli develops in the intestinal tract of triatomines and, particularly in species of the genus Rhodnius, invades the hemolymph and salivary glands, where subsequent metacyclogenesis takes place. Many aspects of the interaction between T. rangeli and triatomines are still unclear, especially concerning the development of the parasite in the salivary glands and how the parasite interacts with the saliva. In this work, we describe new findings on the process of T. rangeli infection of the salivary glands and the impact of infection on the saliva composition. To ensure a complete infection (intestinal tract, hemolymph and salivary glands), 3rd instar Rhodnius prolixus nymphs were fed on blood containing T. rangeli epimastigotes using an artificial feeder. After molt to the 4th instar, the nymphs were inoculated with epimastigotes in the hemolymph. The results showed that the flagellates started to invade the salivary glands by the 7th day after the injection. The percentage of trypomastigotes inside the salivary glands continuously increased until the 25th day, at which time the trypomastigotes were more than 95% of the T. rangeli forms present. The salivary contents from T. rangeli-infected insects showed a pH that was significantly more acidic (<6.0) and had a lower total protein and hemeprotein contents compared with non-infected insects. However, the ratio of hemeprotein to total protein was similar in both control and infected insects. qPCR demonstrated that the expression levels of three housekeeping genes (18S rRNA, β-actin and α-tubulin) and nitrophorins 1–4 were not altered in the salivary glands after an infection with T. rangeli. In addition, the four major nitrophorins (NPs 1–4) were knocked down using RNAi and their suppression impacted T. rangeli survival in the salivary glands to the point that the parasite burden inside the R. prolixus salivary glands was reduced by more than 3-fold. These results indicated that these parasites most likely non-specifically incorporated the proteins that were present in R. prolixus saliva as nutrients, without impairing the biosynthesis of the antihemostatic molecules. 相似文献
25.
Düsman E Berti AP Mariucci RG Lopes NB Vicentini VE 《Radiation and environmental biophysics》2011,50(4):579-584
Iodine-131 (131I) is a radioisotope used for the diagnosis and treatment of thyroidal disorders such as hyperthyroidism and cancer. During
its decay, 131I emits beta particles and gamma rays; its physical half-life is 8 days, and it is accumulated preferentially in the thyroid
tissue. This study aimed to evaluate the cytotoxicity and mutagenicity of diagnostic and therapeutic doses of 131I using bone marrow cells of rats treated in vivo in a test system with a single dose by gavage. Concentrations of 5, 25,
50 and 250 μCi in 1 ml of water were used, and after 24 h, the animals were killed. Also, a concentration of 25 μCi/ml of
water was used, and the animals were killed after 5 days. The results showed that no concentration of 131I was cytotoxic and that all concentrations were mutagenic. As a result, there was no statistically significant difference
detected by the χ2 test in the induction of chromosomal aberrations between the different doses. Thus, the present study demonstrated a significant
increase in chromosomal aberration in bone marrow cells exposed to 131I regardless of the dose or the treatment time. 相似文献
26.
Aline Blaya Martins Fernando Neves Hugo Betina Soldateli Paim Liese Ilha Paula Güntzel Juliana Romanini 《Gerodontology》2011,28(1):37-43
doi: 10.1111/j.1741‐2358.2009.00355.x How primary health care professionals and residents assess issues related to the oral health of older persons? Background and objectives: It is known that older persons need integrated primary health care. However, oral health may not be a frequent concern of multi‐professional teams taking care of older persons. The aim of the present study was to evaluate knowledge and practices related to oral health care, as reported by professionals and residents in a primary health care service. Material and methods: One hundred and seventy‐three health professionals and residents were assessed in this cross‐sectional study by means of a structured questionnaire containing questions pertaining to oral health practices and beliefs. Participants were grouped based on their professions into “primary health care dentists” or “other primary health care professionals” and based on their working status into “permanent team” or “residents”. Results: Permanent team members (other professionals) assessed and recommended dental care more frequently than residents. Permanent team members (other professionals) also reported that they felt they were able to inform older patients in respect to oral health‐related issues more frequently than did residents (68.7% vs. 31.3%, respectively). Conclusion: Oral health‐related knowledge and beliefs were frequent among non‐dentists primary health care workers, suggesting that primary health care which integrates oral health represents an attainable goal. 相似文献
27.
Paim FC Da Silva AS Wolkmer P Costa MM Da Silva CB Paim CB Oliveira MS Silva LF Mello CF Monteiro SG Mazzanti CM Lopes ST 《Experimental parasitology》2011,(1):27-30
Nitric oxide (NO) is involved in many physiological processes, such as blood pressure control, neurotransmission, inhibition of platelet and neutrophil adherence, and the ability to kill tumor cells and parasites. The indirect determination of NO can be made by detection of 3-nitrotyrosine (3-NT) residues. The aim of this study was to measure the concentration of 3-NT in the brain of rats experimentally infected with Trypanosoma evansi. Twenty-four were inoculated intraperitoneally with cryopreserved blood containing 1 × 106 trypomastigotes per animal. Twenty-four animals were used as negative controls and received 0.2 mL of saline by the same route. The experimental groups (group C and T) were established according to the time after infection and the degree of parasitemia as follows: four control subgroups (C3, C5, C10 and C20) with six non-inoculated animals each and four test subgroups (T3, T5, T10 and T20) with six animals infected with T. evansi in each group. The animals were anesthetized with isoflurane and subsequently euthanized at the days 3 (C3, T3), 5 (C5, T5), 10 (C10, T10) and 20 (C20, T20) post-infection (PI). The brain was removed and dissected into cerebellum, cerebral cortex, striatum and hippocampus. Concentration of 3-NT in the brain was determined by Slot blot technique. At the day 3 PI no changes were observed in the concentration of 3-NT among the groups. There was a significant reduction (p < 0.05) of 3-NT concentration in the striatum and cerebellum at the days 5 and 10 PI, respectively. At the day 20 PI a significant increase (p < 0.05) of 3-NT was observed in the cerebellum, cerebral cortex and hippocampus from the infected animals. Therefore, T. evansi infection caused changes in the concentrations of 3-NT in the central nervous system (CNS), which may be related to clinical signs and infection management. 相似文献
28.
Alcoholism is a significant public health problem. A picture of the genetic architecture underlying alcohol-related phenotypes
is emerging from genome-wide association studies and work on genetically tractable model organisms. 相似文献
29.
Forbes SH; Hogg JT; Buchanan FC; Crawford AM; Allendorf FW 《Molecular biology and evolution》1995,12(6):1106-1113
We compared genotypes at eight (AC)n microsatellite loci in domestic sheep
(Ovis aries) and wild Rocky Mountain bighorn sheep (O. canadensis). The
domestic sheep had greater genetic variation, higher allele-size variances,
and larger allele sizes than the wild sheep. Accumulating evidence from
higher taxonomic comparisons shows that these parameters are biased if
microsatellite loci are selected in one taxon and used in another. Our
results demonstrate similar biases between congeneric species. We compared
standard measures of genetic variation, differentiation, and distance
within and between species (H, D, FST) to newer measures based on
allele-size variance (SW, SB, RST). The size-based distances better
detected species-level divergence, but standard measures better
distinguished allopatric populations. Empirical calibration of these
measures at the subspecies level is needed to establish their useful
ranges.
相似文献
30.
Diffusion of carbon dioxide through lipid bilayer membranes. Effects of carbonic anhydrase, bicarbonate, and unstirred layers 下载免费PDF全文
Diffusion of (14)C-labeled CO(2) was measured through lipid bilayer membranes composed of egg lecithin and cholesterol (1:1 mol ratio) dissolved in n-decane. The results indicate that CO(2), but not HCO(3-), crosses the membrane and that different steps in the transport process are rate limiting under different conditions. In one series of experiments we studied one-way fluxes between identical solutions at constant pCO(2) but differing [HCO(3-)] and pH. In the absence of carbonic anhydrase (CA) the diffusion of CO(2) through the aqueous unstirred layers is rate limiting because the uncatalyzed hydration-dehydration of CO(2) is too slow to permit the high [HCO(3-)] to facilitate tracer diffusion through the unstirred layers. Addition of CA (ca. 1 mg/ml) to both bathing solutions causes a 10-100-fold stimulation of the CO(2) flux, which is proportional to [HCO(3-)] over the pH range 7-8. In the presence of CA the hydration- dehydration reaction is so fast that CO(2) transport across the entire system is rate limited by diffusion of HCO(3-) through unstirred layers. However, in the presence of CA when the ratio [HCO(3-) + CO(3=)]:[CO(2)] more than 1,000 (pH 9-10) the CO(2) flux reaches a maximum value. Under these conditions the diffusion of CO(2) through the membrane becomes rate limiting, which allows us to estimate a permeability coefficient of the membrane to CO(2) of 0.35 cm s(-1). In a second series of experiments we studied the effects of CA and buffer concentration on the net flux of CO(2). CA stimulates the net CO(2) flux in well buffered, but no in unbuffered, solutions. The buffer provides a proton source on the upstream side of the membrane and proton sink on the downstream side, thus allowing HCO(3-) to facilitate the net transport of CO(2) through the unstirred layers. 相似文献