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61.
62.
Lumefantrine (LF) is an aryl‐amino alcohol antimalarial drug used in artemisinin‐based combination therapies against malaria worldwide. In this study, we investigated the genotoxic effects of LF in human lymphocytes in vitro, and the potential noncovalent interaction of LF with DNA using a 3D DNA‐docking model. The number of DNA breaks and the frequency of nuclear buds (NBUDS) was significantly increased (P < 0.01 and P <0. 05, respectively) at LF concentrations of 60, 80, and 100 µg/mL (LF60, LF80, and LF100, respectively). Frequency (‰) of micronuclei (MN) formation also increased after LF treatments. However, this was only significant for LF100 (P = 0.01) and LF80 (P = 0.001). LF did not affect the frequency of nucleoplasmic bridges (NPBs) (P = 0.12) or the nuclear division index (NDI) (P = 0.32). Computational analysis suggests that LF may interact noncovalently with DNA via the DNA minor groove surface with a predicted binding affinity energy of ?7.2 kcal/mol and showing a favorable shape complementary to this groove. Our results suggest that LF has clastogenic effects in human lymphocytes in vitro due to noncovalent interaction with the minor groove of DNA. Environ. Mol. Mutagen. 56:556–562, 2015. © Wiley Periodicals, Inc.  相似文献   
63.
OBJECTIVE: This study was carried out in order to evaluate the etiology of monosymptomatic childhood short stature (below the third percentile or with growth rate of less than 5 cm/year) with emphasis on causes due to intestinal malabsorption. METHODS: Each patient was submitted to endocrinological, biochemical and hematological investigation. Determination of serum anti-gliadin antibodies, fecal fat, chloride levels in sweat, jejunal biopsy and bone age was also obtained.RESULTS: A total of 51 children was studied, most of them belonging to the group of normal variants. Four children had abnormally high sweat chloride, compatible with the diagnosis of cystic fibrosis. These children were asymptomatic regarding respiratory and gastrointestinal tract. CONCLUSIONS: We conclude that cystic fibrosis, besides celiac disease, must be included in the differential diagnosis of short stature in childhood.  相似文献   
64.
We investigated the possibility that Chagas' patients develop an autoimmune response to human UsnRNPs (small nuclear ribonucleoprotein) or Sm epitopes. Using purified human UsnRNPs, we detected anti-human UsnRNPs antibodies in sera from patients suffering from Chagas' disease. The antibodies were also detected using peptide enzyme-linked immunosorbent assays containing the Sm-motif 1 domain. The latter technique showed that 61% (31/51) of the Chagas' patients' sera contained antibodies against Sm-motif 1. The detection of anti-UsnRNPs autoantibodies in Chagas' patients' sera strongly encourages further studies using animal models to determine how these autoantibodies appear. Received: 4 April 1998 / Accepted: 13 May 1998  相似文献   
65.
Topical application of natural antioxidants has proven to be effective in protecting the skin against ultraviolet-mediated oxidative damage and provides a straightforward way to strengthen the endogenous protection system. However, natural products can provoke skin adverse effects, such as allergic and irritant contact dermatitis. Skin irritation potential of Castanea sativa leaf ethanol:water (7:3) extract was investigated by performing an in vivo patch test in 20 volunteers. Before performing the irritation test, the selection of the solvent and extraction method was guided by the 1,1-diphenyl-2-picryl hydrazyl (DPPH) free radical scavenging test and polyphenols extraction (measured by the Folin Ciocalteu assay). Iron-chelating activity and the phenolic composition (high performance liquid chromatography/diode array detection) were evaluated for the extract obtained under optimized conditions. The extraction method adopted consisted in 5 short extractions (10 min.) with ethanol:water (7:3), performed at 40 degrees. The IC(50) found for the iron chelation and DPPH scavenging assays were 132.94 +/- 9.72 and 12.58 +/- 0.54 microg/ml (mean +/- S.E.M.), respectively. The total phenolic content was found to be 283.8 +/- 8.74 mg GAE/g extract (mean +/- S.E.M.). Five phenolic compounds were identified in the extract, namely, chlorogenic acid, ellagic acid, rutin, isoquercitrin and hyperoside. The patch test carried out showed that, with respect to irritant effects, this extract can be regarded as safe for topical application.  相似文献   
66.
Mycobacterium leprae infection gives rise to the immunologically and histopathologically classified spectrum of leprosy. At present, several tools for the stratification of patients are based on acquired immunity markers. However, the role of innate immunity, particularly the complement system, is largely unexplored. The present retrospective study was undertaken to explore whether the systemic levels of complement activation components and regulators can stratify leprosy patients, particularly in reference to the reactional state of the disease. Serum samples from two cohorts were analysed. The cohort from Bangladesh included multi‐bacillary (MB) patients with (n = 12) or without (n = 46) reaction (R) at intake and endemic controls (n = 20). The cohort from Ethiopia included pauci‐bacillary (PB) (n = 7) and MB (n = 23) patients without reaction and MB (n = 15) patients with reaction. The results showed that the activation products terminal complement complex (TCC) (P ≤ 0·01), C4d (≤ 0·05) and iC3b (P ≤ 0·05) were specifically elevated in Bangladeshi patients with reaction at intake compared to endemic controls. In addition, levels of the regulator clusterin (P ≤ 0·001 without R; P < 0·05 with R) were also elevated in MB patients, irrespective of a reaction. Similar analysis of the Ethiopian cohort confirmed that, irrespective of a reaction, serum TCC levels were increased significantly in patients with reactions compared to patients without reactions (P ≤ 0·05). Our findings suggests that serum TCC levels may prove to be a valuable tool in diagnosing patients at risk of developing reactions.  相似文献   
67.
A set of 54 studied flavonoid inhibitors of aldose reductase (ALR2) enzyme has been utilized for pharmacophore modeling and 3D-QSAR analysis using “PHASE” program of Schrödinger software. The generated pharmacophore model (AADRR.1109) was challenged to screen “PHASE” database to identify new ALR2 inhibitors. The retrieved hits were employed for docking analysis and pharmacokinetic parameter calculation to obtain orally active molecules. To predict the activity of final retrieved hits, 3D-QSAR model was developed, and the best model was selected on the basis of various statistical parameters (R train 2 0.719; Q test 2 0.647 and SD 0.663). Totally five screened molecules which showed better enhanced predicted activity were synthesized and evaluated for in vitro ALR2 inhibitory activity. All tested molecules showed ALR2 inhibitory activity (IC50) below 40 µM. Additionally, the free radical scavenging potential of synthesized molecules was also determined which played a useful role to control the progression of diabetic complications. All molecules showed good antioxidant potential, thus the designed molecules, in future, could be explored to ameliorate the development of diabetic complications.  相似文献   
68.

Introduction

The purpose of this study was to evaluate the torsional behavior of rotary ProTaper Universal instruments after multiple clinical uses with and without lateral pressure motion.

Methods

Thirty sets of ProTaper Universal instruments were divided into 3 groups (n = 10): control group (CG) involving new instruments tested in torsion on the basis of ISO 3630-1, lateral pressure (LP) group involving instruments that were clinically used on 5 molars by using the shaping instruments S1 and S2 with lateral pressure motion, and no lateral pressure (NLP) group involving instruments that were clinically used on 5 molars without lateral pressure motion. The instruments in the LP and NLP groups were subsequently tested in torsion. Data were analyzed by using analysis of variance (α = 0.05).

Results

Multiple clinical uses caused a reduction in the maximum torque in the analyzed instruments. When the effect of using lateral pressure motion with the shaping instruments was assessed, a tendency of reduction in the maximum torque for the S1 and S2 instruments and of increase for the F1 and F2 instruments was observed in the group with lateral pressure motion.

Conclusions

The use of lateral pressure motion with the shaping instruments S1 and S2 tended to produce smaller decreases in the torsional resistance of the finishing instruments F1 and F2.  相似文献   
69.
Complement activation products are elevated in cerebrospinal fluid, spinal cord and motor cortex of patients with amyotrophic lateral sclerosis (ALS) but are untested in models. We determined complement expression and activation in the SOD1 G93A mouse model of familial ALS (fALS). At 126days, C3 mRNA was upregulated in spinal cord and C3 protein accumulated in astrocytes and motor neurons. C3 activation products C3b/iC3b were localized exclusively on motor neurons. At the neuromuscular junction, deposits of C3b/iC3b and C1q were detected at day 47, before the appearance of clinical symptoms, and remained detectable at symptomatic stage (126days). Our findings implicate complement in the denervation of the muscle endplate by day 47 and destruction of the neuromuscular junction and spinal neuron loss by day 126 in the SOD1 G93A mouse model of fALS.  相似文献   
70.
Trailing the whole group of trends and changes in the scenario of relations between the public and the private, this article analyses the effects of the rise in the rates of return of health plan operators and health insurance companies in 2007. Special attention is given to the segmentation of the system, the complaints about the naturalization of inequitable access to health services and to the depreciation of the original concepts of the Unified Health System. The study also gathers information regarding the production of knowledge about supplementary care with the intent to systemize the bases and methodological approaches adopted by a selected sub-group of scientific papers. Finally, the article develops conjectures and hypotheses with regard to possible associations between growth and stability of the health plan and insurance market and as refers to the nature of scientific production about this issue, taking into consideration the contradictions between the political and economical circuit in which the health plan and insurance companies are operating and the universality of the Brazilian Health System.  相似文献   
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