Search

Objective: To analyze the hypothesis that a reduction in sensitivity of the nasal visual hemifield would lead to an increase in the nasotemporal asymmetry of the visual field in patients under two years of age with early-onset convergent strabismus in comparison with normal patients., Methods: Both eyes of 66 patients - 33 esotropes and 33 normals - were studied. Patients' age ranged from 7 to 30 years. The examination consisted of a static perimetry using the Humphrey field analyzer 700 Series' Sita Standard program., Results: An accentuation of the nasotemporal asymmetry was seen in the 33 esotropes and was related to an evident decrease of sensitivity in the most peripheral of the points studied along the horizontal meridian of the visual field. The quantitative sum of values of sensitivity of these points showed an average reduction of -15.71% in relation to the normal patients., Conclusion: There was a clear accentuation of the nasotemporal asymmetry of sensitivity in esotropes when compared to normal patients. There was no difference in sensitivity between the two eyes in either normals or esotropes.

Three naphthoimidazoles presenting aromatic groups attached to the imidazole ring were the most active against trypomastigotes of Trypanosoma cruzi between 45 derivatives from beta-lapachone. N1 is active against the three forms of the parasite. In this work, we investigated N2 and N3 and analyzed the effect of the three derivatives on metacyclogenesis, endocytosis, and cell cycle. In epimastigotes, N2 and N3 blocked the cell cycle, inhibited succinate cytochrome c reductase, metacyclogenesis, and induced damage to mitochondrion, Golgi, and reservosomes. In treated trypomastigotes, there were alterations in the mitochondrion, nucleus and kinetoplast, and DNA fragmentation. Preincubation with cysteine protease inhibitors reversed the effect of N1, N2, and N3. Such reversion and ultrastructural alterations suggest the involvement of autophagy in parasite death. Ultrastructural, flow cytometry, and biochemical studies suggest that naphthoimidazoles interferes with the energetic metabolism and induces DNA fragmentation.

We aimed to characterize folate-related changes in mitochondrial (mt) DNA of various tissues of young rats. Weaning Wistar rats were fed folate-deficient (FD) or folate-replete (control) diet for 2 or 4 wk. The mtDNA 4834-bp large deletion (mtDNA(4834) deletion) and mtDNA content were analyzed by quantitative real-time PCR. Compared with pooled 2-wk and 4-wk control groups, 4-wk folate deprivation significantly increased the frequency of the mtDNA(4834) deletion in pancreas, heart, brain, liver, and kidney and reduced mtDNA contents in brain, heart, and liver (P < 0.05). Decreased mt folate levels were correlated with increased mtDNA(4834) deletion frequency in tissues from FD rats after 2 wk (r = -0.380, P = 0.001) and 4 wk FD (r = -0.275, P = 0.033) and with reduced mtDNA content after 4 wk (r = 0.513, P = 0.005). In liver of 4-wk FD rats, the accumulated mtDNA large deletions and decline in mtDNA accompanied increased expressions of messenger RNAs (mRNA) of factors that regulate mtDNA proliferation and transcription, including nuclear respiratory factor 1, mt transcriptional factor A, mt single-strand DNA-binding protein, and mt polymerase r. In parallel, expression of mRNA for nuclear-encoded cytochrome c oxidase subunits (CcOX) IV, V, cytochrome c, and mtDNA-encoded CcOX III increased significantly. This enhanced mt biogenesis in 4-wk FD liver coincided with an elevated ratio of 8 hydroxydeoxyguanosine (8-OHdG):deoxyguanosine (dG) (2.67 +/- 1.41) relative to the controls (0.99 +/- 0.36; P = 0.0002). The 8-OHdG:dG levels in FD liver were correlated with liver mt folate (r = -0.819, P < 0.001), mtDNA deletions (r = 0.580, P = 0.001), and mtDNA contents (r = -0.395, P = 0.045). Thus, folate deprivation induced aberrant changes of mtDNA(4834) deletion and mtDNA content in a manner that was dependent on mt folate and oxidative DNA injuries. The folate-related mt biogenesis provides a molecular mechanism to compensate mtDNA impairment in FD tissues.

This study describes the design, synthesis and trypanocidal evaluation of new azaheterocyclic derivatives (4-8). These compounds were designed as megazol (1) analogs based on bioisosterism tools and were synthesized to investigate the possible pharmacophoric contribution of the 1,2,4-triazole nucleus, the position of the heterocyclic nucleus and presence of the nitro group, to the activity against the bloodstream trypomastigote forms of Trypanosoma cruzi. The most potent compound was 6, a nitro derivative obtained by substitution of a thiadiazole by a triazole ring and by moving the nitro group from C-5 position, as in 1, to the C-4 position. Finally, we have used semi-empirical theoretical calculations to discuss the correlation of some stereo electronic properties with biological activity in an attempt to understand the possible mechanism of action of the designed series of compounds.

We investigate a set of directed sandpile models on the Apollonian network, which are inspired by the work of Dhar and Ramaswamy [Phys. Rev. Lett. 63, 1659 (1989)] on Euclidian lattices. They are characterized by a single parameter q , which restricts the number of neighbors receiving grains from a toppling node. Due to the geometry of the network, two- and three-point correlation functions are amenable to exact treatment, leading to analytical results for avalanche distributions in the limit of an infinite system for q=1,2 . The exact recurrence expressions for the correlation functions are numerically iterated to obtain results for finite-size systems when larger values of q are considered. Finally, a detailed description of the local flux properties is provided by a multifractal scaling analysis.

Objective: To investigate serum levels of folate, B12, and total homocysteine (tHcy) in elderly post-stroke patients, and the possible correlations with radiological markers of neuropathology., Design: Cross-sectional study., Setting: Department of Neurology, Cardinal Tien Hospital., Subjects: Eighty-nine elderly post-stroke patients were enrolled for dietary assessment and blood tests. Neuroradiological assessment was done in 62 of these patients., Main Outcome Measures: Dietary folate and vitamin B12 intakes were evaluated by a 24-h recall system using a semi-quantitative questionnaire. Circulating levels of folate, B12, and tHcy were measured. Magnetic resonance imaging (MRI) or computed tomography (CT) was used for evaluation of brain lesions including infarction and atrophy., Results: Mean folate and B12 intakes of these post-stroke patients were 69% and 261% of the recommended dietary allowances (RDA), respectively. Inadequate folate levels, defined as serum folate < 6 ng/mL, was noted in 68% of these patients. Hyperhomocysteinemia levels (tHcy >or=15 micromol/L) were observed in 48%. According to tertiles of serum tHcy and folate levels, the rate of brain atrophy, but not brain infarctions, are significantly associated with elevated tHcy (P = 0.0126) and decreased folate levels (P = 0.0273). After adjustments for age, sex, disease status, brain infarctions and carotid stenosis, the odds ratio of brain atrophy was 9.8 (95% CI: 1.7-56.4, P = 0.0101) in the hyperhomocysteinemia group and 9.6 (95% CI: 1.1-81.3, P = 0.0377) in the low folate group (serum folate < 3.0 ng/mL) compared with the group with normal tHcy and folate levels. No significant association was noted between vitamin B12 levels and brain lesions., Conclusions: Our data shows that folate deficiency and hyperhomocysteinemia are prevalent in elderly post-stroke patients. These two conditions are strongly and independently associated with the development of brain atrophy.

Little is known about the biological effect of folate in the protection against mitochondrial (mt) oxidative decay. The objective of the present study was to examine the consequence of folate deprivation on mt oxidative degeneration, and the mechanistic link underlying the relationship. Male Wistar rats were fed with an amino acid-defined diet containing either 8 (control) or 0 (folate-deficient, FD) mg folic acid/kg diet. After a 4-week FD feeding period, significant elevation in oxidative stress was observed inside the liver mitochondria with a 77% decrease in mt folate level (P<0.001), a 28 % reduction in glutathione peroxidase activity (P= 0.0333), a 1.2-fold increase of mt protein carbonyls (P=0.0278) and an accumulated 4834 bp large-scale deletion in mtDNA. The elicited oxidative injuries in FD liver mitochondria were associated with 30 % reduction of cytochrome c oxidase (CcOX) activity (P=0.0264). The defective CcOX activity in FD hepatocytes coincided with mt membrane potential dissipation and intracellular superoxide elevation. Exposure of FD hepatocytes to pro-oxidant challenge (32 microM-copper sulphate for 48 h) led to a further loss in CcOX activity and mt membrane potential with a simultaneous increase in superoxide production. Preincubation of pro-oxidant-treated FD hepatocytes with supplemental folic acid (10-1000 microM) reversed the mt oxidative defects described earlier and diminished superoxide overproduction. Increased supplemented levels of folic acid strongly correlated with decreased lipid peroxidation (gamma - 0.824, P=0.0001) and protein oxidative injuries (gamma -0.865, P=0.0001) in pro-oxidant-challenged FD liver mitochondria. Taken together, the results demonstrated that folate deprivation induces oxidative stress in liver mitochondria, which is associated with CcOX dysfunction, membrane depolarization and superoxide overproduction. The antioxidant activity of supplemental folic acid may partially, if not fully, contribute to the amelioration of pro-oxidant-elicited mt oxidative decay.

In the present work, we have investigated the effect of essential oils obtained from Origanum vulgare L. (oregano) and Thymus vulgaris L. (thyme) on growth and ultrastructure of diverse evolutive forms of Trypanosoma cruzi. Culture epimastigotes and bloodstream trypomastigotes were incubated for 24 h with different concentrations of oregano or thyme essential oils and with thymol (the main constituent of thyme), and the inhibitory concentration (IC)(50) was determined by cell counting. Crude extract of oregano essential oil inhibited epimastigote growth (IC(50)/24 h = 175 microg/ml) and also induced trypomastigote lysis (IC(50)/24 h = 115 microg/ml). Thyme essential oil presented IC(50)/24 h values of 77 microg/ml for epimastigotes and 38 mug/ml for trypomastigotes, while treatment with thymol resulted in an IC(50)/24 h of 62 microg/ml for epimastigotes and 53 microg/ml for trypomastigotes. Scanning electron microscopy of treated cells showed few morphological alterations at the plasma membrane. Observation by transmission electron microscopy showed cytoplasmic swelling with occasional morphological alterations in plasma and flagellar membrane. Our data indicate that oregano and thyme essential oils are effective against T. cruzi, with higher activity of thyme, and that thymol may be the main component responsible for the trypanocidal activity.

We have developed an empirical residue-based potential (E(z) potential) for protein insertion in lipid membranes. Propensities for occurrence as a function of depth in the bilayer were calculated for the individual amino acid types from their distribution in known structures of helical membrane proteins. The propensities were then fit to continuous curves and converted to a potential using a reverse-Boltzman relationship. The E(z) potential demonstrated a good correlation with experimental data such as amino acid transfer free energy scales (water to membrane center and water to interface), and it incorporates transmembrane helices of varying composition in the membrane with trends similar to those obtained with translocon-mediated insertion experiments. The potential has a variety of applications in the analysis of natural membrane proteins as well as in the design of new ones. It can help in calculating the propensity of single helices to insert in the bilayer and estimate their tilt angle with respect to the bilayer normal. It can be utilized to discriminate amphiphilic helices that assume a parallel orientation at the membrane interface, such as those of membrane-active peptides. In membrane protein design applications, the potential allows an environment-dependent selection of amino acid identities.

Mast cells are involved in many disorders where the triggering mechanism that leads to degranulation and/or cytokine secretion has not been defined. Several chronic inflammatory diseases are associated with increased mast cell numbers and upregulation of the TNF receptor family member CD30, but the role of elevated CD30 expression is poorly understood. Here we report what we believe to be a novel way to activate mast cells with CD30 that leads to degranulation-independent secretion of chemokines. CD30 induced a de novo synthesis and secretion of the chemokines IL-8, macrophage inflammatory protein-1alpha (MIP-1alpha), and MIP-1beta, a process involving the MAPK/ERK pathway. Mast cells were found to be the predominant CD30 ligand-positive (CD30L-positive) cell in the chronic inflammatory skin diseases psoriasis and atopic dermatitis, and both CD30 and CD30L expression were upregulated in lesional skin in these conditions. Furthermore, the number of IL-8-positive mast cells was elevated both in psoriatic and atopic dermatitis lesional skin as well as in ex vivo CD30-treated healthy skin organ cultures. In summary, characterization of CD30 activation of mast cells has uncovered an IgE-independent pathway that is of importance in understanding the entirety of the role of mast cells in diseases associated with mast cells and CD30 expression. These diseases include Hodgkin lymphoma, atopic dermatitis, and psoriasis.

The fold of a helical membrane protein is largely determined by interactions between membrane-imbedded helices. To elucidate recurring helix-helix interaction motifs, we dissected the crystallographic structures of membrane proteins into a library of interacting helical pairs. The pairs were clustered according to their three-dimensional similarity (rmsd

Both increased copper and reduced folate levels are commonly found in patients with liver diseases. To better understand the mechanisms by which folate deprivation interacts with copper to contribute to hepatocellular toxicity, rat primary hepatocytes were isolated, cultured in folate-deprived (FD) RPMI medium, and assayed for cytotoxicity after copper sulfate (CuSO4) exposure. MTT measurement and trypan blue assay showed that elevated CuSO4 levels aggravated cell death of folate-deprived but not folate-sufficient hepatocytes. CuSO4 treatment increased the levels of intracellular reactive oxygen species (ROS) by 3 times in FD hepatocytes and tripled the proportion of FD hepatocytes with hypodiploid DNA contents. Measurement of membrane phosphatidylserine exposure indicated that the CuSO4-mediated toxicity in FD hepatocytes was not mediated by the apoptotic pathway. Real-time polymerase chain reaction (PCR) analysis revealed that CuSO4 treatment did not increase the occurrence of a 4834-bp mtDNA (mtDNA4834) deletion in FD hepatocytes. Preincubation of FD hepatocytes with various concentrations of folate prior to CuSO4 treatment did not modulate the mtDNA4834 deletion. Taken together, the data suggest that elevated copper levels potentiate cell death of folate-deprived hepatocytes, which is primarily associated with increased ROS generation and chromosomal DNA loss. The cytotoxicity exerted by folate depletion and elevated copper levels, however, is not due to apoptosis or accumulated mtDNA4834 deletions in primary hepatocytes.

The synthesis and differential antiproliferative activity of monastrol (1a), oxo-monastrol (1b) and eight oxygenated derivatives 3a,b-6a,b on seven human cancer cell lines are described. For all evaluated cell lines, monastrol (1a) was shown to be more active than its oxo-analogue, except for HT-29 cell line, suggesting the importance of the sulfur atom for the antiproliferative activity. Monastrol (1a) and the thio-derivatives 3a, 4a and 6a displayed relevant antiproliferative properties with 3,4-methylenedioxy derivative 6a being approximately more than 30 times more potent than monastrol (1a) against colon cancer (HT-29) cell line.

Myopia studies are notoriously difficult to carry out. Past studies on intervention in myopia progression have given conflicting results. Beside inaccurate and inadequate measurements, the most important cause for this is the very variable nature of myopia, which makes it difficult to achieve baseline comparability between the control and the study group. Although there were inclusion criteria in these studies, for age, sex, race, degree of myopia and stigmatism, the most important variate-- the rate of myopia progression-- was not included. Randomisation can achieve baseline comparability of the myopia progression rate, provided the sample sizes are large enough. Unfortunately, past studies have been limited to 100 to 200 children only. Studies on twins are more reliable than random groups because myopia progression rates are more likely to be the same in a pair of twins. Studies on the same subject, comparing the right eye and the left eye would be even better, but this method is practicable for some studies only (e.g., we cannot have a spectacle lens for one eye and a contact lens on the fellow eye). There is another method of doing an interventional study on myopia. Because myopia progression is linear in its early stage until the early teenage years, it is possible to observe what happens to the linear progression upon intervention. In this way, we avoid the problem of trying to compare "apples with apples" but use the "same apple" instead.

A concept of neighborhood in complex networks is addressed based on the criterion of the minimal number of steps to reach other vertices. This amounts to, starting from a given network R1, generating a family of networks Rl, l = 2, 3,... such that, the vertices that are l steps apart in the original R1, are only 1 step apart in Rl. The higher order networks are generated using Boolean operations among the adjacency matrices Ml that represent Rl. The families originated by the well known linear and the Erdös-Renyi networks are found to be invariant, in the sense that the spectra of Ml are the same, up to finite size effects. A further family originated from small world network is identified.

Objectives: Investigation of the mode of action of the naphthoimidazole N1, obtained from the reaction of beta-lapachone with benzaldehyde, which among 45 semi-synthetic derivatives of naphthoquinones isolated from Tabebuia sp. was one of the most active compounds against Trypanosoma cruzi trypomastigotes., Methods: Quantification of the effect of N1 against the proliferative forms of T. cruzi, and investigation of potential targets in the parasite using electron microscopy and flow cytometry techniques., Results: N1 presented the following order of activity: amastigotes > trypomastigotes > epimastigotes. The effect on intracellular forms was approximately 25 times higher than on macrophages and heart muscle cells. N1-treated parasites presented an abnormal chromatin condensation and mitochondrial damage. In epimastigotes, alterations of reservosomes were observed, and in trypomastigotes, a decrease in the electron density of acidocalcisomes was observed. In epimastigotes, the naphthoimidazole inhibited the activity of succinate cytochrome c reductase. Labelling with rhodamine 123 or Acridine Orange was decreased in both forms treated with N1., Conclusions: The results suggest that epimastigotes, reservosomes, mitochondrion, and nucleus contain N1 targets. In trypomastigotes, in which reservosomes are absent, the organelles affected by the compound were also the mitochondrion and nucleus, as well as acidocalcisomes, in which the decrease in electron density could be due to the use of polyphosphate as an alternative energy supply.

Complaining constitutes one facet of all reactions to noise annoyance and is one way to cope with annoyance due to aircraft noise. In order to value and to establish the usefulness of complaint data as an index of annoyance, four questions need to be answered: Which factors lead annoyed residents to complain about aircraft noise or related issues? Which factors keep annoyed residents from complaining? Are the existing ways to handle annoyance adequate and efficient (e.g. keeping track of complaints, reaction to complains, kinds of complaint services)? Which are new ways to handle annoyance adequately and efficiently? In this paper a first attempt to answer these questions is made. Obviously, complaint data do not reflect noise annoyance in the surroundings of airports to the full extent as there are residents living in affected areas who do not complain, as well as residents living in areas with relatively low noise levels who complain. Also there is a large group of people who declare to be highly annoyed and yet, they do not lodge any complaint. Possible intervening factors are gathered that determine if an annoyed resident takes action and complains. It was found that noise levels per se are not the crucial factor for residents' decisions to complain or not to complain. Personal as well as feasibility factors play a vital role. Yet, the ongoing controversy on the relation between annoyance and complaint behaviour seems not resolved yet. However, complaint behaviour seems to be influenced by various aspects and complaint data consequently cannot be accepted as an accurate measure of public annoyance. Further research is required to address the preferred method of handling reaction to noise and the extent to which complaint itself helps with coping, for different groups of residents.

Thermodynamic and magnetic properties of Ising models defined on the triangular Apollonian network are investigated. This and other similar networks are inspired by the problem of covering a Euclidian domain with circles of maximal radii. Maps for the thermodynamic functions in two subsequent generations of the construction of the network are obtained by formulating the problem in terms of transfer matrices. Numerical iteration of this set of maps leads to very precise values for the thermodynamic properties of the model. Different choices for the coupling constants between only nearest neighbors along the lattice are taken into account. For both ferromagnetic and antiferromagnetic constants, long-range magnetic ordering is obtained. With exception of a size-dependent effective critical behavior of the correlation length, no evidence of asymptotic criticality was detected.

A numerically efficient transfer matrix (TM) approach is introduced to investigate the long-range Ising spin chain. Results obtained within this procedure are primarily used to verify the Tsallis scaling hypothesis for long-range systems with an alpha power-law decay of the interaction constants, both in the extensive (alpha>1) and nonextensive (alpha<1) regimes. Results for finite-size systems, taking into account all interactions between spins up to 24 sites apart, show that the conjecture is satisfied with a very good precision (less than 0.004%) for all temperature intervals. This TM procedure is further used to investigate several other thermodynamic and critical properties of this system, and it may also be extended to similar one-dimensional long-range systems.

We introduce a new family of networks, the Apollonian networks, that are simultaneously scale-free, small-world, Euclidean, space filling, and with matching graphs. These networks describe force chains in polydisperse granular packings and could also be applied to the geometry of fully fragmented porous media, hierarchical road systems, and area-covering electrical supply networks. Some of the properties of these networks, namely, the connectivity exponent, the clustering coefficient, and the shortest path are calculated and found to be particularly rich. The percolation, the electrical conduction, and the Ising models on such networks are also studied and found to be quite peculiar. Consequences for applications are also discussed.

To investigate the relationship between folate status and dietary folate intake in the Taiwanese elderly, we analyzed plasma folate levels and dietary folate intake in 725 males and 705 females aged 65-90 years, sampled from the Elderly Nutrition and Health Survey in Taiwan (1999-2000) (Elderly NAHSIT). Results showed that the mean plasma folate levels were 22.9+/-1.4 nmol/L (10.1+/-0.6 ng/ml) for males and 29.5+/-1.6 nmol/L (13.0+/-0.7 ng/ml) for females. The average plasma folate concentrations of males from all age groups were significantly lower than those of females (P<0.0001). None of the study subjects had a plasma folate below 7 nmol/L (3 ng/ml). However, 18.6% of males and 12.1% of females had marginal folate deficiency, with plasma folate between 7-14 nmol/L (3-6 ng/ml). This suggests that elderly males have a poorer folate status than elderly females in the Taiwanese population. The percentage of marginal folate deficiency tended to increase with age among females (P trend=0.0137). The average estimated folate intakes were 379+/-18 microg/d in males and 351+/-27 microg/d in females. However, 45.5% of males and 48.8% of females had a dietary folate intake below 2/3 of the RDA of 400 microg/d. Our results indicated that dietary folate intake is positively correlated with plasma folate levels (r=0.10, P<0.05). In addition, dietary folate intake increased with increased intakes of vegetables, mushrooms and fruit. A lower intake of fruit appeared to be responsible for the higher prevalence of marginal folate deficiency among females over the age of 80 years.

Folate has recently been proposed as a new antioxidant. Folate supplementation may have a protective effect in counteracting oxidant-induced apoptotic damage. The present studies were undertaken to examine whether there is a direct link between folate levels, antioxidant capability and reduced apoptotic damage. Using an in vitro cellular model of 7-ketocholesterol (KC)-induced apoptosis, U937 cells were pre-cultured with a folate-deficient medium supplemented with various levels of folate (2-1500 micromol/l) before treatment with 7-KC. Apoptotic markers, mitochondria-associated death signals and levels of reactive oxygen species were assayed. After treatment with 7-KC for 30 h, low and high levels of folate supplementation significantly (P<0.05) reduced nuclear DNA loss. Only high levels of folate supplementation (>1000 micromol/l) were effective in counteracting 7-KC-promoted apoptotic membrane phosphatidylserine exposure and DNA laddering. The attenuation of 7-KC-induced apoptotic damage by high-dose folate supplementation coincided with a partial normalization of mitochondria membrane potential dissipation, a suppression of cytochrome c release and an inhibition of procaspase 3 activation. The prevention of mitochondrial dysfunctions and apoptotic processes was associated with antioxidant actions of high-dose folate by a marked scavenging of intracellular superoxide. Collectively, our present results demonstrate that in vitro folate supplementation exerts differentially protective effects against 7-KC-induced damage. High-dose supplementation alleviates oxidative stress, mitochondria-associated death signalling and apoptosis induced by 7-KC. However, the in vivo relevance is not clear and requires further study.

Background: The red blood cells of the McLeod phenotype have weak expression of Kell System antigens due to no expression of XK protein., Study Design and Methods: One blood donor reacted as K:-4 [Kp(b-)] during a screening assay. Subsequent serologic studies demonstrated weak expression of K:4 and all other high-incidence Kell system antigens tested; however, no expression of Kx antigen was observed., Results: One apparently healthy blood donor demonstrated low expression of K:2, K:4, K:5, K:7, K:14, K:22, and no Kx antigen in his red blood cells. His brother and mother showed the same weak expression, and his father showed normal expression of antigens tested. Flow cytometry studies confirmed the mother's status as a McLeod carrier female. Genotyping determined the presence of KEL2 and KEL4 alleles in mother and siblings. Southern blot with an exon-1 probe showed fragments shorter than predicted for the siblings and the mother, suggesting a deletion. Polymerase chain reaction with primers spanning exon 1 and flanking regions displayed a similar pattern. Deoxyribonucleic acid sequence allowed the precise characterization of a deletion of 392 bp, beginning at the 5' of the coding region up to nucleotide 201 of exon 1, which putatively abrogates the production of XK protein., Conclusion: Two brothers with McLeod phenotype in a Brazilian blood-donor population were identified. The molecular basis for this phenotype is a 392-bp deletion spanning from 5' of the coding region to exon 1 of the XK gene, never described before.

We synthesized new naphthoimidazoles from beta-lapachone with an aromatic moiety linked to the imidazole ring, using phenylic and heterocyclic aldehydes. The most active compound against Trypanosoma cruzi had a p-methyl group linked to the phenyl ring, presenting an EC(50) value of 15.5 +/- 2.9 microM. No reliable correlation could be established with the biological activity and the structure of in the phenylic series. For the heterocyclic series, activity was associated with a three bond-distance from nitrogen to the imidazole ring, in accordance with our previous work.

The aim of this study was to investigate the effects of genistein supplementation in a vitamin E-deficient diet on the genistein concentrations and the lipid oxidation of serum, liver and low-density lipoprotein (LDL) of hamsters. Thirty-six male hamsters were randomly divided into three groups and fed a vitamin E-deficient semisynthetic diet (AIN-76) containing different levels of genistein, i.e., G0 (control group, genistein-free diet), G50 (50 mg genistein/kg diet) and G200 (200 mg genistein/kg diet) for 5 weeks. The concentrations of genistein in serum and liver significantly increased with the increase of genistein supplementation. The vitamin E contents in LDL were higher in hamsters fed G50 or G200 diets than in hamsters fed genistein-free diet. Genistein supplementation to hamsters significantly reduced the propagation rate during conjugated diene formation of LDL oxidation, and the lag time of LDL oxidation in hamsters fed G200 diets was significantly lower than that of G0 diets. In addition, genistein supplementation significantly raised serum total antioxidant capacity and decreased the thiobarbituric acid-reactive substances (TBARS) of LDL and liver in hamsters. However, no significant differences in TBARS were found in serum, irrespective of genistein addition. On the other hand, the relative contents of polyunsaturated fatty acids in LDL were decreased after genistein supplementation. There was a negative correlation between lag time and P/S ratio, and a positive correlation between lag time and vitamin E contents. These data demonstrate that genistein supplementation markedly increased its concentrations in body tissues and reduced oxidative stress of lipid oxidation of serum, liver and LDL.

Peri-urban visceral leishmaniasis (VL) caused by Leishmania chagasi is emerging in a new epidemiologic pattern in Brazilian cities. We studied peri-urban VL in endemic neighborhoods surrounding Natal, Brazil, identified through hospitalized individuals with VL. Clinical and environmental information obtained for 1106 members of 216 families living in endemic neighborhoods enabled us to identify 4 groups: VL: individuals with current or prior symptomatic visceral leishmaniasis (n = 135); DTH+: individuals with positive delayed-type hypersensitivity response with no history of VL (n = 390); Ab +: individuals with negative DTH response and seropositive (n = 21); DTH -: individuals with negative DTH and seronegative (n = 560). The mean +/-SD age of VL was 9.3+/-12.3 y. The gender distribution was nearly equal below age 5, but skewed toward males at higher ages. Acutely infected VL subjects had significantly lower hematocrits, neutrophils, and eosinophils than other categories. AB+ subjects also had lower eosinophil counts than others, a possible immune marker of early infection. VL was not associated with ownership of dogs or other animals, raising the question whether the reservoir differs in peri-urban settings. This new pattern of L. chagasi infection enables us to identify epidemiological and host factors underlying this emerging infectious disease.

This study describes an approach to obtaining 3-D scaffolds for tissue engineering that allows the incorporation and release of biologically active proteins to stimulate cell function. Laminin was adsorbed on the textured surfaces of binary 70S30C (70 mol % SiO(2), 30 mol % CaO) and ternary 58S (60 mol % SiO(2), 36 mol % CaO, 4 mol % P(2)O(5)) foams. The covalent bonds between the binding sites of the proteins and the ligands on the scaffolds' surfaces did not denaturate the proteins. In vitro studies show that the foams modified with chemical groups and coated with laminin were bioactive, as demonstrated by the formation of a crystalline hydroxy carbonate apatite (HCA) layer formed on the surfaces of the foams upon exposure to simulated body fluid (SBF). The release of proteins from the foams also was investigated. Sustained and controlled release from the scaffolds over a 30-day period was achieved. Laminin release from the bioactive foams followed the dissolution rate of the material network. These results suggest that bioactive foams have the potential to act as scaffolds for soft-tissue engineering with a controlled release of proteins that can induce tissue formation or regeneration., (Copyright 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 121-129, 2003)

A periurban outbreak of visceral leishmaniasis (VL) caused by the protozoan Leishmania chagasi is ongoing outside Natal, northeast Brazil. Manifestations range from asymptomatic infection to disseminated visceral disease. Literature reports suggest that both genetic and environmental factors influence the outcome of infection. Due to the association of the tumor necrosis factor (TNF) locus with other infectious diseases, we examined whether polymorphic alleles at this locus are associated with the outcome of L. chagasi infection. Neighborhoods with ongoing transmission were identified through patients admitted to local hospitals. Altogether, 1,024 individuals from 183 families were classified with the following disease phenotypes: (i) symptomatic VL, (ii) asymptomatic infection (positive delayed-type hypersensitivity [DTH+]), or (iii) no evidence of infection (DTH-). Genotypes were determined at a microsatellite marker (MSM) upstream of the TNFB gene encoding TNF-beta and at a restriction fragment length polymorphism (RFLP) at position -307 in the promoter of the TNFA gene encoding TNF-alpha. Analyses showed that the distribution of TNFA RFLP alleles (TNF1 and TNF2) and the TNF MSM alleles (TNFa1 to TNFa15) differed between individuals with VL and those with DTH+ phenotypes. TNF1 was transmitted more frequently than expected from heterozygous parents to DTH+ offspring (P = 0.0006), and haplotypes containing TNF2 were associated with symptomatic VL (P = 0.0265, transmission disequilibrium test). Resting serum TNF-alpha levels were higher in TNF1/2 heterozygotes than in TNF1/1 homozygotes (P < 0.05). These data led us to hypothesize that an individual's genotype at the TNF locus may be associated with whether he or she develops asymptomatic or symptomatic disease after L. chagasi infection. The results preliminarily suggest that this may be the case, and follow-up with larger populations is needed for verification.

The sensitivity and specificity of a Leishmania chagasi recombinant K39 (rK39)-based enzyme-linked immunosorbent assay (ELISA) for visceral leishmaniasis (VL) was assessed in Natal, Brazil. Anti-rK39 antibodies were detected in 93.3% of patients with parasitologically confirmed VL (n = 120) and in 33 others with clinically diagnosed disease. Anti-rK39 antibodies decreased significantly following treatment. The presence of antibodies was inversely correlated with development of a positive leishmanin skin test result. Anti-rK39 antibodies were detected in only 2.9% of asymptomatic subjects with a positive skin test result (n = 168). They were not detected in healthy controls (n = 30) or in persons with Chagas' disease (n = 13) or active tuberculosis (n = 31). Antibodies were found in only one of 13 patients with cutaneous leishmaniasis. In contrast, an ELISA using total L. chagasi promastigote antigen was sensitive, but not specific. The results indicate that the rK39-based ELISA is a sensitive and specific diagnostic test for symptomatic VL and can differentiate progressive from self-resolving infection.

The aim of this work was to use sol-gel processing to develop bioactive materials to serve as scaffolds for tissue engineering that will allow the incorporation and release of proteins to stimulate cell function and tissue growth. We obtained organofunctionalized silica with large content of amine and mercaptan groups (up to 25%). The developed method can allow the incorporation and delivery of proteins at a controlled rate. We also produced bioactive foams with binary SiO(2)-CaO and ternary SiO(2)-CaO-P(2)O(5) compositions. In order to enhance peptide-material surface properties, the bioactive foams were modified with amine and mercaptan groups. These materials exhibit a highly interconnected macroporous network and high surface area. These textural features together with the incorporation of organic functionally groups may enable them to be used as scaffolds for the engineering of soft tissue.

We showed previously that homocysteine thiolactone (HcyT) is a potent inducer of apoptosis in HL-60 cells. In the present study, the role of some radical scavengers (N-acetylcysteine, vitamin C, vitamin E and folate) on the reduction of HcyT-induced apoptosis was investigated. Preincubation of HcyT-treated HL-60 cells with vitamin C (Vit C; 100 micro mol/L) or vitamin E (Vit E; 100 micro mol/L) for 2 h significantly reduced the proportion of apoptotic cells with hypodiploid DNA contents or with membrane phosphatidylserine exposure, and attenuated the apoptotic DNA fragmentation. Preincubation of cells with N-acetylcysteine (NAC; 5 mmol/L) for 2 h significantly reduced HcyT-promoted apoptosis measured by membrane phosphatidylserine exposure only. The reduction of HcyT-induced apoptosis by NAC, Vit C or Vit E occurred simultaneously with a significant decrease in intracellular H(2)O(2) levels and reduced caspase-3 enzymatic activity. In contrast, folate had no H(2)O(2) scavenging capacity and did not suppress caspase-3 activity 6 h after HcyT treatment, although folate exhibited antioxidant behavior toward superoxide anions, hydroxyl radicals and peroxynitrite. Preincubation of cells with folate (10 micro mol/L) for 3 d did not affect the extent of HcyT-promoted apoptotic damage. Taken together, our findings suggest that antioxidant pretreatment with NAC, Vit C or Vit E exerts more beneficial effects than folate on reducing apoptotic cell damage induced by homocysteine thiolactone.

Study Objective: To examine the effects of chronic exposure to aircraft noise on children's school performance taking into account social class and school characteristics., Design: This is a cross sectional study using the National Standardised Scores (SATs) in mathematics, science, and English (11 000 scores from children aged 11 years). The analyses used multilevel modelling to determine the effects of chronic aircraft noise exposure on childrens' school performance adjusting for demographic, socioeconomic and school factors in 123 primary schools around Heathrow Airport. Schools were assigned aircraft noise exposure level from the 1994 Civil Aviation Authority aircraft noise contour maps., Setting: Primary schools., Participants: The sample were approximately 11 000 children in year 6 (approximately 11 years old) from 123 schools in the three boroughs surrounding Heathrow Airport., Main Results: Chronic exposure to aircraft noise was significantly related to poorer reading and mathematics performance. After adjustment for the average socioeconomic status of the school intake (measured by percentage of pupils eligible for free school meals) these associations were no longer statistically significant., Conclusions: Chronic exposure to aircraft noise is associated with school performance in reading and mathematics in a dose-response function but this association is confounded by socioeconomic factors.

This work relates the development of an analytical methodology to simultaneously determine three methylxanthines (caffeine, theobromine, and theophylline) in beverages and urine samples based on reversed-phase high-performance liquid chromatography. Separation is made with a Bondesil C18 column using methanol-water-acetic acid or ethanol-water-acetic acid (20:75:5, v/v/v) as the mobile phase at 0.7 mL/min. Identification is made by absorbance detection at 273 nm. Under optimized conditions, the detection limit of the HPLC method is 0.1 pg/mL for all three methylxanthines. This method is applied to urine and to 25 different beverage samples, which included coffee, tea, chocolate, and coconut water. The concentration ranges determined in the beverages and urine are: < 0.1 pg/mL to 350 microg/mL and 3.21 microg/mL to 71.2 microg/mL for caffeine; < 0.1 pg/mL to 32 microg mL and < 0.1 pg/mL to 13.2 microg/mL for theobromine; < 0.1 pg/mL to 47 microg/mL and < 0.1 pg/mL to 66.3 microg/mL for theophylline. The method proposed in this study is rapid and suitable for the simultaneous quantitation of methylxanthines in beverages and human urine samples and requires no extraction step or derivatization.

Abstract Twenty-eight Wistar rats treated orally with 20% ethanol solution, were divided into two groups: adult group (n = 19) and aged group (n = 9) consisting of animals aged 4 and 12 months, respectively, at the beginning of the treatment. Neurons from the basal nucleus region were counted and the percentage of choline acetyltransferase-immunoreactive cholinergic neurons was determined in adjacent sections. Acetylcholine release and choline-acetyltransferase activity in the cerebral cortex were assessed in the same animals. Nutritional parameters of the ethanol treated animals were monitored and found to be normal. Chronic exposure to ethanol did not result in global neuronal loss or loss of cholinergic neurons in the basal nucleus region. However, a greater expression of ChAT-immunoreactivity in the basal nucleus region and a tendency toward increased ChAT activity in the cerebral cortex of the control and treated aged animals, compared respectively to adult ones, were observed. These findings suggest adaptive changes of the aged rats in response to the possible cholinergic hypofunction, manifested as a decreased release of acetylcholine under stimulated conditions.