Oral administration of Coenzyme Q10 protects mice against oxidative stress and neuro-inflammation during experimental cerebral malaria.

In animal model of experimental cerebral malaria (ECM), the genesis of neuropathology is associated with oxidative stress and inflammatory mediators. There is limited progress in the development of new approaches to the treatment of cerebral malaria. Here, we tested whether oral supplementation of Coenzyme Q10 (CoQ10) would offer protection against oxidative stress and brain associated inflammation following Plasmodium berghei ANKA (PbA) infection in C57BL/6 J mouse model. For this purpose, one group of C57BL/6 mice was used as control; second group of mice were orally supplemented with 200 mg/kg CoQ10 and then infected with PbA and the third group was PbA infected alone. Clinical, biochemical, immunoblot and immunological features of ECM was monitored. We observed that oral administration of CoQ10 for 1 month and after PbA infection was able to improve survival, significantly reduced oedema, TNF-α and MIP-1ß gene expression in brain samples in PbA infected mice. The result also shows the ability of CoQ10 to reduce cholesterol and triglycerides lipids, levels of matrix metalloproteinases-9, angiopoietin-2 and angiopoietin-1 in the brain. In addition, CoQ10 was very effective in decreasing NF-κB phosphorylation. Furthermore, CoQ10 supplementation abrogated Malondialdehyde, and 8-OHDG and restored cellular glutathione. These results constitute the first demonstration that oral supplementation of CoQ10 can protect mice against PbA induced oxidative stress and neuro-inflammation usually observed in ECM. Thus, the need to study CoQ10 as a candidate of antioxidant and immunomodulatory molecule in ECM and testing it in clinical studies either alone or in combination with antimalaria regimens to provide insight into a potential translatable therapy.

Expanding the Genotype of Sjögren-Larsson Syndrome: A New Case Due to Two Novel Mutations / Ampliando el genotipo del síndrome de Sjögren-Larsson: un nuevo caso causado por dos nuevas mutaciones

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Lesiones nodulares periestomales / Nodular Peristomal Lesions

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A D3h-symmetry hexaazatriphenylene-tris-N-heterocyclic carbene ligand and its coordination to iridium and gold: preliminary catalytic studies.

A new D3h-symmetry tris-N-heterocyclic carbene ligand has been prepared and coordinated to iridium and gold. The ligand contains an electron-poor hexaazatriphenylene core; thus, the resulting tris-NHC ligand is a poor electron donor. The tris-Au(i) complex was tested in the hydroamination of terminal alkynes and in the three-component Strecker reaction.

Estudio epidemiológico, observacional y retrospectivo de la sensibilización a tiosulfato sódico de oro en la consulta de alergias de contacto de un hospital de tercer nivel / Retrospective observational epidemiologic study of sensitization to gold sodium thiosulfate in the allergy clinic of a tertiary hospital

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Mono and dimetallic pyrene-imidazolylidene complexes of iridium(iii) for the deuteration of organic substrates and the C-C coupling of alcohols.

Three different Ir(iii) complexes with pyrene-containing N-heterocyclic carbenes have been prepared and characterized. Two complexes contain a monodentate pyrene-imidazolylidene ligand, and have the formulae [IrCp*Cl2(pyrene-NHC)] and [IrCp*(CO3)(pyrene-NHC)]. The third complex is a dimetallic complex with a pyrene-di-imidazolylidene bridging ligand, with the formula [{IrCp*(CO3)}2(µ-pyrene-di-NHC)]. The catalytic activity of the three complexes was tested in the H/D exchange of organic substrates, and in the ß-alkylation of 1-phenylethanol with primary alcohols. In the deuteration of organic substrates, the carbonate complexes are active even in the absence of additives. The dimetallic complex is the most active one in the catalytic coupling of alcohols, a result that may be interpreted as a consequence of the cooperativity between the two metal centres.

Quantification of the effects of audible rattle and source type on the human response to environmental vibration.

The present research quantifies the influence of source type and the presence of audible vibration-induced rattle on annoyance caused by vibration in residential environments. The sources of vibration considered are railway and the construction of a light rail system. Data were measured in the United Kingdom using a socio-vibration survey (N = 1281). These data are analyzed using ordinal logit models to produce exposure-response relationships describing community annoyance as a function of vibration exposure. The influence of source type and the presence of audible vibration-induced rattle on annoyance are investigated using dummy variable analysis, and quantified using odds-ratios and community tolerance levels. It is concluded that the sample population is more likely to express higher levels of annoyance if the vibration source is construction compared to railway, and if vibration-induced rattle is audible.

Pincer-CNC mononuclear, dinuclear and heterodinuclear Au(III) and Pt(II) complexes supported by mono- and poly-N-heterocyclic carbenes: synthesis and photophysical properties.

A family of cyclometallated Au(iii) and Pt(ii) complexes containing a CNC-pincer ligand (CNC = 2,6-diphenylpyridine) supported by pyrene-based mono- or bis-NHC ligands have been synthesized and characterized, together with the preparation of a Pt-Au hetero-dimetallic complex based on a Y-shaped tris-NHC ligand. The photophysical properties of all the new species and of two related Ru(ii)-arene complexes were studied and compared. Whereas the pyrene-based complexes only exhibit emission in solution, those containing the Y-shaped tris-NHC ligand are only luminescent when dispersed in poly(methyl methacrylate) (PMMA). In particular, the pyrene-based complexes were found to be emissive in the range of 373-440 nm, with quantum yields ranging from 3.1 to 6.3%, and their emission spectra were found to be almost superimposable, pointing to the fluorescent pyrene-centered nature of the emission. This observation suggests that the emission properties of the pyrene fragment may be combined with some of the numerous applications of NHCs as supporting ligands allowing, for instance, the design of biological luminescent agents.

Human annoyance, acceptability and concern as responses to vibration from the construction of Light Rapid Transit lines in residential environments.

The aim of this paper is to investigate the use of different self-reported measures for assessing the human response to environmental vibration from the construction of an urban LRT (Light Rapid Transit) system. The human response to environmental stressors such as vibration and noise is often expressed in terms of exposure-response relationships that describe annoyance as a function of the magnitude of the vibration. These relationships are often the basis of noise and vibration policy and the setting of limit values. This paper examines measures other than annoyance by expressing exposure-response relationships for vibration in terms of self-reported concern about property damage and acceptability. The exposure-response relationships for concern about property damage and for acceptability are then compared with those for annoyance. It is shown that concern about property damage occurs at vibration levels well below those where there is any risk of damage. Earlier research indicated that concern for damage is an important moderator of the annoyance induced. Acceptability, on the other hand, might be influenced by both annoyance and concern, as well as by other considerations. It is concluded that exposure-response relationships expressing acceptability as a function of vibration exposure could usefully complement existing relationships for annoyance in future policy decisions regarding environmental vibration. The results presented in this paper are derived from data collected through a socio-vibration survey (N=321) conducted for the construction of an urban LRT in the United Kingdom.

Effects of adenotonsillectomy on plasma inflammatory biomarkers in obese children with obstructive sleep apnea: A community-based study.

BACKGROUND: Obesity and obstructive sleep apnea syndrome (OSA) are highly prevalent and frequently overlapping conditions in children that lead to systemic inflammation, the latter being implicated in the various end-organ morbidities associated with these conditions. AIM: To examine the effects of adenotonsillectomy (T&A) on plasma levels of inflammatory markers in obese children with polysomnographically diagnosed OSA who were prospectively recruited from the community. METHODS: Obese children prospectively diagnosed with OSA, underwent T&A and a second overnight polysomnogram (PSG) after surgery. Plasma fasting morning samples obtained after each of the two PSGs were assayed for multiple inflammatory and metabolic markers including interleukin (IL)-6, IL-18, plasminogen activator inhibitor-1 (PAI-1), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), adiponectin, apelin C, leptin and osteocrin. RESULTS: Out of 122 potential candidates, 100 obese children with OSA completed the study with only one-third exhibiting normalization of their PSG after T&A (that is, apnea-hypopnea index (AHI) ≤1/hour total sleep time). However, overall significant decreases in MCP-1, PAI-1, MMP-9, IL-18 and IL-6, and increases in adropin and osteocrin plasma concentrations occurred after T&A. Several of the T&A-responsive biomarkers exhibited excellent sensitivity and moderate specificity to predict residual OSA (that is, AHI⩾5/hTST). CONCLUSIONS: A defined subset of systemic inflammatory and metabolic biomarkers is reversibly altered in the context of OSA among community-based obese children, further reinforcing the concept on the interactive pro-inflammatory effects of sleep disorders such as OSA and obesity contributing to downstream end-organ morbidities.

Effect of resveratrol on visceral white adipose tissue inflammation and insulin sensitivity in a mouse model of sleep apnea.

BACKGROUND: Sleep fragmentation (SF) increases food intake and the risk of obesity, and recruits macrophages to visceral white adipose tissue (VWAT) promoting tissue inflammation and insulin resistance. Administration of resveratrol (Resv) has been associated with significant improvements in high-fat diet-induced obesity, inflammation and insulin resistance. METHODS: Male mice were subjected to SF or sleep control conditions for 8 weeks, and treated with either Resv or vehicle (Veh). Fasting plasma levels of glucose, insulin and leptin were obtained and VWAT insulin sensitivity tests were performed (phosphorylated AKT/total AKT), along with flow-cytometric assessments for VWAT macrophages (M1 and M2) and T-cell lymphocytes (CD4+, CD8+ and T regulatory cell (Treg)). RESULTS: SF-Veh and SF-Resv mice showed increased food consumption and weight gain. However, although SF-Veh mice exhibited increased fasting insulin and leptin levels, and reduced VWAT p-AKT/AKT responses to insulin, such alterations were abrogated in SF-Resv-treated mice. Increases in M1, reduced M2 counts and increased tumor necrosis factor-α release emerged in SF-Veh macrophages compared with all other three groups. Similarly, increased CD8+ and reduced Treg lymphocyte counts were apparent in SF-Veh. CONCLUSIONS: Resveratrol does not reverse the SF-induced increases in food intake and weight gain, but markedly attenuates VWAT inflammation and insulin resistance, thereby providing a potentially useful adjunctive therapy in the context of sleep disorders manifesting metabolic morbidity.

Design of measurement methodology for the evaluation of human exposure to vibration in residential environments.

Exposure-response relationships are important tools for policy makers to assess the impact of an environmental stressor on the populace. Their validity lies partly in their statistical strength which is greatly influenced by the size of the sample from which the relationship is derived. As such, the derivation of meaningful exposure-response relationships requires estimates of vibration exposure at a large number of receiver locations. In the United Kingdom a socio-vibrational survey has been conducted with the aim of deriving exposure-response relationships for annoyance due to vibration from (a) railway traffic and (b) the construction of a new light rail system. Response to vibration was measured via a questionnaire conducted face-to-face with residents in their own homes and vibration exposure was estimated using data from a novel measurement methodology. In total, 1281 questionnaires were conducted: 931 for vibration from railway traffic and 350 for vibration from construction sources. Considering the interdisciplinary nature of this work along with the volume of experimental data required, a number of significant technical and logistical challenges needed to be overcome through the planning and implementation of the fieldwork. Four of these challenges are considered in this paper: the site identification for providing a robust sample of the residents affected, the strategies used for measuring both exposure and response and the coordination between the teams carrying out the social survey and the vibration measurements.

Organochlorinated pesticides in sediments from the Lake Albufera of Valencia (Spain).

Bottom sediment samples from 121 sites of the Lake Albufera of Valencia were analyzed. Dieldrin, endrin, heptachlor and op'-DDT were not detected (<0.01 ng g(-1)) in 88-93% of the sites. Aldrin and HCB concentration ranges were between <0.01 and 0.1 ng g(-1) in 86% and 94% of the sites, respectively. Heptachlor-epoxide and lindane 95% confidence intervals were 0.2-0.5 and 0.06-0.12, respectively. The greatest average concentration corresponds to pp'-DDE, pp'-DDD and pp'-DDT. The sum of six isomers and derivatives of the DDT average concentration reaches 2.1 ng g(-1), as opposed to 2.7 ng g(-1) for the sum of 13 pesticides considered. In the site with a major contamination, 27.0 ng g(-1) of pp'-DDD and 12.8 ng g(-1) of pp'-DDT were accumulated. The DDE:DDT proportion average was 0.37, indicating an aged DDT contamination. Concentrations of pesticides in sediments were compared to three sediment quality guidelines, and indicated that a low biological effects level can be expected in either sediments or aquatic organisms.

Effects of unfractionated and low molecular weight heparins on plasma levels of hemostatic factors in patients with acute coronary syndromes.

BACKGROUND AND OBJECTIVES: Unfractionated heparin (UFH) and enoxaparin (low molecular weight heparin) constitute fundamental therapies in the treatment of patients with acute coronary syndrome (ACS). Since enoxaparin appears to offer clinical advantages over UFH in managing ACS, markers of thrombin generation, endothelial function and acute phase response could manifest different responses to UFH or enoxaparin. The purpose of the present study was to investigate the effect that treatment with either UFH or enoxaparin has on plasma hemostatic markers in 24 patients with ACS. DESIGN AND METHODS: The patients were randomized to receive 5,000 IU intravenous bolus and continuous infusion of 18 IU/Kg/h UFH (n=11) or 1 mg/kg/12h subcutaneous enoxaparin (n=13). The plasma levels of fibrinogen (Fg), prothrombin fragment 1+2 (F1+2), thrombin antithrombin complex (TAT), von Willebrand factor (vWF), tissue factor (TF) and tissue factor pathway inhibitor (TFPI) were assayed at admission and 6, 12, 24 and 48 hours after heparin treatment. RESULTS: Upon admission, UFH and enoxaparin patients showed a significant increase in all the hemostatic parameters measured with respect to the levels in the control subjects. In comparison with the baseline levels of the UFH- and enoxaparin-treated patients, Fg showed a significant increase at 48 h and TFPI at 6, 12 and 24 hours. However, at 48 hours TFPI levels were not significantly higher than the basal values. There were no significant changes in F1+2, TAT, vWF or TF. INTERPRETATION AND CONCLUSIONS: Markers of thrombin generation, endothelial function and acute-phase reactants manifest a similar response to UFH and enoxaparin. An increase in thrombin generation may be a result of persistently activated inflammatory and endothelial processes, despite UFH and enoxaparin treatment.

3-acetylaltholactone and related styryl-lactones, mitochondrial respiratory chain inhibitors.

A novel furano-pyrone, 3-acetylaltholactone, and two other known styryl-lactones, altholactone and 5-acetoxyisogoniothalamin oxide, have been isolated from Goniothalamus arvensis (Annonaceae) stem bark. We report here the isolation and structural elucidation of these compounds with furane-pyrone and styryl-pyrone skeletons, postulating also for the first time their mechanism of cytotoxicity based on inhibition on mammalian mitochondrial respiratory chain.

Ocular dysfunction associated with mental handicap.

The aim of this article is to show the main general and ocular characteristics of a group of 46 mentally handicapped people of different IQ and age who were provided with visual care. Many different syndromes and neurological alterations have been described in the literature. The case types and number of people studied for each condition attending our clinics were: syndromes: Down's (25), Soto (2), West (2), Rubinstein-Taybi (1), triple X (1); neurological conditions: cerebral palsy (8), microcephaly (5), hydrocephaly (2). In our study the ocular findings were high incidence of ametropies: 58.7% hyperopia, 21.7% myopia, 19.5% astigmatism and 28% strabismus.

Visual problems in people with severe mental handicap.

The incidence of visual problems in people with mental handicaps is very high. Nine severely mentally handicapped patients were studied. Several objective and subjective optometric tests were performed. The results showed the presence of different kinds of visual problems that were compensated for by optical methods. The subjects showed a general change in their behaviour. It is essential to give optometric care to such people.