Potentiation of dapsone induced methemoglobinemia by N-acetylcysteinc in rats

Dapsone (DDS) (4,4` diaminodiphenylsulfone), the drug of choice for the treatment of leprosy, frequently induces hemolytic anemia and methemoglobinemia. N-hydroxylation, one of the major pathways of biotransformation, has been constantly related to the methemeglobinemia after the use of the drug. In order to prevent the dapsone-induced hemotoxicity, N-acetylcysteine, a drug precursor of glutathione, was administered in combination with DDS to male Wistar rats, weighting 220-240 g. The animals were then anaesthetized and blood was collected from the aorta for determination of plasma DDS concentration by HPLC, determination of methemoglobinemia and glutathione by spectrophotometry, and for biochemical and hematological parameters. Our results showed that N-acetylcysteine enhanced dapsone-induced methemoglobinemia due to increased dapasone plasmatic concentration and consequent increased N-hydroxylamine formation. We concluded that drug interactions with dapsone require individually studies in order to avoid undesirable effects of dapsone.

Effect of zinc supplementation in pregnant mice during experimental Trypanosoma cruzi infection

Zinc is an essential micronutrient and has significant effects on human growth, development, and immune function. Zinc supplementation or deficiency may affect the course of infection. Zinc enhances immune response against a wide range of viral, bacterial, and parasitic pathogens. In the present study, we investigated the effects of zinc sulphate (ZnSO(4)) supplementation (20 mg/kg/day) during pregnancy in mice, Swiss Webster strain infected by the Y strain of Trypanosoma cruzi. Oral supplementation of zinc sulphate in pregnant and non-pregnant infected animals did not affect the count of blood parasites as well as tissue parasitism in the heart, liver, and spleen. Zinc supplementation did not alter female body weight, the length of fetuses and neonates, placental size/weight and mortality rate. Among zinc supplied animals, no significant plasmatic zinc concentrations were observed. Concerning to tissue zinc concentrations, only the liver displayed enhanced values as compared to other organs. For placental parasitism, zinc supplied group displayed a significant decrease in amastigote burdens (P < 0.05). However due to the reduced number of parasite burdens in placenta of animals supplied with zinc, these data suggest that zinc was partially effective in up-regulating the host`s immune response against parasite, probably attenuating the infection in fetuses. (C) 2010 Elsevier Ltd. All rights reserved.

Chemical composition of bovine milk from Minas Gerais State, Brazil

Aiming at international competitiveness of the Brazilian dairy sector, new governmental policies were released to improve quality and safety of bovine milk. In this context, it is important to quantify essential and toxic chemical elements. Here, the composition of milk samples taken at 32 dairy farms in Minas Gerais State was assessed by instrumental neutron activation analysis (INAA) and inductively coupled plasma mass spectrometry (ICP-MS), besides the evaluation of usual quality parameters. Significant differences were found for Ba, K, Na and fat content amongst dairy farms with diverse quality levels established on basis of somatic cell and total bacterial count.

Amphotericin B in poly(lactic-co-glycolic acid) (PLGA) and dimercaptosuccinic acid (DMSA) nanoparticles against paracoccidioidomycosis

The present study reports on the preparation and testing of a desoxycholate amphotericin B (D-AMB) sustained delivery system based on poly(lactic-co-glycolic acid) (PLGA) and dimercaptosuccinic acid (DMSA) polymeric blends (Nano-D-AMB) aimed at reducing the number of AMB administrations required to treat mycosis. BALB/c mice were infected with the yeast Paracoccidioides brasiliensis intravenously to mimic the chronic form of paracoccidioidomycosis. At 30 days post-infection, the animals were treated with Nano-D-AMB [6 mg/kg of encapsulated D-AMB, intraperitoneally (ip), interval of 72 h] or D-AMB (2 mg/kg, ip, interval of 24 h). Drug efficacy was investigated by the fungal burden recovery from tissues. Toxicity was assessed by renal and hepatic biochemical parameters, physical appearance of the animals and haematological investigation. The control groups used were non-infected and the infected mice mock treated with PBS. Nano-D-AMB presented results comparable to free D-AMB, with a marked antifungal efficacy. The Nano-D-AMB-treated group presented lower loss of body weight and absence of stress sign (piloerection and hypotrichosis) observed after D-AMB treatment. No renal [blood urea nitrogen (BUN), creatinine] or hepatic (pyruvic and oxalacetic glutamic transaminases) biochemical abnormalities were found. The micronucleus assay showed no significant differences in both the micronucleus frequency and percentage of polychromatic erythrocytes for Nano-D-AMB, indicating the absence of genotoxicity and cytotoxic effects. The D-AMB-coated PLGA-DMSA nanoparticle showed antifungal efficacy, fewer undesirable effects and a favourable extended dosing interval. Nano-D-AMB comprises an AMB formulation able to lessen the number of drug administrations. Further studies would elucidate whether Nano-D-AMB would be useful to treat systemic fungal infections such as paracoccidioidomycosis, candidiasis, aspergillosis and cryptococcosis.

Genetic basis of inosine triphosphate pyrophosphohydrolase (ITPA) deficiency

Inosine triphosphate pyrophosphohydrolase (ITPase) deficiency is a common inherited condition characterized by the abnormal accumulation of inosine triphosphate (ITP) in erythrocytes. The genetic basis and pathological consequences of ITPase deficiency are unknown. We have characterized the genomic structure of the ITPA gene, showing that it has eight exons. Five single nucleotide polymorphisms were identified, three silent (138GMA, 561GMA, 708GMA) and two associated with ITPase deficiency (94CMA, IVS2+21AMC). Homozygotes for the 94CMA missense mutation (Pro32 to Thr) had zero erythrocyte ITPase activity, whereas 94CMA heterozygotes averaged 22.5% of the control mean, a level of activity consistent with impaired subunit association of a dimeric enzyme. ITPase activity of IVS2+21AMC homozygotes averaged 60% of the control mean. In order to explore further the relationship between mutations and enzyme activity, we examined the association between genotype and ITPase activity in 100 healthy controls. Ten subjects were heterozygous for 94CMA (allele frequency: 0.06), 24 were heterozygotes for IVS2+21AMC (allele frequency: 0.13) and two were compound heterozygous for these mutations. The activities of IVS2+21AMC heterozygotes and 94CMA/IVS2+21AMC compound heterozygotes were 60% and 10%, respectively, of the normal control mean, suggesting that the intron mutation affects enzyme activity. In all cases when ITPase activity was below the normal range, one or both mutations were found. The ITPA genotype did not correspond to any identifiable red cell phenotype. A possible relationship between ITPase deficiency and increased drug toxicity of purine analogue drugs is proposed.

Quality of Reporting of Observational Longitudinal Research

Observational longitudinal research is particularly useful for assessing etiology and prognosis and for providing evidence for clinical decision making. However, there are no structured reporting requirements for studies of this design to assist authors, editors, and readers. The authors developed and tested a checklist of criteria related to threats to the internal and external validity of observational longitudinal studies. The checklist criteria concerned recruitment, data collection, biases, and data analysis and descriptive issues relevant to study rationale, study population, and generalizability. Two raters independently assessed 49 randomly selected articles describing stroke research published from 1999 to 2003 in six journals: American Journal of Epidemiology, Journal of Epidemiology and Community Health, Stroke, Annals of Neurology, Archives of Physical Medicine and Rehabilitation, and American Journal of Physical Medicine and Rehabilitation. On average, 17 of the 33 checklist criteria were reported. Criteria describing the study design were better reported than those related to internal validity. No relation was found between study type (etiologic or prognostic) or word count and quality of reporting. A flow diagram for summarizing participant flow through a study was developed. Editors and authors should consider using a checklist and flow diagram when reporting on observational longitudinal research.

Methemoglobin Reduction in Crocodile Blood: Are High Levels of MetHb Typical of Healthy Reptiles?

In 82 wild-caught Crocodylus porosus, levels of NADH-MetHb reductase and GSH seem adequate to maintain hemoglobin in its reduced functional state. Studies of C. porosus erythrocytes in vitro show reduction of metHb in the presence of lactate, glucose and plasma, but not pyruvate. These findings, together with recent data which show low metHb in a variety of reptiles, cast doubt on the accepted view that high levels of MetHb are typical of healthy reptiles. One explanation for the sharp contrast between earlier and more recent data could be technical. We found low metHb in Crocodylus johnstoni, Chelodina longicollis and Sphenomorphus quoyi. However, high and variable values reminiscent of many of the earlier data were obtained by omitting final centrifugation prior to spectrophotometry. Interestingly, this step is not part of the standard clinical method but is necessary in analyses of blood with nucleated red cells. These observations suggest that high metHb may not be typical of reptiles after all.

Turbulent Time and Length Scale Measurements in High-Velocity Open Channel Flows

In high-velocity open channel flows, the measurements of air-water flow properties are complicated by the strong interactions between the flow turbulence and the entrained air. In the present study, an advanced signal processing of traditional single- and dual-tip conductivity probe signals is developed to provide further details on the air-water turbulent level, time and length scales. The technique is applied to turbulent open channel flows on a stepped chute conducted in a large-size facility with flow Reynolds numbers ranging from 3.8 E+5 to 7.1 E+5. The air water flow properties presented some basic characteristics that were qualitatively and quantitatively similar to previous skimming flow studies. Some self-similar relationships were observed systematically at both macroscopic and microscopic levels. These included the distributions of void fraction, bubble count rate, interfacial velocity and turbulence level at a macroscopic scale, and the auto- and cross-correlation functions at the microscopic level. New correlation analyses yielded a characterisation of the large eddies advecting the bubbles. Basic results included the integral turbulent length and time scales. The turbulent length scales characterised some measure of the size of large vortical structures advecting air bubbles in the skimming flows, and the data were closely related to the characteristic air-water depth Y90. In the spray region, present results highlighted the existence of an upper spray region for C > 0.95 to 0.97 in which the distributions of droplet chord sizes and integral advection scales presented some marked differences with the rest of the flow.

Turbulence in Hydraulic Jumps: Experimental Measurements

A hydraulic jump is the transition from a supercritical open channel flow to a subcritical regime. It is characterised by a highly turbulent flow with macro-scale vortices, some kinetic energy dissipation and a bubbly two-phase flow structure. New air-water flow measurements were performed in hydraulic jump flows for a range of inflow Froude numbers. The experiments were conducted in a large-size facility using two types of phase-detection intrusive probes: i.e., single-tip and double-tip conductivity probes. These were complemented by some measurements of free-surface fluctuations using ultrasonic displacement meters. The present study was focused on the turbulence characteristics of hydraulic jumps with partially-developed inflow conditions. The void fraction measurements showed the presence of an advective diffusion shear layer in which the void fractions profiles matched closely an analytical solution of the advective diffusion equation for air bubbles. The present results highlighted some influence of the inflow Froude number onto the air bubble entrainment process. At the largest Froude numbers, the advected air bubbles were more thoroughly dispersed vertically, and larger amount of air bubbles were detected in the turbulent shear layer. In the air-water mixing layer, the maximum void fraction and bubble count rate data showed some longitudinal decay function in the flow direction. Such trends were previously reported in the literature. The measurements of interfacial velocity and turbulence level distributions provided new information on the turbulent velocity field in the highly-aerated shear region. The present data suggested some longitudinal decay of the turbulence intensity. The velocity profiles tended to follow a wall jet flow pattern. The air–water turbulent time and length scales were deduced from some auto- and cross-correlation analyses based upon the method of CHANSON (2006,2007). The results provided the integral turbulent time and length scales of the eddy structures advecting the air bubbles in the developing shear layer. The experimental data showed that the auto-correlation time scale Txx was larger than the transverse cross-correlation time scale Txz. The integral turbulence length scale Lxz was a function of the inflow conditions, of the streamwise position (x-x1)/d1 and vertical elevation y/d1. Herein the dimensionless integral turbulent length scale Lxz/d1 was closely related to the inflow depth: i.e., Lxz/d1 = 0.2 to 0.8, with Lxz increasing towards the free-surface. The free-surface fluctuations measurements showed large turbulent fluctuations that reflected the dynamic, unsteady structure of the hydraulic jumps. A linear relationship was found between the normalized maximum free-surface fluctuation and the inflow Froude number.

Experimental Analysis of Froude Number Effect on Air Entrainment in the Hydraulic Jump

A hydraulic jump is characterized by strong energy dissipation and mixing, large-scale turbulence, air entrainment, waves and spray. Despite recent pertinent studies, the interaction between air bubbles diffusion and momentum transfer is not completely understood. The objective of this paper is to present experimental results from new measurements performed in rectangular horizontal flume with partially-developed inflow conditions. The vertical distributions of void fraction and air bubbles count rate were recorded for inflow Froude number Fr1 in the range from 5.2 to 14.3. Rapid detrainment process was observed near the jump toe, whereas the structure of the air diffusion layer was clearly observed over longer distances. These new data were compared with previous data generally collected at lower Froude numbers. The comparison demonstrated that, at a fixed distance from the jump toe, the maximum void fraction Cmax increases with the increasing Fr1. The vertical locations of the maximum void fraction and bubble count rate were consistent with previous studies. Finally, an empirical correlation between the upper boundary of the air diffusion layer and the distance from the impingement point was provided.

Surface Waves and Roughness in Self-Aerated Supercritical Flow

In high-velocity open channel flows, free-surface aeration is commonly observed. The effects of surface waves on the air-water flow properties are tested herein. The study simulates the air-water flow past a fixed-location phase-detection probe by introducing random fluctuations of the flow depth. The present model yields results that are close to experimental observations in terms of void fraction, bubble count rate and bubble/droplet chord size distributions. The results show that the surface waves have relatively little impact on the void fraction profiles, but that the bubble count rate profiles and the distributions of bubble and chord sizes are affected by the presence of surface waves.

Acquisition of the English article system in SLA and the Missing Surface Inflection Hypothesis

This paper examines the article system in interlanguage grammar focusing on Japanese learners of English, whose native language lacks articles. It will be demonstrated that for the acquisition of the English article system, count/mass distinctions and definiteness are the crucial factors. Although Japanese does not employ the article system to encode these aspects, it will be argued that they are nevertheless syntactically encoded through its classifier system. Hence, the problem for these learners must be to map these features onto the appropriate surface forms as the Missing Surface Inflection Hypothesis predicts (Prévost & White 2000). This suggestion will further be supported empirically by a fill-in-the article task. It will be concluded that these Japanese learners understand the English article system fairly well, possibly due to their native language, yet have problems with realizing the relevant features (i.e. count/mass distinctions and definiteness) in the target language.

Self-Similarity of Air-Water Flows in Skimming Flows on Stepped Spillways

Skimming flows on stepped spillways are characterised by a significant rate of turbulent dissipation on the chute. Herein an advanced signal processing of traditional conductivity probe signals is developed to provide further details on the turbulent time and length scales. The technique is applied to a 22° stepped chute operating with flow Reynolds numbers between 3.8 and 7.1 E+5. The new correlation analyses yielded a characterisation of large eddies advecting the bubbles. The turbulent length scales were related to the characteristic depth Y90. Some self-similar relationships were observed systematically at both macroscopic and microscopic levels. These included the distributions of void fraction, bubble count rate, interfacial velocity and turbulence level, and turbulence time and length scales. The self-similarity results were significant because they provided a picture general enough to be used to characterise the air-water flow field in prototype spillways.

Air Bubble Entrainment in Hydraulic Jumps: Physical Modelling and Scale Effects

A hydraulic jump is characterised by strong energy dissipation and air entrainment. In the present study, new air-water flow measurements were performed in hydraulic jumps with partially-developed flow conditions in relatively large-size facilities with phase-detection probes. The experiments were conducted with identical Froude numbers, but a range of Reynolds numbers and relative channel widths. The results showed drastic scale effects at small Reynolds numbers in terms of void fraction and bubble count rate distributions. The void fraction distributions implied comparatively greater detrainment at low Reynolds numbers leading to a lesser overall aeration of the jump roller, while dimensionless bubble count rates were drastically lower especially in the mixing layer. The experimental results suggested also that the relative channel width had little effect on the air-water flow properties for identical inflow Froude and Reynolds numbers.

Dynamic Similarity and Scale Effects Affecting Air Bubble Entrainment in Hydraulic Jumps

In an open channel, the transition from super- to sub-critical flow is a flow singularity (the hydraulic jump) characterised by a sharp rise in free-surface elevation, strong turbulence and air entrainment in the roller. A key feature of the hydraulic jump flow is the strong free-surface aeration and air-water flow turbulence. In the present study, similar experiments were conducted with identical inflow Froude numbers Fr1 using a geometric scaling ratio of 2:1. The results of the Froude-similar experiments showed some drastic scale effects in the smaller hydraulic jumps in terms of void fraction, bubble count rate and bubble chord time distributions. Void fraction distributions implied comparatively greater detrainment at low Reynolds numbers yielding some lesser aeration of the jump roller. The dimensionless bubble count rates were significantly lower in the smaller channel, especially in the mixing layer. The bubble chord time distributions were quantitatively close in both channels, and they were not scaled according to a Froude similitude. Simply the hydraulic jump remains a fascinating two-phase flow motion that is still poorly understood.