Chemokines and chemokine receptors coordinate the inflammatory immune response in human cutaneous leishmaniasis

Cutaneous leishmaniasis (CL) includes different clinical manifestations displaying diverse intensities of dermal Inflammatory infiltrate Diffuse CL (DCL) cases are hyporesponsive and lesions show very few lymphocytes and a predominance of macrophages In contrast localized CL (LCL) cases are responsive to leishmanial antigen and lesions exhibit granulocytes and mononuclear cell infiltration in the early phases changing to a pattern with numerous lymphocytes and macrophages later in the lesion Therefore different chemokines may affect the predominance of cell infiltration in distinct clinical manifestations In lesions from LCL patients we examined by flow cytometry the presence of different chemokines and their receptors in T cells and we verified a higher expression of CXCR3 in the early stages of LCL (less than 30 days of infection) and a higher expression of CCR4 in the late stages of disease (more than 60 days of infection) We also observed a higher frequency of T cells producing IL-10 in the late stage of LCL Using immunohistochemistry we observed a higher expression of CCL7 CCL17 in lesions from late LCL as well as CCR4 suggesting a preferential recruitment of regulatory T cells in the late LCL Comparing lesions from LCL and DCL patients we observed a higher frequency of CCL7 in DCL lesions These results point out the Importance of the chemokines defining the different types of cells recruited to the site of the infection which could be related to the outcome of infection as well as the clinical form observed (C) 2010 American Society for Histocompatibility and Immunogenetics Published by Elsevier Inc All rights reserved

The Influence of Calcium Chloride on the Setting Time, Solubility, Disintegration, and pH of Mineral Trioxide Aggregate and White Portland Cement with a Radiopacifier

This study evaluated the influence of addition of 10% calcium chloride (CaCl(2)) on the setting time, solubility, disintegration, and pH of white MTA (WMTA) and white Portland cement (WPC). A test of the setting time was performed following the #57 ADA specifications and a test of the final setting time according to the ASTM. For the solubility tests disintegration and pH, Teflon rings were filled with the cements and weighed after setting. After 24 h in a desiccator, they were once again weighed. Thereafter, they were immersed in MiliQ water for 24 and 72 h and 7, 14, and 28 days, with maintenance in the desiccator and weighing between periods. The pH of water in which the rings were immersed was measured immediately after contact with them and in the other periods. The addition of CaCl(2) provided a significant reduction (50%) in the initial setting time of cements. The final setting time of WMTA was reduced in 35.5% and the final setting time of WPC in 68.5%. The WMTA with CaCl(2) absorbed water and gained weight with time, except for in the 24-h period. The addition of CaCl(2) to the WPC reduced its solubility. The addition of CaCl(2) increased the pH of WMTA in the immediate period and at 24 and 72 h and for WPC in the immediate period and at 24 h. The addition of CaCl(2) to WMTA and WPC reduced the setting times and solubility of both and increased the pH of cements in the initial periods. (J Endod 2009;35:550-554)

Improvement of the electrolytic properties of Y2O3-based materials using a crystallographic index

Y2O3 is a c-type rare earth oxide with a fluorite-related structure. This material has been used to refractory because of its high thermal stability and excellent resistance to hydration. In this study, the effective index was suggested in order to improve the electrolytic properties of Y2O3-based oxide. (CexY1-x)(2)O3+delta (x = 0.25 and 0.3) and [LaaSrbCe0.25Y(1-a-b)](2)O3+delta (a = 0.05, 0.1 and 0.15, b = 0, 0.006 and 0.0125) were prepared as the examples with intermediate and high index, respectively. The specimens with high index value such as (La0.15Ce0.25Y0.60)(2)O-3.25 and (La0.1Sr0.0125Ce0.25Y0.6375)(2)O-3.24 consisted of two phases such as c-type and fluorite, although (Ce0.25Y0.75)(2)O-3.25 with intermediate index value had a single phase of c-type rare earth oxide. Microanalysis indicates that a grain in the (La0.1Sr0.0125Ce0.25Y0.6375)(2)O-3.23(7) sintered body consists of c-type and fluorite phases. An interface between c-type and fluorite phases is coherent in a grain. This suggests that this effective index guides the crystal structure in the specimen to fluorite and the examined composition introduces the interface between c-type and fluorite in the microstructure. The electrochemical properties of specimens including Y2O3 were characterized on the basis of the suggested index. The electrical conductivity of Y2O3-based materials increased with an increase of the index. The apparent activation energy of Y2O3-based materials decreased with increasing index. The ionic transport number of oxygen of the specimens was improved by enhancement of the index, confirming validity of the index. The oxide ionic conductive region of (La0.1Sr0.0125Ce0.25Y0.(6375))(2)O-3.23(7) with high effective index extended up to P-O2 = 10(-18) atm at 800 degreesC, although the specimens with low or intermediate index showed p- or n-type semi-conduction in the same P-O2 region at 800 and 1000 degreesC. These results suggest that the interface between c-type and fluorite phases also contributes to improve the electrolytic properties in the grain. It is concluded that the improvement of electrolytic properties in Y2O3-based materials is attributable to the microstructure with interface between two phases in a grain and the fluorite structure guided by the suggested index. (C) 2001 Published by Elsevier Science B.V.

COX-2 inhibition decreases VEGF expression and alveolar bone loss during the progression of experimental periodontitis in rats

Background: Vascular endothelial growth factor (VEGF) is a macromolecule of importance in inflammation that has been implicated in periodontitis. The aims of this study were to investigate VEGF expression during the progression of periodontal disease and to evaluate the effect of a preferential cyclooxygenase (COX)-2 inhibitor meloxicam on VEGF expression and alveolar bone loss in experimentally induced periodontitis. Methods: A total of 120 Wistar rats were randomly separated into groups 1 (control) and 2 (meloxicam, 3 mg/kg/day, intraperitoneally, for 3, 7, 14, or 30 days). Silk ligatures were placed at the gingival margin level of the lower right first molar of all rats. VEGF expression was assessed by reverse transcription-polymerase chain reaction (RT-PCR), Western blot (WB), and immunohistochemical (IHC) analyses. The hemiarcades were processed for histopathologic analysis. RT-PCR and WB results were submitted to analysis of variance, the Tukey test, and Pearson correlation analysis (P<0.05). Results: A reduction in alveolar bone resorption was observed in the meloxicam-treated group compared to the control group at all periods studied. There was a positive correlation between COX-2 mRNA and VEGF mRNA in the gingival tissues and periodontal disease (R = 0.80; P = 0.026). Meloxicam significantly reduced the increased mRNA VEGF expression in diseased tissues after 14 days of treatment (P = 0.023). Some alterations in VEGF receptor I mRNA expression were observed, but these were not statistically significant. VEGF protein expression in WB experiments was significantly higher in diseased sites compared to healthy sites (P<0.05). After 14 days of treatment with meloxicam, an important decrease in VEGF protein expression was detected in diseased tissues (P = 0.08). Qualitative IHC analysis revealed that VEGF protein expression was higher in diseased tissues and decreased in tissues from rats treated with meloxicam. Conclusions: The present data suggest an important role for VEGF in the progression of periodontal disease. Systemic therapy with meloxicam can modify the progression of experimentally induced periodontitis in rats by reducing VEGF expression and alveolar bone loss.

Can increasing the viscosity of formulations be used to reduce the human skin penetration of the sunscreen oxybenzone?

The effect of adding thickening agents on the penetration of a sunscreen benzophenone-3 through epidermal and a high-density polyethylene membrane was studied using both very thick (infinite dose) and thin tin use) applications. Contradictory results were obtained. Thickening agents retard skin penetration, in a manner consistent with a diffusional resistance in the formulation, when applied as an infinite dose. In contrast, when applied as in thin (in use) doses, thickening agents promote penetration, most likely through greater stratum corneum diffusivity arising from an enhanced hydration by the thicker formulations. The two key implications from this work are (i) a recognition of the danger in the potential extrapolation of infinite dosing to in use situations, and (ii) to recognize that thicker formulations may sometimes enhance the penetration of other topical agents when applied in use.

Microdialysis and response during regional chemotherapy by isolated limb infusion of melphalan for limb malignancies

This study sought to use a microdialysis technique to relate clinical and biochemical responses to the time course of melphalan concentrations in the subcutaneous interstitial space and in tumour tissue (melanoma, malignant fibrous histiocytoma, Merkel cell tumour and osteosarcoma) in patients undergoing regional chemotherapy by Isolated Limb Infusion (ILI). 19 patients undergoing ILI for treatment of various limb malignancies were monitored for intra-operative melphalan concentrations in plasma and, using microdialysis, in subcutaneous and tumour tissues. Peak and mean concentrations of melphalan were significantly higher in plasma than in subcutaneous or tumour microdialysate. There was no significant difference between drug peak and mean concentrations in interstitial and tumour tissue, indicating that there was no preferential uptake of melphalan into the tumours. The time course of melphalan in the microdialysate could be described by a pharmacokinetic model which assumed melphalan distributed from the plasma into the interstitial space. The model also accounted for the vascular dispersion of melphalan in the limb. Tumour response in the whole group to treatment was partial response: 53.8% (n = 7); complete response: 33.3% (n = 5); no responses 6.7% (n = 1). There was a significant association between tumour response and melphalan concentrations measured over time in subcutaneous microdialysate (P < 0.01). No significant relationship existed between the severity of toxic reactions in the limb or peak plasma creatine phosphokinase levels and peak melphalan microdialysate or plasma concentrations. It is concluded that microdialysis is a technique well suited for measuring concentrations of cytotoxic drug during ILI. The possibility of predicting actual concentrations of cytotoxic drug in the limb during ILI using our model opens an opportunity for improved drug dose calculation. The combination of predicting tissue concentrations and monitoring in microdialysate of subcutaneous tissue could help optimise ILI with regard to post-operative limb morbidity and tumour response. (C) 2001 Cancer Research Campaign http:,//www.bjcancer.com.

Analysis of thermodynamic non-ideality in terms of protein solvation

The effects of thermodynamic non-ideality on the forms of sedimentation equilibrium distributions for several isoelectric proteins have been analysed on the statistical-mechanical basis of excluded volume to obtain an estimate of the extent of protein solvation. Values of the effective solvation. parameter delta are reported for ellipsoidal as well as spherical models of the proteins, taken to be rigid, impenetrable macromolecular structures. The dependence of the effective solvated radius upon protein molecular mass exhibits reasonable agreement with the relationship calculated for a model in which the unsolvated protein molecule is surrounded by a 0.52-nm solvation shell. Although the observation that this shell thickness corresponds to a double layer of water molecules may be of questionable relevance to mechanistic interpretation of protein hydration, it augurs well for the assignment of magnitudes to the second virial coefficients of putative complexes in the quantitative characterization of protein-protein interactions under conditions where effects of thermodynamic non-ideality cannot justifiably be neglected. (C) 2001 Elsevier Science B.V. All rights reserved.

Cloning of a catalytic subunit of cAMP-dependent protein kinase from the honeybee (Apis mellifera) and its localization in the brain

In the honeybee the cAMP-dependent signal transduction cascade has been implicated in processes underlying learning and memory, The cAMP-dependent protein kinase (PKA) is the major mediator of cAMP action. To characterize the PKA system in the honeybee brain we cloned a homologue of a PKA catalytic subunit from the honeybee,The deduced amino acid sequence shows 80-94% identity with catalytic subunits of PKA from Drosophila melanogaster, Aplysia californica and mammals. The corresponding gene is predominantly expressed in the mushroom bodies, a structure that is involved in learning and memory processes. However, expression can also be found in the antennal and optic lobes,The level of expression varies within all three neuropiles.

Characterization of the EphA1 receptor tyrosine kinase: Expression in epithelial tissues

The Eph family (of receptor tyrosine kinases plays a crucial role during development and is implicated in oncogenesis. Using a partial cDNA clone of an Eph-related kinase (Esk) we isolated the complete coding region of a gene which we show to be murine EphA1 by both structural and functional criteria. The chromosomal localization is shown to be syntenic to hEphA1 and the genomic organization also shows distinct features found in the hEphA1 gene. Functionally, in keeping with findings for the human homologue, both soluble recombinant and native mEphA1 show preferential binding to ephrin A1. However, we also observed significant binding to other A-type ligands as has been observed for other Eph receptors. We analysed the expression of mEphA1 mRNA by in situ hybridization on tissue sections. mEphA1 was expressed in epithelial elements of skin, adult thymus, kidney and adrenal cortex. Taken together with previous Northern blotting data these results suggest that mEphA1 is expressed widely in differentiated epithelial cells.

Pro re nata medication for psychoses: an audit of practice in two metropolitan hospitals

Objective: To examine the use of pro re nata (PRN) (as needed) medication in hospitalized patients with psychotic disorders. Methods: Retrospective chart reviews were conducted at two large public psychiatry units situated in inner city general hospitals. Pro re nata medication prescription, administration and outcomes were examined during inpatient episodes of care for 184 consecutive admissions of patients diagnosed with a psychotic disorder. Patient demographics, diagnoses, and regularly prescribed medication were also recorded. All admissions were drawn from a three-month period from December 1998-February 1999. Results: The most prevalent diagnoses were schizophrenia related disorders (n = 111) and mania (n = 34). Substance use disorders (n = 49) were the most common comorbid dis-orders. Pro re nata medication was administered during the acute phase of 82% of admissions. Drugs prescribed Pro re nata were mostly typical antipsychotics, benzodiazepines and/or anti-cholinergics. Coprescription of typical antipsychotics PRN with regularly scheduled atypical antipsychotics was common (64%). Pro re nata medications accounted for 31% of the total antipsychotic dose and 28% of the total anxiolytic dose administered during acute treatment. Higher daily doses of PRN medication were given to manic patients, males, younger patients and those with substance use disorders. Pro re nata prescriptions usually specified a maximum daily dose (87%) but rarely gave indications for use (6%). Adminis-tration records frequently lacked a specified reason for use (48%) or a notation of outcome (64%). Unit staff noted medication-related morbidity in 37% of patients receiving PRN medication, compared to 3% of patients receiving only regularly scheduled medication. Extrapyramidal symptoms (EPS) were most frequently associated with administration of PRN haloperidol (Relative Risk vs other PRN medications = 5.61, 95% CI = 2.36-13.73). Conclusions: Pro re nata medications comprised a significant part of the treatment which psychotic patients received. The common practice of coprescribing PRN typical antipsychotics with scheduled atypical antipsychotics is potentially problematical since administration of PRN medication is associated with significant medication related morbidity. Preferential use of benzodiazepines as PRN agents may minimize this morbidity and foster subsequent compliance with regularly prescribed antipsychotics.

Development of preferences for the human body shape in infancy

Two studies investigated the development of infants' visual preferences for the human body shape. In Study 1, infants of 12,15 and 18 months were tested in a standard preferential looking experiment, in which they were shown paired line drawings of typical and scrambled bodies. Results indicated that the 18-month-olds had a reliable preference for the scrambled body shapes over typical body shapes, while the younger infants did not show differential responding. In Study 2, 12- and 18-month-olds were tested with the same procedure, except that the typical and scrambled body stimuli were photographic images. The results of Study 2 again indicated that only the 18-month-olds had a reliable preference for the scrambled body shapes. This finding contrasts sharply with infants' precocious preferences for human faces, suggesting that infants' learning about human faces and human bodies follow different developmental trajectories. (C) 2002 Elsevier Science B.V. All rights reserved.

Polarised infrared and differential scanning calorimetry studies on oriented vinyl pipe materials

The molecular orientation in a conventionally extruded PVC pipe, a uniaxially oriented PVC pipe and a biaxially oriented PVC pipe has been studied via Infrared dichroism. The degree of order or crystallinity has also been studied by Differential Scanning Calorimetry and also via Infrared Spectroscopy. The fundamental structural difference between the conventional and oriented pipes was that polymer chains were preferentially aligning in the hoop direction for oriented pipes whereas they were fairly isotropic in the conventional pipe with a slight preferential alignment in the axial direction. Analysis of the C-Cl stretching mode indicated that the uniaxially oriented pipe had much higher alignment of the C-Cl bond in the axial direction than the biaxial pipe, which correlates with higher fracture toughness for circumferential cracking in the biaxial pipe. Both DSC and Infrared spectroscopy detected little change in the crystallinity or order in the oriented pipes compared to the conventionally extruded pipes. (C) 2002 Kluwer Academic Publishers.

Hydrofluoric acid pre-treatment for improving 13C CPMAS NMR spectral quality of forest soils in south-east Queensland, Australia

Hydrofluoric acid (HF) was used to pre-treat forest soils of south-east Queensland for assessing the effectiveness of iron (Fe) removal, carbon (C) composition using C-13 cross-polarisation (CP) with magic-angle-spinning (MAS) nuclear magnetic resonance (NMR) before and after the HF pre-treatment, and the improvement of C-13 CPMAS NMR spectra. Soil samples were collected from 4 experimental sites of different soil types, harvest residue management or prescribed burning, and tree species. More than 86% of Fe was in all soil types removed by the HF treatment. The C-13 NMR spectral quality was improved with increased resolution, especially in the alkyl C and O-alkyl C regions, and reduced NMR run-time (1-5 h per sample compared with >20 h per sample without the pre-treatment). The C composition appeared to alter slightly after the pre-treatment, but this might be largely due to improved spectrometer conditions and increased resolution leading to more accurate NMR spectral integration. Organic C recovery after HF pre-treatment varied with soil types and forest management, and soluble soil organic matter (SOM) could be lost during the pre-treatment. The Fourier Transform-Infrared (FT-IR) spectra of HF extracts indicated the preferential removal of carboxylic C groups during the pre-treatment, but this could also be due to adsorbed water on the mineral matter. The NMR spectra revealed some changes in C composition and quality due to residue management and decomposition. Overall, the HF treatment was a useful pre-treatment for obtaining semi-quantitative C-13 CPMAS NMR spectra of subtropical Australian forest soils.

Selective ingestion of pelagic versus benthic algae by the cockle Cerastoderma edule (Linne, 1758)

The pre-ingestive selection of microphytobenthic algae by the cockle Cerastoderma edule was studied in comparison with diets containing the pelagic diatom Phaeodactylum tricomutum. Treatments with the different diets covered a range of seston concentrations and organic content similar to field conditions. Rejection rates of C. edule exposed to the different treatments were significantly correlated with the concentration of total particulate matter. No significant differences in total rejection rates were found between pelagic and benthic diets. Organic rejection rate was significantly correlated with particulate organic matter of the treatments and no significant differences were found between both diets. Selection efficiency was significantly correlated with particulate organic matter concentration in both diets and no significant differences were found between the diets. Analysis of the pseudofeces composition by flow cytometry from cockles exposed to a mixed diet of microphytobenthic algae and P. tricornutum, showed a preferential ingestion of the pelagic diatom. Benthic species, such as small pennates and Navicula sp., were preferentially ingested in comparison to larger microphytobenthic species. The largest microphytobenthic species, Cylindrotheca sp., was significantly rejected. In general, C. edule is an opportunistic filter feeder that takes advantage of both pelagic and benthic algal cells.

Mast cells and oral inflammation

Mast cells are mobile granule-containing secretory cells that are distributed preferentially about the microvascular endothelium in oral mucosa and dental pulp. The enzyme profile of mast cells in oral tissues resembles that of skin, with most mast cells expressing the serine proteases tryptase and chymase. Mast cells in oral tissues contain the pro-inflammatory cytokine tumour necrosis factor-alpha in their granules, and release of this promotes leukocyte infiltration during evolving inflammation in several conditions, including lichen planus, gingivitis, pulpitis, and periapical inflammation, through induction of endothelial-leukocyte adhesion molecules. Mast cell synthesis and release of other mediators exerts potent immunoregulatory effects on other cell types, while several T-lymphocyte-derived cytokines influence mast cell migration and mediator release. Mast cell proteases may contribute to alterations in basement membranes in inflammation in the oral cavity, such as the disruptions that allow cytotoxic lymphocytes to enter the epithelium in oral lichen planus. A close relationship exists among mast cells, neural elements, and laminin, and this explains the preferential distribution of mast cells in tissues. Mast cells are responsive to neuropeptides and, through their interaction with neural elements, form a neural immune network with Langerhans cells in mucosal tissues. This facilitates mast cell degranulation in response to a range of immunological and non-immunological stimuli. Because mast cells play a pivotal role in inflammation, therapies that target mast cell functions could have value in the treatment of chronic inflammatory disorders in the oral cavity.