A new small molecule C5a receptor antagonist inhibits the reverse-passive arthus reaction and endotoxic shock in rats

C5a is implicated as a pathogenic factor in a wide range of immunoinflammatory diseases, including sepsis and immune complex disease, Agents that antagonize the effects of C5a could be useful in these diseases. We have developed some novel C5a antagonists and have determined the acute anti-inflammatory properties of a new small molecule C5a receptor antagonist against C5a- and LPS-induced neutrophil adhesion and cytokine expression, as well as against some hallmarks of the reverse Arthus reaction in rats. We found that a single i.v. dose (1 mg/kg) of this antagonist inhibited both C5a- and LPS-induced neutropenia and elevated levels of circulating TNF-alpha, as well as polymorphonuclear leukocyte migration, increased TNF-alpha levels and vascular leakage at the site of immune complex deposition. These results indicate potent anti-inflammatory activities of a new C5a receptor antagonist and provide more evidence for a key early role for C5a in sepsis and the reverse Arthus reaction. The results support a role for antagonists of C5a receptors in the therapeutic intervention of immunoinflammatory disease states such as sepsis and immune complex disease.

Numerical modelling of double diffusion driven reactive flow transport in deformable fluid-saturated porous media with particular consideration of temperature-dependent chemical reaction rates

Numerical methods ave used to solve double diffusion driven reactive flow transport problems in deformable fluid-saturated porous media. in particular, thp temperature dependent reaction rate in the non-equilibrium chemical reactions is considered. A general numerical solution method, which is a combination of the finite difference method in FLAG and the finite element method in FIDAP, to solve the fully coupled problem involving material deformation, pore-fluid flow, heat transfer and species transport/chemical reactions in deformable fluid-saturated porous media has been developed The coupled problem is divided into two subproblems which are solved interactively until the convergence requirement is met. Owing to the approximate nature of the numerical method, if is essential to justify the numerical solutions through some kind of theoretical analysis. This has been highlighted in this paper The related numerical results, which are justified by the theoretical analysis, have demonstrated that the proposed solution method is useful for and applicable to a wide range of fully coupled problems in the field of science and engineering.

Both beta(2)- and beta(1)-adrenergic receptors mediate hastened relaxation and phosphorylation of phospholamban and troponin I in ventricular myocardium of fallot infants, consistent with selective coupling of beta(2)-adrenergic receptors to G(s)-protein

Background-In adult human heart, both beta(1)- and beta(2)-adrenergic receptors mediate hastening of relaxation; however, it is unknown whether this also occurs in infant heart. We compared the effects of stimulation of beta(1)- and beta(2)-adrenergic receptors on relaxation and phosphorylation of phospholamban and troponin I in ventricle obtained from infants with tetralogy of Fallot. Methods and Results-Myocardium dissected from the right ventricular outflow tract of 27 infants (age range 2-1/2 to 35 months) with tetralogy of Fallot was set up to contract 60 times per minute. Selective stimulation of beta(1)-adrenergic receptors with (-)-norepinephrine (NE) and beta(2)-adrenergic receptors with (-)-epinephrine (EPI) evoked phosphorylation of phospholamban (at serine-16 and threonine-17) and troponin I and caused concentration-dependent increases in contractile force (-log EC50 [mol/L] NE 5.5+/-0.1, n=12; -EPI 5.6+/-0.1, n=13 patients), hastening of the time to reach peak force (-log EC50 [mol/L] NE 5.8+/--0.2; EPI 5.8+/-0.2) and 50% relaxation (-log EC50 [mol/L] NE 5.7+/-0.2: EPI 5.8+/-0.1), Ventricular membranes from Fallot infants, labeled with (-)-[I-125]-cyanopindolol, revealed a greater percentage of beta(1)- (71%) than beta(2)-adrenergic receptors (29%). Binding of (-)-epinephrine to beta(2)-receptors underwent greater GTP shifts than binding of (-)-norepinephrine to beta(1)-receptors. Conclusions-Despite their low density, beta(2)-adrenergic receptors are nearly as effective as beta(1)-adrenergic receptors of infant Fallot ventricle in enhancing contraction, relaxation, and phosphorylation of phospholamban and troponin I, consistent with selective coupling to G(s)-protein.

Prediction of rock alteration patterns: a potential tool in mineral exploration

Hydrothermal alteration of a quartz-K-feldspar rock is simulated numerically by coupling fluid flow and chemical reactions. Introduction of CO2 gas generates an acidic fluid and produces secondary quartz, muscovite and/or pyrophyllite at constant temperature and pressure of 300 degrees C and 200 MPa. The precipitation and/or dissolution of the secondary minerals is controlled by either mass-action relations or rate laws. In our simulations the mass of the primary elements are conserved and the mass-balance equations are solved sequentially using an implicit scheme in a finite-element code. The pore-fluid velocity is assumed to be constant. The change of rock volume due to the dissolution or precipitation of the minerals, which is directly related to their molar volume, is taken into account. Feedback into the rock porosity and the reaction rates is included in the model. The model produces zones of pyrophyllite quartz and muscovite due to the dissolution of K-feldspar. Our model simulates, in a simplified way, the acid-induced alteration assemblages observed in various guises in many significant mineral deposits. The particular aluminosilicate minerals produced in these experiments are associated with the gold deposits of the Witwatersrand Basin.

General scales of community reaction to noise (dissatisfaction and perceived affectedness) are more reliable than scales of annoyance

General measures of reaction to noise, which assess the respondent's perceived affectedness or dissatisfaction, appear to be more valid and internally consistent than more narrow measures, such as specific assessment of noise annoyance. However, the test-retest reliability of general and specific measures has yet to be compared. As a part of the large-scale Sydney Airport Health Study, 97 respondents participated in the same interview twice, several weeks apart. Test-retest reliabilities were found to be significant (p

Large mitochondrial repeats multiplied during the polymerase chain reaction

The number of repeats in repetitive DNA like micro- and minisatellites is often determined by polymerase chain reaction (PCR). When we counted repeats in an array of mitochondrial repeats in the cattle tick (Boophilus microplus) we found that the number of repeats increased during PCR. Multiplication of the repeats was independent of the primers used to amplify the region, the PCR annealing temperature and the length of the PCR product. The use of PCR to determine the number of repeats in arrays needs to be reassessed. For long repeats, a subset of samples should always be analysed by Southern blot hybridization to confirm the PCR results.

Identification of the coupling between skeletal muscle store-operated Ca2+ entry and the inositol trisphosphate receptor

Examination of store-operated Ca2+ entry (SOC) in single, mechanically skinned skeletal muscle cells by confocal microscopy shows that the inositol 1,4,5-trisphosphate (IP3) receptor acts as a sarcoplasmic reticulum [Ca2+] sensor and mediates SOC by physical coupling without playing a key role in Ca2+ release from internal stores, as is the case with various cell types in which SOC was investigated previously. The results have broad implications for understanding the mechanism of SOC that is essential for cell function in general and muscle function in particular. Moreover, the study ascribes an important role to the IN receptors in skeletal muscle, the role of which with respect to Ca2+ homeostasis was ill defined until now.

Discriminating between task-relevant and task-irrelevant stimuli - The effects on autonomic orienting and secondary task reaction time

The effect that the difficulty of the discrimination between task-relevant and task-irrelevant stimuli has on the relationship between skin conductance orienting and secondary task reaction time (RT) was examined. Participants (N = 72) counted the number of longer-than-usual presentations of one shape (task-relevant) and ignored presentations of another shape (task-irrelevant). The difficulty of discriminating between the two shapes varied across three groups (low, medium, and high difficulty). Simultaneous with the primary counting task, participants performed a secondary RT task to acoustic probes presented 50, 150, and 2000 ms following shape onset. Skin conductance orienting was larger, and secondary RT at the 2000 ms probe position was slower during task-relevant shapes than during task-irrelevant shapes in the low-difficulty group. This difference declined as the discrimination difficulty was increased, such that there was no difference in the high-difficulty group. Secondary RT was slower during task-irrelevant shapes than during task-relevant shapes only in the medium-difficulty group-and only at the 150 ms probe position in the first half of the experiment. The close relationship between autonomic orienting and secondary RT at the 2000 ms probe position suggests that orienting reflects the resource allocation that results from the number of matching features between a stimulus input and a mental representation primed as significant.

On the solute coupling at the moving solid/liquid interface during equiaxed solidification

Integral mass conservation was widely accepted for the solute coupling to solve solute redistribution during equiaxed solidification so far. The present study revealed that the integral form was invalid for moving boundary problems as it could not represent the mass balance at the moving interface. Accordingly, differential mass conservation at the solid/liquid interface was used to solve solute diffusion for spherical geometry. The model was applied for hydrogen diffusion in solidification to validate that the hydrogen enrichment was significant and depended on the growth rate. (c) 2006 American Institute of Physics.

Visitors' reaction to Pinnawala Elephant Orphanage in Sri Lanka

Pinnawala Elephant Orphanage (PEO) is a unique captive elephant-based recreation facility in Sri Lanka. Over 35,000 visitors (both local and foreign) visit the PEO per month on average for a variety of reasons. However, little or no attempt has been made to examine their reaction to its activities. This paper reports preliminary findings from two visitor surveys (one local and one foreign) conducted at the PEO to examine the characteristics of visitors, the satisfaction they gained from the visit, their attitudes towards conservation of the elephant, their reactions to the current facilities available at the orphanage, and their opinions and maximum willingness to pay (WTP) to enter the PEO. It is found that, although some variations occurred between the samples, the majority of all respondents showed a similar reaction to the activities and facilities at the Orphanage. However, some differences are evident between these two samples in relation to satisfaction received, responses to the WTP elicitation and attitudes towards the information and interpretive facilities. Overall, the majority of the respondents indicated that their support for the conservation of the Asian elephant had increased considerably with their visit to the Orphanage. This indicates that considerable unrecorded and as yet unutilised support could be generated both financially and otherwise to conserve this endangered species through wildlife based recreation facilities such as PEO in Sri Lanka.

Epstein-Barr virus encephalitis in a renal allograft recipient diagnosed by polymerase chain reaction on cerebrospinal fluid and successfully treated with ganciclovir

Epstein–Barr virus (EBV) encephalitis has been reported rarely in the context of solid-organ and bone-marrow transplantation [1]. We report a case of a renal transplant recipient who developed EBV encephalitis following OKT3 therapy for acute allograft rejection. The diagnosis was expedited by the detection of EBV DNA in the cerebrospinal fluid (CSF) by nested polymerase chain reaction (PCR). Moreover, clinical recovery and clearance of CSF EBV DNA appeared to follow the institution of parenteral ganciclovir treatment.