Enhanced oxygen diffusivity in interfaces of nanocrystalline ZrO2.Y2O3

First measurements of oxygen grain boundary diffusion coefficients in nanocrystalline yttria-doped ZrO(2) (n-ZrO(2).6.9 mol % Y(2)O(3)) are presented. The (18)O diffusion profiles measured by secondary ion mass spectroscopy are much deeper in the nanocrystalline specimens than in single crystals. An oxygen diffusivity, D(B), in the grain boundaries can be deduced, which is approximately 3 orders of magnitude higher than in single crystals. From the present data the temperature variation of the oxygen grain boundary diffusivity, D(B) = 2.0 x 10(-5) exp (-0.91 eVk(B)T) m(2)s, and the oxygen surface exchange coefficient, k = 1.4 x 10(-2) exp (-1.13 eVk(B)T) ms, are derived.     

Pain perception is altered by a nucleotide polymorphism in SCN9A

The gene SCN9A is responsible for three human pain disorders. Nonsense mutations cause a complete absence of pain, whereas activating mutations cause severe episodic pain in paroxysmal extreme pain disorder and primary erythermalgia. This led us to investigate whether single nucleotide polymorphisms (SNPs) in SCN9A were associated with differing pain perception in the general population. We first genotyped 27 SCN9A SNPs in 578 individuals with a radiographic diagnosis of osteoarthritis and a pain score assessment. A significant association was found between pain score and SNP rs6746030; the rarer A allele was associated with increased pain scores compared to the commoner G allele (P = 0.016). This SNP was then further genotyped in 195 pain-assessed people with sciatica, 100 amputees with phantom pain, 179 individuals after lumbar discectomy, and 205 individuals with pancreatitis. The combined P value for increased A allele pain was 0.0001 in the five cohorts tested (1277 people in total). The two alleles of the SNP rs6746030 alter the coding sequence of the sodium channel Nav1.7. Each was separately transfected into HEK293 cells and electrophysiologically assessed by patch-clamping. The two alleles showed a difference in the voltage-dependent slow inactivation (P = 0.042) where the A allele would be predicted to increase Nav1.7 activity. Finally, we genotyped 186 healthy females characterized by their responses to a diverse set of noxious stimuli. The A allele of rs6746030 was associated with an altered pain threshold and the effect mediated through C-fiber activation. We conclude that individuals experience differing amounts of pain, per nociceptive stimulus, on the basis of their SCN9A rs6746030 genotype.     

Effect of complement consumption by cobra venom factor on the the course of primary infection with simian immunodeficiency virus in rhesus monkeys

Cobra venom factor (CVF)-induced consumption of complement proteins was used to investigate the role of complement in vivo in the immunopathogenesis of simian immunodeficiency virus of macaques (SIVmac) infection in rhesus monkeys. Repeated administration of CVF was shown to deplete complement to <5% of baseline hemolytic activity of serum complement for 10 days in a normal monkey. Three groups of SIVmac-infected animals were then evaluated: monkeys treated with CVF resulting in complement depletion from days -1 to 10 postinfection, monkeys treated with CVF resulting in complement depletion from days 10 to 21 postinfection, and control monkeys that received no CVF. CD8+ SIVmac-specific cytotoxic T lymphocyte (CTL) generation and CD4+ T lymphocyte depletion during primary infection were not affected by CVF treatment. Viral load, assessed by measurements of plasma p27gag antigen and viral RNA, was transiently higher during the first 4 weeks following infection in the CVF-treated monkeys and the subsequent clinical course in these treated animals was accelerated. These results suggest that complement proteins may participate in immune defense mechanisms that decrease virus replication following the initial burst of intense viremia during primary SIVmac infection. However, we cannot rule out that the observed increased virus replication was induced by immune activation resulting from the administration of a foreign antigen to these monkeys.     

Defensive active coping facilitates chronic hyperglycaemia and endothelial dysfunction in African men: The SABPA study

Background

Dissociation between behavioural defensive active coping (AC) control albeit physiological “loss of control” responses was associated with silent ischaemia and structural wall abnormalities in African men. Whether it applies to structural alterations and endothelial dysfunction is uncertain. We therefore aimed to determine AC ethnic-gender specific receiver operating characteristic (ROC) carotid intima media far wall (CIMTf) cut points best associated with 24-h BP, -silent ischaemia and glycated haemoglobin (HbA1c).

Methods

Participants included African and Caucasians (N = 317) without pre-existing stroke or atrial fibrillation, aged 45 ± 9 years. The Coping Strategy Indicator was used to measure AC. Ultrasound CIMTf, ambulatory BP, silent ischaemia and fasting blood samples were obtained.

Results

Between 69 and 77% of AC African men showed above normal diastolic BP and HbA1c levels compared to 44–48% of AC Caucasian men. In AC African women, 41–60% showed above normal BP, silent ischaemia and HbA1c levels compared to 17–44% of their Caucasian counterparts. ROC curve analyses, detecting optimal CIMTf cut points, ranged between 0.57 and 0.65 mm (BP) and 0.71 and 0.74 mm (silent ischaemia) in AC ethnic-gender groups. Only HbA1C (> 5.7%), with a sensitivity/specificity 47%/74%, after controlling for confounders, predicted structural alterations at an optimal cut point of 0.69 mm in AC African men (OR 4.5; 95% CI 2.93–18.73).

Conclusion

Novel findings of behavioural resilience were apparent in the AC African female despite a high prevalence of risk markers. In AC males, chronic hyperglycaemia facilitated endothelial dysfunction, i.e. a physiological “loss of control” and susceptibility to stroke risk.     

Questionable effects of Myocrisin in experimental arthritis in rabbits.

In 18 rabbits arthritis was induced in one knee joint by injection with 0.2 ml 3% ovalbumin 4 weeks after sensitization by 3% ovalbumin and 2 mg/ml tubercle bacilli suspended in Freunds incomplete adjuvant. Half of the rabbits were treated with Myocrisin 4 mg i.m. once a week during the experimental period lasting 4-5 months. At killing, both knee joints were examined macroscopically and microscopically. In all rabbits a distinct synovitis was found in the injected knee joint. Histologically, the changes were most pronounced in the rabbits not treated with Myocrisin. An activity index of the synovial membrane changes in the Myocrisin-treated and untreated cases was calculated to 6.3 and 3.6 respectively. Some changes were also found in the uninjected knee joints of 50% of the rabbits. In contrast to some other works, this preliminary investigation suggests that antigen-induced experimental arthritis is suppressed by gold. We feel that this model of experimental arthritis may be suitable for trying out the effect of various drugs.     

Biomechanical finite-element investigation of the position of the centre of resistance of the upper incisors

The position of the centre of resistance (CR) is an essential parameter regarding the planning of orthodontic tooth movements. In the present investigation, the combined CR of the upper four incisors was determined numerically using the finite-element (FE) method. Based on a commercially available three-dimensional data set of a maxilla, including all 16 teeth, as well as known and earlier determined material parameters, FE models of the upper incisors and their surrounding tooth-supporting structures were generated. In the FE system, the model of the anterior segment was loaded with torques of 10 Nmm each at the lateral incisors. The FE model indicated that the individual incisors moved independently, although they were blocked with a steel wire of dimension 0.46 x 0.65 mm(2). The individual CRs were located at 5 mm distal and 9 and 12 mm apical to the centre of the lateral brackets. Thus, the classical view of a combined CR for the anterior segment was disproved and the planning of orthodontic tooth movements of the upper incisors should no longer be based on that concept.     

Contact areas of the tibiotalar joint.

The contact areas between the articular surfaces of the talus and tibia are essential for understanding the mobility of the ankle joint. The purpose of our study was to reveal the contact area among the superior articular surface of the trochlea tali (target surface T) and the inferior articular surface of the tibia (query surface Q) under non-weight-bearing conditions in plantar flexion and dorsiflexion. Twenty cadaveric foot specimens were dissected and scanned by a three-dimensional (3D) laser scanner to obtain data point sets. These point sets were triangulated and a registration procedure performed to avoid any intersection of the two joint surfaces. For all points of the query surface Q, the closest distance to T was measured. In 11 of the 20 ankle joints, the contact area was larger in plantar flexion, in 5 it was nearly of equal size, and in 4 the two surfaces were found in a better congruence in dorsiflexion. The two articular surfaces can be in point or line contact and cause different motions while T is gliding on Q, so the original geometry of ligaments must be carefully reconstructed after injury or during total ankle replacement.     

A comparative assessment of the roles of CD8 and CD2 in the functions of activated murine CD8+ T lymphocytes.

Both CD8 and CD2 are T cell surface receptors involved in physical cell interaction and in transmembrane signalling. The present paper addresses their role in the induction of two different functions of the cloned murine cytotoxic T cell C196: target cell lysis and IFN-gamma production. These functions were induced in C196 either by stimulation with the specific stimulator/target cell P815 or, bypassing specific recognition, by the aCD3 hybridoma 145-2C11 or by solid phase aTCR antibodies. These responses were tested for their susceptibility to inhibition/enhancement by a panel of aCD8 and aCD2 mAb. In addition, CD8 deficient and CD8/CD2 double-deficient variants of C196 were transfected with the CD8 and CD2 genes and the resulting cell lines were analysed for their functional capacities. The following results were obtained: (i) CD8 is primarily important in the specific recognition process of activated CTL; (ii) transmembrane signalling of activated CTL through the TCR does not require CD8, nor is it sensitive to modification through CD8; (iii) CTL can nevertheless be directly activated through CD8; however, this is restricted to induction of cytotoxicity but does not result in IFN-gamma production; (iv) CD2 does not seem to be important in any of these responses.     

Monitoring of a single post-infusion blood sample to estimate the actual peak and trough concentration of tobramycin in critically ill patients

The therapy of critically ill patients with aminoglycoside antibiotics requires a careful dosing to achieve effective drug concentrations and to avoid toxic effects.

Objective: To evaluate if a single blood sample per dosing interval 3 or 8 hours after infusion of tobramycin is appropriate to estimate the actual serum concentration 30 minutes after infusion (C_peak30) and at the end of the dosing interval (C_22h) in critically ill patients. Methods: A total of 32 patients of the intensive care unit (ICU) with an individualized once-daily dosing regimen involved in an intensified drug monitoring of tobramycin were analyzed retrospectively. The first day, serum concentrations 3 and 8 hours after the end of infusion (C_3h and C_8h) were both used for calculations of C_peak30 and C_22h performed by a one-compartmental Bayesian estimation method (ABBOTTBASE). The subsequent days, each calculation included a single blood sample (C_3h or C_8h) as well as the corresponding available monitoring data of the previous dosing intervals. Estimation error was analyzed including bias and precision. The influence of some factors such as severity of illness (APACHE II score) and renal function (creatinine clearance) on the estimation error was investigated by multiple linear regression analysis (MLRA). Results: In the first monitored dosing interval, C_peak30 was overestimated and C_22h underestimated by 1.72 and –0.29 μg/ml on median, respectively. The maximum deviation from the true C_peak30 and C_22h was –9.20/+8.57 and –1.90 μg/ml, respectively. The first day, prediction of potentially toxic C_22h above 1 mg/ml by an estimation value above 1 mg/ml was possible in 4 of 6 cases only. The subsequent days, mean error (ME) of peak estimations of –0.34 μg/ml and a root mean squared error (RMSE) of 1.84 μg/ml indicated a small underestimation when C_3h was used and an overestimation when C_8h was used for calculation (ME 1.04 and RMSE 2.83 μg/ml). The difference on ME and RMSE was statistically significant. C_22h values outside of the target range (a total of 10 observations) were predicted with sensitivity of 60% in each case. Prediction error of increased C_22h was partly considerable and showed the trend to greater underestimation with increasing C_22h in MLRA. Increasing serum creatinine (β = 0.429, p = 0.011) and decreasing creatinine clearance (β = –0.324, p = 0.039) were only identified as variables affecting the trough level in MLRA. Conclusions: In the critically ill, C_3h but not C_8h of tobramycin permitted the estimation of the C_peak30 in most cases with satisfactory bias and precision starting with 2^nd monitored dosing interval. However, high trough levels requiring an adjustment of dose or dosing interval could not be safely predicted; prediction error was intolerable when C_22h exceeded the target range of trough level. Data indicate that at least in patients with any sign of renal dysfunction, the measuring of the interesting levels should be preferred to the tested single-point based estimations.